Isotamine 300 mg

Absorption: Isoniazid is readily absorbed from the gastrointestinal tract. When given with food, the extent of absorption and peak plasma concentrations of the drug may be reduced. Following oral application of the drug, peak plasma concentrations are attained within 1 to 2 hours. Plasma concentrations of the drug in rapid isoniazid inactivators are 20 to 50% of those in slow isoniazid inactivators.

Distribution: Isoniazid is distributed into all body tissues and fluids (including cerebrospinal fluid, pleural and ascitic fluids, skin, sputum, saliva, lungs, muscle, and caseous tissue). The drug concentrations found in the cerebrospinal fluid are reported to be 90 to 100% of concurrent plasma concentrations. Isoniazid is not substantially bound to plasma proteins (0 to 10%). Isoniazid readily crosses the placenta. Isoniazid is distributed into milk in concentrations approximately equal to maternal concentrations.

Biotransformation: Biotransformation of isoniazid occurs mainly in the liver. Isoniazid is acetylated by N-acetyl transferase to N-acetylisoniazid; it is biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P-450 mixed oxidase system. The rate of acetylation is genetically determined; slow acetylators are characterized by a relative lack of hepatic N-acetyl transferase.

Half-life: Adults, including elderly patients: Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours. Acute and chronic liver disease: may be prolonged to 6.7 h vs 3.2 h in controls. Children (age 1.5 to 15 years): 2.3 to 4.9 hours. Neonates 7.8 and 19.8 hours found in 2 newborns who received isoniazid transplacentally. The long half-life may be due to the limited acetylation capacity of neonates.

Peak Serum Concentrations: 3 to 7 µg/mL after a single 300 mg oral dose.

Time to Peak Serum Concentrations: 1 to 2 hours.

Elimination: The plasma half-life of isoniazid in patients with normal renal and hepatic function ranges from 1 to 4 hours, depending on the rate of metabolism. In patients with severely impaired renal or hepatic function, the plasma half-life may be prolonged.

The rate of isoniazid acetylation does not appear to alter efficacy when the drug is administered daily or 2 or 3 times weekly; however, a relationship between rapid inactivation and poor therapeutic response has been noted in once-weekly intermittent regimens.

In adults with normal renal function, approximately 75 to 96% of a 5 mg/kg oral dose of isoniazid is excreted in urine within 24 hours as unchanged drug and metabolites. Small amounts of the drug are also excreted in saliva, sputum and feces. Isoniazid is removed by hemodialysis or peritoneal dialysis.

The following drug interactions and/or related problems have been reported:

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Acetaminophen: potential of increased hepatotoxicity and, possibly, nephrotoxicity.

Adrenocorticoids, glucocorticoids: increased hepatic metabolism and/or excretion of isoniazid, leading to decreased plasma concentrations and effectiveness of isoniazid, especially in rapid acetylators.

Alcohol: Concurrent daily intake of alcohol may result in increased incidence of isoniazid-induced hepatotoxicity and increased metabolism of isoniazid.

Alfentanil: Chronic preoperative or perioperative use of isoniazid, a hepatic enzyme inhibitor, may decrease the plasma clearance and prolong the duration of action of alfentanil.

Antacids: Antacids may delay and decrease absorption and serum concentrations of orally administered isoniazid.

Anticoagulants: may result in increased anticoagulant effect because of the inhibition of enzymatic metabolism of anticoagulants.

Benzodiazepines: Isoniazid may decrease the hepatic metabolism of benzodiazepines.

Carbamazepine: Serum carbamazepine levels and toxicity may be increased by isoniazid.

Cheese (Swiss, Cheshire) or Fish (tuna, skipjack Sardinella): redness or itching of skin, hot feeling, rapid or pounding heartbeat, sweating, chills or clammy feeling, headache, lightheadedness due to the inhibition of plasma monoamine oxidase and diamine oxidase by isoniazid.

Cycloserine: Increased incidence of CNS effects such as dizziness or drowsiness may occur.

Each mL of strawberry-flavored syrup contains: isoniazid, USP 10 mg. Nonmedicinal ingredients: citric acid, glycerin, methylparaben, propylparaben, sodium citrate and flavor. Bottles of 500 mL.

When a dose less than or not a multiple of 5 mL is prescribed, the syrup may be diluted with water.

Syrup must not be used as diluent as isoniazid is unstable in the presence of sugars. When stored in filled unopened containers at a temperature not exceeding 25°C, the syrup is expected to retain its potency for 1 year. When dispensed, each container should be filled and the contents should represent not more than 1 month's supply.

Each white, scored, compressed tablet, imprinted ICN I22, contains: isoniazid, USP 300 mg. Nonmedicinal ingredients: colloidal silicon dioxide, magnesium stearate and microcrystalline cellulose. Bottles of 100 and 1000. Store in well-closed, light-resistant containers at controlled room temperature (15 to 30°C).

