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medicines-dataset-2

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[ { "from": "human", "value": "{\"METFORMIN HYDROCHLORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': '{\"CONTRAINDICATIONS Metformin Hydrochloride Tablets USP are contraindicated in patients with: 1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS ). 2. Known hypersensitivity to metformin hydrochloride 3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Metformin Hydrochloride Tablets USP should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (See also PRECAUTIONS .)\"}', 'adverse_reactions': '{\"ADVERSE REACTIONS In a US double-blind clinical study of Metformin Hydrochloride Tablets USP in patients with type 2 diabetes, a total of 141 patients received Metformin Hydrochloride Tablets USP therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the Metformin Hydrochloride Tablets USP patients, and that were more common in Metformin Hydrochloride Tablets USP- than placebo-treated patients, are listed in Table 9 . Table 9: Most Common Adverse Reactions (>5.0 Percent) in a Placebo-Controlled Clinical Study of Metformin Hydrochloride Tablets Monotherapy * Adverse Reaction Metformin Hydrochloride Tablets Monotherapy (n=141) Placebo (n=145) % of Patients Diarrhea 53.2 11.7 Nausea/Vomiting 25.5 8.3 Flatulence 12.1 5.5 Asthenia 9.2 5.5 Indigestion 7.1 4.1 Abdominal Discomfort 6.4 4.8 Headache 5.7 4.8 * Reactions that were more common in metformin hydrochloride tablets than placebo-treated patients. Diarrhea led to discontinuation of study medication in 6% of patients treated with Metformin Hydrochloride Tablets USP. Additionally, the following adverse reactions were reported in ≥1.0 to ≤5.0% of Metformin Hydrochloride Tablets USP patients and were more commonly reported with Metformin Hydrochloride Tablets USP than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. Pediatric Patients In clinical trials with Metformin Hydrochloride Tablets USP in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.\"}', 'drug_interactions': '{\"DRUG INTERACTIONS (Clinical Evaluation of Drug Interactions Conducted with Metformin Hydrochloride Tablets USP) Glyburide —In a single-dose interaction study in type 2 diabetes patients, coadministration of metformin and glyburide did not result in any changes in either metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and C max were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain (see DOSAGE AND ADMINISTRATION: Concomitant Metformin Hydrochloride Tablets USP and Oral Sulfonylurea Therapy in Adult Patients ). Furosemide —A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood C max by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the C max and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when coadministered chronically. Nifedipine —A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C max and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. T max and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine. Cationic drugs —Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Metformin Hydrochloride Tablets USP and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system. Other —Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Metformin Hydrochloride Tablets USP, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Metformin Hydrochloride Tablets USP, the patient should be observed closely for hypoglycemia. In healthy volunteers, the pharmacokinetics of metformin and propranolol, and metformin and ibuprofen were not affected when coadministered in single-dose interaction studies. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.\"}', 'indications_and_usage': '{\"INDICATIONS & USAGE Metformin Hydrochloride Tablets USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.\"}', 'warnings_and_cautions': None, 'overdosage': '{\"OVERDOSAGE Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases (see WARNINGS ). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.\"}', 'active_flag': 'Y', 'generic_name': '{\"METFORMIN HCL\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"WARNINGS Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with Metformin Hydrochloride Tablets USP; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking Metformin Hydrochloride Tablets USP and by use of the minimum effective dose of Metformin Hydrochloride Tablets USP. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin Hydrochloride Tablets USP treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, Metformin Hydrochloride Tablets USP should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, Metformin Hydrochloride Tablets USP should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking Metformin Hydrochloride Tablets USP, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, Metformin Hydrochloride Tablets USP should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin Hydrochloride Tablets USP should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of Metformin Hydrochloride Tablets USP, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking Metformin Hydrochloride Tablets USP do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking Metformin Hydrochloride Tablets USP, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)\"}', 'precautions': '{\"PRECAUTIONS GENERAL PRECAUTIONS Macrovascular Outcomes —There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Metformin Hydrochloride Tablets USP for any other anti-diabetic drug. Monitoring of renal function —Metformin is known to be substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive Metformin Hydrochloride Tablets USP. In patients with advanced age, Metformin Hydrochloride Tablets USP should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those ≥80 years of age, renal function should be monitored regularly and, generally, Metformin Hydrochloride Tablets USP should not be titrated to the maximum dose (see WARNINGS and DOSAGE AND ADMINISTRATION ). Before initiation of Metformin Hydrochloride Tablets USP therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and Metformin Hydrochloride Tablets USP discontinued if evidence of renal impairment is present. Use of concomitant medications that may affect renal function or metformin disposition —Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion (see PRECAUTIONS: Drug Interactions ), should be used with caution. Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials) —Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin (see CONTRAINDICATIONS ). Therefore, in patients in whom any such study is planned, Metformin Hydrochloride Tablets USP should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal. Hypoxic states —Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on Metformin Hydrochloride Tablets USP therapy, the drug should be promptly discontinued. Surgical procedures —Metformin Hydrochloride Tablets USP therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. Alcohol intake —Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving Metformin Hydrochloride Tablets USP. Impaired hepatic function —Since impaired hepatic function has been associated with some cases of lactic acidosis, Metformin Hydrochloride Tablets USP should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Vitamin B 12 levels —In controlled clinical trials of Metformin Hydrochloride Tablets USP of 29 weeks duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B 12 absorption from the B 12 -intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of Metformin Hydrochloride Tablets USP or vitamin B 12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on Metformin Hydrochloride Tablets USP and any apparent abnormalities should be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests ). Certain individuals (those with inadequate vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B 12 levels. In these patients, routine serum vitamin B 12 measurements at two- to three-year intervals may be useful. Change in clinical status of patients with previously controlled type 2 diabetes —A patient with type 2 diabetes previously well controlled on Metformin Hydrochloride Tablets USP who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If acidosis of either form occurs, Metformin Hydrochloride Tablets USP must be stopped immediately and other appropriate corrective measures initiated (see also WARNINGS ). Hypoglycemia —Hypoglycemia does not occur in patients receiving Metformin Hydrochloride Tablets USP alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Loss of control of blood glucose —When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold Metformin Hydrochloride Tablets USP and temporarily administer insulin. Metformin Hydrochloride Tablets USP may be reinstituted after the acute episode is resolved. The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level decreases in many patients over a period of time. This phenomenon, which may be due to progression of the underlying disease or to diminished responsiveness to the drug, is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective during initial therapy. Should secondary failure occur with either Metformin Hydrochloride Tablets USP or sulfonylurea monotherapy, combined therapy with Metformin Hydrochloride Tablets USP and sulfonylurea may result in a response. Should secondary failure occur with combined Metformin Hydrochloride Tablets USP/sulfonylurea therapy, it may be necessary to consider therapeutic alternatives including initiation of insulin therapy. INFORMATION FOR PATIENTS Patients should be informed of the potential risks and benefits of Metformin Hydrochloride Tablets USP and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters. The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue Metformin Hydrochloride Tablets USP immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of Metformin Hydrochloride Tablets USP, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Patients should be counselled against excessive alcohol intake, either acute or chronic, while receiving Metformin Hydrochloride Tablets USP. Metformin Hydrochloride Tablets USP alone do not usually cause hypoglycemia, although it may occur when Metformin Hydrochloride Tablets USP are used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. (See Patient Information printed below.) LABORATORY TESTS Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal of decreasing these levels toward the normal range. During initial dose titration, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Measurements of glycosylated hemoglobin may be especially useful for evaluating long-term control (see also DOSAGE AND ADMINISTRATION ) Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with Metformin Hydrochloride Tablets USP therapy, if this is suspected, vitamin B 12 deficiency should be excluded. DRUG INTERACTIONS (Clinical Evaluation of Drug Interactions Conducted with Metformin Hydrochloride Tablets USP) Glyburide —In a single-dose interaction study in type 2 diabetes patients, coadministration of metformin and glyburide did not result in any changes in either metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and C max were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain (see DOSAGE AND ADMINISTRATION: Concomitant Metformin Hydrochloride Tablets USP and Oral Sulfonylurea Therapy in Adult Patients ). Furosemide —A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood C max by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the C max and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when coadministered chronically. Nifedipine —A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C max and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. T max and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine. Cationic drugs —Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Metformin Hydrochloride Tablets USP and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system. Other —Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Metformin Hydrochloride Tablets USP, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Metformin Hydrochloride Tablets USP, the patient should be observed closely for hypoglycemia. In healthy volunteers, the pharmacokinetics of metformin and propranolol, and metformin and ibuprofen were not affected when coadministered in single-dose interaction studies. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins. DRUG & OR LABORATORY TEST INTERACTIONS CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day. There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative. Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons. PREGNANCY Teratogenic Effects: Pregnancy Category B Recent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, Metformin Hydrochloride Tablets USP should not be used during pregnancy unless clearly needed. There are no adequate and well-controlled studies in pregnant women with Metformin Hydrochloride Tablets USP. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. LABOR & DELIVERY NURSING MOTHERS Studies in lactatingrats show that metformin is excreted into milk and reaches levels comparable tothose in plasma. Similar studies have not been conducted in nursing mothers.Because the potential for hypoglycemia in nursing infants may exist, a decisionshould be made whether to discontinue nursing or to discontinue the drug,taking into account the importance of the drug to the mother. If Metformin HydrochlorideTablets USP are discontinued, and if diet alone is inadequate for controllingblood glucose, insulin therapy should be considered. PEDIATRIC USE The safety and effectiveness of Metformin Hydrochloride Tablets USP for the treatment of type 2 diabetes have been established in pediatric patients ages 10 to 16 years (studies have not been conducted in pediatric patients below the age of 10 years). Use of Metformin Hydrochloride Tablets USP in this age group is supported by evidence from adequate and well-controlled studies of Metformin Hydrochloride Tablets USP in adults with additional data from a controlled clinical study in pediatric patients ages 10 to 16 years with type 2 diabetes, which demonstrated a similar response in glycemic control to that seen in adults. (See CLINICAL PHARMACOLOGY: Pediatric Clinical Studies .) In this study, adverse effects were similar to those described in adults. (See ADVERSE REACTIONS: Pediatric Patients. ) A maximum daily dose of 2000 mg is recommended. (See DOSAGE AND ADMINISTRATION: Recommended Dosing Schedule: Pediatrics. ) GERIATRIC USE Controlled clinical studies of Metformin Hydrochloride Tablets USP did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, Metformin Hydrochloride Tablets USP should only be used in patients with normal renal function (see CONTRAINDICATIONS, WARNINGS , and CLINICAL PHARMACOLOGY: Pharmacokinetics ). Because aging is associated with reduced renal function, Metformin Hydrochloride Tablets USP should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of Metformin Hydrochloride Tablets USP (see also WARNINGS and DOSAGE AND ADMINISTRATION ).\"}', 'information_for_patients': '{\"INFORMATION FOR PATIENTS Patients should be informed of the potential risks and benefits of Metformin Hydrochloride Tablets USP and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters. The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue Metformin Hydrochloride Tablets USP immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of Metformin Hydrochloride Tablets USP, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Patients should be counselled against excessive alcohol intake, either acute or chronic, while receiving Metformin Hydrochloride Tablets USP. Metformin Hydrochloride Tablets USP alone do not usually cause hypoglycemia, although it may occur when Metformin Hydrochloride Tablets USP are used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. (See Patient Information printed below.)\"}', 'pregnancy': '{\"PREGNANCY Teratogenic Effects: Pregnancy Category B Recent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, Metformin Hydrochloride Tablets USP should not be used during pregnancy unless clearly needed. There are no adequate and well-controlled studies in pregnant women with Metformin Hydrochloride Tablets USP. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin.\"}', 'pediatric_use': '{\"PEDIATRIC USE The safety and effectiveness of Metformin Hydrochloride Tablets USP for the treatment of type 2 diabetes have been established in pediatric patients ages 10 to 16 years (studies have not been conducted in pediatric patients below the age of 10 years). Use of Metformin Hydrochloride Tablets USP in this age group is supported by evidence from adequate and well-controlled studies of Metformin Hydrochloride Tablets USP in adults with additional data from a controlled clinical study in pediatric patients ages 10 to 16 years with type 2 diabetes, which demonstrated a similar response in glycemic control to that seen in adults. (See CLINICAL PHARMACOLOGY: Pediatric Clinical Studies .) In this study, adverse effects were similar to those described in adults. (See ADVERSE REACTIONS: Pediatric Patients. ) A maximum daily dose of 2000 mg is recommended. (See DOSAGE AND ADMINISTRATION: Recommended Dosing Schedule: Pediatrics. )\"}', 'geriatric_use': '{\"GERIATRIC USE Controlled clinical studies of Metformin Hydrochloride Tablets USP did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, Metformin Hydrochloride Tablets USP should only be used in patients with normal renal function (see CONTRAINDICATIONS, WARNINGS , and CLINICAL PHARMACOLOGY: Pharmacokinetics ). Because aging is associated with reduced renal function, Metformin Hydrochloride Tablets USP should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of Metformin Hydrochloride Tablets USP (see also WARNINGS and DOSAGE AND ADMINISTRATION ).\"}'}" } ]

