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Contraindicated in patients with known hypersensitivity to naproxen and naproxen sodium.

Naproxen should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (See WARNINGS: Anaphylactoid Reactions and PRECAUTIONS: Preexisting Asthma in package insert).

Naproxen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (See WARNINGS in package insert).

• Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis or osteoarthritis are listed below. In general, reactions in patients treated chronically were reported 2 to 10 times more frequently than they were in short-term studies in the 962 patients treated for mild to moderate pain or for dysmenorrhea. The most frequent complaints reported related to the gastrointestinal tract.
• A clinical study found gastrointestinal reactions to be more frequent and more severe in rheumatoid arthritis patients taking daily doses of 1500 mg naproxen compared to those taking 750 mg naproxen (see CLINICAL PHARMACOLOGY in package insert).
• In controlled clinical trials with about 80 pediatric patients and in well-monitored, open-label studies with about 400 pediatric patients with juvenile arthritis treated with naproxen, the incidence of rash and prolonged bleeding times were increased, the incidence of gastrointestinal and central nervous system reactions were about the same, and the incidence of other reactions were lower in pediatric patients than in adults.
• In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are:
  • Gastrointestinal (GI) experiences, including: heartburn, abdominal pain, nausea, constipation, diarrhea, dyspepsia, stomatitis.
  • Central nervous system: headache, dizziness, drowsiness, lightheadedness, vertigo.
  • Dermatologic: pruritus (itching), skin eruptions, ecchymoses, sweating, purpura.
  • Special senses: tinnitus, visual disturbances, hearing disturbances.
  • Cardiovascular: edema, palpitations.
  • General: dyspnea, thirst
• In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1% to 10% of patients.
  • Gastrointestinal (GI) experiences, including: flatulence, gross bleeding/perforation, GI ulcers (gastric/duodenal), vomiting
  • General: abnormal renal function, anemia, elevated liver enzymes, increased bleeding time, rashes
• The following are additional adverse experiences reported in <1% of patients taking naproxen during clinical trials and through postmarketing reports. Those adverse reactions observed through postmarketing reports are italicized.
  • Body as a whole: anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills and fever).
  • Cardiovascular: congestive heart failure, vasculitis, hypertension, pulmonary edema.
  • Gastrointestinal: inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, perforation and obstruction of the upper or lower gastrointestinal tract. Esophagitis, stomatitis, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease).
  • Hepatobiliary: jaundice, abnormal liver function tests, hepatitis (some cases have been fatal)
  • Hemic and lymphatic: eosinophilia, leucopenia, melena, thrombocytopenia, agranulocytosis, granulocytopenia, hemolytic anemia, aplastic anemia.
  • Metabolic and nutritional: hyperglycemia, hypoglycemia.
  • Nervous system: inability to concentrate, depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions
  • Respiratory: eosinophilic pneumonitis, asthma
  • Dermatologic: alopecia, urticaria, skin rashes, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa. If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.
  • Special senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema.
  • Urogenital: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine.
  • Reproduction (female): infertility.
• In patients taking NSAIDs, the following adverse experiences have also been reported in <1% of patients.
  • Body as a whole: fever, infection, sepsis, anaphylactic reactions, appetite changes, death.
  • Cardiovascular: hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction.
  • Gastrointestinal: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, glossitis, eructation.
  • Hepatobiliary: hepatitis, liver failure.
  • Hemic and lymphatic: rectal bleeding, lymphadenopathy, pancytopenia.
  • Metabolic and nutritional: weight changes.
  • Nervous system: anxiety, asthenia, confusion, nervousness, paresthesia, somnolence, tremors, convulsions, coma, hallucinations.
  • Respiratory: asthma, respiratory depression, pneumonia.
  • Dermatologic: exfoliative dermatitis.
  • Special senses: blurred vision, conjunctivitis.
  • Urogenital: cystitis, dysuria, oliguria/polyuria, proteinuria.
• Consult package insert for additional information.

• Cardiovascular effects:
  • Cardiovascular thrombotic events:
    • Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
    • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS: Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation in package insert).
    • Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS in package insert).
  • Hypertension: NSAIDs, including naproxen, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including naproxen, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
  • Congestive heart failure and edema: Fluid retention, edema, and peripheral edema have been observed in some patients taking NSAIDs. Naproxen should be used with caution in patients with fluid retention, hypertension, or heart failure. Since each ANAPROX or ANAPROX DS tablet contains 25 mg or 50 mg of sodium (about 1 mEq per each 250 mg of naproxen), and each teaspoonful of NAPROSYN Suspension contains 39 mg (about 1.5 mEq per each 125 mg of naproxen) of sodium, this should be considered in patients whose overall intake of sodium must be severely restricted.
• Gastrointestinal effects – risk of ulceration, bleeding, and perforation:
  • NSAIDs, including naproxen, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal.
  • These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only 1 in 5 patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic.
  • NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
  • Epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of an NSAID or aspirin potentiated the risk of bleeding (see PRECAUTIONS: Drug Interactions in package insert). Although these studies focused onupper gastrointestinal bleeding, there is reason to believe that bleeding at other sites may be similarly potentiated.
  • NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated.
  • Renal effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and the elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state (see WARNINGS: Advanced Renal Disease).
• Advanced renal disease: No information is available from controlled clinical studies regarding the use of naproxen in patients with advanced renal disease. Therefore, treatment with naproxen is not recommended in these patients with advanced renal disease. If naproxen therapy must be initiated, close monitoring of the patient's renal function is advisable and patients should be adequately hydrated.
• Anaphylactoid reactions: As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen. Naproxen should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma in package insert). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.
• Skin reactions: NSAIDs, including naproxen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
• Pregnancy: In late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus.
• General:
  • Naproxen-containing products such as NAPROSYN, EC-NAPROSYN, ANAPROX, ANAPROX DS, NAPROSYN SUSPENSION, ALEVE®, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
  • Naproxen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.
  • Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically.
  • The pharmacological activity of naproxen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, noninflammatory painful conditions.
  • Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.
• Hepatic effects:
  • Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including naproxen. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
  • A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with naproxen.
  • If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), naproxen should be discontinued.
  • Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. It is prudent to use the lowest effective dose.
• Hematological Effects
  • Anemia is sometimes seen in patients receiving NSAIDs, including naproxen. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including naproxen, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
  • NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving naproxen who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
• Preexisting asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin- sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, naproxen should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
• Information for patients: Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
  • Naproxen, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS: Cardiovascular Effects in package insert).
  • Naproxen, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation in package insert).
  • Naproxen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
  • Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
  • Patients should be informed of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
  • Patients should be informed of the signs of an anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS in package insert).
  • In late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus.
  • Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with naproxen.

