Each AKINETON Tablet for oral administration contains 2 mg biperiden hydrochloride. Other ingredients may include corn syrup, lactose, magnesium stearate, potato starch and talc. Each 1 mL AKINETON Ampule for intramuscular or intravenous administration contains 5 mg biperiden lactate in an aqueous 1.4 percent sodium lactate solution. No added preservative. AKINETON is an anticholinergic agent. Biperiden is (alpha)-5-Norbornen-2-yl-(alpha)-phenyl-1-piperidine propanol. It is a white, crystalline, odorless powder, slightly soluble in water and alcohol. It is stable in air at normal temperatures. The structual formula is:

• 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)

Drug-Induced Extapyramidal Symptoms:

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.

AKINETON (biperiden hydrochloride) Tablets, 2 mg each, white, embossed on one face with a triangle, bisected on the reverse and imprinted with the number "11." Bottles of 100 - NDC # 49884-693-01

Storage: Store at 25°C (77°F); excursions permitted to 15- 30°C (59-86°F) [see USP Controlled Room Temperature]. Dispense in tight, light-resistant container as defined in USP.

AKINETON is a registered trademark of Knoll AG.

03-5161-R1 Revised: November, 2001

Manufactured for:
PAR PHARMACEUTICAL, INC.
Spring Valley, New York 10977

Manufactured by:
ABBOTT LABORATORIES
NORTH CHICAGO, IL 60064, U.S.A.

Atropine-like side effects such as dry mouth; blurred vision; drowsiness; euphoria or disorientation; urinary retention; postural hypotension; constipation; agitation; disturbed behavior may been seen. A case of generalized choreic movements has been reported in a Parkinson's disease patient when biperiden was added to carbidopa/ levodopa. A reduction in rapid eye movement (REM) sleep, characterized by increased REM latency and decreased percentage of REM sleep, has been reported. There usually are no significant changes in blood pressure or heart rate in patients who have been given the parenteral form of AKINETON. 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.

Drug Interactions:    The central anticholinergic syndrome can occur when anticholinergic agents such as AKINETON 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.

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 AKINETON therapy.

Drug Interactions:    The central anticholinergic syndrome can occur when anticholinergic agents such as AKINETON 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.

Pregnancy:   Pregnancy Category C. Animal reproduction studies have not been conducted with AKINETON. It is also not known whether AKINETON can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. AKINETON 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 AKINETON is administered to a nursing woman.

Pediatric Use:   Safety and effectiveness in children have not been established.

Signs and Symptoms:   Overdosage with AKINETON 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 AKINETON 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 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 LD ₅₀ of biperiden in the white mouse is 545 mg/kg orally, 195 mg/kg subcutaneously, and 56 mg/kg intravenously. The acute oral toxicity (LD ₅₀ ) in rats is 750 mg/kg. The intraperitoneal toxicity (LD ₅₀ ) of biperiden lactate in rats was 270 mg/kg and the intravenous toxicity (LD ₅₀ ) 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 LD ₅₀ in dogs was 340 mg/kg. Chronic toxicity studies in both rat and dog have been reported.

1) Hypersensitivity to biperiden 2) Narrow angle glaucoma 3) Bowel obstruction 4) Megacolon

AKINETON is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, AKINETON 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 AKINETON 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 AKINETON 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 AKINETON, 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 AKINETON 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.

No Information Provided.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BIPERIDEN - ORAL

(bye-PER-i-den)

COMMON BRAND NAME(S): Akineton

USES: Biperiden is used to treat symptoms of Parkinson's disease or involuntary movements due to the side effects of certain psychiatric drugs (antipsychotics such as chlorpromazine/haloperidol). Biperiden belongs to a class of medication called anticholinergics that work by blocking a certain natural substance (acetylcholine). This helps decrease muscle stiffness, sweating, and the production of saliva, and helps improve walking ability in people with Parkinson's disease.

Anticholinergics can stop severe muscle spasms of the back, neck, and eyes that are sometimes caused by psychiatric drugs. It can also decrease other side effects such as muscle stiffness/rigidity (extrapyramidal signs-EPS). It is not helpful in treating movement problems caused by tardive dyskinesia and may worsen them.