[ { "from": "human", "value": "{\"CARBAMIDE PEROXIDE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Directions FOR USE IN THE EAR ONLY adults and children over 12 years of age: tilt head sideways and place 5 to 10 drops into ear tip of applicator should not enter ear canal keep drops in ear for several minutes by keeping head tilted or placing cotton in ear use twice daily for up to four days if needed, or as directed by a doctor any way remaining after treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear syringe children under 12 years: consult a doctor\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"CARBAMIDE PEROXIDE\"}', 'route': '{\"AURICULAR (OTIC)\"}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if you need to use for more than four days excessive earwax remains after use of this product\"}', 'do_not_use': None, 'when_using': None, 'warnings': '{\"Warnings Ask a doctor before use if you have ear drainage or discharge ear pain dizziness irritation or rash in the ear recently had ear surgery an injury or perforation (hole) of the eardrum\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"METHYLPHENIDATE HYDROCHLORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': '{\"CONTRAINDICATIONS Marked anxiety, tension, and agitation are contraindications to Methylphenidate Hydrochloride, since the drug may aggravate these symptoms. Methylphenidate Hydrochloride is contraindicated also in patients known to be hypersensitive to the drug, in patients with glaucoma, and in patients with motor tics or with a family history or diagnosis of Tourette\\'s syndrome. Methylphenidate Hydrochloride is contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive crises may result).\"}', 'adverse_reactions': '{\"ADVERSE REACTIONS Nervousness and insomnia are the most common adverse reactions but are usually controlled by reducing dosage and omitting the drug in the afternoon or evening. Other reactions include hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; blood pressure and pulse changes, both up and down; tachycardia; angina; cardiac arrhythmia; abdominal pain; weight loss during prolonged therapy; libido changes; and rhabdomyolysis. There have been rare reports of Tourette’s syndrome. Toxic psychosis has been reported. Although a definite causal relationship has not been established, the following have been reported in patients taking this drug: instances of abdominal liver function, ranging from transaminase elevation to hepatic coma; isolated cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood; a few instances of scalp hair loss. Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a ten year old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed above may also occur.\"}', 'drug_interactions': None, 'indications_and_usage': '{\"INDICATIONS AND USAGE Attention Deficit Disorders, Narcolepsy Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children). Other terms being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction. Methylphenidate Hydrochloride is indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted. Special Diagnostic Considerations Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Characteristics commonly reported include: chronic history of short attention span, distractibility, emotional lability, impulsivity, and moderate-to-severe hyperactivity; minor neurological signs and abnormal EEG. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of one or more of these characteristics. Drug treatment is not indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is generally necessary. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician\\'s assessment of the chronicity and severity of the child\\'s symptoms.\"}', 'warnings_and_cautions': None, 'overdosage': '{\"OVERDOSAGE Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central nervous system and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, dryness of mucous membranes, and rhabdomyolysis. Consult with a Certified Poison Control Center regarding treatment for up-to-date guidance and advice. Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage. In the presence of severe intoxication, use a carefully titrated dosage of a short-acting barbiturate before performing gastric lavage. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia. Efficacy of peritoneal dialysis or extracorporeal hemodialysis for methylphenidate overdosage has not been established.\"}', 'active_flag': 'Y', 'generic_name': '{\"METHYLPHENIDATE HYDROCHLORIDE\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"WARNINGS Serious Cardiovascular Events Sudden Death and Pre-Existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents - Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. Adults - Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs. Hypertension and Other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia. Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation. Psychiatric Adverse Events Pre-Existing Psychosis - Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Bipolar Illness - Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Emergence of New Psychotic or Manic Symptoms - Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients. Aggression - Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility. Seizures There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued. Priapism Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or discontinuation): Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention. Peripheral Vasculopathy, Including Raynaud’s Phenomenon Stimulants, including Methylphenidate Hydrochloride, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Long-Term Suppression of Growth Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. Visual Disturbance Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. USE IN CHILDREN LESS THAN SIX YEARS OF AGE Methylphenidate Hydrochloride should not be used in children under six years, since safety and efficacy in this age group have not been established. DRUG ABUSE AND DEPENDENCE Methylphenidate Hydrochloride should be given cautiously to emotionally unstable patients, such as those with a history of drug dependence or alcoholism, because such patients may increase dosage on their own initiative. Chronically abusive use can lead to marked tolerance and psychic dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal, since severe depression as well as the effects of chronic overactivity can be unmasked. Long-term follow-up may be required because of the patient\\'s basic personality disturbances.\"}', 'precautions': '{\"PRECAUTIONS General Patients with an element of agitation may react adversely; discontinue therapy if necessary. Periodic CBC, differential, and platelet counts are advised during prolonged therapy. Drug treatment is not indicated in all cases of this behavioral syndrome and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe Methylphenidate Hydrochloride should depend on the physician\\'s assessment of the chronicity and severity of the child\\'s symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics. When these symptoms are associated with acute stress reactions, treatment with Methylphenidate Hydrochloride is usually not indicated. Long-term effects of Methylphenidate Hydrochloride in children have not been well established. Information for Patients Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for Methylphenidate Hydrochloride Oral Solution. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Priapism Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism. Instruct the patient to seek immediate medical attention in the event of priapism. Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon] Instruct patients beginning treatment with Methylphenidate Hydrochloride about the risk of peripheral vasculopathy, including Raynaud’s Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Methylphenidate Hydrochloride. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Drug Interactions Methylphenidate Hydrochloride may decrease the hypotensive effect of guanethidine. Use cautiously with pressor agents. Human pharmacologic studies have shown that Methylphenidate Hydrochloride may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and tricyclic drugs (imipramine, clomipramine, desipramine). Downward dosage adjustments of these drugs may be required when given concomitantly with Methylphenidate Hydrochloride. Carcinogenesis, Mutagenesis, Impairment of Fertility In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas, at a daily dose of approximately 60 mg/kg/day. This dose is approximately 30 times and 2.5 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 22 times and 4 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or in the in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary (CHO) cells. The genotoxic potential of methylphenidate has not been evaluated in an in vivo assay. Usage in Pregnancy Adequate animal reproduction studies to establish safe use of Methylphenidate Hydrochloride during pregnancy have not been conducted. However, in a recently conducted study, methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 167 times and 78 times the maximum recommended human dose on a mg/kg and a mg/m 2 basis, respectively. In rats, teratogenic effects were not seen when the drug was given in doses of 75 mg/kg/day, which is approximately 62.5 and 13.5 times the maximum recommended human dose on a mg/kg and a mg/m 2 basis, respectively. Therefore, until more information is available, methylphenidate should not be prescribed for women of childbearing age unless, in the opinion of the physician, the potential benefits outweigh the possible risks.\"}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"RABEPRAZOLE SODIUM\"}" }, { "from": "gpt", "value": "{'contraindications': '{\"4 CONTRAINDICATIONS Patients with a history of hypersensitivity to rabeprazole ( 4 ). PPIs, including rabeprazole sodium delayed-release tablets, are contraindicated in patients receiving rilpivirine-containing products ( 4 , 7 ). Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when administered in combination with rabeprazole ( 4 ). Rabeprazole sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see ADVERSE REACTIONS ( 6 )]. PPIs, including rabeprazole sodium delayed-release tablets, are contraindicated with rilpivirine-containing products [see DRUG INTERACTIONS ( 7 )] . For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with rabeprazole sodium delayed-release tablets, refer to the CONTRAINDICATIONS section of their package inserts.\"}', 'adverse_reactions': '{\"6 ADVERSE REACTIONS Most common adverse reactions in adults (>2%) are pain, pharyngitis, flatulence, infection, and constipation ( 6.1 ). Most common adverse reactions in adolescents (≥2%) are headache, diarrhea, nausea, vomiting, and abdominal pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse reactions are described below and elsewhere in labeling: Acute Interstitial Nephritis [see WARNINGS AND PRECAUTIONS ( 5.3 )] Clostridium difficile- Associated Diarrhea [see WARNINGS AND PRECAUTIONS ( 5.4 )] Bone Fracture [see WARNINGS AND PRECAUTIONS ( 5.5 )] Cutaneous and Systemic Lupus Erythematosus [see WARNINGS AND PRECAUTIONS ( 5.6 )] Cyanocobalamin (Vitamin B-12) Deficiency [see WARNINGS AND PRECAUTIONS ( 5.7 )] Hypomagnesemia [see WARNINGS AND PRECAUTIONS ( 5.8 )] Fundic Gland Polyps [see WARNINGS AND PRECAUTIONS ( 5.10 )] 6.1 Clinical Studies Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The data described below reflect exposure to rabeprazole sodium delayed-release tablets in 1064 adult patients exposed for up to 8 weeks. The studies were primarily placebo- and active-controlled trials in adult patients with Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD), Duodenal Ulcers and Gastric Ulcers. The population had a mean age of 53 years (range 18 to 89 years) and had a ratio of approximately 60% male: 40% female. The racial distribution was 86% Caucasian, 8% African American, 2% Asian, and 5% other. Most patients received either 10 mg, 20 mg or 40 mg per day of rabeprazole sodium delayed-release tablets. An analysis of adverse reactions appearing in ≥2% of patients treated with rabeprazole sodium delayed-release tablets (n=1064) and with a greater frequency than placebo (n=89) in controlled North American and European acute treatment trials, revealed the following adverse reactions: pain (3% vs. 1%), pharyngitis (3% vs. 2%), flatulence (3% vs. 1%), infection (2% vs. 1%), and constipation (2% vs. 1%). Three long-term maintenance studies consisted of a total of 740 adult patients; at least 54% of adult patients were exposed to rabeprazole sodium delayed-release tablets for 6 months and at least 33% were exposed for 12 months. Of the 740 adult patients, 247 (33%) and 241 (33%) patients received 10 mg and 20 mg of rabeprazole sodium delayed-release tablets, respectively, while 169 (23%) patients received placebo and 83 (11%) received omeprazole. The safety profile of rabeprazole in the maintenance studies in adults was consistent with what was observed in the acute studies. Less common adverse reactions seen in controlled clinical trials (<2% of patients treated with rabeprazole sodium delayed-release tablets and greater than placebo) and for which there is a possibility of a causal relationship to rabeprazole, include the following: headache, abdominal pain, diarrhea, dry mouth, dizziness, peripheral edema, hepatic enzyme increase, hepatitis, hepatic encephalopathy, myalgia, and arthralgia. Combination Treatment with Amoxicillin and Clarithromycin: In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse reactions unique to this drug combination were observed. In the U.S. multicenter study, the most frequently reported drug related adverse reactions for patients who received RAC therapy for 7 or 10 days were diarrhea (8% and 7%) and taste perversion (6% and 10%), respectively. No clinically significant laboratory abnormalities particular to the drug combinations were observed. For more information on adverse reactions or laboratory changes with amoxicillin or clarithromycin, refer to their respective prescribing information, ADVERSE REACTIONS section. Pediatrics In a multicenter, open-label study of adolescent patients 12 to 16 years of age with a clinical diagnosis of symptomatic GERD or endoscopically proven GERD, the adverse event profile was similar to that of adults. The adverse reactions reported without regard to relationship to rabeprazole sodium delayed-release tablets that occurred in ≥2% of 111 patients were headache (9.9%), diarrhea (4.5%), nausea (4.5%), vomiting (3.6%), and abdominal pain (3.6%). The related reported adverse reactions that occurred in ≥2% of patients were headache (5.4%) and nausea (1.8%). There were no adverse reactions reported in this study that were not previously observed in adults. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of rabeprazole. 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: Blood and Lymphatic System Disorders: agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia Ear and Labyrinth Disorders: vertigo Eye Disorders: blurred vision Gastrointestinal Disorders: fundic gland polyps General Disorders and Administration Site Conditions: sudden death Hepatobiliary Disorders: jaundice Immune System Disorders: anaphylaxis, angioedema, systemic lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal) Infections and Infestations: Clostridium difficile-associated diarrhea Investigations: Increases in prothrombin time/INR (in patients treated with concomitant warfarin), TSH elevations Metabolism and Nutrition Disorders: hyperammonemia, hypomagnesemia Musculoskeletal System Disorders: bone fracture, rhabdomyolysis Nervous System Disorders: coma Psychiatric Disorders: delirium, disorientation Renal and Urinary Disorders: interstitial nephritis Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonia Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions including bullous and other drug eruptions of the skin, cutaneous lupus erythematosus, erythema multiforme\"}', 'drug_interactions': '{\"7 DRUG INTERACTIONS See full prescribing information for a list of clinically important drug interactions ( 7 ). Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with rabeprazole sodium delayed-release tablets and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with Rabeprazole Sodium Delayed-Release Tablets and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPI on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with rabeprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with rabeprazole may increase toxicity . There are other antiretroviral drugs which do not result in clinically relevant interactions with rabeprazole. Intervention: Rilpivirine-containing products: Concomitant use with rabeprazole sodium delayed-release tablets is contraindicated [see CONTRAINDICATIONS ( 4 )] . See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with rabeprazole sodium delayed-release tablets. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals: See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death [see WARNINGS AND PRECAUTIONS ( 5.2 )]. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Methotrexate Clinical Impact: Concomitant use of rabeprazole with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of methotrexate with PPIs have been conducted [see WARNINGS AND PRECAUTIONS ( 5.9 )]. Intervention: A temporary withdrawal of rabeprazole sodium delayed-release tablets may be considered in some patients receiving high dose methotrexate administration. Digoxin Clinical Impact: Potential for increased exposure of digoxin [see CLINICAL PHARMACOLOGY ( 12.3 )]. Intervention: Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole) Clinical Impact: Rabeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving rabeprazole sodium delayed-release tablets and MMF. Use rabeprazole sodium delayed-release tablets with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS in prescribing information for clarithromycin. See DRUG INTERACTIONS in prescribing information for amoxicillin. Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19 . Intervention: Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors . Intervention: Temporarily stop rabeprazole sodium delayed-release tablets treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Intervention: Temporarily stop treatment with rabeprazole sodium delayed-release tablets at least 14 days before assessing to allow gastrin levels to return to baseline. False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs. Intervention: An alternative confirmatory method should be considered to verify positive results.\"}', 'indications_and_usage': '{\"1 INDICATIONS AND USAGE Rabeprazole sodium delayed-release tablet is a proton-pump inhibitor (PPI) indicated in adults for: Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) ( 1.1 ). Maintenance of Healing of Erosive or Ulcerative GERD ( 1.2 ). Treatment of Symptomatic GERD ( 1.3 ). Healing of Duodenal Ulcers ( 1.4 ). Helicobacter pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence ( 1.5 ). Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome ( 1.6 ). In adolescent patients 12 years of age and older for: Short-term Treatment of Symptomatic GERD ( 1.7 ). 1.1 Healing of Erosive or Ulcerative GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD). For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of rabeprazole sodium delayed-release tablets may be considered. 1.2 Maintenance of Healing of Erosive or Ulcerative GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for maintaining healing and reduction in relapse rates of heartburn symptoms in patients with erosive or ulcerative gastroesophageal reflux disease (GERD Maintenance). Controlled studies do not extend beyond 12 months. 1.3 Treatment of Symptomatic GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD in adults for up to 4 weeks. 1.4 Healing of Duodenal Ulcers in Adults Rabeprazole sodium delayed-release tablets are indicated for short-term (up to four weeks) treatment in the healing and symptomatic relief of duodenal ulcers. Most patients heal within four weeks. 1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults Rabeprazole sodium delayed-release tablets, in combination with amoxicillin and clarithromycin as a three drug regimen, are indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history within the past 5 years) to eradicate H. pylori . Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see CLINICAL PHARMACOLOGY ( 12.2 ) and the full prescribing information for clarithromycin ]. 1.6 Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults Rabeprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome. 1.7 Treatment of Symptomatic GERD in Adolescent Patients 12 Years of Age and Older Rabeprazole sodium delayed-release tablets are indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.\"}', 'warnings_and_cautions': '{\"5 WARNINGS AND PRECAUTIONS Gastric Malignancy : In adults, symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing ( 5.1 ). Use with Warfarin : Monitor for increases in INR and prothombin time ( 5.2 , 7 ). Acute Interstitial Nephritis: Observed in patients taking PPIs ( 5.3 ). Clostridium difficile- Associated Diarrhea : PPI therapy may be associated with increased risk of ( 5.4 ). Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine ( 5.5 ). Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous, new onset or exacerbation of existing disease; discontinue rabeprazole sodium delayed-release tablets and refer to specialist for evaluation ( 5.6 ). Cyanocobalamin (Vitamin B-12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin ( 5.7 ). Hypomagnesemia : Reported rarely with prolonged treatment with PPIs ( 5.8 ). Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of rabeprazole delayed-release tablets ( 5.9 , 7 ). Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy ( 5.10 ). 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. 5.2 Interaction with Warfarin Steady state interactions of rabeprazole and warfarin have not been adequately evaluated in patients. There have been reports of increased INR and prothrombin time in patients receiving a proton pump inhibitor and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with rabeprazole sodium delayed-release tablets and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time [see DRUG INTERACTIONS ( 7 )] . 5.3 Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including rabeprazole sodium. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue rabeprazole sodium if acute interstitial nephritis develops [see CONTRAINDICATIONS ( 4 )]. 5.4 Clostridium difficile-Associated Diarrhea Published observational studies suggest that PPI therapy like rabeprazole sodium may be associated with an increased risk of Clostridium difficile- associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see ADVERSE REACTIONS ( 6.2 )]. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with rabeprazole sodium, refer to WARNINGS AND PRECAUTIONS sections of the corresponding prescribing information. 5.5 Bone Fracture Several published observational studies in adults suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see DOSAGE AND ADMINISTRATION ( 2 ) and ADVERSE REACTIONS ( 6.2 )]. 5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including rabeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving rabeprazole sodium delayed-release tablets, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.7 Cyanocobalamin (Vitamin B-12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with rabeprazole sodium delayed-release tablets. 5.8 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see ADVERSE REACTIONS ( 6.2 )]. 5.9 Interaction with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information ) may elevate and prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see DRUG INTERACTIONS ( 7 )]. 5.10 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.\"}', 'overdosage': '{\"10 OVERDOSAGE Seven reports of accidental overdosage with rabeprazole have been received. The maximum reported overdose was 80 mg. There were no clinical signs or symptoms associated with any reported overdose. Patients with Zollinger-Ellison syndrome have been treated with up to 120 mg rabeprazole once daily. No specific antidote for rabeprazole is known. Rabeprazole is extensively protein bound and is not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.\"}', 'active_flag': 'Y', 'generic_name': '{\"RABEPRAZOLE SODIUM\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{\"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Acute Interstitial Nephritis Advise the patient or caregiver to call the patient\\'s healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis [see WARNINGS AND PRECAUTIONS ( 5.3 )] . Clostridium difficile -Associated Diarrhea Advise the patient or caregiver to immediately call the patient\\'s healthcare provider if they experience diarrhea that does not improve [see WARNINGS AND PRECAUTIONS ( 5.4 )] . Bone Fracture Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient\\'s healthcare provider [see WARNINGS AND PRECAUTIONS ( 5.5 )] . Cutaneous and Systemic Lupus Erythematosus Advise the patient or caregiver to immediately call the patient\\'s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see WARNINGS AND PRECAUTIONS ( 5.6 )] . Cyanocobalamin (Vitamin B-12) Deficiency Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient\\'s healthcare provider if they have been receiving rabeprazole sodium delayed-release tablets for longer than 3 years [see WARNINGS AND PRECAUTIONS ( 5.7 )] . Hypomagnesemia Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia to the patient\\'s healthcare provider, if they have been receiving rabeprazole sodium delayed-release tablets for at least 3 months [see WARNINGS AND PRECAUTIONS ( 5.8 )] . Drug Interactions Advise patients to report to their healthcare provider if they are taking rilpivirine-containing products [see CONTRAINDICATIONS ( 4 )], warfarin, digoxin or high-dose methotrexate [see WARNINGS AND PRECAUTIONS ( 5.2 , 5.8 , 5.9 )] . Administration Swallow rabeprazole sodium delayed-release tablets whole. Do not chew, crush or split the tablets. For the treatment of duodenal ulcers take rabeprazole sodium delayed-release tablets after a meal. For Helicobacter pylori eradication take rabeprazole sodium delayed-release tablets with food. For all other indications rabeprazole sodium delayed-release tablets can be taken with or without food. Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to the normal schedule. Do not take two doses at the same time. The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. Manufactured for: Lupin Pharmaceuticals, Inc. Baltimore, Maryland 21202 United States Manufactured by: Lupin Limited Goa 403722 INDIA Revised: July 7, 2018 ID#: 255833\"}', 'pregnancy': '{\"8.1 Pregnancy Risk Summary There are no available human data on rabeprazole sodium delayed-release tablets use in pregnant women to inform the drug associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. No evidence of adverse developmental effects were seen in animal reproduction studies with rabeprazole administered during organogenesis at 13 and 8 times the human area under the plasma concentration-time curve (AUC) at the recommended dose for GERD, in rats and rabbits, respectively [see Data]. Changes in bone morphology were observed in offspring of rats treated with oral doses of a different PPI through most of pregnancy and lactation. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see Data]. Data Animal Data: Embryo-fetal developmental studies have been performed in rats during organogenesis at intravenous doses of rabeprazole up to 50 mg/kg/day (plasma AUC of 11.8 mcg•hr/mL, about 13 times the human exposure at the recommended oral dose for GERD) and rabbits at intravenous doses up to 30 mg/kg/day (plasma AUC of 7.3 mcg•hr/mL, about 8 times the human exposure at the recommended oral dose for GERD) and have revealed no evidence of harm to the fetus due to rabeprazole. Administration of rabeprazole to rats in late gestation and during lactation at an oral dose of 400 mg/kg/day (about 195-times the human oral dose based on mg/m 2 ) resulted in decreases in body weight gain of the pups. A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with a different PPI at about 3.4 to 57 times an oral human dose on a body surface area basis. Decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate, and minimal to mild bone marrow hypocellularity were noted at doses of this PPI equal to or greater than 3.4 times an oral human dose on a body surface area basis. Physeal dysplasia in the femur was also observed in offspring after in utero and lactational exposure to the PPI at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis. Effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when the PPI was administered at oral doses of 3.4 to 57 times an oral human dose on a body surface area basis. When rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis. A follow-up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with a different PPI at oral doses of 280 mg/kg/day (about 68 times an oral human dose on a body surface area basis) where drug administration was from either gestational day 7 or gestational day 16 until parturition. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.