EyeMedsNow

Contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin/clavulanate.

• The following are discussed in more detail in other sections of the labeling:
  • Anaphylactic reactions [See Warnings and Precautions (5.1) in package insert].
  • Hepatic dysfunction [See Warnings and Precautions (5.2) in package insert].
  • CDAD  [See Warnings and Precautions (5.3) in package insert].
• The most frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy because of drug related adverse reactions. The overall incidence of adverse reactions, and in particular diarrhea, increased with the higher recommended dose.
• Other less frequently reported adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache.
• In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of amoxicillin/clavulanate for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of amoxicillin/clavulanate for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse event profile seen was comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes. [See Clinical Studies (14.2) in package insert.]
• The following adverse reactions have been reported during postmarketing use of amoxicillin/clavulanate:
  • Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black“hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. [See Warnings and Precautions (5.3) in package insert.]
  • Hypersensitivity reactions: Pruritus, angioedema, serumsickness–like reactions (urticaria or skinrash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens Johnson syndrome, acute generalized exanthematouspustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. [See Warnings and Precautions (5.1) in package insert.]
  • Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin/clavulanate. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported. [See Contraindications (4.2), Warnings and Precautions (5.2) in package insert.]
  • Renal: Interstitial nephritis, hematuria, and crystalluria have been reported. [See Overdosage (10) in package insert].
  • Hemic and lymphatic systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of the patients treated with amoxicillin/clavulanate. There have been reports of increased prothrombin time in patients receiving amoxicillin/clavulanate and anticoagulant therapy concomitantly. [See Drug Interactions (7.2) in package insert.]
  • Central nervous system: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.
  • Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin/clavulanate. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with amoxicillin/clavulanate, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin/clavulanate should be discontinued and appropriate therapy instituted.
• Hepatic dysfunction: Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin/clavulanate. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
• Clostridioides difficile (formerly Clostridium difficile) associated diarrhea (CDAD):
  • CDAD has been reported with use of nearly all antibacterial agents, including amoxicillin/clavulanate, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
  • C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin- producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
  • If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
• Skin rash in patients with mononucleosis: A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin/clavulanate should not be administered to patients with mononucleosis.
• Potential for microbial overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin/clavulanate potassium should be discontinued and appropriate therapy instituted.
• Phenylketonurics: Amoxicillin/clavulanate chewable tablets and amoxicillin/clavulanate powder for oral solution contain aspartame which contains phenylalanine. Each 200 mg chewable tablet of amoxicillin/clavulanate contains 2.1 mg phenylalanine; each 400 mg chewable tablet contains 4.2 mg phenylalanine; each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL oral suspension contains 7 mg phenylalanine. The other formulations of amoxicillin/clavulanate do not contain phenylalanine.
• Development of drug-resistant bacteria: Prescribing amoxicillin/clavulanate in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug resistant bacteria.
• Information for the patient: 
  • Amoxicillin/clavulanate may be taken every 8 hours or every 12 hours, depending on the dose prescribed.
  • Antibacterial drugs, including amoxicillin/clavulanate, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin/clavulanate is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
  • Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin/clavulanate or other antibacterial drugs in the future.
  • Diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician.
  • Keep suspension refrigerated.
  • Shake well before using.
  • When dosing a child with the suspension (liquid) of amoxicillin/clavulanate, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use.
  • Bottles of suspension of amoxicillin/clavulanate may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with hypersensitivity to apraclonidine or any other component of this medication, as well as systemic clonidine. It is also contraindicated in patients receiving monoamine oxidase inhibitors (MAO inhibitors).

• In clinical studies the overall discontinuation rate related to Apraclonidine Ophthalmic Solution was 15%.
• The most commonly reported events leading to discontinuation included (in decreasing order of frequency), hyperemia, pruritus, tearing, discomfort, lid edema, dry mouth, and foreign body sensation.
• The following adverse reactions (incidences) were reported in clinical studies of Apraclonidine Ophthalmic Solution as being possibly, probably, or definitely related to therapy:
  • Ocular:
    • The following adverse reactions were reported in 5% to 15% of the patients: discomfort, hyperemia, and pruritus.
    • The following adverse reactions were reported in 1% to 5% of the patients: blanching, blurred vision, conjunctivitis, discharge, dry eye, foreign body sensation, lid edema, and tearing.
    • The following adverse reactions were reported in less than 1% of the patients: abnormal vision, blepharitis, blepharoconjunctivitis, conjunctival edema, conjunctival follicles, corneal erosion, corneal infiltrate, corneal staining, edema, irritation, keratitis, keratopathy, lid disorder, lid erythema, lid margin crusting, lid retraction, lid scales, pain, photophobia.
  • Non-ocular:
    • Dry mouth occurred in approximately 10% of the patients.
    • The following adverse reactions were reported in less than 3% of the patients: abnormal coordination, asthenia, arrhythmia, asthma, chest pain, constipation, contact dermatitis, depression, dermatitis, dizziness, dry nose, dyspnea, facial edema, headache, insomnia, malaise, myalgia, nausea, nervousness, paresthesia, parosmia, peripheral edema, pharyngitis, rhinitis, somnolence, and taste perversion.
• Consult package insert for additional information.

• Not for injection or oral ingestion.
• FOR TOPICAL OPHTHALMIC USE ONLY.
• General:
  • Glaucoma patients on maximally tolerated medical therapy who are treated with apraclonidine 0.5% ophthalmic solution to delay surgery should have their visual fields monitored periodically. 
  • Although the topical use of Apraclonidine Ophthalmic Solution has not been studied in renal failure patients, structurally related clonidine undergoes a significant increase in half-life in patients with severe renal impairment. Close monitoring of cardiovascular parameters in patients with impaired renal function is advised if they are candidates for topical apraclonidine therapy. Close monitoring of cardiovascular parameters in patients with impaired liver function is also advised as the systemic dosage form of clonidine is partly metabolized in the liver.
  • While the topical administration of Apraclonidine Ophthalmic Solution had minimal effect on heart rate or blood pressure in clinical studies evaluating glaucoma patients, the preclinical pharmacology profile of this drug suggests that caution should be observed in treating patients with severe, uncontrolled cardiovascular disease, including hypertension.
  • Apraclonidine 0.5% Ophthalmic Solution should be used with caution in patients with coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, Raynaud's disease, or thromboangiitis obliterans. Caution and monitoring of depressed patients are advised since apraclonidine has been infrequently associated with depression.
  • Apraclonidine can cause dizziness and somnolence. Patients who engage in hazardous activities requiring mental alertness should be warned of the potential for a decrease in mental alertness while using apraclonidine.
  • Topical ocular administration of two drops of 0.5, 1.0 and 1.5% apraclonidine ophthalmic solution to New Zealand albino rabbits three times daily for one month resulted in sporadic and transient instances of minimal corneal edema in the 1.5% group only; no histopathological changes were noted in those eyes.
  • Use of Apraclonidine Ophthalmic Solution can lead to an allergic-like reaction characterized wholly or in part by the symptoms of hyperemia, pruritus, discomfort, tearing, foreign body sensation, and edema of the lids and conjunctiva. If ocular allergic-like symptoms occur, apraclonidine ophthalmic solution therapy should be discontinued.
• Consult package insert for additional information.

None listed in package insert.

Should not be used in anyone who has demonstrated a previous hypersensitivity or known allergic reaction to any ingredient of the formulation because it may recur.