Adverse hematologic effects include agranulocytosis, eosinophilia, thrombocytopenia, methemoglobinemia, and hemolytic, sideroblastic, or aplastic anemia.

Mild hepatic dysfunction (mild and transient increases in serum AST, ALT and bilirubin concentrations has occurred in approximately 10 to 20% of patients receiving isoniazid, usually during the first 4 to 6 months of therapy. In most cases, enzyme concentrations return to pretreatment values despite continuation of isoniazid, but progressive liver dysfunction, bilirubinuria, jaundice, and severe and sometimes fatal hepatitis have occurred rarely. If symptoms of hepatitis or signs suggestive of hepatic damage occur during isoniazid therapy, the drug should be discontinued promptly.

Hypersensitivity reactions include fever, skin eruptions (morbilliform, maculopapular, purpuric, exfoliative), lymphadenopathy, vasculitis and, rarely, hypotension, usually 3 to 7 weeks following initiation of therapy. At the first sign of hypersensitivity reaction, all drugs should be discontinued. If isoniazid is reinstituted, the drug should be restarted in small and gradually increasing doses only after symptoms have cleared. If there is any indication of recurrence of hypersensitivity, isoniazid should be discontinued immediately.

Peripheral neuritis, usually preceded by paresthesia of the feet and hands, is the most common adverse effect of isoniazid and occurs most frequently in malnourished patients and those predisposed to neuritis (e.g., alcoholics, diabetics). Rarely, other nervous system side effects have also occurred including: seizures, toxic encephalopathy, muscle twitching, ataxia, stupor, tinnitus, euphoria, memory impairment, separation of ideas and reality, loss of self-control, dizziness, and toxic psychosis. Neurotoxic effects may be prevented or relieved by the administration of 10 to 50 mg of pyridoxine HCl daily during isoniazid therapy. In addition, optic neuritis and atrophy have been reported with isoniazid.

nausea, vomiting, epigastric distress, dryness of the mouth, pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, and urinary retention and gynecomastia in males. A systemic lupus erythematosus-like syndrome and a rheumatic syndrome with arthralgia have also occurred.

Symptoms of overdosage usually occur within 30 minutes to 3 hours following ingestion of the drug. Overdosage of isoniazid has produced nausea, vomiting, dizziness, slurred speech, blurred vision, and visual hallucinations, including bright colors and strange designs. After marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to coma, severe intractable seizures, metabolic acidosis, acetonuria, and hyperglycemia have occurred. If untreated or treated inadequately, isoniazid overdosage may be fatal. Isoniazid-induced seizures are thought to be associated with decreased g-aminobutyric acid (GABA) concentrations in the CNS, possibly resulting from inhibition by isoniazid of brain pyridoxal-5-phosphate activity.

In the management of isoniazid overdosage, an airway should be secured and adequate respiratory exchange established immediately. Seizures may be controlled with i.v. administration of diazepam or short-acting barbiturates and a dosage of pyridoxine HCl equal to the amount of isoniazid ingested. Generally, 1 to 4 g of pyridoxine HCl is given i.v. followed by 1 g i.m. every 30 minutes until the entire dose has been given. If seizures are controlled and overdosage is recent, within the last 2 to 3 hours, the stomach should be emptied by gastric lavage. Blood gases, serum electrolytes, glucose, and BUN determinations should be performed. Blood should be typed and crossmatched in case hemodialysis is required. I.V. administration of sodium bicarbonate should be considered to control metabolic acidosis and repeated as needed; dosage should be adjusted on the basis of laboratory test results. Pyridoxine has also had a beneficial effect in correcting acidosis in some patients, possibly by controlling seizures and resulting lactic acidosis. Pyridoxine has been effective in treating isoniazid-induced seizures as well as other mental status changes associated with isoniazid overdosage. In several patients who remained comatose following initial treatment of seizures with diazepam and pyridoxine, administration of an additional 3 to 5 g dose of pyridoxine HCl after 36 to 42 hours of coma resulted in complete awakening within 30 minutes. The fact that administration of high doses of pyridoxine can result in adverse neurologic effects should be considered whenever the drug is used in the treatment of isoniazid-induced seizures and/or coma.

Forced osmotic diuresis should be initiated as soon as possible following isoniazid overdosage to increase renal clearance of the drug and should be continued several hours after clinical improvement to ensure complete clearance of the drug and prevent relapse. Fluid intake and output should be monitored. In severe cases, hemodialysis or, if hemodialysis is not available, peritoneal dialysis should be used in conjunction with forced diuresis. In addition, measures should be taken to protect against hypoxia, hypotension, and aspiration pneumonia.