\"}', 'pediatric_use': '{\"8.4 Pediatric Use The safety and effectiveness of rabeprazole sodium delayed-release tablets have been established in pediatric patients for adolescent patients 12 years of age and older for the treatment of symptomatic GERD. Use of rabeprazole sodium delayed-release tablets in this age group is supported by adequate and well controlled studies in adults and a multicenter, randomized, open-label, parallel-group study in 111 adolescent patients 12 to 16 years of age. Patients had a clinical diagnosis of symptomatic GERD, or suspected or endoscopically proven GERD and were randomized to either 10 mg or 20 mg once daily for up to 8 weeks for the evaluation of safety and efficacy. The adverse reaction profile in adolescent patients was similar to that of adults. The related reported adverse reactions that occurred in ≥2% of patients were headache (5%) and nausea (2%). There were no adverse reactions reported in these studies that were not previously observed in adults. The safety and effectiveness of rabeprazole sodium delayed-release tablets have not been established in pediatric patients for: Healing of Erosive or Ulcerative GERD Maintenance of Healing of Erosive or Ulcerative GERD Treatment of Symptomatic GERD Healing of Duodenal Ulcers Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome Rabeprazole sodium delayed-release 20 mg tablets are not recommended for use in pediatric patients less than 12 years of age because the tablet strength exceeds the recommended dose for these patients [see DOSAGE AND ADMINISTRATION ( 2 )]. For pediatric patients 1 year to less than 12 years of age consider another rabeprazole formulation. The safety and effectiveness of a different dosage form and dosage strength of rabeprazole has been established in pediatric patients 1 to 11 years for the treatment of GERD. Juvenile Animal Data Studies in juvenile and young adult rats and dogs were performed. In juvenile animal studies rabeprazole sodium was administered orally to rats for up to 5 weeks and to dogs for up to 13 weeks, each commencing on Day 7 post-partum and followed by a 13-week recovery period. Rats were dosed at 5, 25, or 150 mg/kg/day and dogs were dosed at 3, 10, or 30 mg/kg/day. The data from these studies were comparable to those reported for young adult animals. Pharmacologically mediated changes, including increased serum gastrin levels and stomach changes, were observed at all dose levels in both rats and dogs. These observations were reversible over the 13-week recovery periods. Although body weights and/or crown-rump lengths were minimally decreased during dosing, no effects on the development parameters were noted in either juvenile rats or dogs. When juvenile animals were treated for 28 days with a different PPI at doses equal to or greater than 34 times the daily oral human dose on a body surface area basis, overall growth was affected and treatment-related decreases in body weight (approximately 14%) and body weight gain, and decreases in femur weight and femur length were observed.\"}', 'geriatric_use': '{\"8.5 Geriatric Use Of the total number of subjects (n=2009) in clinical studies of rabeprazole sodium delayed-release tablets, 19% were 65 years and over, while 4% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.\"}'}" } ]

[ { "from": "human", "value": "{\"BENZALKONIUM CHLORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Uses handwash to help reduce bacteria that potentially can cause disease helps to prevent cross-contamination by hand contact helps to prevent drying of the skin recommended for repeated use\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"BENZALKONIUM CHLORIDE\"}', 'route': '{TOPICAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if irritation and redness develop.\"}', 'do_not_use': None, 'when_using': '{\"When using this product do not use in or near eyes.\"}', 'warnings': '{\"Warnings For external use only\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{ALCOHOL}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Use For handwashing to decrease bacteria on the skin.\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if irritation or rash develops and continues for more than 72 hours.\"}', 'do_not_use': None, 'when_using': '{\"When using this product avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water.\"}', 'warnings': '{\"Warnings For external use only Flammable. Keep away from fire or flame. When using this product avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water. Stop use and ask a doctor if irritation or rash develops and continues for more than 72 hours. Keep out of reach of children If swallowed, get medical help or contact a Poison Control Center right away.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"DIPHENHYDRAMINE HYDROCHLORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Uses for relief of occasional sleeplessness reduces time to fall asleep if you have difficulty falling asleep\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"DIPHENHYDRAMINE HCL\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of a serious underlying medical illness.\"}', 'do_not_use': '{\"Do not use for children under 12 years of age with any other product containing diphenhydramine, even one used on skin\"}', 'when_using': '{\"When using this product avoid alcoholic beverages.\"}', 'warnings': '{\"Warnings Do not use for children under 12 years of age with any other product containing diphenhydramine, even one used on skin Ask a doctor before use if you have a breathing problem such as emphysema or chronic bronchitis glaucoma difficulty in urination due to enlargement of the prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers. When using this product avoid alcoholic beverages. Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of a serious underlying medical illness. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{ALCOHOL}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Use Decrease bacteria on hands.\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"Warnings For external use only. Flammable. Keep product away from fire or flame. When using this product avoid contact with eyes; in case of contact, flush eyes with water. Stop use and ask a doctor if irritation or redness develops and persists. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{RIBAVIRIN}" }, { "from": "gpt", "value": "{'contraindications': '{\"4 CONTRAINDICATIONS Pregnancy and men whose female partners are pregnant ( 4 , 5.1, 8.1 , 8.3 ) Known hypersensitivity reactions such as Stevens Johnson syndrome, toxic, epidermal necrolysis, and erythema multiforme to ribavirin or any component of the product ( 4 ) Autoimmune hepatitis ( 4 ) Hemoglobinopathies ( 4 ) Creatinine clearance less than 50 mL/min ( 4 , 12.3 ) Coadministration with didanosine ( 4 , 7.1 ) Ribavirin capsules combination therapy is contraindicated in: pregnancy. Ribavirin may cause fetal harm when administered to a pregnant woman. Ribavirin is contraindicated in women who are pregnant or planning to become pregnant. If a patient becomes pregnant while taking ribavirin, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )] . men whose female partners are pregnant [see Use in Specific Populations ( 8.3 )] patients with known hypersensitivity reactions such as Stevens-Johnson syndrome, toxic, epidermal necrolysis, and erythema multiforme to ribavirin or any component of the product patients with autoimmune hepatitis patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia) patients with creatinine clearance less than 50 mL/min [see Clinical Pharmacology ( 12.3 )] when coadministered with didanosine because exposure to the active metabolite of didanosine (dideoxyadenosine 5\\'-triphosphate) is increased. Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis, has been reported in patients receiving didanosine in combination with ribavirin [see Drug Interactions ( 7.1 )] .\"}', 'adverse_reactions': '{\"6 ADVERSE REACTIONS Hemolytic anemia occurred in more than 10% of adult patients receiving ribavirin/PegIntron or INTRON A combination therapy. ( 6.1 ) Most common adverse reactions (40% or greater) in adult patients receiving ribavirin/PegIntron or INTRON A combination therapy are injection site reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia and anxiety/emotional lability/irritability. ( 6.1 ) Most common adverse reactions (greater than 25%) in pediatric patients receiving ribavirin /PegIntron therapy are: pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse drug reactions are discussed in other sections of the labeling: Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.1 )] Anemia [see Warnings and Precautions ( 5.2 )] Pancreatitis [see Warnings and Precautions ( 5.3 )] Pulmonary Disorders [see Warnings and Precautions ( 5.4 )] Ophthalmic Disorders [see Warnings and Precautions ( 5.5 )] Dental and Periodontal Disorders [see Warnings and Precautions ( 5.7 )] Impact on Growth in Pediatric Patients [see Warnings and Precautions ( 5.9 )] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical trials with ribavirin in combination with PegIntron or INTRON A have been conducted in over 7,800 subjects from 3 to 76 years of age. The primary toxicity of ribavirin is hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of oral therapy. Cardiac and pulmonary reactions associated with anemia occurred in approximately 10% of patients [see Warnings and Precautions ( 5.2 ) ]. Greater than 96% of all subjects in clinical trials experienced one or more adverse reactions. The most commonly reported adverse reactions in adult subjects receiving PegIntron or INTRON A in combination with ribavirin were injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia and anxiety/emotional lability/irritability. The most common adverse reactions in pediatric subjects, ages 3 and older, receiving ribavirin in combination with PegIntron or INTRON A were pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, and vomiting. The Adverse Reactions section references the following clinical trials: Ribavirin /PegIntron combination therapy trials: Clinical Study 1–evaluated PegIntron monotherapy (not further described in this label; see labeling for PegIntron for information about this trial). Study 2–evaluated ribavirin 800 mg/day flat dose in combination with 1.5 mcg/kg/week PegIntron or with INTRON A. Study 3–evaluated PegIntron/weight-based ribavirin in combination with PegIntron/flat dose ribavirin regimen. Study 4–compared two PegIntron (1.5 mcg/kg/week and 1 mcg/kg/week) doses in combination with ribavirin and a third treatment group receiving Pegasys ® (180 mcg/week)/Copegus ® (1,000 to 1,200 mg/day). Study 5–evaluated PegIntron (1.5 mcg/kg/week) in combination with weight-based ribavirin in prior treatment failure subjects. PegIntron/ribavirin combination therapy in Pediatric Patients Ribavirin/INTRON A combination therapy trials for adults and pediatrics Serious adverse reactions have occurred in approximately 12% of subjects in clinical trials with PegIntron with or without ribavirin [see Boxed Warning, Warnings and Precautions ( 5 )] . The most common serious events occurring in subjects treated with PegIntron and ribavirin were depression and suicidal ideation [see Warnings and Precautions ( 5.10 )] , each occurring at a frequency of less than 1%. Suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up [see Warnings and Precautions ( 5.10 )] . The most common fatal reaction occurring in subjects treated with PegIntron and ribavirin was cardiac arrest, suicidal ideation, and suicide attempt [see Warnings and Precautions ( 5.10 )] , all occurring in less than 1% of subjects. Adverse Reaction -Ribavirin/PegIntron Combination Therapy Adult Subjects Adverse reactions that occurred in the clinical trial at greater than 5% incidence are provided by treatment group from the ribavirin /PegIntron Combination Therapy (Study 2) in Table 5 . Table 5 Adverse Reactions Occurring in Greater Than 5% of Adult Subjects * A subject may have reported more than one adverse reaction within a body system/organ class category. Adverse Reactions Percentage of Subjects Reporting Adverse Reactions * Adverse Reactions Percentage of Subjects Reporting Adverse Reactions * PegIntron 1.5 mcg/kg/ Ribavirin Capsules (N=511) INTRON A/ Ribavirin Capsules (N=505) PegIntron 1.5 mcg/kg/ Ribavirin Capsules (N=511) INTRON A/ Ribavirin Capsules (N=505) Application Site Musculoskeletal Injection Site Inflammation 25 18 Myalgia 56 50 Injection Site Reaction 58 36 Arthralgia 34 28 Autonomic Nervous System Musculoskeletal Pain 21 19 Dry Mouth 12 8 Psychiatric Increased Sweating 11 7 Insomnia 40 41 Flushing 4 3 Depression 31 34 Body as a Whole Anxiety/Emotional Lability/Irritability 47 47 Fatigue/Asthenia 66 63 Concentration Impaired 17 21 Headache 62 58 Agitation 8 5 Rigors 48 41 Nervousness 6 6 Fever 46 33 Reproductive, Female Weight Loss 29 20 Menstrual Disorder 7 6 Right Upper Quadrant Pain 12 6 Resistance Mechanism Chest Pain 8 7 Viral Infection 12 12 Malaise 4 6 Fungal Infection 6 1 Central/Peripheral Nervous System Respiratory System Dizziness 21 17 Dyspnea 26 24 Endocrine Coughing 23 16 Hypothyroidism 5 4 Pharyngitis 12 13 Gastrointestinal Rhinitis 8 6 Nausea 43 33 Sinusitis 6 5 Anorexia 32 27 Skin and Appendages Diarrhea 22 17 Alopecia 36 32 Vomiting 14 12 Pruritus 29 28 Abdominal Pain 13 13 Rash 24 23 Dyspepsia 9 8 Skin Dry 24 23 Constipation 5 5 Special Senses, Other Hematologic Disorders Taste Perversion 9 4 Neutropenia 26 14 Vision Disorders Anemia 12 17 Vision Blurred 5 6 Leukopenia 6 5 Conjunctivitis 4 5 Thrombocytopenia 5 2 Liver and Biliary System Hepatomegaly 4 4 Table 6 summarizes the treatment-related adverse reactions in Study 4 that occurred at a greater than or equal to 10% incidence. Table 6 Treatment-Related Adverse Reactions (Greater Than or Equal to 10% Incidence) By Descending Frequency Study 4 Percentage of Subjects Reporting Treatment-Related Adverse Reactions Adverse Reactions PegIntron 1.5 mcg/kg with Ribavirin Capsules (N=1019) PegIntron 1 mcg/kg with Ribavirin Capsules (N=1016) Pegasys 180 mcg with Copegus (N=1035) Fatigue 67 68 64 Headache 50 47 41 Nausea 40 35 34 Chills 39 36 23 Insomnia 38 37 41 Anemia 35 30 34 Pyrexia 35 32 21 Injection Site Reactions 34 35 23 Anorexia 29 25 21 Rash 29 25 34 Myalgia 27 26 22 Neutropenia 26 19 31 Irritability 25 25 25 Depression 25 19 20 Alopecia 23 20 17 Dyspnea 21 20 22 Arthralgia 21 22 22 Pruritus 18 15 19 Influenza-like Illness 16 15 15 Dizziness 16 14 13 Diarrhea 15 16 14 Cough 15 16 17 Weight Decreased 13 10 10 Vomiting 12 10 9 Unspecified Pain 12 13 9 Dry Skin 11 11 12 Anxiety 11 11 10 Abdominal Pain 10 10 10 Leukopenia 9 7 10 The incidence of serious adverse reactions was comparable in all trials. In Study 2, the incidence of serious adverse reactions was 17% in the PegIntron/ ribavirin groups compared to 14% in the INTRON A/ ribavirin group. In Study 3, there was a similar incidence of serious adverse reactions reported for the weight-based ribavirin group (12%) and for the flat-dose ribavirin regimen. In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some subjects experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In Study 2, many subjects continued to experience adverse reactions several months after discontinuation of therapy. By the end of the 6-month follow-up period, the incidence of ongoing adverse reactions by body class in the PegIntron 1.5 mcg/ ribavirin group was 33% (psychiatric), 20% (musculoskeletal), and 10% (for endocrine and for GI). In approximately 10 to 15% of subjects, weight loss, fatigue, and headache had not resolved. There have been 28 subject deaths that occurred during treatment or follow-up in Studies 2, 3, and 4. In Study 2, there was 1 suicide in a subject receiving PegIntron/ribavirin combination therapy; and 1 subject death in the INTRON A/ribavirin group (motor vehicle accident). In Study 3, there were 14 deaths, 2 of which were probable suicides and 1 was an unexplained death in a person with a relevant medical history of depression. In Study 4, there were 12 deaths, 6 of which occurred in subjects who received PegIntron/ribavirin combination therapy, 5 in the PegIntron 1.5 mcg/ ribavirin arm (N=1,019) and 1 in the PegIntron 1 mcg/ribavirin arm (N=1,016), and 6 of which occurred in subjects receiving Pegasys/Copegus (N=1,035); there were 3 suicides that occurred during the off treatment follow-up period in subjects who received PegIntron (1.5 mcg/kg)/ribavirin combination therapy. In Studies 1 and 2, 10 to 14% of subjects receiving PegIntron, alone or in combination with ribavirin, discontinued therapy compared with 6% treated with INTRON A alone and 13% treated with INTRON A in