• The following serious adverse reactions are described below and elsewhere in the labeling:
  • Photophobia and blurred vision [See Warnings and Precautions (5.1) in package insert].
  • Elevation in blood pressure [See Warnings and Precautions (5.2) in package insert].
• The following adverse reactions have been identified following use of atropine sulfate ophthalmic solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Ocular adverse reactions: Eye pain and stinging occurs upon instillation of atropine sulfate ophthalmic solution. Other commonly occurring adverse reactions include: blurred vision, photophobia, superficial keratitis and decreased lacrimation. Allergic reactions such as papillary conjunctivitis, contact dermatitis, and lid edema may also occur less commonly.
• Systemic adverse reactions: Systemic effects of atropine are related to its anti-muscarinic activity. These adverse events reported include: dryness of skin, mouth, and throat from decreased secretions from mucus membranes, restlessness, irritability or delirium from stimulation of the central nervous system; tachycardia; flushed skin of the face and neck.

• Photophobia and blurred vision: Photophobia and blurred vision due to pupil unresponsiveness and cycloplegia may last up to 2 weeks.
• Elevation of blood pressure: Elevation of blood pressure from systemic absorption has been reported following conjunctival instillation of recommended doses of atropine sulfate ophthalmic solution, USP 1%.

None listed in package insert.

Contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with AUGMENTIN.

• The following are discussed in more detail in other sections of the labeling:
  • Anaphylactic reactions [See Warnings and Precautions (5.1) in package insert].
  • Hepatic dysfunction [See Warnings and Precautions (5.2) in package insert].
  • CDAD  [See Warnings and Precautions (5.3) in package insert].
• The most frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy because of drug related adverse reactions. The overall incidence of adverse reactions, and in particular diarrhea, increased with the higher recommended dose.
• Other less frequently reported adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache.
• In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of AUGMENTIN for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of AUGMENTIN for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse event profile seen was comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes. [See Clinical Studies (14.2) in package insert.]
• The following adverse reactions have been reported during postmarketing use of AUGMENTIN:
  • Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black“hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. [See Warnings and Precautions (5.3) in package insert.]
  • Hypersensitivity reactions: Pruritus, angioedema, serumsickness–like reactions (urticaria or skinrash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens Johnson syndrome, acute generalized exanthematouspustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. [See Warnings and Precautions (5.1) in package insert.]
  • Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with AUGMENTIN. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported. [See Contraindications (4.2), Warnings and Precautions (5.2) in package insert.]
  • Renal: Interstitial nephritis, hematuria, and crystalluria have been reported. [See Overdosage (10) in package insert].
  • Hemic and lymphatic systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of the patients treated with AUGMENTIN. There have been reports of increased prothrombin time in patients receiving AUGMENTIN and anticoagulant therapy concomitantly. [See Drug Interactions (7.2) in package insert.]
  • Central nervous system: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.
  • Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including AUGMENTIN. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with AUGMENTIN, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, AUGMENTIN should be discontinued and appropriate therapy instituted.
• Hepatic dysfunction: Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of AUGMENTIN. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
• Clostridioides difficile (formerly Clostridium difficile) associated diarrhea (CDAD):
  • CDAD has been reported with use of nearly all antibacterial agents, including AUGMENTIN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
  • C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin- producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
  • If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
• Skin rash in patients with mononucleosis: A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, AUGMENTIN should not be administered to patients with mononucleosis.
• Potential for microbial overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin/clavulanate potassium should be discontinued and appropriate therapy instituted.
• Phenylketonurics: AUGMENTIN Chewable tablets and AUGMENTIN Powder for Oral Solution contain aspartame which contains phenylalanine. Each 200 mg chewable tablet of AUGMENTIN contains 2.1 mg phenylalanine; each 400 mg chewable tablet contains 4.2 mg phenylalanine; each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL oral suspension contains 7 mg phenylalanine. The other formulations of AUGMENTIN do not contain phenylalanine.
• Development of drug-resistant bacteria: Prescribing AUGMENTIN in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug resistant bacteria.
• Information for the patient: 
  • AUGMENTIN may be taken every 8 hours or every 12 hours, depending on the dose prescribed.
  • Antibacterial drugs, including AUGMENTIN, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When AUGMENTIN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
  • Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by AUGMENTIN or other antibacterial drugs in the future.
  • Diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician.
  • Keep suspension refrigerated.
  • Shake well before using.
  • When dosing a child with the suspension (liquid) of AUGMENTIN, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use.
  • Bottles of suspension of AUGMENTIN may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine.
• Consult package insert for additional information.

None listed in package insert.

None listed in package insert.

• The following serious adverse reactions are discussed in greater detail in other sections of the package insert:
  • Gastrointestinal perforations and fistulae [See Warnings and Precautions (5.1) in package insert].
  • Surgery and wound healing complications [See Warnings and Precautions (5.2) in package insert]
  • Hemorrhage [See Warnings and Precautions (5.3) in package insert].
  • Arterial thromboembolic events [See Warnings and Precautions (5.4) in package insert].
  • Venous thromboembolic events [See Warnings and Precautions (5.5) in package insert].
  • Hypertension [See Warnings and Precautions (5.6) in package insert].
  • Posterior reversible encephalopathy syndrome [See Warnings and Precautions (5.7) in package insert].
  • Renal injury and proteinuria [See Warnings and Precautions (5.8) in package insert].
  • Infusion-related reactions [See Warnings and Precautions (5.9) in package insert].
  • Ovarian failure [See Warnings and Precautions (5.11) in package insert].
  • Congestive heart failure [See Warnings and Precautions (5.12). in package insert].
• The most common adverse reactions observed in clinical studies in patients receiving Avastin as a single agent or in combination with other anti-cancer therapies at a rate > 10% were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.
• Across clinical studies, Avastin was discontinued in 8% – 22% of patients because of adverse reactions [See Clinical Studies (14) in package insert].
• Consult package insert for additional information.