• Cardiovascular Risk:
  • NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS in package insert).
  • Naproxen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS in package insert).
• Gastrointestinal Risk:
  • NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).

Contraindicated in individuals who have shown hypersensitivity to any of this drug's components.

• The events, which have been chosen for inclusion due to their seriousness, frequency of reporting, possible causal connection to NATACYN^®, or a combination of these factors include: allergic reaction, change in vision, chest pain, corneal opacity, dyspnea, eye discomfort, eye edema, eye hyperemia, eye irritation, eye pain, foreign body sensation, paresthesia, and tearing.
• Consult package insert for additional information.

• General:
  • FOR TOPICAL OPHTHALMIC USE ONLY— NOT FOR INJECTION.
  • Failure of improvement of keratitis following 7 – 10 days of administration of the drug suggests that the infection may be caused by a microorganism not susceptible to natamycin.
  • Continuation of therapy should be based on clinical re-evaluation and additional laboratory studies.
  • Adherence of the suspension to areas of epithelial ulceration or retention of the suspension in the fornices occurs regularly. 
  • Use only if the container is undamaged.
• Information for patients:
  • Do not touch dropper tip to any surface, as this may contaminate the suspension.
  • Patients should be advised not to wear contact lenses if they have signs and symptoms of fungal blepharitis, conjunctivitis, and keratitis.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in most viral diseases of the cornea and conjunctiva including: epithelial herpes simplex keratitis (dendritic keratitis), vaccinia and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.

Neomycin and polymyxin B sulfates and bacitracin zinc with hydrocortisone acetate ophthalmic ointment is also contraindicated in individuals who have shown hypersensitivity to any of its components. Hypersensitivity to the antibiotic component occurs at a higher rate than for other components.

• Adverse reactions have occurred with corticosteroid/anti-infective combination drugs which can be attributed to the corticosteroid component, the anti-infective component, or the combination. The exact incidence is not known.
• Reactions occurring most often from the presence of the anti-infective ingredient are allergic sensitization reactions including itching, swelling, and conjunctival erythema (See WARNINGS in package insert).
• More serious hypersensitivity reactions, including anaphylaxis, have been reported rarely.
• The reactions due to the corticosteroid component in decreasing order of frequency are: Elevation of intraocular pressure (IOP) with possible development of glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound healing.
• Secondary infection: The development of the secondary ocular infection has occurred after use of combinations containing corticosteroids and antimicrobials. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of a corticosteroid.
• The possibility of fungal invasion must be considered in any persistent corneal ulceration where corticosteroid treatment has been used (See WARNINGS in package insert). Local irritation on installation has been reported. If signs and symptoms fail to improve after two days, the patient should be re-evaluated (See PRECAUTIONS in package insert).

• NOT FOR INJECTION INTO THE EYE.
• Neomycin and polymyxin B sulfates and bacitracin zinc with hydrocortisone acetate ophthalmic ointment should never be directly introduced into the anterior chamber of the eye. Ophthalmic ointments may retard corneal wound healing. Prolonged use of corticosteroids may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may suppress the host immune response and thus increase the hazard of secondary ocular infections. 
• Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. Acute purulent infections of the eye may be masked or enhanced by the presence of corticosteroid medication. If these products are used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in uncooperative patients.
• Corticosteroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently. The use of corticosteroids after cataract surgery may delay healing and increase the incidence of filtering blebs. Use of the ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex).
• Employment of corticosteroid medication in the treatment of herpes simplex requires great caution; frequent slit lamp microscopy is recommended. Topical antibiotics, particularly neomycin sulfate, may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical antibiotics is not known.
• The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a failure to heal.
• During long-term use of topical antibiotic products, periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. Symptoms usually subside quickly on withdrawing the medication. Applications of products containing these ingredients should be avoided for the patient thereafter (See PRECAUTIONS: General in package insert).
• General:
  • The initial prescription and renewal of the medication order beyond 8 grams should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
  • If signs and symptoms fail to improve after two days, the patient should be re-evaluated. As fungal infections of the cornea are particularly prone to develop coincidentally with long-term corticosteroid applications, fungal invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.
  • If this product is used for 10 days or longer, intraocular pressure should be monitored (See WARNINGS in package insert).
  • There have been reports of bacterial keratitis associated with the use of topical ophthalmic products in multiple-dose containers which have been inadvertently contaminated by patients, most of whom had a concurrent corneal disease or a disruption of the ocular epithelial surface (See PRECAUTIONS: Information for Patients in package insert).
  • Allergic cross-reactions may occur which could prevent the use of any or all of the following antibiotics for the treatment of future infections: kanamycin, paromomycin, streptomycin, and possibly gentamicin.
• Information for patients:
  • If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue use of the medication and consult a physician.
  • This product is sterile when packaged. To prevent contamination, care should be taken to avoid touching the tip of the tube to eyelids or to any other surface. The use of this tube by more than one person may spread infection.
  • Store at 15° – 25°C (59° – 77°F).
  • Keep out of the reach of children.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in individuals who have shown hypersensitivity to any of this drug's components.

• Reactions occurring most often are allergic sensitization reactions including itching, swelling, and conjunctival erythema (See WARNINGS in package insert). 
• More serious hypersensitivity reactions, including anaphylaxis, have been reported rarely.
• Local irritation on instillation has also been reported.
• Consult package insert for additional information.