combination with ribavirin. In Study 3, 15% of subjects receiving PegIntron in combination with weight-based ribavirin and 14% of subjects receiving PegIntron with flat dose ribavirin discontinued therapy due to an adverse reaction. The most common reasons for discontinuation were related to known interferon effects of psychiatric, systemic (e.g., fatigue, headache), or gastrointestinal adverse reactions. In Study 4, 13% of subjects in the PegIntron 1.5 mcg/ribavirin arm, 10% in the PegIntron 1 mcg/ribavirin arm and 13% in the Pegasys 180 mcg/Copegus arm discontinued due to adverse events. In Study 2, dose reductions for ribavirin were similar across all three groups [see Clinical Studies ( 14.1 )] , 33 to 35%. The most common reasons for dose modifications were neutropenia (18%), or anemia (9%) (see Laboratory Values ). Other common reasons included depression, fatigue, nausea, and thrombocytopenia. In Study 3, dose modifications due to adverse reactions occurred more frequently with weight-based ribavirin dosing compared to flat dosing (29% and 23%, respectively). In Study 4, 16% of subjects had a dose reduction of PegIntron to 1 mcg/kg in combination with ribavirin, with an additional 4% requiring the second dose reduction of PegIntron to 0.5 mcg/kg due to adverse events compared to 15% of subjects in the Pegasys/Copegus arm, who required a dose reduction to 135 mcg/week with Pegasys, with an additional 7% in the Pegasys/Copegus arm requiring second dose reduction to 90 mcg/week with Pegasys. In the PegIntron/ribavirin combination trials the most common adverse reactions were psychiatric, which occurred among 77% of subjects in Study 2 and 68% to 69% of subjects in Study 3. These psychiatric adverse reactions included most commonly depression, irritability, and insomnia, each reported by approximately 30% to 40% of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2% of all subjects during treatment or during follow-up after treatment cessation [see Warnings and Precautions ( 5 )] . In Study 4, psychiatric adverse reactions occurred in 58% of subjects in the PegIntron 1.5 mcg/ribavirin arm, 55% of subjects in the PegIntron 1 mcg/ribavirin arm, and 57% of subjects in the Pegasys 180 mcg/Copegus arm. In Study 2, PegIntron/ribavirin combination therapy induced fatigue or headache in approximately two-thirds of subjects, with fever or rigors in approximately half of the subjects. The severity of some of these systemic symptoms (e.g., fever and headache) tended to decrease as treatment continued. Subjects receiving ribavirin/PegIntron as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to those previously associated with this regimen during clinical trials of treatment-naïve subjects. Pediatric Subjects In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. In the pediatric trial, the most prevalent adverse reactions were pyrexia (80%), headache (62%), neutropenia (33%), fatigue (30%), anorexia (29%), injection-site erythema (29%) and vomiting (27%). The majority of adverse reactions were mild or moderate in severity. Severe adverse reactions were reported in 7% (8/107) of all subjects and included injection site pain (1%), pain in extremity (1%), headache (1%), neutropenia (1%), and pyrexia (4%). Important adverse reactions that occurred in this subject population were nervousness (7%; 7/107), aggression (3%; 3/107), anger (2%; 2/107), and depression (1%; 1/107). Five subjects received levothyroxine treatment, three with clinical hypothyroidism and two with asymptomatic TSH elevations. Weight and height gain of pediatric subjects treated with PegIntron plus ribavirin lagged behind that predicted by normative population data for the entire length of treatment. Severely inhibited growth velocity (less than 3rd percentile) was observed in 70% of the subjects while on treatment. Dose modifications of PegIntron and/or ribavirin were required in 25% of subjects due to treatment-related adverse reactions, most commonly for anemia, neutropenia and weight loss. Two subjects (2%; 2/107) discontinued therapy as the result of an adverse reaction. Adverse reactions that occurred with a greater than or equal to 10% incidence in the pediatric trial subjects are provided in Table 7 . Table 7 Percentage of Pediatric Subjects with Treatment-Related Adverse Reactions (in At Least 10% of All Subjects) System Organ Class Preferred Term All Subjects (N=107) Blood and Lymphatic System Disorders Neutropenia 33% Anemia 11% Leukopenia 10% Gastrointestinal Disorders Abdominal Pain 21% Abdominal Pain Upper 12% Vomiting 27% Nausea 18% General Disorders and Administration Site Conditions Pyrexia 80% Fatigue 30% Injection-site Erythema 29% Chills 21% Asthenia 15% Irritability 14% Investigations Weight Loss 19% Metabolism and Nutrition Disorders Anorexia 29% Decreased Appetite 22% Musculoskeletal and Connective Tissue Disorders Arthralgia 17% Myalgia 17% Nervous System Disorders Headache 62% Dizziness 14% Skin and Subcutaneous Tissue Disorders Alopecia 17% Ninety-four of 107 subjects enrolled in a 5-year follow-up trial. The long-term effects on growth were less in subjects treated for 24 weeks than in those treated for 48 weeks. Twenty-four percent of subjects (11/46) treated for 24 weeks and 40% of subjects (19/48) treated for 48 weeks had a >15 percentile height-for-age decrease from pre-treatment baseline to the end of 5-year follow-up. Eleven percent of subjects (5/46) treated for 24 weeks and 13% of subjects (6/48) treated for 48 weeks had a >30 percentile height-for-age decrease from pre-treatment baseline to the end of the 5-year follow-up. While observed across all age groups, the highest risk for reduced height at the end of long-term follow-up appeared to be initiation of combination therapy during the years of expected peak growth velocity [see Warnings and Precautions ( 5.9 )] . Laboratory Values Adult and Pediatric Subjects The adverse reaction profile in Study 3, which compared PegIntron/weight-based ribavirin combination to a PegIntron/flat dose ribavirin regimen, revealed an increased rate of anemia with weight-based dosing (29% vs. 19% for weight-based vs. flat dose regimens, respectively). However, the majority of cases of anemia were mild and responded to dose reductions. Changes in selected laboratory values during treatment in combination with ribavirin treatment are described below. Decreases in hemoglobin, leukocytes, neutrophils, and platelets may require dose reduction or permanent discontinuation from therapy [see Dosage and Administration ( 2.5 )] . Changes in selected laboratory values during therapy are described in Table 8 . Most of the changes in laboratory values in the PegIntron/ribavirin trial with pediatrics were mild or moderate. Table 8 Selected Laboratory Abnormalities During Treatment with Ribavirin Capsules and PegIntron or Ribavirin Capsules and INTRON A in Previously Untreated Subjects * The table summarizes the worst category observed within the period per subject per laboratory test. Only subjects with at least one treatment value for a given laboratory test are included. † ULN=Upper limit of normal. Laboratory Parameters * Percentage of Subjects Adults (Study 2) Pediatrics PegIntron/Ribavirin Capsules (N=511) INTRON A/ Ribavirin Capsules (N=505) PegIntron/Ribavirin Capsules (N=107) * Hemoglobin (g/dL) 9.5 to <11 26 27 30 8 to <9.5 3 3 2 6.5 to 7.9 0.2 0.2 - Leukocytes (x 10 9 /L) 2 to 2.9 46 41 39 1.5 to <2 24 8 3 1 to 1.4 5 1 - Neutrophils (x 10 9 /L) 1 to 1.5 33 37 35 0.75 to <1 25 13 26 0.5 to <0.75 18 7 13 <0.5 4 2 3 Platelets (x 10 9 /L) 70 to 100 15 5 1 50 to <70 3 0.8 - 30 to 49 0.2 0.2 - 25 to <50 - - 1 Total Bilirubin (mg/dL) (μmole/L) 1.5 to 3 10 13 - 1.26 to 2.59 x ULN † - - 7 3.1 to 6 0.6 0.2 - 2.6 to 5 x ULN † - - - 6.1 to 12 0 0.2 - ALT (U/L) 2 x Baseline 0.6 0.2 1 2.1 to 5 x Baseline 3 1 5 5.1 to 10 x Baseline 0 0 3 Hemoglobin. In Study 2, hemoglobin levels decreased to less than 11 g/dL in about 30% of subjects. In Study 3, 47% of subjects receiving weight-based dosing of ribavirin and 33% on flat-dose ribavirin had decreases in hemoglobin levels to less than 11 g/dL. Reductions in hemoglobin to less than 9 g/dL occurred more frequently in subjects receiving weight-based dosing compared to flat dosing (4% and 2%, respectively). In Study 2, dose modification was required in 9% and 13% of subjects in the PegIntron/ribavirin and INTRON A/ribavirin groups. In Study 4, subjects receiving PegIntron (1.5 mcg/kg)/ribavirin had decreases in hemoglobin levels to between 8.5 to less than 10 g/dL (28%) and to less than 8.5 g/dL (3%), whereas in patients receiving Pegasys 180 mcg/Copegus these decreases occurred in 26% and 4% of subjects, respectively. On average, hemoglobin levels became stable by treatment weeks 4 to 6. The typical pattern observed was a decrease in hemoglobin levels by treatment week 4 followed by stabilization and a plateau, which was maintained to the end of treatment [see Dosage and Administration ( 2.5 )] . Neutrophils. In Study 2, decreases in neutrophil counts were observed in a majority of adult subjects treated with PegIntron/ribavirin (85%) and INTRON A/ribavirin (60%). Severe, potentially life-threatening neutropenia (less than 0.5 x 109/L) occurred in approximately 4% of subjects treated with PegIntron/ribavirin and 2% of subjects treated with INTRON A/ribavirin. Eighteen percent of subjects receiving PegIntron/ribavirin required modification of interferon dosage. Few subjects (less than 1%) required permanent discontinuation of treatment. Neutrophil counts generally returned to pre-treatment levels 4 weeks after cessation of therapy [see Dosage and Administration ( 2.5 )] . Platelets. In Study 2, platelet counts decreased to less than 100,000/mm 3 in approximately 20% of subjects treated with PegIntron alone or with ribavirin and in 6% of adult subjects treated with INTRON A/ribavirin. Severe decreases in platelet counts (less than 50,000/mm 3 ) occur in less than 4% of adult subjects. In Study 2, 1% or 3% of subjects required dose modification of INTRON A or PegIntron, respectively. Platelet counts generally returned to pretreatment levels 4 weeks after the cessation of therapy [see Dosage and Administration ( 2.5 )] . Thyroid Function. In Study 2, clinically apparent thyroid disorders occurred among subjects treated with either INTRON A or PegIntron (with or without ribavirin) at a similar incidence (5% for hypothyroidism and 3% for hyperthyroidism). Subjects developed new onset TSH abnormalities while on treatment and during the follow-up period. At the end of the follow-up period, 7% of subjects still had abnormal TSH values. Bilirubin and Uric Acid. In Study 2, 10 to 14% of subjects developed hyperbilirubinemia and 33 to 38% developed hyperuricemia in association with hemolysis. Six subjects developed mild to moderate gout. Adverse Reactions with ribavirin/INTRON A Combination Therapy Adult Subjects In clinical trials, 19% and 6% of previously untreated and relapse subjects, respectively, discontinued therapy due to adverse reactions in the combination arms compared to 13% and 3% in the interferon-only arms. Selected treatment-related adverse reactions that occurred in the US trials with incidence 5% or greater are provided by treatment group (see Table 9 ). In general, the selected treatment-related adverse reactions were reported with lower incidence in the international trials as compared to the US trials, except for asthenia, influenza-like symptoms, nervousness, and pruritus. Pediatric Subjects In clinical trials of 118 pediatric subjects 3 to 16 years of age, 6% discontinued therapy due to adverse reactions. Dose modifications were required in 30% of subjects, most commonly for anemia and neutropenia. In general, the adverse-reaction profile in the pediatric population was similar to that observed in adults. Injection site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in pediatric subjects compared to adult subjects. Conversely, pediatric subjects experienced less fatigue, dyspepsia, arthralgia, insomnia, irritability, impaired concentration, dyspnea, and pruritus compared to adult subjects. Selected treatment-related adverse reactions that occurred with incidence 5% or greater among all pediatric subjects who received the recommended dose of ribavirin/INTRON A combination therapy are provided in Table 9. Table 9 Selected Treatment-Related Adverse Reactions: Previously Untreated and Relapse Adult Subjects and Previously Untreated Pediatric Subjects Subjects Reporting Adverse Reactions Subjects reporting one or more adverse reactions. A subject may have reported more than one adverse reaction within a body system/organ class category. Percentage of Subjects US Previously Untreated Study US Relapse Study Pediatric Subjects 24 weeks of treatment 48 weeks of treatment 24 weeks of treatment 48 weeks of treatment INTRON A/Ribavirin Capsules (N=228) INTRON A/Placebo (N=231) INTRON A/ Ribavirin Capsules (N=228) INTRON A/ Placebo (N=225) INTRON A/ Ribavirin Capsules (N=77) INTRON A/ Placebo (N=76) INTRON A/ Ribavirin Capsules (N=118) Application Site Disorder s Injection Site Inflammation 13 10 12 14 6 8 14 Injection Site Reaction 7 9 8 9 5 3 19 Body as a Whole - General Disorders Headache 63 63 66 67 66 68 69 Fatigue 68 62 70 72 60 53 58 Rigors 40 32 42 39 43 37 25 Fever 37 35 41 40 32 36 61 Influenza-like Symptoms 14 18 18 20 13 13 31 Asthenia 9 4 9 9 10 4 5 Chest Pain 5 4 9 8 6 7 5 Central & Peripheral Nervous System Disorders Dizziness 17 15 23 19 26 21 20 Gastrointestinal System Disorders Nausea 38 35 46 33 47 33 33 Anorexia 27 16 25 19 21 14 51 Dyspepsia 14 6 16 9 16 9 <1 Vomiting 11 10 9 13 12 8 42 Musculoskeletal System Disorders Myalgia 61 57 64 63 61 58 32 Arthralgia 30 27 33 36 29 29 15 Musculoskeletal Pain 20 26 28 32 22 28 21 Psychiatric Disorders Insomnia 39 27 39 30 26 25 14 Irritability 23 19 32 27 25 20 10 Depression 32 25 36 37 23 14 13 Emotional Lability 7 6 11 8 12 8 16 Concentration Impaired 11 14 14 14 10 12 5 Nervousness 4 2 4 4 5 4 3 Respiratory System Disorders Dyspnea 19 9 18 10 17 12 5 Sinusitis 9 7 10 14 12 7 <1 Skin and Appendages Disorders Alopecia 28 27 32 28 27 26 23 Rash 20 9 28 8 21 5 17 Pruritus 21 9 19 8 13 4 12 Special Senses, Other Disorders Taste Perversion 7 4 8 4 6 5 <1 During a 48-week course of therapy there was a decrease in the rate of linear growth (mean percentile assignment decrease of 7%) and a decrease in the rate of weight gain (mean percentile assignment decrease of 9%). A general reversal of these trends was noted during the 24-week post-treatment period. Long-term data in a limited number of patients, however, suggests that combination therapy may induce a growth inhibition that results in reduced final adult height in some patients [see Warnings and Precautions ( 5.9 )]. Laboratory Values Changes in selected hematologic values (hemoglobin, white blood cells, neutrophils, and platelets) during therapy are described below (see Table 10) . Hemoglobin. Hemoglobin decreases among subjects receiving ribavirin therapy began at Week 1, with stabilization by Week 4. In previously untreated subjects treated for 48 weeks, the mean maximum decrease from baseline was 3.1 g/dL in the US trial and 2.9 g/dL in the international trial. In relapse subjects, the mean maximum decrease from baseline was 2.8 g/dL in the US trial and 2.6 g/dL in the international trial. Hemoglobin values returned to pretreatment levels within 4 to 8 weeks of cessation of therapy in most subjects. Bilirubin and Uric Acid . Increases in both bilirubin and uric acid, associated with hemolysis, were noted in clinical trials. Most changes were moderate and reversed within 4 weeks after treatment discontinuation. This observation occurred most frequently in subjects with a previous diagnosis of Gilbert\\'s syndrome. This has not been associated with hepatic dysfunction or clinical morbidity. Table 10 Selected Laboratory Abnormalities During Treatment With Ribavirin Capsules and INTRON A: Previously Untreated and Relapse Adult Subjects and Previously Untreated Pediatric Subjects Percentage of Subjects US Previously Untreated Study US Relapse Study Pediatric Subjects 24 weeks of treatment 48 weeks of treatment 24 weeks of treatment 48 weeks of treatment INTRON A Ribavirin Capsules (N=228) INTRON A Placebo (N=231) INTRON A Ribavirin Capsules (N=228) INTRON A Placebo (N=225) INTRON A Ribavirin Capsules (N=77) INTRON A Placebo (N=76) INTRON A Ribavirin Capsules (N=118) Hemoglobin (g/dL) 9.5 to 10.9 24 1 32 1 21 3 24 8.0 to 9.4 5 0 4 0 4 0 3 6.5 to 7.9 0 0 0 0.4 0 0 0 < 6.5 0 0 0 0 0 0 0 Leukocytes (x10 9 /L) 2.0 to 2.9 40 20 38 23 45 26 35 1.5 to 1.9 4 1 9 2 5 3 8 1.0 to 1.4 0.9 0 2 0 0 0 0 < 1.0 0 0 0 0 0 0 0 Neutrophils (x10 9 /L) 1.0 to 1.49 30 32 31 44 42 34 37 0.75 to 0.99 14 15 14 11 16 18 15 0.5 to 0.74 9 9 14 7 8 4 16 < 0.5 11 8 11 5 5 8 3 Platelets (x10 9 /L) 70 to 99 9 11 11 14 6 12 0.8 50 to 69 2 3 2 3 0 5 2 30 to 49 0 0.4 0 0.4 0 0 0 < 30 0.9 0 1 0.9 0 0 0 Total Bilirubin (mg/dL) 1.5 to 3.0 27 13 32 13 21 7 2 3.1 to 6.0 0.9 0.4 2 0 3 0 0 6.1 to 12.0 0 0 0.4 0 0 0 0 > 12.0 0 0 0 0 0 0 0 6.2 Postmarketing Experiences The following adverse reactions have been identified and reported during post approval use of ribavirin in combination with INTRON A or PegIntron. 