• Gastrointestinal perforations and fistulae:
  • Serious and sometimes fatal gastrointestinal perforation occur at a higher incidence in patients receiving Avastin compared to patients receiving chemotherapy. The incidence ranged from 0.3% to 3% across clinical studies, with the highest incidence in patients with a history of prior pelvic radiation. Perforation can be complicated by intra-abdominal abscess, fistula formation, and the need for diverting ostomies. The majority of perforations occurred within 50 days of the first dose [See Adverse Reactions (6.1) in package insert].
  • Serious fistulae (including, tracheoesophageal, bronchopleural, biliary, vaginal, renal and bladder sites) occur at a higher incidence in patients receiving Avastin compared to patients receiving chemotherapy. The incidence ranged from < 1% to 1.8% across clinical studies, with the highest incidence in patients with cervical cancer. The majority of fistulae occurred within 6 months of the first dose. Patients who develop a gastrointestinal vaginal fistula may also have a bowel obstruction and require surgical intervention, as well as a diverting ostomy.
  • Avoid Avastin in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. Discontinue in patients who develop gastrointestinal perforation, tracheoesophageal fistula or any Grade 4 fistula. Discontinue in patients with fistula formation involving any internal organ.
• Surgery and wound healing complications:
  • In a controlled clinical study in which Avastin was not administered within 28 days of major surgical procedures, the incidence of wound healing complications, including serious and fatal complications, was 15% in patients with mCRC who underwent surgery while receiving Avastin and 4% in patients who did not receive Avastin. In a controlled clinical study in patients with relapsed or recurrent GBM, the incidence of wound healing events was 5% in patients who received Avastin and 0.7% in patients who did not receive Avastin [See Adverse Reactions (6.1) in package insert].
  • In patients who experience wound healing complications during Avastin treatment, withhold Avastin until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer for at least 28 days following major surgery and until adequate wound healing. The safety of resumption of AVASTIN after resolution of wound healing complications has not been established [See Dosage and Administration (2.9) in package insert].
  • Necrotizing fasciitis including fatal cases, has been reported in patients receiving Avastin, usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Discontinue in patients who develop necrotizing fasciitis.
• Hemorrhage:
  • Avastin can result in two distinct patterns of bleeding: minor hemorrhage, most commonly Grade 1 epistaxis; and serious, and in some cases fatal, hemorrhage. Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, hematemesis, CNS hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin compared to patients receiving chemotherapy alone. Across clinical studies, the incidence of Grades 3-5 hemorrhagic events ranged from 0.4% to 7% in patients receiving Avastin [See Adverse Reactions (6.1) in package insert].
  • Serious or fatal pulmonary hemorrhage occurred in 31% of patients with squamous NSCLC and 4% of patients with non-squamous NSCLC receiving Avastin with chemotherapy compared to none of the patients receiving chemotherapy alone.
  • An evaluation for the presence of varices is recommended within 6 months of initiation of Avastin in patients with HCC. There is lack of clinical data to support the safety of Avastin in patients with variceal bleeding within 6 months prior to treatment, untreated or incompletely treated varices with bleeding, or high risk of bleeding because these patients were excluded from clinical trials of Avastin in HCC [See Clinical Studies (14.10) in package insert].
  • Do not administer Avastin to patients with recent history of hemoptysis of ½ teaspoon or more of red blood. Discontinue in patients who develop a Grades 3-4 hemorrhage.
• Arterial thromboembolic events:
  • Serious, sometimes fatal, arterial thromboembolic events (ATE) including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina, occurred at a higher incidence in patients receiving Avastin compared to patients receiving chemotherapy. Across clinical studies, the incidence of Grades 3-5 ATE was 5% in patients receiving Avastin with chemotherapy compared to ≤ 2% in patients receiving chemotherapy alone; the highest incidence occurred in patients with GBM. The risk of developing ATE was increased in patients with a history of arterial thromboembolism, diabetes, or greater than 65 years old [See Use in Specific Populations (8.5) in package insert].
  • Discontinue in patients who develop a severe ATE. The safety of reinitiating Avastin after an ATE is resolved is not known.
• Venous thromboembolic events:
  • An increased risk of venous thromboembolic events (VTE) was observed across clinical studies. In Study GOG-0240, Grade 3-4 VTE was reported in 11% of patients receiving Avastin with chemotherapy compared with 5% of patients receiving chemotherapy alone. In EORTC 26101, the incidence of Grade 3-4 VTE was 5% in patients receiving Avastin with chemotherapy compared to 2% in patients receiving chemotherapy alone.
  • Discontinue Avastin in patients with a Grade 4 VTE, including pulmonary embolism [See Adverse Reactions (6.1) in package insert].
• Hypertension:
  • The incidence of severe hypertension is increased in patients receiving Avastin as compared to patients receiving chemotherapy alone. Across clinical studies, the incidence of Grade 3-4 hypertension ranged from 5% to 18%.
  • Monitor blood pressure every two to three weeks during treatment with Avastin. Treat with appropriate anti-hypertensive therapy and monitor blood pressure regularly. Continue to monitor blood pressure at regular intervals in patients with Avastin-induced or -exacerbated hypertension after discontinuing Avastin. Withhold Avastin in patients with severe hypertension that is not controlled with medical management; resume once controlled with medical management. Discontinue in patients who develop hypertensive crisis or hypertensive encephalopathy.
• Posterior reversible encephalopathy syndrome (PRES):
  • PRES was reported in < 0.5% of patients across clinical studies. The onset of symptoms occurred from 16 hours to 1 year after the first dose. PRES is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of PRES.
  • Discontinue Avastin in patients who develop PRES. Symptoms usually resolve or improve within days after discontinuing Avastin, although some patients have experienced ongoing neurologic sequelae. The safety of reinitiating Avastin in patients who developed PRES is not known.
• Renal injury and proteinuria:
  • The incidence and severity of proteinuria is higher in patients receiving Avastin as compared to patients receiving chemotherapy. Grade 3 (defined as urine dipstick 4+ or ˃ 3.5 grams of protein per 24 hours) to Grade 4 (defined as nephrotic syndrome) ranged from 0.7% to 7% in clinical studies. The overall incidence of proteinuria (all grades) was only adequately assessed in Study BO17705, in which the incidence was 20%. Median onset of proteinuria was 5.6 months (15 days to 37 months) after initiating Avastin. Median time to resolution was 6.1 months (95% CI: 2.8, 11.3). Proteinuria did not resolve in 40% of patients after median follow-up of 11.2 months and required discontinuation of Avastin in 30% of the patients who developed proteinuria [See Adverse Reactions (6.1) in package insert].
  • In an exploratory, pooled analysis of patients from seven randomized clinical studies, 5% of patients receiving Avastin with chemotherapy experienced Grades 2-4 (defined as urine dipstick 2+ or greater or ˃ 1 gram of protein per 24 hours or nephrotic syndrome) proteinuria. Grades 2-4 proteinuria resolved in 74% of patients. Avastin was reinitiated in 42% of patients. Of the 113 patients who reinitiated Avastin, 48% experienced a second episode of Grade 2-4 proteinuria.
  • Nephrotic syndrome occurred in ˂ 1% of patients receiving Avastin across clinical studies, in some instances with fatal outcome. In a published case series, kidney biopsy of 6 patients with proteinuria showed findings consistent with thrombotic microangiopathy. Results of a retrospective analysis of 5805 patients who received Avastin with chemotherapy and 3713 patients who received chemotherapy alone, showed higher rates of elevated serum creatinine levels (between 1.5 to 1.9 times baseline levels) in patients who received Avastin. Serum creatinine levels did not return to baseline in approximately one-third of patients who received Avastin.
  • Monitor proteinuria by dipstick urine analysis for the development or worsening of proteinuria with serial urinalyses during Avastin therapy. Patients with a 2+ or greater urine dipstick reading should undergo further assessment with a 24-hour urine collection. Withhold for proteinuria greater than or equal to 2 grams per 24 hours and resume when less than 2 grams per 24 hours. Discontinue in patients who develop nephrotic syndrome.
  • Data from a post-marketing safety study showed poor correlation between UPCR (Urine Protein/Creatinine Ratio) and 24-hour urine protein [Pearson Correlation 0.39 (95% CI: 0.17, 0.57)].
• Infusion-related reactions:
  • Infusion-related reactions reported across clinical studies and postmarketing experience include hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, Grade 3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis. In clinical studies, infusion-related reactions with the first dose occurred in < 3% of patients and severe reactions occurred in 0.4% of patients.
  • Decrease the rate of infusion for mild, clinically insignificant infusion reactions. Interrupt the infusion in patients with clinically significant infusion reactions and consider resuming at a slower rate following resolution. Discontinue in patients who develop a severe infusion reaction and administer appropriate medical therapy (e.g., epinephrine, corticosteroids, intravenous antihistamines, bronchodilators and/or oxygen).
• Embryo-fetal toxicity: Avastin may cause fetal harm based on its mechanism of action and findings from animal studies. Congenital malformations were observed with the administration of bevacizumab to pregnant rabbits during organogenesis every 3 days at a dose as low as a clinical dose of 10 mg/kg. Furthermore, animal models link angiogenesis and VEGF and VEGFR 2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with and for 6 months after the last dose of Avastin [See Use in Specific Populations (8.1, 8.3) in package insert].
• Ovarian failure: The incidence of ovarian failure was 34% vs. 2% in premenopausal women receiving Avastin with chemotherapy as compared to those receiving chemotherapy alone for adjuvant treatment of a solid tumor. After discontinuing Avastin, recovery of ovarian function at all time points during the post-treatment period was demonstrated in 22% of women receiving Avastin. Recovery of ovarian function is defined as resumption of menses, a positive serum β-HCG pregnancy test, or a FSH level < 30 mIU/mL during the post-treatment period. Long-term effects of Avastin on fertility are unknown. Inform females of reproductive potential of the risk of ovarian failure prior to initiating Avastin [See Adverse Reactions (6.1), Use in Specific Populations (8.3) in package insert].
• Congestive heart failure (CHF):
  • Avastin is not indicated for use with anthracycline-based chemotherapy. The incidence of Grade ≥ 3 left ventricular dysfunction was 1% in patients receiving Avastin compared to 0.6% of patients receiving chemotherapy alone. Among patients who received prior anthracycline treatment, the rate of CHF was 4% for patients receiving Avastin with chemotherapy as compared to 0.6% for patients receiving chemotherapy alone.
  • In previously untreated patients with a hematological malignancy, the incidence of CHF and decline in left ventricular ejection fraction (LVEF) were increased in patients receiving Avastin with anthracycline-based chemotherapy compared to patients receiving placebo with the same chemotherapy regimen. The proportion of patients with a decline in LVEF from baseline of ≥ 20% or a decline from baseline of 10% to < 50%, was 10% in patients receiving Avastin with chemotherapy compared to 5% in patients receiving chemotherapy alone. Time to onset of left-ventricular dysfunction or CHF was 1 to 6 months after the first dose in at least 85% of the patients and was resolved in 62% of the patients who developed CHF in the Avastin arm compared to 82% in the placebo arm. Discontinue Avastin in patients who develop CHF.