• NOT FOR INJECTION INTO THE EYE. NEOSPORIN Ophthalmic Ointment should never be directly introduced into the anterior chamber of the eye.
• Ophthalmic ointments may retard corneal wound healing.
• Topical antibiotics, particularly neomycin sulfate, may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical antibiotics is not known. The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a failure to heal.
• During long-term use of topical antibiotic products, periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. Symptoms usually subside quickly on withdrawing the medication. Application of products containing these ingredients should be avoided for the patient thereafter (See PRECAUTIONS: General in package insert).
• General:
  • As with other antibiotic preparations, prolonged use of NEOSPORIN Ophthalmic Ointment may result in overgrowth of nonsusceptible organisms including fungi. If superinfection occurs, appropriate measures should be initiated. 
  • Bacterial resistance to NEOSPORIN Ophthalmic Ointment may also develop. If purulent discharge, inflammation, or pain becomes aggravated, the patient should discontinue use of the medication and consult a physician.
  • There have been reports of bacterial keratitis associated with the use of topical ophthalmic products in multiple-dose containers which have been inadvertently contaminated by patients, most of whom had a concurrent corneal disease or a disruption of the ocular epithelial surface (See PRECAUTIONS: Information for Patients in package insert).
  • Allergic cross-reactions may occur which could prevent the use of any or all of the following antibiotics for the treatment of future infections: kanamycin, paromomycin, streptomycin, and possibly gentamicin.
• Information for patients:
  • Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, eyelid, fingers, or any other surface.
  • The use of this product by more than one person may spread infection.
  • Patients should also be instructed that ocular products, if handled improperly, 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 products (See PRECAUTIONS: General in package insert).
  • If the condition persists or gets worse, or if a rash or allergic reaction develops, the patient should be advised to stop use and consult a physician. Do not use this product if you are allergic to any of the listed ingredients.
  • Keep tightly closed when not in use.
  • Keep out of reach of children.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in individuals who have shown hypersensitivity to any of this drug's components.

• Reactions occurring most often are allergic reactions including itching, swelling, and conjunctival erythema (See WARNINGS in package insert).
• More serious hypersensitivity reactions, including anaphylaxis, have been reported rarely.
• Local irritation on instillation has also been reported.
• Consult package insert for additional information.

• NOT FOR INJECTION INTO THE EYE. This product should never be directly introduced into the anterior chamber of the eye or injected subconjunctivally.
• Topical antibiotics, particularly neomycin sulfate, may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical antibiotics is not known. The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a failure to heal.
• During long-term use of topical antibiotic products, periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. Symptoms usually subside quickly on withdrawing the medication. Application of products containing these ingredients should be avoided for the patient thereafter (See PRECAUTIONS: General in package insert).
• General:
  • As with other antibiotic preparations, prolonged use of NEOSPORIN Ophthalmic Solution may result in overgrowth of nonsusceptible organisms including fungi. If superinfection occurs, appropriate measures should be initiated.
  • Bacterial resistance to this product may also develop. If purulent discharge, inflammation, or pain becomes aggravated, the patient should discontinue use of the medication and consult a physician.
  • There have been reports of bacterial keratitis associated with the use of topical ophthalmic products in multiple-dose containers which have been inadvertently contaminated by patients, most of whom had a concurrent corneal disease or a disruption of the ocular epithelial surface  (See PRECAUTIONS: Information for Patients in package insert).
  • Allergic cross-reactions may occur which could prevent the use of any or all of the following antibiotics for the treatment of future infections: kanamycin, paromomycin, streptomycin, and possibly gentamicin.
• Information for patients:
  • Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, eyelid, fingers, or any other surface. The use of this product by more than one person may spread infection.
  • Patients should also be instructed that ocular products, if handled improperly, 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 products (See PRECAUTIONS: General in package insert).
  • If the condition persists or gets worse, or if a rash or allergic reaction develops, the patient should be advised to stop use and consult a physician. Do not use this product if you are allergic to any of the listed ingredients.
  • Keep tightly closed when not in use.
  • Keep out of reach of children.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other non-steriodal anti-inflammatory drugs (NSAIDs).

• The following adverse reactions are discussed in greater detail in other sections of labeling:
  • Increased bleeding time [See Warnings and Precautions (5.1) in package insert].
  • Delayed healing [See Warnings and Precautions (5.2) in package insert].
  • Corneal effects [See Warnings and Precautions (5.3) in package insert].
• Most frequently reported ocular adverse events following cataract surgery were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These events occurred in approximately 5% – 10% of patients.
• Other ocular adverse events occurring at an incidence of approximately 1% – 5% included conjunctival edema, corneal edema, dry eye, lid margin crusting, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment. 
• Some of these events may be the consequence of the cataract surgical procedure.
• Non-ocular adverse events reported at an incidence of 1% – 4% included headache, hypertension, nausea/vomiting, and sinusitis.
• Consult package insert for additional information.

• Increased bleeding time:
  • With some nonsteroidal anti-inflammatory drugs including NEVANAC™, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
  • It is recommended that NEVENAC™ be used with caution in patients with known bleeding tendencies, or who are receiving other medications, which may prolong bleeding time.
• Delayed healing: Topical NSAIDs including NEVANAC™, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.
• Corneal effects:
  • Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including NEVANAC™ and should be closely monitored for corneal health.
  • Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.
  • Post-marketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post surgery may increase patient risk for occurrence and severity of corneal adverse events.
• Contact lens wear: NEVANAC™ ophthalmic suspension should not be administered while using contact lenses.
• Patient counseling information:
  • Slow or delayed healing: Advise the patient of the possibility that slow or delayed healing may occur while using NSAIDs [See Warnings and Precautions (5.2) in package insert].
  • Avoiding contamination of the product:
    • Advise the patient to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to 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.
    • Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery.
  • Contact lens wear: Advise the patient that NEVANAC™ should not be administered while wearing contact lenses [See Warnings and Precautions (5.4) in package insert].
  • Intercurrent ocular conditions: Advise the patient that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should immediately seek their physician’s advice concerning the continued use of the multi-dose container [See Warnings and Precautions (5.1) in package insert].
  • Concomitant topical ocular therapy: If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart [See Dosage and Administration (2.2) in package insert].
  • Shake well before use: Advise the patient to shake the container well [See Dosage and Administration (2.1) in package insert].
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with:

• Significant respiratory depression [See WARNINGS in package insert]. 
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [See WARNINGS in package insert]. 
• Known or suspected gastrointestinal obstruction, including paralytic ileus [See WARNINGS in package insert]. 
• Hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) [See WARNINGS, ADVERSE REACTIONS in package insert].