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. Blood and Lymphatic System disorders: Pure red cell aplasia, aplastic anemia Ear and Labyrinth disorders: Hearing disorder, vertigo Respiratory, Thoracic and Mediastinal disorders: Pulmonary hypertension Eye disorders: Serous retinal detachment Endocrine disorders: Diabetes\"}', 'drug_interactions': '{\"7 DRUG INTERACTIONS Nucleoside analogues: Closely monitor for toxicities. Discontinue nucleoside reverse transcriptase inhibitors or reduce dose or discontinue interferon, ribavirin or both with worsening toxicities. ( 7.2 ) 7.1 Didanosine Exposure to didanosine or its active metabolite (dideoxyadenosine 5\\'-triphosphate) is increased when didanosine is coadministered with ribavirin, which could cause or worsen clinical toxicities; therefore, coadministration of ribavirin capsules and didanosine is contraindicated [see Contraindications ( 4 )] . Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials. 7.2 Nucleoside Analogues Hepatic decompensation (some fatal) has occurred in cirrhotic HIV/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and nucleoside reverse transcriptase inhibitors (NRTIs) should be closely monitored for treatment- associated toxicities, especially hepatic decompensation and anemia. Discontinuation of NRTIs should be considered as medically appropriate [see labeling for individual NRTI product ]. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Ribavirin may antagonize the cell culture antiviral activity of stavudine and zidovudine against HIV. Ribavirin has been shown in cell culture to inhibit phosphorylation of lamivudine, stavudine and zidovudine, which could lead to decreased antiretroviral activity. However, in a study with another pegylated interferon in combination with ribavirin, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV/HCV virologic suppress) interaction was observed when ribavirin and lamivudine (n=18), stavudine (n=10), or zidovudine (n=6) were coadministered as part of a multidrug regimen in HIV/HCV co-infected subjects. Concomitant use of ribavirin with any of these drugs should be done with caution. 7.3 Drugs Metabolized by Cytochrome P-450 Results of in vitro studies using both human and rat liver microsome preparations indicated little or no cytochrome P-450 enzyme-mediated metabolism of ribavirin, with minimal potential for P-450 enzyme-based drug interactions. No pharmacokinetic interactions were noted between INTRON A and ribavirin capsules in a multiple-dose pharmacokinetic study. 7.4 Azathioprine The use of ribavirin for the treatment of chronic hepatitis C in patients receiving azathioprine has been reported to induce severe pancytopenia and may increase the risk of azathioprine-related myelotoxicity. Inosine monophosphate dehydrogenase (IMDH) is required for one of the metabolic pathways of azathioprine. Ribavirin is known to inhibit IMDH, thereby leading to accumulation of an azathioprine metabolite, 6-methylthioinosine monophosphate (6-MTITP), which is associated with myelotoxicity (neutropenia, thrombocytopenia, and anemia). Patients receiving azathioprine with ribavirin should have complete blood counts, including platelet counts, monitored weekly for the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage or other therapy changes are necessary [see Warnings and Precautions ( 5.8 ) ].\"}', 'indications_and_usage': '{\"1 INDICATIONS AND USAGE Ribavirin is a nucleoside analogue indicated in combination with interferon alfa- 2b (pegylated and nonpegylated) for the treatment of Chronic Hepatitis C (CHC) in patients 3 years of age or older with compensated liver disease. ( 1.1 ) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. 1.1 Chronic Hepatitis C (CHC) Ribavirin capsules in combination with interferon alfa-2b (pegylated and nonpegylated) is indicated for the treatment of Chronic Hepatitis C (CHC) in patients 3 years of age and older with compensated liver disease [see Warnings and Precautions ( 5.9 , 5.10 ), and Use in Specific Populations ( 8.4 )]. The following points should be considered when initiating ribavirin capsules combination therapy with PegIntron ® or INTRON A ® : Combination therapy with ribavirin /PegIntron is preferred over ribavirin /INTRON A as this combination provides substantially better response rates [see Clinical Studies ( 14 ) ]. Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection [see Clinical Studies ( 14 ) ]. No safety and efficacy data are available for treatment duration lasting longer than one year.\"}', 'warnings_and_cautions': '{\"5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity: May cause fetal harm. Patients should have a negative pregnancy test prior to therapy and use effective contraception and undergo periodic pregnancy tests. ( 5.1 , 8.1 , 8.3 ) Patients exhibiting the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy: Hemolytic anemia may occur with a significant initial drop in hemoglobin. ( 5.2 ) Pancreatitis. ( 5.3 ) Pulmonary infiltrates or pulmonary function impairment. ( 5.4 ) New or worsening ophthalmologic disorders ( 5.5 ) Severe decreases in neutrophil and platelet counts, and hematologic, endocrine (e.g., TSH), and hepatic abnormalities. ( 5.6 ) Dental/periodontal disorders reported with combination therapy. ( 5.7 ) Concomitant administration of azathioprine. ( 5.8 ) Weight loss and growth inhibition reported during combination therapy in pediatric patients. Long-term growth inhibition (height) reported in some patients. ( 5.9 ) Monotherapy with ribavirin is not permitted. ( 5.10 ) 5.1 Embryo-Fetal Toxicity Ribavirin capsules and oral solution may cause birth defects, miscarriage or stillbirth. Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use effective contraception and have periodic monitoring with pregnancy tests during treatment and during the 6-month period after treatment has been stopped. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin has demonstrated significant teratogenic and embryocidal effects in all animal species tested. These effects occurred at doses as low as one twentieth of the recommended human dose of ribavirin [see Boxed Warning, Contraindications ( 4 ), and Use in Specific Populations ( 8.1 , 8.3 )] . 5.2 Anemia Hemolytic anemia was observed in approximately 10% of ribavirin/INTRON A-treated subjects in clinical trials. The anemia associated with ribavirin occurs within 1 to 2 weeks of initiation of therapy. Because the initial drop in hemoglobin may be significant, obtain hemoglobin or hematocrit levels before the start of treatment and at week 2 and week 4 of therapy, or more frequently if clinically indicated. Patients should then be followed as clinically appropriate [see Dosage and Administration ( 2.5 , 2.6 )] . Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused by ribavirin. Patients should be assessed for underlying cardiac disease before initiation of ribavirin therapy. Patients with pre-existing cardiac disease should have electrocardiograms administered before treatment and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be suspended or discontinued [see Dosage and Administration ( 2.5 , 2.6 )] . Because cardiac disease may be worsened by drug-induced anemia, patients with a history of significant or unstable cardiac disease should not use ribavirin. 5.3 Pancreatitis Suspend ribavirin and INTRON A or PegIntron combination therapy in patients with signs and symptoms of pancreatitis and discontinue in patients with confirmed pancreatitis. 5.4 Pulmonary Disorders Pulmonary symptoms, including dyspnea, pulmonary infiltrates, pneumonitis, pulmonary hypertension, and pneumonia, have been reported during ribavirin with alpha interferon combination therapy; occasional cases of fatal pneumonia have occurred. In addition, sarcoidosis or the exacerbation of sarcoidosis has been reported. If there is evidence of pulmonary infiltrates or pulmonary function impairment, closely monitor the patient, and if appropriate, discontinue combination therapy. 5.5 Ophthalmologic Disorders Ribavirin is used in combination therapy with INTRON A or PegIntron. Refer to labeling for PegIntron for additional information. 5.6 Laboratory Tests PegIntron in combination with ribavirin may cause severe decreases in neutrophil and platelet counts, and hematologic, endocrine (e.g., TSH), and hepatic abnormalities. Obtain hematology and blood chemistry testing in patients on PegIntron/ribavirin combination therapy before the start of treatment and then periodically thereafter. In the adult clinical trial, complete blood counts (including hemoglobin, neutrophil, and platelet counts) and chemistries (including AST, ALT, bilirubin, and uric acid) were measured during the treatment period at weeks 2, 4, 8, 12, and then at 6-week intervals, or more frequently if abnormalities developed. In pediatric subjects, the same laboratory parameters were evaluated with additional assessment of hemoglobin at treatment week 6. TSH levels were measured every 12 weeks during the treatment period. HCV-RNA should be measured periodically during treatment [see Dosage and Administration ( 2 ) ]. 5.7 Dental and Periodontal Disorders Dental and periodontal disorders have been reported in patients receiving ribavirin and interferon or peginterferon combination therapy. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of ribavirin and pegylated or nonpegylated interferon alfa-2b. Advise patients to brush their teeth thoroughly twice daily and have regular dental examinations. If vomiting occurs, advise patients to rinse out their mouth thoroughly afterwards. 5.8 Concomitant Administration of Azathioprine Pancytopenia (marked decreases in red blood cells, neutrophils, and platelets) and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the concomitant administration of pegylated interferon/ribavirin and azathioprine. In this limited number of patients (n=8), myelotoxicity was reversible within 4 to 6 weeks upon withdrawal of both HCV antiviral therapy and concomitant azathioprine and did not recur upon reintroduction of either treatment alone. Discontinue PegIntron, ribavirin, and azathioprine for pancytopenia, and do not reintroduce pegylated interferon/ribavirin with concomitant azathioprine [see Drug Interactions ( 7.4 )] . 5.9 Impact on Growth in Pediatric Patients Data on the effects of PegIntron and ribavirin on growth come from an open-label study in subjects 3 through 17 years of age, in which weight and height changes were compared to US normative population data. In general, the weight and height gain of pediatric subjects treated with PegIntron and ribavirin lagged behind that predicted by normative population data for the entire length of treatment. Severely inhibited growth velocity (less than 3 rd percentile) was observed in 70% of the subjects while on treatment. Following treatment, rebound growth and weight gain occurred in most subjects. Long-term follow-up data in pediatric subjects, however, indicates that PegIntron in combination therapy with ribavirin may induce a growth inhibition that results in reduced adult height in some patients [see Adverse Reactions ( 6.1 )]. Similarly, an impact on growth was seen in subjects after treatment with ribavirin and INTRON A combination therapy for one year. In a long-term follow-up trial of a limited number of these subjects, combination therapy resulted in reduced final adult height in some subjects [see Adverse Reactions ( 6.1 ) ]. 5.10 Not Recommended for Monotherapy and Risks Associated with Combination Therapy Based on results of clinical trials, ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection; therefore, ribavirin capsules must not be used alone. The safety and efficacy of ribavirin capsules have only been established when used together with INTRON A or PegIntron (not other interferons) as combination therapy. The safety and efficacy of ribavirin with INTRON A or PegIntron combination therapy for the treatment of HIV infection, adenovirus, RSV, parainfluenza, or influenza infections have not been established. Ribavirin capsules should not be used for these indications. There are significant adverse reactions caused by ribavirin/INTRON A or PegIntron combination therapy, including severe depression and suicidal or homicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. Suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up. Labeling for INTRON A and PegIntron should be reviewed in their entirety for additional safety information prior to initiation of combination treatment.\"}', 'overdosage': '{\"10 OVERDOSAGE There is limited experience with overdosage. Acute ingestion of up to 20 g of ribavirin capsules, INTRON A ingestion of up to 120 million units, and subcutaneous doses of INTRON A up to 10 times the recommended doses have been reported. Primary effects that have been observed are increased incidence and severity of the adverse reactions related to the therapeutic use of INTRON A and ribavirin capsules. However, hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with administration of single subcutaneous doses of INTRON A that exceed dosing recommendations. There is no specific antidote for INTRON A or ribavirin overdose, and hemodialysis and peritoneal dialysis are not effective for treatment of overdose of these agents.\"}', 'active_flag': 'Y', 'generic_name': '{RIBAVIRIN}', 'route': '{ORAL}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{\"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Anemia The most common adverse experience occurring with ribavirin capsules is anemia, which may be severe [see Warnings and Precautions (5.2) and Adverse Reactions (6)] . Advise patients that laboratory evaluations are required prior to starting therapy and periodically thereafter [see Dosage and Administration (2.4)] . Advise patients to be well hydrated, especially during the initial stages of treatment. Embryo-Fetal Toxicity Inform females of reproductive potential and pregnant women that ribavirin capsules and oral solution may cause birth defects, miscarriage, and stillbirth. Advise females of reproductive potential that they must have a pregnancy test prior to initiating treatment and periodically during therapy. Advise females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment with ribavirin and for 6 months post therapy. Advise patients to notify the physician immediately in the event of a pregnancy [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )] . Missed Dose Inform patients that in the event a dose is missed, the missed dose should be taken as soon as possible during the same day. Patients should not double the next dose. Advise patients to contact their healthcare provider if they have questions. Dental and Periodontal Disorders Advise patients to brush their teeth thoroughly twice daily and have regular dental examinations. If vomiting occurs, advise patients to rinse out their mouth thoroughly afterwards [see Warnings and Precautions ( 5.7 )] . Trademarks depicted herein are the property of their respective owners. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. Manufactured by: Cadila Healthcare Ltd. Ahmedabad, India. Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Rev.: 11/20\"}', 'pregnancy': '{\"5.1 Embryo-Fetal Toxicity Ribavirin capsules and oral solution may cause birth defects, miscarriage or stillbirth. Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use effective contraception and have periodic monitoring with pregnancy tests during treatment and during the 6-month period after treatment has been stopped. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin has demonstrated significant teratogenic and embryocidal effects in all animal species tested. These effects occurred at doses as low as one twentieth of the recommended human dose of ribavirin [see Boxed Warning, Contraindications ( 4 ), and Use in Specific Populations ( 8.1 , 8.3 )] .\",\"8.1 Pregnancy Risk Summary Ribavirin is contraindicated for use in pregnant women and in men whose female partners are pregnant [see Contraindications ( 4 )] . Based on animal data, ribavirin use in pregnancy may be associated with birth defects. Data from the Ribavirin Pregnancy Registry are insufficient to identify a drug-associated risk of birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Ribavirin is known to accumulate in intracellular components from where it is cleared very slowly. In animal studies, ribavirin exposure was shown to have teratogenic and/or embryocidal effects (see Data). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from the Ribavirin Pregnancy Registry on 88 live births from pregnancies in women directly exposed and 98 live births from pregnancies in women indirectly exposed (by a male partner) to ribavirin during pregnancy or during the 6 months prior to pregnancy show a higher rate of birth defects (9.09% and 6.12%, respectively) compared to a background birth defect rate of 2.72% in the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defects surveillance system. No pattern of birth defects can be identified from these reports. The miscarriage rate was approximately 21%. The current sample size is insufficient for reaching definitive conclusions based on statistical analysis. Trends suggesting a common etiology or relationship with ribavirin exposure were not observed. Methodologic limitations of the Ribavirin Pregnancy Registry include the use of MACDP as the external comparator group. Limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease and comorbidities. Animal Data Embryotoxicity/teratogenicity studies with ribavirin were conducted in rats (oral doses of 0.3, 1.0 and 10 mg/kg on Gestation Days 6 to 15) and rabbits (oral dose of 0.1, 0.3 and 1.0 mg/kg on Gestation Days 6 to 18).Ribavirin demonstrated significant embryocidal and teratogenic effects at doses well below the recommended human dose in all animal species in which adequate studies have been conducted. Malformations of the skull, palate, eye, jaw, limbs, skeleton, and gastrointestinal tract were noted. The incidence and severity of teratogenic effects increased with escalation of the drug dose. Survival of fetuses and offspring was reduced [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] .\"}', 'pediatric_use': None, 'geriatric_use': '{\"8.5 Geriatric Use Clinical trials of ribavirin combination therapy did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently from younger subjects. Ribavirin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients often have decreased renal function, care should be taken in dose selection. Renal function should be monitored and dosage adjustments made accordingly. Ribavirin should not be used in patients with creatinine clearance less than 50 mL/min [ see Contraindications ( 4 ) ]. In general, ribavirin capsules should be administered to elderly patients cautiously, starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and cardiac function, and of concomitant disease or other drug therapy. In clinical trials, elderly subjects had a higher frequency of anemia (67%) than younger patients (28%) [see Warnings and Precautions ( 5.2 ) ].\"}'}" } ]

[ { "from": "human", "value": "{GUAIFENESIN}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Uses • helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{GUAIFENESIN}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or persistent headache. These could be signs of a serious illness.\"}', 'do_not_use': '{\"Do not use • for children under 12 years of age\"}', 'when_using': None, 'warnings': '{\"Warnings Do not use • for children under 12 years of age Ask a doctor before use if you have • persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema • cough accompanied by too much phlegm (mucus) Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or persistent headache. These could be signs of a serious illness. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222).\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{ACETAMINOPHEN,\"DEXTROMETHORPHAN HYDROBROMIDE\",\"DOXYLAMINE SUCCINATE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Uses temporarily relieves these common cold/flu symptoms: minor aches and pains headache fever sore throat runny nose and sneezing cough due to minor throat and bronchial irritation\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"ACETAMINOPHEN, DEXTROMETHORPHAN HYDROBROMIDE, DOXYLAMINE SUCCINATE\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if pain or cough gets worse or lasts more than 7 days fever gets worseor lasts more than 3 days redness or swelling is present new symptoms occur cough comes back or occurs with rash or headache that lasts. These could be signs of a serious condition.\"}', 'do_not_use': '{\"Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.\"}', 'when_using': '{\"When using this product excitability may occur, especially in children marked drowsiness may occur avoid alcoholic drinks be careful when driving a motor vehicle or operating machinery alcohol, sedatives and tranquilizers may increase drowsiness\"}', 'warnings': '{\"Warnings Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take more than 4,000 doses of acetaminophen in 24 hours with other drugs containing acetaminophen 3 or more alcoholic drinks every day while using this product Allergy alert : Acetaminophen may cause severe skin reactions. Symptoms may include: skin reddening blisters rash If a skin reaction occurs, stop use and seek medical help right away. Sore throat warning : If sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, nausea, or vomiting, consult a doctor promptly. Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have liver disease glaucoma a breathing problem or chronic cough that that lasts or as occurs with smoking, asthma, chronic bronchitis, or emphysema trouble urinating due to an enlarged prostate gland cough that occurs with too much phlegm (mucus) Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers the blood thinning drug warfarin When using this product excitability may occur, especially in children marked drowsiness may occur avoid alcoholic drinks be careful when driving a motor vehicle or operating machinery alcohol, sedatives and tranquilizers may increase drowsiness Stop use and ask a doctor if pain or cough gets worse or lasts more than 7 days fever gets worseor lasts more than 3 days redness or swelling is present new symptoms occur cough comes back or occurs with rash or headache that lasts. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. Overdose warning : Taking more than the recommended dose (overdose) may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) right away. Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"OXALIS STRICTA WHOLE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Directions: FOR ORAL USE ONLY.\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"OXALIS 3 SPECIAL ORDER\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"Warnings: Claims based on traditional homeopathic practice, not accepted medical evidence. Not FDA evaluated. Contains sugar. Diabetics and persons intolerant of sucrose (sugar): Consult a doctor before use. Do not use if allergic to any ingredient. Consult a doctor before use for serious conditions or if conditions worsen or persist. If pregnant or nursing, consult a doctor before use. Do not use if safety seal is broken or missing.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{DIMENHYDRINATE}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Uses for prevention and treatment of these symptoms associated with motion sickness: nausea vomiting dizziness\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{DIMENHYDRINATE}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': None, 'do_not_use': '{\"Do not use for children under 2 years of age unless directed by a doctor.\"}', 'when_using': '{\"When using this product marked drowsiness may occur avoid alcoholic beverages alcohol, sedatives, and tranquilizers may increase drowsiness use caution when driving a motor vehicle or operating machinery\"}', 'warnings': '{\"Warnings Do not use for children under 2 years of age unless directed by a doctor. Ask a doctor before use if you have a breathing problem such as emphysema or chronic bronchitis glaucoma difficulty in urination due to enlargement of the prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers. When using this product marked drowsiness may occur avoid alcoholic beverages alcohol, sedatives, and tranquilizers may increase drowsiness use caution when driving a motor vehicle or operating machinery If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"CYCLOBENZAPRINE HYDROCHLORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': '{\"CONTRAINDICATIONS Hypersensitivity to any component of this product. Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation. Hyperpyretic crisis seizures, and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitor drugs. Acute recovery phase of myocardial infarction, and patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure. Hyperthyroidism.\"}', 'adverse_reactions': '{\"ADVERSE REACTIONS Incidence of most common adverse reactions in the 2 double-blind ‡ , placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine HCl 5 mg): Cyclobenzaprine HCl Tablets Cyclobenzaprine HCl Tablets Placebo 5 mg 10 mg N=464 N=249 N=469 Drowsiness 29% 38% 10% Dry Mouth 21% 32% 7% Fatigue 6% 6% 3% Headache 5% 5% 8% ‡ Note: Cyclobenzaprine HCl Tablets 10 mg data are from one clinical trial. Cyclobenzaprine HCl Tablets 5 mg and placebo data are from two studies. Adverse reactions which were reported in 1% to 3% of the patients were: abdominal pain, acid regurgitation, constipation, diarrhea, dizziness, nausea, irritability, mental acuity decreased, nervousness, upper respiratory infection, and pharyngitis. The following list of adverse reactions is based on the experience in 473 patients treated with cyclobenzaprine HCl 10 mg in additional controlled clinical studies, 7607 patients in the postmarketing surveillance program, and reports received since the drug was marketed. The overall incidence of adverse reactions among patients in the surveillance program was less than the incidence in the controlled clinical studies. The adverse reactions reported most frequently with cyclobenzaprine HCl were drowsiness, dry mouth and dizziness. The incidence of these common adverse reactions was lower in the surveillance program than in the controlled clinical studies: Clinical Studies with Surveillance Program with Cyclobenzaprine HCl Tablets 10 mg Cyclobenzaprine HCl Tablets 10 mg Drowsiness 39% 16% Dry mouth 27% 7% Dizziness 11% 3% Among the less frequent adverse reactions, there was no appreciable difference in incidence in controlled clinical studies or in the surveillance program. Adverse reactions which were reported in 1% to 3% of the patients were: fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness, and confusion. The following adverse reactions have been reported in postmarketing experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg tablet: Body as a Whole: Syncope; malaise. Cardiovascular: Tachycardia; arrhythmia; vasodilatation; palpitation; hypotension. Digestive: Vomiting; anorexia; diarrhea; gastrointestinal pain; gastritis; thirst; flatulence; edema of the tongue; abnormal liver function and rare reports of hepatitis, jaundice and cholestasis. Hypersensitivity: Anaphylaxis; angioedema; pruritus; facial edema; urticaria; rash. Musculoskeletal: Local weakness. Nervous System and Psychiatric: Seizures, ataxia; vertigo; dysarthria; tremors; hypertonia; convulsions; muscle twitching; disorientation; insomnia; depressed mood; abnormal sensations; anxiety; agitation; psychosis, abnormal thinking and dreaming; hallucinations; excitement; paresthesia; diplopia, serotonin syndrome. Skin: Sweating. Special Senses: Ageusia; tinnitus. Urogenital: Urinary frequency and/or retention. Causal Relationship Unknown Other reactions, reported rarely for cyclobenzaprine HCl under circumstances where a causal relationship could not be established or reported for other tricyclic drugs, are listed to serve as alerting information to physicians: Body as a Whole: Chest pain; edema. Cardiovascular: Hypertension; myocardial infarction; heart block; stroke. Digestive: Paralytic ileus, tongue discoloration; stomatitis; parotid swelling. Endocrine: Inappropriate ADH syndrome. Hematic and Lymphatic: Purpura; bone marrow depression; leukopenia; eosinophilia; thrombocytopenia. Metabolic, Nutritional and Immune: Elevation and lowering of blood sugar levels; weight gain or loss. Musculoskeletal: Myalgia. Nervous System and Psychiatric: Decreased or increased libido; abnormal gait; delusions; aggressive behavior; paranoia; peripheral neuropathy; Bell’s palsy; alteration in EEG patterns; extrapyramidal symptoms. Respiratory: Dyspnea. Skin: Photosensitization; alopecia. Urogenital: Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea. To report SUSPECTED ADVERSE EVENTS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions .\"}', 'drug_interactions': '{\"Drug Interactions Cyclobenzaprine HCl may have life-threatening interactions with MAO inhibitors (see CONTRAINDICATIONS ). Postmarketing cases of serotonin syndrome have been reported during combined use of Cyclobenzaprine Hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. If concomitant treatment with Cyclobenzaprine Hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see WARNINGS ). Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants. Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds. Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol. † ____________________________________________________________________ † ULTRAM ® (tramadol HCl tablets, PriCar, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) † ULTRACET ® (tramadol HCl and acetaminophen tablets, PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) _____________________________________________________________________\"}', 'indications_and_usage': '{\"INDICATIONS AND USAGE Cyclobenzaprine HCl is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living. Cyclobenzaprine HCl should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted. Cyclobenzaprine HCl has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.\"}', 'warnings_and_cautions': None, 'overdosage': '{\"OVERDOSAGE Although rare, deaths may occur from overdosage with cyclobenzaprine HCl. Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible. The acute oral LD 50 of cyclobenzaprine HCl is approximately 338 and 425 mg/kg in mice and rats, respectively. Manifestations The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rare but potentially critical manifestations of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity. Other potential effects of overdosage include any of the symptoms listed under ADVERSE REACTIONS . Management General As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. In order to protect against the rare but potentially critical manifestations described above, obtain an ECG and immediately initiate cardiac monitoring. Protect the patient’s airway, establish an intravenous line and initiate gastric decontamination. Observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Monitoring of plasma drug levels should not guide management of the patient. Dialysis is probably of no value because of low plasma concentrations of the drug. Gastrointestinal Decontamination All patients suspected of an overdose with cyclobenzaprine HCl should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage and emesis is contraindicated. Cardiovascular A maximal limb-lead QRS duration of ≥0.10 seconds may be the best indication of the severity of the overdose. Serum alkalinization, to a pH of 7.45 to 7.55, using intravenous sodium bicarbonate and hyperventilation (as needed), should be instituted for patients with dysrhythmias and/or QRS widening. A pH > 7.60 or a pCO 2 < 20 mmHg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide). CNS In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g. phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in close consultation with a poison control center. Psychiatric Follow-Up Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate. Pediatric Management The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.\"}', 'active_flag': 'Y', 'generic_name': '{\"CYCLOBENZAPRINE HYDROCHLORIDE\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"WARNINGS Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with Cyclobenzaprine Hydrochloride when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. The concomitant use of Cyclobenzaprine Hydrochloride with MAO inhibitors is contraindicated (see CONTRAINDICATIONS ). Serotonin syndrome symptoms may include mental status changes (e.g., confusion, agitation, hallucinations), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., tremor, ataxia, hyperreflexia, clonus, muscle rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Treatment with Cyclobenzaprine Hydrochloride and any concomitant serotonergic agents should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. If concomitant treatment with Cyclobenzaprine Hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see PRECAUTIONS , Drug Interactions ). Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine. In short term studies for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those recommended for skeletal muscle spasm, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred (see WARNINGS , below, and ADVERSE REACTIONS ). Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke. Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants.\"}', 'precautions': '{\"PRECAUTIONS General Because of its atropine-like action, cyclobenzaprine HCl should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic medication. Impaired Hepatic Function The plasma concentration of cyclobenzaprine is increased in patients with hepatic impairment (see CLINICAL PHARMACOLOGY, Pharmacokinetics , Hepatic Impairment ). These patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine. Cyclobenzaprine HCl should be used with caution in subjects with mild hepatic impairment starting with a 5 mg dose and titrating slowly upward. Due to the lack of data in subjects with more severe hepatic insufficiency, the use of cyclobenzaprine HCl in subjects with moderate to severe impairment is not recommended. Information for Patients Cyclobenzaprine HCl, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without concomitant medications, is increased. In elderly patients, cyclobenzaprine HCl should be initiated with a 5 mg dose and titrated slowly upward. Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Cyclobenzaprine Hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Patients should be advised of the signs and symptoms of serotonin syndrome, and be instructed to seek medical care immediately if they experience these symptoms (see WARNINGS , and see PRECAUTIONS , Drug Interactions ). Drug Interactions Cyclobenzaprine HCl may have life-threatening interactions with MAO inhibitors (see CONTRAINDICATIONS ). Postmarketing cases of serotonin syndrome have been reported during combined use of Cyclobenzaprine Hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. If concomitant treatment with Cyclobenzaprine Hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see WARNINGS ). Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants. Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds. Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol. † ____________________________________________________________________ † ULTRAM ® (tramadol HCl tablets, PriCar, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) † ULTRACET ® (tramadol HCl and acetaminophen tablets, PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) _____________________________________________________________________ Carcinogenesis, Mutagenesis, Impairment of Fertility In rats treated with cyclobenzaprine HCl for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks. Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat. At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose. Pregnancy Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to cyclobenzaprine HCl. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because cyclobenzaprine is closely related to the tricyclic antidepressants, some of which are known to be excreted in human milk, caution should be exercised when cyclobenzaprine HCl is administered to a nursing woman. Pediatric Use Safety and effectiveness of cyclobenzaprine HCl in pediatric patients below 15 years of age have not been established. Use in the Elderly The plasma concentration of cyclobenzaprine is increased in the elderly (see CLINICAL PHARMACOLOGY, Pharmacokinetics , Elderly ). The elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions. For these reasons, in the elderly, cyclobenzaprine should be used only if clearly needed. In such patients cyclobenzaprine HCl should be initiated with a 5 mg dose and titrated slowly upward.\"}', 'information_for_patients': '{\"Information for Patients Cyclobenzaprine HCl, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without concomitant medications, is increased. In elderly patients, cyclobenzaprine HCl should be initiated with a 5 mg dose and titrated slowly upward. Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Cyclobenzaprine Hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Patients should be advised of the signs and symptoms of serotonin syndrome, and be instructed to seek medical care immediately if they experience these symptoms (see WARNINGS , and see PRECAUTIONS , Drug Interactions ).\"}', 'pregnancy': '{\"Pregnancy Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to cyclobenzaprine HCl. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.\"}', 'pediatric_use': '{\"Pediatric Use Safety and effectiveness of cyclobenzaprine HCl in pediatric patients below 15 years of age have not been established.\"}', 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{\"SODIUM FLUORIDE\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Use aids in the prevention of dental cavities\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"SODIUM FLUORIDE\"}', 'route': '{ORAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"Warning for this product\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]

[ { "from": "human", "value": "{HYDROCORTISONE,\"NEOMYCIN SULFATE\",\"POLYMYXIN B SULFATE\"}" }, { "from": "gpt", "value": "{'contraindications': '{\"CONTRAINDICATIONS This product is contraindicated in those individuals who have shown hypersensitivity to any of its components, and in herpes simplex, vaccinia, and varicella infections.\"}', 'adverse_reactions': '{\"ADVERSE REACTIONS Neomycin occasionally causes skin sensitization. Ototoxicity and nephrotoxicity have also been reported [see Warnings ]. Adverse reactions have occurred with topical use of antibiotic combinations including neomycin and polymyxin B. Exact incidence figures are not available since no denominator of treated patients is available. The reaction occurring most often is allergic sensitization. In one clinical study, using a 20% neomycin patch, neomycin-induced allergic skin reactions occurred in two of 2,175 (0.09%) individuals in the general population. 2 In another study, the incidence was found to be approximately 1%. 3 The following local adverse reactions have been reported with topical corticosteroids, especially under occlusive dressings: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. Stinging and burning have been reported rarely when this product has gained access to the middle ear. To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.\"}', 'drug_interactions': None, 'indications_and_usage': '{\"INDICATIONS AND USAGE For the treatment of superficial bacterial infections of the external auditory canal caused by organisms susceptible to the action of the antibiotics, and for the treatment of infections of mastoidectomy and fenestration cavities caused by organisms susceptible to the antibiotics.\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"NEOMYCIN SULFATE, POLYMYXIN B SULFATE AND HYDROCORTISONE\"}', 'route': '{\"AURICULAR (OTIC)\"}', 'product_type': '{\"HUMAN PRESCRIPTION DRUG\"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{\"WARNINGS Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk is greater with prolonged use. Therapy should be limited to 10 consecutive days [see Error! Hyperlink reference not valid. ] . Patients being treated with eardrops containing neomycin should be under close clinical observation. Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension should not be used in any patient with a perforated tympanic membrane. Discontinue promptly if sensitization or irritation occurs. Neomycin sulfate may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical neomycin is not known. When using neomycin-containing products to control secondary infection in the chronic dermatoses, such as chronic otitis externa or stasis dermatitis, it should be borne in mind that the skin in these conditions is more liable than is normal skin to become sensitized to many substances, including neomycin. The manifestation of sensitization to neomycin is usually a low-grade reddening with swelling, dry scaling, and itching; it may be manifest simply as a failure to heal. Periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. These symptoms regress quickly on withdrawing the medication. Neomycin-containing applications should be avoided for the patient thereafter.\"}', 'precautions': '{\"PRECAUTIONS General As with other antibiotic preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If the infection is not improved after 1 week, cultures and susceptibility tests should be repeated to verify the identity of the organism and to determine whether therapy should be changed. Treatment should not be continued for longer than 10 days. 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 Avoid contaminating the bottle tip with material from the ear, fingers, or other source. This caution is necessary if the sterility of the drops is to be preserved. If sensitization or irritation occurs, discontinue use immediately and contact your physician. Do not use in the eyes. SHAKE WELL BEFORE USING. Laboratory Tests Systemic effects of excessive levels of hydrocortisone may include a reduction in the number of circulating eosinophils and a decrease in urinary excretion of 17-hydroxycorticosteroids. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals (rats, rabbits, mice) showed no evidence of carcinogenicity attributable to oral administration of corticosteroids. Pregnancy Teratogenic Effects Pregnancy Category C. Corticosteroids have been shown to be teratogenic in rabbits when applied topically at concentrations of 0.5% on days 6 to 18 of gestation and in mice when applied topically at a concentration of 15% on days 10 to 13 of gestation. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Hydrocortisone appears in human milk following oral administration of the drug. Since systemic absorption of hydrocortisone may occur when applied topically, caution should be exercised when Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension is used by a nursing woman. Pediatric Use The safety and effectiveness of Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension in otitis externa have been established in the pediatric age group 2 years to 16 years of age. There is inadequate data to establish safety and effectiveness in otitis externa for pediatric patients under 2 years of age. 1 Geriatric Use Clinical studies of Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.\"}', 'information_for_patients': '{\"Information for Patients Avoid contaminating the bottle tip with material from the ear, fingers, or other source. This caution is necessary if the sterility of the drops is to be preserved. If sensitization or irritation occurs, discontinue use immediately and contact your physician. Do not use in the eyes. SHAKE WELL BEFORE USING.\"}', 'pregnancy': '{\"Pregnancy Teratogenic Effects Pregnancy Category C. Corticosteroids have been shown to be teratogenic in rabbits when applied topically at concentrations of 0.5% on days 6 to 18 of gestation and in mice when applied topically at a concentration of 15% on days 10 to 13 of gestation. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.\"}', 'pediatric_use': '{\"Pediatric Use The safety and effectiveness of Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension in otitis externa have been established in the pediatric age group 2 years to 16 years of age. There is inadequate data to establish safety and effectiveness in otitis externa for pediatric patients under 2 years of age. 1\"}', 'geriatric_use': '{\"Geriatric Use Clinical studies of Neomycin and Polymyxin B Sulfates and Hydrocortisone OTIC Suspension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.\"}'}" } ]

[ { "from": "human", "value": "{\"COAL TAR\"}" }, { "from": "gpt", "value": "{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{\"Use controls the symptom of: dandruff seborrheic dermatitis psoriasis\"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{\"COAL TAR\"}', 'route': '{TOPICAL}', 'product_type': '{\"HUMAN OTC DRUG\"}', 'stop_use': '{\"Stop use and ask a doctor if condition worsens or does not improve after regular use of this product as directed.\"}', 'do_not_use': None, 'when_using': '{\"When using this product avoid contact with the eyes. If contact occurs, rinse eyes thoroughly with water use caution in exposing skin to sunlight after applying this product. It may increase your tendency to sunburn for up to 24 hours after application. do not use for prolonged periods without consulting a doctor. do not use this product with other forms of psoriasis therapy such as ultraviolet radiation or prescription drugs unless directed to do so by a doctor.\"}', 'warnings': '{\"Warnings For external use only. Ask a doctor before using this product if condition covers a large area of the body. When using this product avoid contact with the eyes. If contact occurs, rinse eyes thoroughly with water use caution in exposing skin to sunlight after applying this product. It may increase your tendency to sunburn for up to 24 hours after application. do not use for prolonged periods without consulting a doctor. do not use this product with other forms of psoriasis therapy such as ultraviolet radiation or prescription drugs unless directed to do so by a doctor. Stop use and ask a doctor if condition worsens or does not improve after regular use of this product as directed. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center (1-800-222-1222) right away.\"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}" } ]