None listed in package insert.

Contraindicated in patients with hypersensitivity to any component of this product.

• The most frequently reported ocular adverse reaction reported in patients receiving AzaSite was eye irritation. This reaction occurred in approximately 1% – 2% of patients.
• Other adverse reactions associated with the use of AzaSite were reported in less than 1% of patients and included ocular reactions (blurred vision, burning, stinging and irritation upon instillation, contact dermatitis, corneal erosion, dry eye, eye pain, itching, ocular discharge, punctate keratitis, visual acuity reduction) and non-ocular reactions (dysgeusia, facial swelling, hives, nasal congestion, periocular swelling, rash, sinusitis, urticaria).
• Consult package insert for additional information.

• Topical ophthalmic use only: NOT FOR INJECTION. AzaSite is indicated for topical ophthalmic use only, and should not be administered systemically, injected subconjunctivally, or introduced directly into the anterior chamber of the eye.
• Anaphylaxis and hypersensitivity with systemic use of Azithromycin: In patients receiving systemically administered azithromycin, serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported. The potential for anaphylaxis or other hypersensitivity reactions should be considered based on known hypersensitivity to azithromycin when administered systemically.
• Growth of resistant organisms with prolonged use: As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If super-infection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and where appropriate, fluorescein staining.
• Avoidance of contact lenses: Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.

None listed in package insert.

Contraindicated in persons with known or suspected hypersensitivity to any of this medication's components.

• The most frequently reported adverse reactions were transient eye burning/stinging (approximately 30%), headaches (approximately 15%), and bitter taste (approximately 10%). The occurrence of these events was generally mild.
• The following events were reported in 1% – 10% of patients: asthma, conjunctivitis, dyspnea, eye pain, fatigue, influenza-like symptoms, pharyngitis, pruritus, rhinitis and temporary blurring. Some of these events were similar to the underlying disease being studied.
• Consult package insert for additional information.

• Azelastine Hydrochloride Ophthalmic Solution is for ocular use only and not for injection or oral use. 
• Information for patients:
  • To prevent contaminating the dropper tip and solution, care should be taken not to touch any surface, the eyelids, or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use. This product is sterile when packaged.
  • Patients should be advised not to wear a contact lens if their eye is red. OPTIVAR™ should not be used to treat contact lens related irritation. The preservative in OPTIVAR™, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling OPTIVAR™ before they insert their contact lenses.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug.

Contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

• In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related adverse reactions was 0.6%.
• In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse reactions was approximately 1%. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see Clinical Studies (14.2) in package insert].
• Adults:
  • Multiple-dose regimens:
    • Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (4% – 5%), nausea (3%) and abdominal pain (2% – 3%) being the most frequently reported.
    • No other treatment-related adverse reactions occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following:
      • Cardiovascular: Palpitations, chest pain.
      • Gastrointestinal: Dyspepsia, flatulence, vomiting, melena and cholestatic jaundice.
      • Genitourinary: Monilia, vaginitis and nephritis.
      • Nervous system: Dizziness, headache, vertigo and somnolence.
      • General: Fatigue.
      • Allergic: Rash, pruritus, photosensitivity and angioedema.
  • Single 1-gram dose regimen:
    • Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.
    • Adverse reactions that occurred in patients on the single one-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%) and vaginitis (1%).
  • Single 2-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Adverse reactions that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%) and dizziness (1%). The majority of these complaints were mild in nature.
• Pediatric patients:
  • Single and multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients.
  • With any of the treatment regimens, no other adverse reactions occurred in pediatric patients treated with azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:
    • Cardiovascular: Chest pain.
    • Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools and oral moniliasis.
    • Hematologic and lymphatic: Anemia and leukopenia.
    • Nervous system: Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness and insomnia.
    • General: Fever, face edema, fatigue, fungal infection, malaise and pain.
    • Allergic: Rash and allergic reaction.
    • Respiratory: Cough increased, pharyngitis, pleural effusion and rhinitis.
    • Skin and appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria and vesiculobullous rash.
    • Special senses: Conjunctivitis.
• Consult package insert for additional information.

• Hypersensitivity:
  • Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including acute generalized exanthematous pustulosis (AGEP), Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported. (See CONTRAINDICATIONS (4.1) in package insert).
  • Fatalities have been reported. Cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present.
  • If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
• Hepatotoxicity: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
• Infantile hypertrophic pyloric stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.
• QT prolongation: 
  • Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:
    • Patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure.
    • Patients on drugs known to prolong the QT interval.
    • Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
  • Elderly patients may be more susceptible to drug-associated effects on the QT interval.
• Clostridioides difficile (formerly Clostridium difficile) associated diarrhea (CDAD):
  • CDAD has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
  • C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
  • If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
• Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
• Use in sexually transmitted infections: azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.
• Development of drug-resistant bacteria: Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
• General patient counseling:
  • Azithromycin tablets and oral suspension can be taken with or without food.
  • Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously.
  • The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.
  • Direct patients or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant.
  • Patients should be counseled that antibacterial drugs including azithromycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future.
  • Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients who are hypersensitive to any component of this product.

• The most frequently reported adverse reactions reported in 5% to 10% of patients were blurred vision and bitter, sour or unusual taste. Adverse reactions occurring in 1% to 5% of patients were blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis.
• The following adverse reactions were reported at an incidence below 1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or sticky sensation, nausea, pharyngitis, tearing and urticaria.
• Consult package insert for additional information.

• ​Sulfonamide hypersensitivity reactions:
  • AZOPT® (brinzolamide ophthalmic suspension) 1% is a sulfonamide and although administered topically it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of AZOPT^® (brinzolamide ophthalmic suspension) 1%.
  • Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
  • Sensitization may recur when a sulfonamide is re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.
• Corneal endothelium: Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing AZOPT^® (brinzolamide ophthalmic suspension) 1% to this group of patients.
• Severe renal impairment: AZOPT^® (brinzolamide ophthalmic suspension) 1% has not been studied in patients with severe renal impairment (CrCl < 30 mL/min). Because AZOPT^® (brinzolamide ophthalmic suspension) 1% and its metabolite are excreted predominantly by the kidney, AZOPT^® (brinzolamide ophthalmic suspension) 1% is not recommended in such patients.
• Acute angle-closure glaucoma: The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. AZOPT^® (brinzolamide ophthalmic suspension) 1% has not been studied in patients with acute angle-closure glaucoma.
• Contact lens wear: The preservative in AZOPT^® (brinzolamide ophthalmic suspension) 1%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of AZOPT^® (brinzolamide ophthalmic suspension) 1%, but may be reinserted 15 minutes after instillation.