• The following adverse reactions have been identified during post approval use of NORCO^®. 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.
• The most frequently reported adverse reactions are light-headedness, dizziness, sedation, nausea and vomiting. Other adverse reactions include:
  • Central nervous system: Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychological dependence, mood changes.
  • Gastrointestinal system: Constipation.
  • Genitourinary system: Ureteral spasm, spasm of vesical sphincters, and urinary retention.
  • Special senses: Cases of hearing impairment or permanent loss have been reported predominately in patients with chronic overdose.
  • Dermatological: Skin rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, allergic reactions.
  • Hematological: Thrombocytopenia, agranulocytosis.
  • Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs: 
  • Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
  • Anaphylaxis: Anaphylaxis has been reported with ingredients contained in NORCO^®.
  • Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [See CLINICAL PHARMACOLOGY in package insert].
• Drug abuse and dependence:
  • Controlled substance. Norco^® contains hydrocodone, a Schedule II controlled substance.
  • Consult package insert for additional information on abuse, dependence, and overdosage.

• Addiction, abuse, and misuse:
  • NORCO^® contains hydrocodone, a Schedule II controlled substance. As an opioid, NORCO exposes users to the risks of addiction, abuse, and misuse [See DRUG ABUSE AND DEPENDENCE in package insert].
  • Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NORCO^®. Addiction can occur at recommended dosages and if the drug is misused or abused.
  • Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NORCO^®, and monitor all patients receiving NORCO for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NORCO^®, but use in such patients necessitates intensive counseling about the risks and proper use of NORCO^® along with intensive monitoring for signs of addiction, abuse, and misuse.
  • Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NORCO^®. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [See PRECAUTIONS; Information for Patients in package insert]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
• Opioid analgesic Risk Evaluation and Mitigation Strategy (REMS):
  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:
    • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
    • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
    • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
    • Consider using other tools to improve patient, household, and community safety, such as patientprescriber agreements that reinforce patient-prescriber responsibilities.
  • To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.
• Life-threatening respiratory depression:
  • Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [See OVERDOSAGE in package insert]. Carbon dioxide (CO₂) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
  • While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NORCO^®, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 – 72 hours of initiating therapy with and following dosage increases of NORCO^®.
  • To reduce the risk of respiratory depression, proper dosing and titration of NORCO^® is essential [See DOSAGE AND ADMINISTRATION in package insert]. Overestimating the NORCO^® dosage when converting patients from another opioid product can result in a fatal overdose.
  • Accidental ingestion of NORCO^®, especially by children, can result in respiratory depression and death due to an overdose of NORCO^®.
  • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [See DOSAGE AND ADMINISTRATION in package insert].
• Neonatal opioid withdrawal syndrome: Prolonged use of NORCO^® Tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [See PRECAUTIONS; Information for Patients, Pregnancy in package insert].
• Risks of concomitant use or discontinuation of Cytochrome P450 3A4 inhibitors and inducers:
  • Concomitant use of NORCO^® Tablets with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of NORCO^® Tablets and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [See WARNINGS in package insert], particularly when an inhibitor is added after a stable dose of NORCO^® Tablets is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in NORCO^® Tablets-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions. When adding CYP3A4 inhibitors or discontinuing CYP3A4 inducers in NORCO Tablets-treated patients, follow patients at frequent intervals and consider dosage reduction of NORCO^® Tablets until stable drug effects are achieved [See PRECAUTIONS; Drug Interactions in package insert].
  • Concomitant use of NORCO^® Tablets with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone.
  • When using NORCO^® Tablets with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, follow patients at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [See PRECAUTIONS; Drug Interactions in package insert].
• Risks from concomitant use with benzodiazepines or other CNS depressants:
  • Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NORCO^® Tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
  • Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [See PRECAUTIONS; Drug Interactions in package insert].
  • If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
  • Advise both patients and caregivers about the risks of respiratory depression and sedation when NORCO^® Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [See PRECAUTIONS; Drug Interactions, Information for Patients in package insert].
• Life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients:
  • The use of NORCO^® Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
  • Patients with chronic pulmonary disease: NORCO^® Tablet-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NORCO^® Tablets [See WARNINGS; Life-Threatening Respiratory Depression in package insert].
  • Elderly, cachectic, or debilitated patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [See WARNINGS; Life-Threatening Respiratory Depression in package insert].
  • Follow such patients closely, particularly when initiating and titrating NORCO^® Tablets and when NORCO^® Tablets are given concomitantly with other drugs that depress respiration [See WARNINGS; Life-Threatening Respiratory Depression in package insert]. Alternatively, consider the use of non-opioid analgesics in these patients.
• Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
• Severe hypotension: NORCO^® Tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [See PRECAUTIONS; Drug Interactions in package insert]. Follow these patients for signs of hypotension after initiating or titrating the dosage of NORCO^® Tablets. In patients with circulatory shock NORCO^® Tablets may cause vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use of NORCO^® Tablets with circulatory shock.
• Hepatotoxicity:
  • Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
  • The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
  • Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well.
• Serious skin reactions: Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
• Hypersensitivity/Anaphylaxis: There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue NORCO^® immediately and seek medical care if they experience these symptoms. Do not prescribe NORCO^® Tablets for patients with acetaminophen allergy [See PRECAUTIONS; Information for Patients in package insert].
• Risks of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness:
  • In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NORCO^® Tablets may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Follow such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NORCO^® Tablets.
  • Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NORCO^® Tablets in patients with impaired consciousness or coma.
• Risks of use in patients with gastrointestinal conditions:
  • NORCO^® Tablets are contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.
  • The administration of NORCO^® Tablets or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
  • Hydrocodone may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
• Increased risk of seizures in patients with seizure disorders: The hydrocodone in NORCO^® Tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Follow patients with a history of seizure disorders for worsened seizure control during NORCO^® tablet therapy.
• Withdrawal:
  • Do not abruptly discontinue NORCO^® Tablets in a patient physically dependent on opioids. When discontinuing NORCO^® Tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of NORCO^® Tablets in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [See DOSAGE AND ADMINISTRATION, DRUG ABUSE AND DEPENDENCE].
  • Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NORCO^® Tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [See PRECAUTIONS; Drug Interactions in package insert].
• Risks of driving and operating machinery:  NORCO^® Tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NORCO^® Tablets and know how they will react to the medication [See PRECAUTIONS; Information for Patients in package insert].
• Information for patients:
  • Advise the patient to read the FDA-approved patient labeling (Medication Guide).
  • Storage and disposal:
    • Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store NORCO securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [See WARNINGS, DRUG ABUSE AND DEPENDENCE in package insert]. Inform patients that leaving NORCO^® unsecured can pose a deadly risk to others in the home.
    • Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused NORCO^® should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal  for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.
  • Addiction, abuse, and misuse: Inform patients that the use of NORCO^®, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS]. Instruct patients not to share NORCO^® with others and to take steps to protect NORCO^® from theft or misuse.
  • Life-threatening respiratory depression: Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting NORCO^® or when the dosage is increased, and that it can occur even at recommended dosages [See WARNINGS in package insert]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
  • Accidental ingestion: Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [See WARNINGS in package insert].
  • Interactions with benzodiazepines and other CNS depressants: Inform patients and caregivers that potentially fatal additive effects may occur if NORCO^® is used with benzodiazepines and other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [See WARNINGS, PRECAUTIONS; Drug Interactions in package insert].
  • Serotonin syndrome: Inform patients that NORCO^® could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medications [See PRECAUTIONS; Drug Interactions in package insert].
  • Monoamine oxidase inhibitor (MAOI) Interaction: Inform patients to avoid taking NORCO^® Tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking NORCO^® Tablets [See PRECAUTIONS; Drug Interactions in package insert].
  • Adrenal insufficiency: Inform patients that NORCO^® could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [See WARNINGS in package insert].
  • Important administration instructions: Instruct patients how to properly take NORCO^® Tablets [See DOSAGE AND ADMINISTRATION, WARNINGS in package insert].
  • Important discontinuation instructions: In order to avoid developing withdrawal symptoms, instruct patients not to discontinue NORCO^® without first discussing a tapering plan with the prescriber [See DOSAGE AND ADMINISTRATION in package insert].
  • Maximum daily dose of acetaminophen: Inform patients not to take more than 4,000 milligrams of acetaminophen per day. Advise patients to call their prescriber if they take more than the recommended dose.
  • Hypotension: Inform patients that NORCO^® Tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [See WARNINGS in package insert].
  • Anaphylaxis: Inform patients that anaphylaxis has been reported with ingredients contained in NORCO^® Tablets. Advise patients how to recognize such a reaction and when to seek medical attention [See CONTRAINDICATIONS, ADVERSE REACTIONS in package insert].
  • Pregnancy:
    • Neonatal opioid withdrawal syndrome: Inform female patients of reproductive potential that prolonged use of NORCO^® during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [See WARNINGS, PRECAUTIONS; Pregnancy in package insert].
    • Embryo-fetal toxicity: Inform female patients of reproductive potential that NORCO^® can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [See PRECAUTIONS; Pregnancy in package insert].
  • Lactation: Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [See PRECAUTIONS; Nursing Mothers in package insert].
  • Infertility: Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [See ADVERSE REACTIONS in package insert].
  • Driving or operating heavy machinery: Inform patients that NORCO^® Tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [See WARNINGS in package insert].
  • Constipation: Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [See ADVERSE REACTIONS, CLINICAL PHARMACOLOGY in package insert].
  • Disposal of unused NORCO^®: Advise patients to dispose of unused NORCO^® Tablets by flushing unused tablets down the toilet.
• Consult package insert for additional information.

WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STEATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

NORCO^® exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing NORCO^®, and monitor all patients regularly for the development of these behaviors and conditions [See WARNINGS in package insert].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [See WARNINGS in package insert]. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to:

• Complete a REMS-compliant education program
• Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• Consider other tools to improve patient, hous ehold, and community safety.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of NORCO^®. Monitor for respiratory depression, especially during initiation of NORCO^® or following a dose increase [See WARNINGS in package insert].

Accidental Ingestion:

Accidental ingestion of NORCO^®, especially by children, can result in a fatal overdose of NORCO^® [See WARNINGS in package insert].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of NORCO^® during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [See WARNINGS in package insert]

Cytochrome P450 3A4 Interaction

The concomitant use of NORCO^® with all Cytochrome P450 3A4 inhibitors may result in an increase in NORCO^® plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used Cytochrome P450 3A4 inducer may result in an increase in NORCO^® plasma concentrations. Monitor patients receiving NORCO^® and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [See CLINICAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS; Drug Interactions in package insert].

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [See WARNINGS, OVERDOSAGE in package insert].

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [See WARNINGS and PRECAUTIONS; Drug Interactions in package insert].

• Reserve concomitant prescribing of NORCO^® and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

Contraindicated in patients with a history of hypersensitivity to ofloxacin, to other quinolones, or to any of the components in this medication (See Warnings in package insert).

• The most frequently reported drug-related adverse reaction was transient ocular burning or discomfort.
• Other reported reactions include stinging, redness, itching, chemical conjunctivitis/keratitis, ocular/periocular/facial edema, foreign body sensation, photophobia, blurred vision, tearing, dryness, and eye pain.
• Rare reports of dizziness and nausea have been received.
• Refer to Warnings (in package insert) for additional adverse reactions.

• NOT FOR INJECTION. 
• OCUFLOX^® solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
• There are rare reports of anaphylactic reaction/shock and fatal hypersensitivity reactions in patients receiving systemic quinolones, some following the first dose, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.
• A rare occurrence of Stevens-Johnson syndrome, which progressed to toxic epidermal necrolysis, has been reported in a patient who was receiving topical ophthalmic ofloxacin.
• If an allergic reaction to ofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation should be administered as clinically indicated.
• General: 
  • As with other anti-infectives, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection 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. Ofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.
  • The systemic administration of quinolones, including ofloxacin, has led to lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species. Ofloxacin, administered systemically at 10 mg/kg/day in young dogs (equivalent to 110 times the maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.
• Information for patients:
  • Avoid contaminating the applicator tip with material from the eye, fingers or other source.
  • Systemic quinolones, including ofloxacin, have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with a history of hypersensitivity to ofloxacin, to other quinolones, or to any of the components in this medication (See Warnings in package insert).

• The most frequently reported drug-related adverse reaction was transient ocular burning or discomfort.
• Other reported reactions include stinging, redness, itching, chemical conjunctivitis/keratitis, ocular/periocular/facial edema, foreign body sensation, photophobia, blurred vision, tearing, dryness, and eye pain.
• Rare reports of dizziness and nausea have been received.
• Refer to Warnings (in package insert) for additional adverse reactions.

