Each tablet contains: Biperiden (as hydrochloride), USP 2 mg.
Pharmacology: Pharmacokinetics: Biperiden is readily absorbed from the gastrointestinal tract, but bioavailability is only about 30% suggesting that it undergoes extensive first-pass metabolism. Biperiden has an elimination half-life of about 20 hours.
Biperiden is used in the symptomatic treatment of parkinsonism including the alleviation of the extrapyramidal syndrome induced by drugs such as phenothiazines.
The initial for Parkinson's disease is 2 mg three or four times daily increased according to response to a maximum of 16 mg daily. The dose for drug-induced extrapyramidal symptoms is 2 mg one to three times daily or as prescribed by the physician.
Signs and Symptoms: Overdosage with biperiden produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Correct diagnosis depends upon recognition of the peripheral signs of parasympathetic blockade including dilated and sluggish pupils; warm, dry skin; facial flushing; decreased secretions of the mouth, pharynx, nose, and bronchi; foul-smelling breath; elevated temperature, tachycardia, cardiac arrhythmias, decreased bowel sounds, and urinary retention. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, loss of memory, paranoia, combativeness, and seizures may be present. The condition can progress to stupor, coma, paralysis, and cardiac and respiratory arrest and death.
Treatment: Treatment of acute overdose revolves around symptomatic and supportive therapy. If biperiden was administered orally, gastric lavage or other measures to limit absorption should be instituted. A small dose of diazepam or a short acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contraindicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-base balance maintained. Urinary catheterization may be necessary.
Routine use of physostigmine for overdose is controversial. Delirium, hallucinations, coma, and supraventricular tachycardia (not ventricular or conduction defects) seem to respond. If indicated, 1 mg (half this amount for the children or elderly) may be given intramuscularly or by slow intravenous infusion. If there is no response within 20 minutes, and additional 1 mg dose may be repeated until a total of 4 mg has been administered, a reversal of the toxic effects occur or excessive cholinergic sign are seen. Frequent monitoring of clinical signs should be done. Since physostigmine is rapidly destroyed, additional injections may be required every one or two hours to maintain control. The relapse intervals tend to lengthen as the toxic anticholinergic agent is metabolized, so the patient should be carefully observed for 8 to 12 hours following the last lapse.
In overdosage, the peripheral effects become more pronounced and other symptoms such as hyperthermia, hypertension, increased respiratory rate, and nausea and vomiting may occur. A rash may appear on the face or upper trunk. Toxic doses also cause CNS stimulation marked by restlessness, confusion, excitement, ataxia, incoordination, paranoid and psychotic reactions, hallucinations and delirium, and occasionally seizures. However, in severe intoxication, central stimulation may give way to CNS depression, coma, circulatory and respiratory failure, and death.
Hypersensitivity to biperiden; narrow angle glaucoma; bowel obstruction; megacolon.
Isolated instances of mental confusion, euphoria, agitation and disturbed behavior have been reported in susceptible patients. Also, the central anticholinergic syndrome can occur as an adverse reaction to properly prescribed anticholinergic medication, although it is more frequently due to overdosage. It may also result from concomitant administration of an anticholinergic agent and a drug that has secondary anticholinergic actions. Caution should be observed in patients with manifest glaucoma, though no prohibitive rise in intraocular pressure has been noted following either oral parenteral administration. Patients with prostatism, epilepsy or cardiac arrhythmia should be given this drug with caution.
Occasionally, drowsiness may occur, and patients who drive a car or operate any other potentially dangerous machinery should be warned of this possibility. As with other drugs action on the central nervous system, the consumption of alcohol should be avoided during biperiden therapy.
Should be used with caution in children and the elderly, who may be more susceptible to its adverse effects.
Biperiden should not be given to patients with angle-closure glaucoma or with a narrow angle between the iris and the cornea, since it may raise intra-ocular pressure and precipitate an acute attack.
Biperiden need to be used with caution in conditions characterised by tachycardia such as thyrotoxicosis, heart failure, and in cardiac surgery, where they may further accelerate the heart rate. Care is required in patients with acute myocardial infarction, as ischaemia and infarction may be made worse, and in patients with hypertension.
Biperiden may cause confusion, especially in the elderly. Reduced bronchial secretion caused by systemic administration of biperiden may be associated with the formation of mucous plugs.
In the treatment of parkinsonism, increases in dosage and transfer to other forms of treatment should be gradual should not be withdrawn abruptly.
Use in Children: Safety and effectiveness in children have not been established.
Use in Pregnancy: Pregnancy Category C: Animal reproduction studies have been conducted with biperiden. It is also not known whether biperiden can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Biperiden should be given to a pregnant woman only if clearly needed.
Use in Lactation: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when biperiden is administered to a nursing woman.
The pattern of adverse effects seen with atropine and other antimuscarinics can mostly be related to their pharmacological actions at muscarinic and, at high doses, nicotinic receptors. These effects are dose-related and are usually reversible when therapy is discontinued. The peripheral effects of atropine and other antimuscarinics are a consequence of their inhibitory effect on muscarinic receptors within the autonomic nervous system. At therapeutic doses, adverse effects include dryness of the mouth with difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, with palpitations and arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation. Some of the central effects of atropine and other tertiary antimuscarinics seen at toxic doses (see as follows) may also occur at therapeutic doses.
The effects of atropine and other antimuscarinics may be enhanced by the concomitant use of other drugs with antimuscarinic properties, such as amantadine, some antihistamines, phenothiazine antipsychotics, and tricyclic antidepressants. Inhibition of drug-metabolising enzymes by MAOIs may possibly enhance the effects of antimuscarinics. The reduction in gastric motility caused by antimuscarinics may affect the absorption of other drugs. Antimuscarinics may also antagonise the gastrointestinal effects of cisapride, domperidone, and metoclopramide. Antimuscarinics and parasympathomimetics may counteract each other's effects.
Store at temperatures not exceeding 30°C.
N04AA02 - biperiden ; Belongs to the class of tertiary amines anticholinergic agents. Used in the management of Parkinson's disease.