None listed in package insert.

This product should not be used in patients with a history of hypersensitivity to Bacitracin.

• Bacitracin has such a low incidence of allergenicity that for all practical purposes side reactions are practically non-existent. However, if such reaction should occur, therapy should be discontinued.

• Should not be used in deep-seated ocular infections or in those that are likely to become systemic.
• The prolonged use of antibiotic containing preparations may result in overgrowth of nonsusceptible organisms particularly fungi. If new infections develop during treatment appropriate antibiotic or chemotherapy should be instituted.

None listed in package insert.

Contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides, in patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides, and in patients with documented megaloblastic anemia due to folate deficiency.

BACTRIM is contraindicated in pediatric patients less than 2 months of age. BACTRIM is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.

Concomitant administration of BACTRIM with dofetilide is also contraindicated (See PRECAUTIONS in package insert.)

• The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). Fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including sulfamethoxazole and trimethoprim (See WARNINGS in package insert).
• Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura.
• Allergic reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, rash, periarteritis nodosa, systemic lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized erythematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND) (See WARNINGS in package insert).
• Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.
• Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine.
• Metabolic and nutritional: Hyperkalemia, hyponatremia (See PRECAUTIONS: Electrolyte Abnormalities in package insert), metabolic acidosis.
• Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.
• Psychiatric: Hallucinations, depression, apathy, nervousness.
• Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
• Musculoskeletal: Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported with BACTRIM, mainly in AIDS patients.
• Respiratory: Cough, shortness of breath and pulmonary infiltrates (See WARNINGS in package insert).
• Miscellaneous: Weakness, fatigue, insomnia.
• Consult package insert for additional information.

• Embryo-fetal toxicity: Some epidemiologic studies suggest that exposure to sulfamethoxazole/trimethoprim during pregnancy may be associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot. If sulfamethoxazole/trimethoprim is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential hazards to the fetus (See PRECAUTIONS in package insert).
• Hypersensitivity and other fatal reactions:
  • Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias.
  • Fatalities and serious adverse reactions including severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including sulfamethoxazole and trimethoprim (See ADVERSE REACTIONS in package insert).
  • Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported in association with sulfomethoxazole and trimethoprim treatment.
  • Other severe pulmonary adverse reactions occurring within days to week of sulfamethoxazole and trimethoprim initiation and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation or death have also been reported in patients and otherwise healthy individuals treated with sulfamethoxazole and trimethoprim products.
  • Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re- challenge with sulfamethoxazole and trimethoprim products, including sulfamethoxazole and trimethoprim, in patients with history of recent (days to weeks) exposure to sulfamethoxazole and trimethoprim.
  • Sulfamethoxazole and trimethoprim should be discontinued at the first appearance of skin rash or any sign of a serious adverse reaction. A skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AFND, AGEP, hepatic necrosis, or serious blood disorders (See PRECAUTIONS and ADVERSE REACTIONS in package insert). Clinical signs, such as rash, pharyngitis, fever, arthralgia, cough, chest pain, dyspnea, pallor, purpura or jaundice may be early indications of serious reactions.
• Thrombocytopenia: Sulfamethoxazole/trimethoprim-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported. Thrombocytopenia usually resolves within a week upon discontinuation of sulfamethoxazole/trimethoprim.
• Streptococcal infections and rheumatic fever: The sulfonamides should not be used for treatment of group A β-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.
• Clostridioides difficile (formerly Clostridium difficile) associated diarrhea (CDAD): 
  • CDAD has been reported with use of nearly all antibacterial agents, including BACTRIM, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
  • C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
  • If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
• Adjunctive treatment with leucovorin for Pneumocystis jiroveci pneumonia: Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for the treatment of HIV positive patients with Pneumocystis jirovecii pneumonia in a randomized placebo controlled trial.[citation to journal article] Co-administration of trimethoprim-sulfamethoxazole and leucovorin during treatment of Pneumocystis jirovecii pneumonia should be avoided.
• Development of drug resistant bacteria: Prescribing Bactrim (sulfamethoxazole and trimethoprim) tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
• Folate deficiency: 
  • BACTRIM should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states) and to those with severe allergies or bronchial asthma.
  • Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid therapy (See PRECAUTIONS, Geriatric Use in package insert).
• Hemolysis: In glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. This reaction is frequently dose-related.
• Hypoglycemia: Cases of hypoglycemia in non-diabetic patients treated with BACTRIM are seen rarely, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of BACTRIM are particularly at risk.
• Phenylalanine metabolism: Trimethoprim has been noted to impair phenylalanine metabolism, but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
• Porphyria and hypothyroidism: Like other drugs containing sulfonamides, BACTRIM can precipitate porphyria crisis and hypothyroidism. Avoid use of BACTRIM in patients with porphyria or thyroid dysfunction.
• Potential risk in the treatment of Pneumocystis jiroveci pneumonia in patients with Acquired Immunodeficiency Syndrome (AIDS):
  • AIDS patients may not tolerate or respond to BACTRIM in the same manner as non-AIDS patients. The incidence of side effects, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with BACTRIM therapy in AIDS patients who are being treated for P. jirovecii pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of BACTRIM in non-AIDS patients. Adverse effects are generally less severe in patients receiving BACTRIM for prophylaxis. A history of mild intolerance to BACTRIM in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis.[citation to journal article] However, if a patient develops skin rash or any sign of adverse reaction, therapy with BACTRIM should be reevaluated (See WARNINGS in package insert).
  • Co-administration of BACTRIM and leucovorin should be avoided with P. jirovecii pneumonia (See WARNINGS in package insert).
• Electrolyte abnormalities: 
  • High dosage of trimethoprim, as used in patients with P. jirovecii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.
  • Severe and symptomatic hyponatremia can occur in patients receiving BACTRIM, particularly for the treatment of P. jirovecii pneumonia. Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.
  • During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.
• Consult package insert for additional information.

None listed in package insert.

• Contraindicated in patients with ocular or periocular infections, in patients with active intraocular inflammation, and in patients with known hypersensitivity to brolucizumab or any of the excipients in BEOVU. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.

• The following potentially serious adverse reactions are described elsewhere in the labeling:
  • Hypersensitivity [See Contraindications (4.3) in package insert].
  • Endophthalmitis and retinal detachments [See Warnings and Precautions (5.1) in package insert].
  • Retinal vasculitis and/or retinal vascular occlusion [See Warnings and Precautions (5.2) in package insert].
  • Increase in intraocular pressure [See Warnings and Precautions (5.3) in package insert].
  • Thromboembolic events [See Warnings and Precautions (5.4) in package insert].
• Adverse reactions reported to occur in ≥ 1% of patients who received treatment with BEOVU pooled across the HAWK and HARRIER wet AMD clinical trials included: vision blurred (10%, including vision blurred, visual acuity reduced, visual acuity reduced transiently and visual impairment); cataract (7%); conjunctival hemorrhage (6%); vitreous floaters (5%); eye pain (5%); intraocular inflammation (4%, including anterior chamber cell, anterior chamber flare, anterior chamber inflammation, chorioretinitis, eye inflammation, iridocyclitis, iritis, retinal vasculitis, retinal vascular occlusion, uveitis, vitreous haze, vitritis); intraocular pressure increased (4%); retinal hemorrhage (4%); vitreous detachment (4%); conjunctivitis (3%); retinal pigment epithelial tear (3%); corneal abrasion (2%); hypersensitivity (2%, including urticaria, rash, pruritis, erythema); punctate keratitis (1%); retinal tear (1%); endophthalmitis (1%); blindness (1%, including blindness, blindness transient, amaurosis, and amaurosis fugax); retinal artery occlusion (1%); retinal detachment (1%); conjunctival hyperemia (1%); lacrimation increased (1%); abnormal sensation in eye (1%); detachment of retinal pigment epithelium (1%).
• Immunogenicity:
  • As with all therapeutic proteins, there is a potential for an immune response in patients treated with BEOVU. The immunogenicity of BEOVU was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to BEOVU in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to BEOVU with the incidence of antibodies to other products may be misleading.
  • Anti-brolucizumab antibodies were detected in the pre-treatment sample of 36% to 52% of treatment naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 67% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU.
  • The significance of anti-brolucizumab antibodies on the clinical effectiveness and safety of BEOVU is not known.