• NOT FOR INJECTION. 
• Ofloxacin ophthalmic solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
• There are rare reports of anaphylactic reaction/shock and fatal hypersensitivity reactions in patients receiving systemic quinolones, some following the first dose, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.
• A rare occurrence of Stevens-Johnson syndrome, which progressed to toxic epidermal necrolysis, has been reported in a patient who was receiving topical ophthalmic ofloxacin.
• If an allergic reaction to ofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation should be administered as clinically indicated.
• General: 
  • As with other anti-infectives, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection 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. Ofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.
  • The systemic administration of quinolones, including ofloxacin, has led to lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species. Ofloxacin, administered systemically at 10 mg/kg/day in young dogs (equivalent to 110 times the maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.
• Information for patients:
  • Avoid contaminating the applicator tip with material from the eye, fingers or other source.
  • Systemic quinolones, including ofloxacin, have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in persons with a known hypersensitivity to olopatadine hydrochloride or any components of olopatadine hydrochloride ophthalmic solution.

• 0.1% Ophthalmic solution:
  • Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion. Some of these events were similar to the underlying disease being studied.
• 0.2% Ophthalmic solution:
  • Symptoms similar to cold syndrome and pharyngitis were reported at an incidence of approximately 10%.
  • The following adverse experiences have been reported in 5% or less of patients:
    • Ocular: Blurred vision, burning or stinging, conjunctivitis, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, pain and ocular pruritus.
    • Non-ocular: Asthenia, back pain, flu syndrome, headache, increased cough, infection, nausea, rhinitis, sinusitis and taste perversion.
  • Some of these events were similar to the underlying disease being studied.

• For topical use only: Not for injection or oral use.
• Information for patients:
  • To prevent 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.
  • Patients should be advised not to wear a contact lens if their eye is red. Olopatadine hydrochloride ophthalmic solution, USP 0.1% or 0.2% should not be used to treat contact lens related irritation. The preservative in olopatadine hydrochloride ophthalmic solution, USP 0.1% or 0.2%, 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 olopatadine hydrochloride ophthalmic solution, USP 0.1% or 0.2% before they insert their contact lenses.
• Consult package insert for additional information.

None listed in package insert.

Contraindicated in patients with a known hypersensitivity to any of this medication's ingredients.

• Frequently reported ocular adverse reactions with an incidence of ≥ 2% of adult patients: Anterior chamber inflammation (24%); intraocular pressure increased (4%); posterior capsule opacification (4%); eye irritation (2%); foreign body sensation in eyes (2%).
• Consult package insert for additional information.

• Elevated blood pressure: Systemic exposure to phenylephrine can cause elevations in blood pressure.
• Cross-sensitivity or hypersensitivity: There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti-inflammatory drugs (NSAIDs). There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac in patients who either have a known hypersensitivity to aspirin/NSAIDs or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these drugs.

None listed in package insert.

Contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. 

Omnipred^® (prednisolone acetate ophthalmic suspension) is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

• Adverse reactions include, in decreasing order of frequency, elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing.
• Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids.
• Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids.
• The development of secondary ocular infection (bacterial, fungal and viral) has occurred. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroid. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used (See WARNINGS in package insert).

• FOR TOPICAL OPHTHALMIC USE ONLY. Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections. Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Steroids should be used with caution in the presence of glaucoma.
• Intraocular pressure should be checked frequently.
• The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.
• Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.
• Corticosteroids are not effective in mustard gas keratitis and Sjögren’s keratoconjunctivitis.
• General precautions:
  • The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. If signs and symptoms fail to improve after two days, the patient should be re-evaluated.
  • As fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid applications, fungal invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.
  • If this product is used for 10 days or longer, intraocular pressure should be monitored (See WARNINGS in package insert).
• Information for patients:
  • If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue use of the medication and consult a physician.
  • This product is sterile when packaged. To prevent contamination, care should be taken to avoid touching the bottle tip to eyelids or to any other surface. The use of this bottle by more than one person may spread infection. Keep bottle tightly closed when not in use. Keep out of the reach of children.
• Consult package insert for additional information.

None listed in package insert.

None listed in package insert.

None listed in package insert.

• Warnings for patients:
  • Should not be used:
    • If patient is sensitive to any ingredient in product.
    • If solution changes color or becomes cloudy.
  • Provider should be consulted if patient has:
    • Heart disease.
    • High blood pressure.
    • Trouble urinating due to an enlarged prostate gland.
    • Narrow angle glaucoma.
  • When using product:
    • Overuse may cause more eye redness.
    • Pupils may become enlarged temporarily.
    • Tip of container should not touch any surface to avoid contamination.
    • There may be brief tingling after drops are instilled.
    • Cap should be replaced after use.
    • Remove contact lenses before use.
  • Use should be stopped if patient experiences:
    • Eye pain.
    • Changes in vision.
    • Redness or irritation of the eye that worsens or lasts more than 72 hours.
  • Keep out of reach of children: If swallowed, get medical help or contact a Poison Control Center right away. Accidental oral ingestion in infants and children may lead to coma and marked reduction in body temperature.

None listed in package insert.

Contraindicated in patients who are hypersensitive to corticosteroids such as prednisolone or any components of this product. Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy.

• Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.
• Allergic reactions: Anaphylactoid reaction, anaphylaxis, angioedema.
• Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.
• Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypo-pigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
• Endocrine: Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon facies, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in children.
• Fluid and electrolyte disturbances: Fluid retention, potassium loss, hypertension, hypokalemic alkalosis, sodium retention.
• Gastrointestinal: Abdominal distention; elevation in serum liver enzyme levels (usually reversible upon discontinuation); hepatomegaly, hiccups, malaise, nausea, pancreatitis; peptic ulcer with possible perforation and hemorrhage; ulcerative esophagitis.
• General: Increased appetite and weight gain.
• Metabolic: Negative nitrogen balance due to protein catabolism.
• Musculoskeletal: Aseptic necrosis of femoral and humeral heads; charcot-like arthropathy, loss of muscle mass; muscle weakness; osteoporosis; pathologic fracture of long bones; steroid myopathy; tendon rupture; vertebral compression fractures.
• Neurological: Arachnoiditis, convulsions; depression, emotional instability, euphoria, headache; increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment; insomnia, meningitis, mood swings, neuritis, neuropathy, paraparesis/paraplegia, paresthesia, personality changes, sensory disturbances, vertigo.
• Ophthalmic: Exophthalmos; glaucoma; increased intraocular pressure; posterior subcapsular cataracts
• Reproductive: Alteration in motility and number of spermatozoa.

