BIPERIDEN
DESCRIPTION:
ACTIONS/CLINICAL PHARMACOLOGY:
BIPERIDEN is a weak peripheral anticholinergic agent. It has, therefore, some
antisecretory, antispasmodic and mydriatic effects. In addition, BIPERIDEN
possesses nicotinolytic activity. Parkinsonism is thought to result from an
imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic)
systems in the corpus striatum. The mechanism of action of centrally active
anticholinergic drugs such as BIPERIDEN is considered to relate to competitive
antagonism of acetylcholine at cholinergic receptors in the corpus striatum,
which then restores the balance.
The parenteral form of BIPERIDEN is an effective and reliable agent for the
treatment of acute episodes of extrapyramidal disturbances sometimes seen during
treatment with neuroleptic agents. Akathisia, akinesia, dyskinetic tremors,
rigor, oculogyric crisis, spasmodic torticollis, and profuse sweating are
markedly reduced or eliminated. With parenteral BIPERIDEN, these drug- induced
disturbances are rapidly brought under control. Subsequently, this can usually
be maintained with oral doses which may be given with tranquilizer therapy in
psychotic and other conditions requiring an uninterrupted therapeutic program.
Pharmacokinetics And Metabolism: Only limited pharmacokinetic studies of
biperiden in humans are available. The serum concentration at 1 to 1.5 hours
following a single, 4 mg oral dose was 4-5 ng/mL. Plasma levels (0.1-0.2 ng/mL)
could be determined up to 48 hours after dosing. Six hours after an oral dose of
250 mg/kg in rats, 87% of the drug had been absorbed. The metabolism of BIPERIDEN
is also incompletely understood, but does involve hydroxylation. In normal
volunteers a single 10 mg intravenous dose of biperiden seemed to cause a
transient rise in plasma cortisol and prolactin.
No change in GH, LH, FSH, or TSH levels were seen. Biperiden lactate (10 mg/mL)
was not irritating to the tissue of rabbits when injected intramuscularly (1.0
mL) into the sacrospinalis muscles and intradermally (0.25 mL) and
subcutaneously (0.5 mL) into the shaved abdominal skin.
INDICATIONS AND USAGE:
. As an adjunct in the therapy of all forms of parkinsonism (idiopathic,
postencephalitic, arteriosclerotic)
. Control of extrapyramidal disorders secondary to neuroleptic drug therapy
(e.g., phenothiazines)
CONTRAINDICATIONS:
1) Hypersensitivity to biperiden 2) Narrow angle glaucoma 3) Bowel obstruction
4) Megacolon
WARNINGS:
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 (see Drug Interactions and
Overdosage sections). Caution should be observed in patients with manifest
glaucoma, though no prohibitive rise in intraocular pressure has been noted
following either oral or 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 acting on the central nervous system, the consumption of
alcohol should be avoided during BIPERIDEN therapy.
PRECAUTIONS:
Pregnancy: Pregnancy Category C. Animal reproduction studies have not 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.
Nursing Mothers: 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.
Pediatric Use: Safety and effectiveness in children have not been established.
DRUG INTERACTIONS:
The central anticholinergic syndrome can occur when anticholinergic agents such
as BIPERIDEN are administered concomitantly with drugs that have secondary
anticholinergic actions, e.g., certain narcotic analgesics such as meperidine,
the phenothiazines and other antipsychotics, tricyclic antidepressants, certain
antiarrhythmics such as the quinidine salts, and antihistamines. See Overdosage
section for signs and symptoms of the central anticholinergic syndrome, and for
treatment.
ADVERSE REACTIONS:
Atropine-like side effects such as dry mouth; blurred vision; drowsiness;
euphoria or disorientation; urinary retention; postural hypotension;
constipation; agitation; disturbed behavior may be seen. There usually are no
significant changes in blood pressure or heart rate in patients who have been
given the parenteral form of BIPERIDEN. Mild transient postural hypotension and
bradycardia may occur.
These side effects can be minimized or avoided by slow intravenous
administration. No local tissue reactions have been reported following
intramuscular injection. If gastric irritation occurs following oral
administration, it can be avoided by administering the drug during or after
meals.
The central anticholinergic syndrome can occur as an adverse reaction to
properly prescribed anticholinergic medication. See Overdosage section for signs
and symptoms of the central anticholinergic syndrome, and for treatment.
OVERDOSAGE:
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
tachycardias or conduction defects) seem to respond. If indicated, 1 mg (half
this amount for children or the elderly) may be given intramuscularly or by slow
intravenous infusion.
If there is no response within 20 minutes, an additional 1 mg dose may be given;
this may be repeated until a total of 4 mg has been administered, a reversal of
the toxic effects occur or excessive cholinergic signs 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 relapse.
Toxicity In Animals: The LD50 of biperiden in the white mouse is 545 mg/kg
orally, 195 mg/kg subcutaneously, and 56 mg/kg intravenously. The acute oral
toxicity (LD50) in rats is 750 mg/kg.
The intraperitoneal toxicity (LD50) of biperiden lactate in rats was 270 mg/kg
and the intravenous toxicity (LD50) in dogs is 222 mg/kg. In dogs under general
anesthesia, respiratory arrest occurred at 33 mg/kg (intravenous) and
circulatory standstill at 45 mg/kg (intravenous).
The oral LD50 in dogs was 340 mg/kg. Chronic toxicity studies in both rat and
dog have been reported.
DOSAGE AND ADMINISTRATION:
Drug-Induced Extrapyramidal Symptoms:
Parenteral: The average adult dose is 2 mg intramuscularly or intravenously. May
be repeated every half-hour until there is resolution of symptoms, but not more
than four consecutive doses should be given in a 24-hour period.
Note: Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration, whenever solution and
container permit.
Oral: One tablet one to three times daily.
Parkinson's Disease: Oral: The usual beginning dose is one tablet three or four
times daily. The dosage should be individualized with the dose titrated upward
to a maximum of 8 tablets (16 mg) per 24 hours.
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