• Endophthalmitis and retinal detachments: Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachments [See Contraindications (4.1) and Adverse Reactions (6.1) in package insert]. Proper aseptic injection techniques must always be used when administering BEOVU. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately [See Dosage and Administration (2.4) and Patient Counseling Information (17) in package insert].
• Retinal vasculitis and/or retinal vascular occlusion: Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU [See Contraindications (4.2) and Adverse Reactions (6.1) in package insert]. Patients should be instructed to report any change in vision without delay.
• Increase in intraocular pressure: Acute increases in intraocular pressure (IOP) have been seen within 30 minutes of intravitreal injection including with BEOVU [See Adverse Reactions (6.1) in package insert]. Sustained IOP increases have also been reported. Both IOP and perfusion of the optic nerve head must be monitored and managed appropriately [See Dosage and Administration (2.4) in package insert].
• Thromboembolic events:
  • Although there was a low rate of arterial thromboembolic events (ATEs) observed in the BEOVU clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
  • The ATE rate in the two controlled 96-week neovascular AMD studies (HAWK and HARRIER) during the first 96-weeks was 4.5% (33 of 730) in the pooled brolucizumab arms compared with 4.7% (34 of 729) in the pooled aflibercept arms [See Clinical Studies (14.1) in package insert].
• Patient counseling information:
  • Advise patients that in the days following BEOVU administration, patients are at risk of developing endophthalmitis, retinal detachment, retinal vasculitis and/or retinal vascular occlusion. If the eye becomes red, sensitive to light, painful, or if a patient develops any change in vision, instruct the patient to seek immediate care from an ophthalmologist [See Warnings and Precautions (5.1, 5.2) in package insert].
  • Patients may experience temporary visual disturbances after an intravitreal injection with BEOVU and the associated eye examination [See Adverse Reactions (6.1) in package insert]. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

None listed in package insert.

Contraindicated in patients with a history of hypersensitivity reactions to bepotastine or any of the other ingredients [See Adverse Reactions (6.2) in package insert].

• The most common reported adverse reaction occurring in approximately 25% of subjects was a mild taste following instillation.
• Other adverse reactions occurring in 2% – 5% of subjects were eye irritation, headache, and nasopharyngitis.

• Contamination of tip and solution: To minimize contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.
• Contact lens wear: BEPREVE™ should not be used to treat contact lens-related irritation. BEPREVE™ should not be instilled while wearing contact lenses. Patient should remove contact lenses prior to instillation of BEPREVE™, because benzalkonium chloride may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of BEPREVE™.

None listed in package insert.

None listed in package insert.

• The most frequently reported ocular adverse reaction was conjunctival redness, reported in approximately 2% of patients. 
• Other adverse reactions reported in patients receiving Besivance^® occurring in approximately 1% – 2% of patients included: blurred vision, eye pain, eye irritation, eye pruritus and headache.
• Consult package insert for additional information.

• Not for injection into the eye.
• Growth of resistant organisms with prolonged use: As with other anti-infectives, prolonged use of BESIVANCE^®ophthalmic suspension may result in overgrowth of non-susceptible organisms, including fungi. If super-infection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.
• Avoidance of contact lenses: Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with Besivance^®.
• Patient counseling information:
  • Handling the container: Advise patients to avoid contaminating the applicator tip with material from the eye, fingers or other source.
  • Use with contact lenses: Advise patients not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with Besivance^®.
  • Dosing instructions: Patients should be instructed to invert closed bottle (upside down) and shake once before each use.

None listed in package insert.

Contraindicated in individuals known to be sensitive to iodine, or other components of this product.

• Local sensitivity has been exhibited by some individuals to povidone-iodine ophthalmic solution.

• FOR EXTERNAL USE ONLY. NOT FOR INTRAOCULAR INJECTION OR IRRIGATION.
• General: No studies are available in patients with thyroid disorders; therefore, caution is advised in using BETADINE^® 5% Sterile Ophthalmic Prep Solution in these patients due to the possibility of iodine absorption.

None listed in package insert.

Contraindicated in those individuals with bronchial asthma, or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease (See WARNINGS in package insert); sinus bradycardia; second and third degree atrioventricular block; overt cardiac failure (See WARNINGS in package insert); cardiogenic shock; or hypersensitivity to any component of these products.

• In clinical trials the use of BETAGAN^® ophthalmic solution has been associated with transient ocular burning and stinging in up to 1 in 3 patients, and with blepharoconjunctivitis in up to 1 in 20 patients. Decreases in heart rate and blood pressure have been reported (See CONTRAINDICATIONS and WARNINGS in package insert).
• The following adverse reactions have been reported rarely with the use of BETAGAN^® ophthalmic solution: Iridocyclitis, headache, transient ataxia, dizziness, lethargy, urticaria, and pruritus.
• Decreased corneal sensitivity has been noted in a small number of patients. Although levobunolol has minimal membrane-stabilizing activity, there remains a possibility of decreased corneal sensitivity after prolonged use.
• The following additional adverse reactions have been reported either with BETAGAN^® ophthalmic solution or ophthalmic use of other beta-adrenergic receptor blocking agents:
  • Body as a whole: headache, asthenia, chest pain.
  • Cardiovascular: bradycardia, arrhythmia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, congestive heart failure, palpitation, cardiac arrest.
  • Digestive: nausea, diarrhea.
  • Psychiatric: depression, confusion, increase in signs and symptoms of myasthenia gravis, paresthesia.
  • Skin: hypersensitivity, including localized and generalized rash, alopecia, Stevens-Johnson Syndrome.
  • Respiratory: bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnea, nasal congestion.
  • Urogenital: impotence.
  • Endocrine: masked symptoms of hypoglycemia in insulin-dependent diabetics (See WARNINGS in package insert).
  • Special senses: signs and symptoms of keratitis or eye allergy, blepharoptosis, visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis, and foreign body sensation in eye.
• ​Other reactions associated with the oral use of non-selective adrenergic receptor blocking agents should be considered potential effects with ophthalmic use of these agents.