• Alterations in endocrine function: 
  • Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use.
  • Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.
  • Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Mineralocorticoid supplementation is of particular importance in infancy.
  • Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.
• Increased risks related to infections:
  • Corticosteroids may increase the risks related to infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections. The degree to which the dose, route and duration of corticosteroid administration correlates with the specific risks of infection is not well characterized, however, with increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.
  • Corticosteroids may mask some signs of infection and may reduce resistance to new infections.
  • Corticosteroids may exacerbate infections and increase risk of disseminated infection. 
    • The use of Orapred in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen.
    • Chickenpox and measles can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In children or adults who have not had these diseases, particular care should be taken to avoid exposure. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
    • Corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
    • Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions.
  • Corticosteroids may increase risk of reactivation or exacerbation of latent infection. 
    • If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.
    • Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.
    • Corticosteroids should not be used in cerebral malaria.
•  Alterations in cardiovascular/renal function:
  • Corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. These agents should be used with caution in patients with hypertension, congestive heart failure, or renal insufficiency.
  • Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with caution in these patients.
• Use in patients with gastrointestinal disorders:
  • There is an increased risk of gastrointestinal (GI) perforation in patients with certain GI disorders. Signs of GI perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids.
  • Corticosteroids should be used with caution if there is a probability of impending perforation, abscess or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; and active or latent peptic ulcer.
• Behavioral and mood disturbances: Corticosteroid use may be associated with central nervous system effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
• Decrease in bone density: Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy and bone density should be monitored in patients on long term corticosteroid therapy.
• Ophthalmic effects:
  • Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.
  • The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes.
  • Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.
  • Patients with ocular herpes simplex: 
    • Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. Corticosteroids should not be used in active ocular herpes simplex.
• Vaccination:
  • Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered; however, the response to such vaccines cannot be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.
  • While on corticosteroid therapy, patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response.
• Effect on growth and development: Long-term use of corticosteroids can have negative effects on growth and development in children. Growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully monitored.
• Embryo-fetal toxicity:
  • Prednisolone can cause fetal harm when administered to a pregnant woman. Human studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester of pregnancy. Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring.
  • Intrauterine growth restriction and decreased birth weight have also been reported with corticosteroid use during pregnancy, however, the underlying maternal condition may also contribute to these risks. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, advise the patient about the potential harm to the fetus. [See Use in Specific Populations (8.1) in package insert].
• Neuromuscular effects:
  • Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. [See Dosage and Administration (3) in package insert].
  • An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
• Kaposi's sarcoma: Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

None listed in package insert.

N/A

N/A

N/A

N/A

None listed in package insert.

• The most common adverse reaction in clinical trials was eye pain following instillation which was reported in approximately 16% of patients.
• Other adverse reactions occurring in 1% – 10% of OXERVATE patients and more frequently than in the vehicle-treated patients included corneal deposits, foreign body sensation, ocular hyperemia, ocular inflammation and tearing.
• Consult package insert for additional information.

• Use with contact lens: Contact lenses should be removed before applying OXERVATE because the presence of a contact lens (either therapeutic or corrective) could theoretically limit the distribution of cenegermin-bkbj onto the area of the corneal lesion. Lenses may be reinserted 15 minutes after administration.
• Eye discomfort: OXERVATE may cause mild to moderate eye discomfort such as eye pain during treatment. The patient should be advised to contact their doctor if a more serious eye reaction occurs.
• Patient counseling information:
  • Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
  • Handling the vials and the delivery system: Advise patients that OXERVATE should be administered using the vial adapters, pipettes, and sterile disinfectant wipes provided in the Delivery System Kit and according to the instructions [See Dosage and Administration (2) in package insert]. One individual pipette should be used per application.
  • Use with contact lenses: Advise patients that contact lenses should be removed before applying OXERVATE and to wait 15 minutes after instillation of the dose before reinserting the contact lenses into the eyes [See Dosage and Administration (2.2) and Warnings and Precautions (5.1) in package insert].
  • Use with other topical products: Advise the patient to administer the eye drops at least 15 minutes apart, if more than one topical ophthalmic product is being used to avoid diluting products. Administer OXERVATE 15 minutes prior to using any eye ointment, gel or other viscous eye drops.
  • Delayed or missed dose: If a dose is missed, treatment should be continued as normal, at the next scheduled administration.
  • Storage information:
    • Instruct the patient to remove the weekly carton containing 7 OXERVATE vials from the insulated pack in the Delivery System Kit within 5 hours of leaving the pharmacy and store the weekly carton in the refrigerator [36° – 46°F (2° – 8°C)]. 
    • Instruct the patient to only remove the number of OXERVATE vials from the weekly carton required for use over the course of a single day. Do not shake the vial.
    • Once opened, the vial can be kept in the original weekly carton in the refrigerator between 36°F to 46°F (2°C – 8°C) for up to 12 hours or at room temperature up to 77°F (25°C), but must be used within 12 hours. After 12 hours, advise patients to discard the vial with any unused amount.

None listed in package insert.

• Contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
• Contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. 
• Contraindicated in patients whose posterior lens capsule is torn or ruptured because of the risk of migration into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for OZURDEX^® use.
• Contraindicatedin patients with known hypersensitivity to any components of this product [See Adverse Reactions (6) in package insert].

• Adverse reactions associated with ophthalmic steroids including OZURDEX^® include elevated intraocular pressure (IOP), which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.
• Retinal vein occlusion and posterior segment uveitis: Adverse reactions reported by greater than 2% of patients.
  • IOP increased (25%); conjunctival hemorrhage (22%); eye pain (8%); conjunctival hyperemia (7%); ocular hypertension (5%); cataract (5%); vitreous detachment (2%); headache (4%).
  • Increased IOP with OZURDEX^® peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received OZURDEX^® required surgical procedures for management of elevated IOP.
  • Following a second injection of OZURDEX^® in cases where a second injection was indicated, the overall incidence of cataracts was higher after 1 year.
  • In a 2-year observational study, among patients who received > 2 injections, the most frequent adverse reaction was cataract (54%). Other frequent adverse reactions from the 283 treated eyes, regardless of lens status at baseline, were increased IOP (24%) and vitreous hemorrhage (6%).
• Diabetic macular edema: 
  • Ocular adverse reactions reported by ≥ 1% of patients:
    Cataract (Includes cataract, cataract nuclear, cataract subcapsular, lenticular opacities in patients who were phakic at baseline. Among these patients, 61% of OZURDEX^® subjects vs. 8% of sham-controlled subjects underwent cataract surgery.) (68%) ( 243 of the 324 OZURDEX^® subjects were phakic at baseline; 230 of 328 sham-controlled subjects were phakic at baseline.); conjunctival hemorrhage (23%); visual acuity reduced (9%); conjunctivitis (6%); vitreous floaters (5%); conjunctival edema (5%); dry eye (5%); vitreous detachment (4%); vitreous opacities (3%); retinal aneurysm (3%); foreign body sensation (2%); corneal erosion (2%); keratitis (2%); anterior chamber inflammation (2%); retinal tear (2%); eyelid ptosis (2%).
  • Non-ocular: hypertension (13%); bronchitis (5%).
    • See Tables 2 and 3 in package insert for additional information.
• Increased IOP: IOP elevation ≥ 10 mm Hg from baseline at any visit (28%); ≥ 30 mm Hg IOP at any visit (15%); any IOP lowering medication (42%); any surgical intervention for elevated IOP (OZURDEX^®: 1 surgical trabeculectomy for steroid-induced IOP increase, 1 surgical trabeculectomy for iris neovascularization, 1 laser iridotomy, 1 surgical iridectomy) (1.2%).
• Cataracts and cataract surgery: At baseline, 243 of the 324 subjects were phakic; 230 of 328 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the OZURDEX^® group (68%) compared with sham (21%). The median time of cataract being reported as an adverse event was approximately 15 months in the OZURDEX^® group and 12 months in the sham group. Among these patients, 61% of OZURDEX^® subjects vs. 8% of sham-controlled subjects underwent cataract surgery, generally between month 18 and month 39 (median month 21 for OZURDEX^® group and 20 for sham) of the studies.
• Consult package insert for additional information.

• Intravitreal injection-related effects: Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure (IOP), and retinal detachments. Patients should be monitored regularly following the injection [See Patient Counseling Information (17) in package insert].
• Steroid-related effects: 
  • Use of corticosteroids including OZURDEX^® may produce posterior subcapsular cataracts, increased intraocular pressure, and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses [See Adverse Reactions (6.1) in package insert].
  • Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection.

None listed in package insert.

Should not be used in patients with angle-closure glaucoma or in those with narrow angles in whom dilation of the pupil may precipitate an attack of angle-closure glaucoma. This product is also contraindicated in patients who are hypersensitive to any of its components.

• Increased intraocular pressure (IOP) has been reported following use of mydriatics.
• Transient stinging, dryness of the mouth, blurred vision, photophobia with or without corneal staining, tachycardia, headache, allergic reactions, nausea, vomiting, pallor and muscle rigidity have been reported with the use of tropicamide and/or hydroxyamphetamine hydrobromide, and thus may occur with PAREMYD^® Solution.
• Central nervous system disturbances have also been reported. Psychotic reactions, behavioral disturbances, and vasomotor or cardiorespiratory collapse have been reported with the use of anticholinergic drugs.
• Rare but serious cardiovascular events, including death due to myocardial infarction, ventricular fibrillation and significant hypotensive episodes have occurred shortly following PAREMYD^® instillation.

• For topical ophthalmic use only; not for injection.
• There is evidence that mydriatics may produce a transient elevation of intraocular pressure in patients with open angle glaucoma.
• This preparation rarely may cause CNS disturbances which may be particularly dangerous in infants, children or the aged. Psychotic reactions, behavioral disturbances and vasomotor or cardio-respiratory collapse have been reported with the use of anticholinergic drugs.
• General: Patients with hypertension, hyperthyroidism, diabetes or cardiac disease (i.e., arrhythmias or chronic ischemic heart disease) should be monitored after instillation. The elderly and others in whom glaucoma or increased intraocular pressure may be encountered following administration of PAREMYD^® Solution should also be monitored closely. To avoid inducing angle-closure glaucoma, an estimation of the depth of the angle of the anterior chamber should be made.
• Information for patients:
  • Patients should be advised not to touch the dropper tip to any surface since this may contaminate the solution. Patients should be advised to use caution when driving or engaging in other hazardous activities while pupils are dilated.
  • Patients may experience photophobia and/or blurred vision and should protect their eyes in bright illumination when pupils are dilated.
  • Parents should be warned not to get this preparation in their child's mouth and to wash their own hands and the child's hands following administration.
• Consult package insert for additional information.

None listed in package insert.

None listed in package insert.

None listed in package insert.

• For external use only.
• Do not use:
  • if solution changes color or becomes cloudy,
  • if you are sensitive to any ingredient in this product, or
  • to treat contact lens related irritation.
• When using this product:
  • do not touch tip of container to any surface to avoid contamination,
  • remove contact lenses before use,
  • wait at least 10 minutes before reinserting contact lenses after use, and
  • do not wear a contact lens if your eye is red.
• Stop use and as k a doctor if you experience:
  • eye pain,
  • changes in vision,
  • increased redness of the eye, or
  • itching worsens or lasts for more than 72 hours.
• Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

None listed in package insert.

None listed in package insert.

None listed in package insert.

• For external use only.
• Do not use:
  • if solution changes color or becomes cloudy,
  • if you are sensitive to any ingredient in this product, or
  • to treat contact lens related irritation.
• When using this product:
  • do not touch tip of container to any surface to avoid contamination,
  • remove contact lenses before use,
  • wait at least 10 minutes before reinserting contact lenses after use, and
  • do not wear a contact lens if your eye is red.
• Stop use and as k a doctor if you experience:
  • eye pain,
  • changes in vision,
  • increased redness of the eye, or
  • itching worsens or lasts for more than 72 hours.
• Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

None listed in package insert.