• As with other topically applied ophthalmic drugs, BETAGAN^® may be absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with topical application of beta-adrenergic blocking agents (See CONTRAINDICATIONS in package insert). Additionally, ophthalmic beta-blockers may impair compensatory tachycardia and increase risk of hypotension.
• Cardiac failure: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure.
• In patients without a history of cardiac failure: Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, BETAGAN^® ophthalmic solution should be discontinued (See CONTRAINDICATIONS in package insert).
• Potentiation of vascular insufficiency: BETAGAN^® may potentiate syndromes associated with vascular insufficiency (i.e. Raynaud's phenomenon), and therefore, should be used with caution in these patients.
• Obstructive pulmonary disease: PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (e.g., CHRONIC BRONCHITIS, EMPHYSEMA) OF MILD OR MODERATE SEVERITY, BRONCHOSPASTIC DISEASE OR A HISTORY OF BRONCHOSPASTIC DISEASE (OTHER THAN BRONCHIAL ASTHMA OR A HISTORY OF BRONCHIAL ASTHMA, IN WHICH BETAGAN^® IS CONTRAINDICATED), SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS, INCLUDING BETAGAN^®. However, if BETAGAN^® is deemed necessary in such patients, then it should be administered cautiously since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta₂ receptors.
• Major surgery: 
  • The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic blocking agents may be appropriate. 
  • If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of such agonists as isoproterenol, dopamine, dobutamine or levarterenol (See OVERDOSAGE in package insert). 
• Diabetes mellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic blocking agents may mask the signs and symptoms of acute hypoglycemia.
• Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.
• Choroidal detachment:
  • Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy. 
  • These products contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
• General: 
  • BETAGAN^® (levobunolol hydrochloride ophthalmic solution, USP) sterile should be used with caution in patients with known hypersensitivity to other beta-adrenoceptor blocking agents. 
  • Use with caution in patients with known diminished pulmonary function. 
  • BETAGAN^® should be used with caution in patients who are receiving a beta-adrenergic blocking agent orally, because of the potential for additive effects on systemic beta-blockade or on intraocular pressure. Patients should not typically use two or more topical ophthalmic beta-adrenergic blocking agents simultaneously. 
  • Because of the potential effects of beta-adrenergic blocking agents on blood pressure and pulse rates, these medications must be used cautiously in patients with cerebrovascular insufficiency. Should signs or symptoms develop that suggest reduced cerebral blood flow while using BETAGAN^® ophthalmic solution, alternative therapy should be considered. 
  • In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires, in most cases, constricting the pupil with a miotic. BETAGAN^® ophthalmic solution has little or no effect on the pupil. When BETAGAN^® ophthalmic solution is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be followed with a miotic and not alone.
  • The preservative in BETAGAN^®, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft (hydrophilic) contact lenses should be instructed to remove contact lenses before administration of the solution and wait at least 15 minutes after instilling BETAGAN^® before reinserting soft contact lenses.
• Muscle weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis and generalized weakness).
• Drug interactions: 
  • Although BETAGAN^® ophthalmic solution used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with BETAGAN^® ophthalmic solution and epinephrine may occur. 
  • Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. 
  • Patients receiving beta-adrenergic blocking agents along with either oral or intravenous calcium antagonists should be monitored for possible atrioventricular conduction disturbances, left ventricular failure and hypotension. In patients with impaired cardiac function, simultaneous use should be avoided altogether. 
  • The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects on prolonging atrioventricular conduction time. 
  • Phenothiazine-related compounds and beta-adrenergic blocking agents may have additive hypotensive effects due to the inhibition of each other's metabolism.
• Risk of anaphylactic reaction: While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with hypersensitivity to any component of this product. Betaxolol ophthalmic solution is contraindicated in patients with sinus bradycardia, greater than a first degree atrioventricular block, cardiogenic shock, or patients with overt cardiac failure.

• Ocular:
  • Discomfort of short duration was experienced by one in four patients, but none discontinued therapy; occasional tearing has been reported. Rare instances of decreased corneal sensitivity, erythema, itching sensation, corneal punctate staining, keratitis, anisocoria, edema, and photophobia have been reported.
  • Additional medical events reported with other formulations of betaxolol include blurred vision, foreign body sensation, dryness of the eyes, inflammation, discharge, ocular pain, decreased visual acuity, and crusty lashes.
• Cardiovascular: Bradycardia, heart block and congestive failure. 
• Pulmonary: Pulmonary distress characterized by dyspnea, bronchospasm, thickened bronchial secretions, asthma and respiratory failure.
• Central nervous system: Insomnia, dizziness, vertigo, headaches, depression, lethargy, and increase in signs and symptoms of myasthenia gravis.
• Other: Hives, toxic epidermal necrolysis, hair loss and glossitis.

• Topically applied beta-adrenergic blocking agents may be absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with topical application of beta-adrenergic blocking agents. 
• Betaxolol ophthalmic solution has been shown to have a minor effect on heart rate and blood pressure in clinical studies. Caution should be used in treating patients with a history of cardiac failure or heart block. Treatment with betaxolol ophthalmic solution should be discontinued at the first signs of cardiac failure.
• General: Do not touch dropper tip to any surface as this may contaminate the solution.
• Diabetes mellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.
• Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents, which might precipitate a thyroid storm.
• Muscle weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopla, ptosis, and generalized weakness).
• Major surgery: Consideration should be given to the gradual withdrawal of beta-adrenergic blocking agents prior to general anesthesia because of the reduced ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli.
• Pulmonary: Caution should be exercised in the treatment of glaucoma patients with excessive restriction of pulmonary function. There have been reports of asthmatic attacks and pulmonary distress during betaxolol treatment. Although rechallenges of some such patients with ophthalmic betaxolol has not adversely affected pulmonary function test results, the possibility of adverse pulmonary effects in patients sensitive to beta-blockers cannot be ruled out.
• Risk from anaphylactic reaction: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.
• Ocular: In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle by constriction of the pupil with a miotic agent. Betaxolol has little or no effect on the pupil. When betaxolol ophthalmic solution is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with overt heart failure, cardiogenic shock, sinus bradycardia, second- or third-degree atrioventricular block, bronchial asthma or history of bronchial asthma, or severe chronic obstructive pulmonary disease, or hypersensitivity to any component of this product.
 

• The most frequently reported ocular reaction in clinical trials was burning/stinging on instillation and was comparable between BETIMOL^® ophthalmic solution and timolol maleate (approximately one in eight patients).
• The following adverse reactions were associated with use of BETIMOL^® ophthalmic solution in frequencies of more than 5% in two controlled, double-masked clinical studies in which 184 patients received 0.25% or 0.5% BETIMOL^® ophthalmic solution:
  • Ocular: dry eyes, itching, foreign body sensation, discomfort in the eye, eyelid erythema, conjunctival injection, and headache.
  • Body as a whole: headache.
• The following side effects were reported in frequencies of 1% to 5%:
  • Ocular: Eye pain, epiphora, photophobia, blurred or abnormal vision, corneal fluorescein staining, keratitis, blepharitis and cataracts.
  • Body as a whole: Allergic reactions, asthenia, common cold and pain in extremities.
  • Cardiovascular: Hypertension.
  • Digestive: Nausea.
  • Metabolic/nutritional: Peripheral edema.
  • Nervous system/psychiatry: Dizziness and dry mouth.
  • Respiratory: Respiratory infection and sinusitis.
• In addition, the following adverse reactions have been reported with ophthalmic use of beta blockers:
  • Ocular: Conjunctivitis, blepharoptosis, decreased corneal sensitivity, visual disturbances including refractive changes, diplopia and retinal vascular disorder.
  • Body as a whole: Chest pain.
  • Cardiovascular: Arrhythmia, palpitation, bradycardia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure and cardiac arrest.
  • Digestive: Diarrhea.
  • Endocrine: Masked symptoms of hypoglycemia in insulin-dependent diabetics (See WARNINGS in package insert).
  • Nervous system/psychiatry: Depression, impotence, increase in signs and symptoms of myasthenia gravis and paresthesia.
  • Respiratory: Dyspnea, bronchospasm, respiratory failure and nasal congestion.
  • Skin: Alopecia, hypersensitivity including localized and generalized rash, urticaria.

• As with other topically applied ophthalmic drugs, BETIMOL^® ophthalmic solution is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely, death in association with cardiac failure have been reported following systemic or topical administration of beta-adrenergic blocking agents.
• Cardiac failure: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe cardiac failure. 
• In patients without a history of cardiac failure, continued depression of the myocardium with betablocking agents over a period of time can, in some cases, lead to cardiac failure. BETIMOL^® ophthalmic solution should be discontinued at the first sign or symptom of cardiac failure.​
• Obstructive pulmonary disease: Patients with chronic obstructive pulmonary disease (e.g. chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma which are contraindications) should in general not receive beta-blocking agents.
• Major surgery: The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to a major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergicaliy mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents is recommended. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of beta-adrenergic agonists.
• Diabetes mellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia. 
• Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g. tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm. 
• General:
  • Because of the potential effects of beta-adrenergic blocking agents relative to blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with BETIMOL® ophthalmic solution, alternative therapy should be considered. 
  • There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. (See PRECAUTIONS, Information for Patients in package insert).
  • Muscle weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis, and generalized weakness). Beta-adrenergic blocking agents have been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
  • In angle-closure glaucoma, the goal of the treatment is to reopen the angle. This requires constricting the pupil. Betimol has no effect on the pupil. Therefore, if timolol is used in angle-closure glaucoma, it should always be combined with a miotic and not used alone.
  • Anaphylaxis: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.
  • The preservative benzalkonium chloride may be absorbed by soft contact lenses. Patients who wear soft contact lenses should wait 5 minutes after instilling Betimol before they insert their lenses.
  • Information for patients:
    • Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.
    • Patients should also be instructed that ocular solutions can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. (See PRECAUTIONS, General in package insert.)
    • Patients requiring concomitant topical ophthalmic medications should be instructed to administer these at least 5 minutes apart.
    • Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second- or third-degree atrioventricular block, or cardiac failure should be advised not to take this product (See CONTRAINDICATIONS in package insert).
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with sinus bradycardia, greater than a first degree atrioventricular block, cardiogenic shock, patients with overt cardiac failure, and hypersensitivity to any component of this product.

• The most frequently reported adverse reaction was transient ocular discomfort.
• The following other adverse reactions have been reported in small numbers of patients:
  • Ocular: Blurred vision, corneal punctate keratitis, foreign body sensation, photophobia, tearing, itching, dryness of eyes, erythema, inflammation, discharge, ocular pain, decreased visual acuity and crusty lashes. 
  • Cardiovascular: bradycardia, heart block and congestive failure.
  • Pulmonary: pulmonary distress characterized by dyspnea, bronchospasm, thickened bronchial secretions, asthma and respiratory failure.
  • Central nervous system: insomnia, dizziness, vertigo, headaches, depression, lethargy, and increase in signs and symptoms of myasthenia gravis.
  • Other: 
    • Hives, toxic epidermal necrolysis, hair loss and glossitis. Perversions of taste and smell have been reported.
    • In a 3-month, double-masked, active-controlled, multicenter study in pediatric patients, the adverse reaction profile of BETOPTIC^® S Ophthalmic Suspension 0.25% was comparable to that seen in adult patients.
• Additional medical events reported with other formulations of betaxolol include allergic reactions, decreased corneal sensitivity, corneal punctate staining which may appear in dendritic formation, edema and anisocoria.
• Consult package insert for additional information.

• General: As with many topically applied ophthalmic drugs, this drug is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic receptor inhibitors may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and death due to cardiac failure, have been reported with topical application of beta-adrenergic receptor inhibitors.
• Cardiac failure: BETOPTIC^® S ophthalmic suspension has been shown to have a minor effect on heart rate and blood pressure in clinical studies. Caution should be used in treating patients with a history of cardiac failure or heart block. Treatment with BETOPTIC^® S ophthalmic suspension should be discontinued at the first signs of cardiac failure.
• Diabetes mellitus: Beta-adrenergic receptor inhibitors should be administered with caution in patients subject to hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.
• Thyrotoxicosis: Beta-adrenergic receptor inhibitors may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic receptor inhibitors, which might precipitate a thyroid storm.
• Muscle weakness: Beta-adrenergic receptor inhibitors have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis and generalized weakness).
• Surgical anesthesia: The necessity or desirability of withdrawal of beta-adrenergic receptor inhibitors prior to major surgery is controversial. Beta-adrenergic receptor inhibitors impair the ability of the heart to respond to beta adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor inhibitors have experienced protracted, severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. In patients undergoing elective surgery, consider gradual withdrawal of beta-adrenergic receptor inhibitors. If necessary during surgery, the effects of beta-adrenergic receptor inhibitors may be reversed by sufficient doses of adrenergic agonists. 
• Bronchospasm and obstructive pulmonary disease: Caution should be exercised in the treatment of glaucoma patients with excessive restriction of pulmonary function. There have been reports of asthmatic attacks and pulmonary distress during betaxolol treatment. Although re-challenges of some such patients with ophthalmic betaxolol has not adversely affected pulmonary function test results, the possibility of adverse pulmonary effects in patients sensitive to beta-adrenergic receptor inhibitors cannot be ruled out.
• Atopy/Anaphylaxis: While taking beta-adrenergic receptor inhibitors, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.
• Angle-closure glaucoma: In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle. This may require constricting the pupil. Betaxolol has little or no effect on the pupil and should not be used alone in the treatment of angle-closure glaucoma.
• Vascular insufficiency: Because of potential effects of beta-adrenergic receptor inhibitors on blood pressure and pulse, these inhibitors should be used with caution in patients with vascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow or Raynaud’s phenomenon develop following initiation of therapy with BETOPTIC^® S, alternative therapy should be considered.
• Bacterial keratitis: Bacterial keratitis may occur with use of multiple dose containers of topical ophthalmic products when these containers are inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. Instruct patients on appropriate instillation techniques [See Patient Counseling Information (17) in package insert].
• Choroidal detachment: Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy.
• Contact lens wear: The preservative in BETOPTIC^® S ophthalmic suspension 0.25%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of BETOPTIC^® S ophthalmic suspension 0.25% but may be reinserted 15 minutes after instillation [See Patient Counseling Information (17) in package insert].

None listed in package insert.

Contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [See Adverse Reactions (6.2) in package insert].

• The following adverse reactions are described elsewhere in the labeling:
  • Pigmentation [See Warnings and Precautions (5.1) in package insert].
  • Eyelash changes [See Warnings and Precautions (5.2) in package insert].
  • Intraocular inflammation [See Warnings and Precautions (5.3) in package insert].
  • Macular edema [See Warnings and Precautions (5.4) in package insert].
  • Hypersensitivity [See Contraindications (4) in package insert].
• In clinical trials, the most frequent events associated with the use of bimatoprost ophthalmic solution, 0.03% occurring in approximately 15% to 45% of patients, in descending order of incidence, included: conjunctival hyperemia, growth of eyelashes, and ocular pruritus. Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.
• Ocular adverse events occurring in approximately 3% to 10% of patients, in descending order of incidence, included: ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, periorbital erythema, ocular irritation, and eyelash darkening. The following ocular adverse events reported in approximately 1% to 3% of patients, in descending order of incidence, included: eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, and conjunctival edema. In less than 1% of patients, intraocular inflammation was reported as iritis.
• Systemic adverse events reported in approximately 10% of patients were infections (primarily colds and upper respiratory tract infections). The following systemic adverse events reported in approximately 1% to 5% of patients, in descending order of incidence, included: headaches, abnormal liver function tests, asthenia and hirsutism.
• Consult package insert for additional information.

• Pigmentation:
  • Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known.
  • Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with bimatoprost ophthalmic solution, 0.03% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.
• Eyelash changes: Bimatoprost ophthalmic solution, 0.03% may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.
• Intraocular inflammation: Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis).
• Macular edema: Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. Bimatoprost ophthalmic solution, 0.03% should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.
• Bacterial keratitis: There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.
• Contact lens use: Bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution, 0.03% and may be reinserted 15 minutes following its administration.

None listed in package insert.