HOW TO USE: Take this medication by mouth, usually 1 to 4 times a day with meals and at bedtime or as directed by your doctor. Your doctor may start you at a low dose and increase your dose slowly to find the best dose for you. The usual maximum dose is 16 milligrams each day. The dosage is based on your medical condition and response to therapy.

Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day.

Take this medication at least 1 hour before antacids containing magnesium, aluminum, or calcium. Allow at least 1-2 hours between doses of biperiden and certain drugs for diarrhea (adsorbent antidiarrheals such as kaolin, pectin, attapulgite). Take this medication at least 2 hours after ketoconazole. Antacids and some drugs for diarrhea may prevent the full absorption of biperiden, and this product may prevent the complete absorption of ketoconazole when these products are taken together.

If you are taking this medication for side effects from another medication, your doctor may instruct you to take it on a regular schedule or only as needed. If you are taking this medication for Parkinson's disease, your doctor may change the dose of your other medications (e.g., levodopa). Follow your doctor's instructions closely.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Rarely, abnormal drug-seeking behavior (addiction) is possible with this medication. Do not increase your dose, take it more frequently, or use it for a longer time than prescribed. Properly stop the medication when so directed. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Drowsiness, dizziness, constipation, flushing, nausea, nervousness, blurred vision, or dry mouth may occur. These effects usually lessen as your body gets used to the medicine. If any of these effects persist or worsen, contact your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: decreased sexual ability, severe stomach/abdominal pain, difficult/painful swallowing, difficulty urinating, vision changes, weakness.

Seek immediate medical attention if any of these very unlikely but very serious side effects occur: chest pain, severe dizziness/fainting, high fever, fast/irregular/slow heartbeat, mental/mood changes (e.g., confusion, hallucinations, memory problems).

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking biperiden, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain eye problem (narrow-angle glaucoma), blockage of the bladder/esophagus/stomach/intestines (e.g., bowel obstruction), severe ulcerative colitis.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: alcohol use, breathing problems (e.g., asthma, emphysema), diarrhea caused by an infection, certain eye problem (open-angle glaucoma), heart problems (e.g., angina, heart attack, heart failure, fast/irregular heartbeat), high/low blood pressure, intestinal problems (e.g., chronic constipation, ileus, ulcerative colitis), kidney disease, liver disease, mental/mood problems (e.g., anxiety, psychosis), certain muscle disease (myasthenia gravis), certain nerve disease (autonomic neuropathy), seizure, stomach problems (e.g., acid reflux, hiatal hernia, ulcer), stroke, overactive thyroid (hyperthyroidism), problems urinating (e.g., due to enlarged prostate, neurogenic bladder).

This drug may make you dizzy/drowsy or cause blurred vision; use caution while engaging in activities requiring alertness or clear vision such as driving or using machinery. Avoid alcohol beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This medication decreases saliva production, an effect that can increase gum and tooth problems (e.g., cavities, gum disease). Take special care with your dental hygiene (e.g., brushing, flossing) and have regular dental check-ups.

This drug can cause decreased sweating, which could cause a severe rise in your body temperature (hyperthermia). The risk of this serious side effect is greater in hot weather, during vigorous exercise, and/or if you drink alcohol. Drink plenty of fluids and dress lightly while in hot weather and when exercising. If you experience signs of hyperthermia such as mental/mood changes, headache, or dizziness, promptly seek cool or air-conditioned shelter and/or stop exercising, and seek immediate medical attention. Consult your doctor for more details.

The elderly may be more sensitive to the effects of this drug, especially dizziness, bladder problems, and constipation.

Children may be more sensitive to the effects of this drug, especially effects on heart rate.

This drug should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: pramlintide.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting biperiden.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: amantadine, anticholinergics/antispasmodics (e.g., belladonna alkaloids, clidinium), certain antiarrhythmics (e.g., disopyramide, procainamide, quinidine), cholinesterase inhibitors (e.g., donepezil, galantamine), corticosteroids (e.g., prednisone), monoamine oxidase inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine), motion sickness medication (e.g., meclizine, scopolamine), narcotic pain relievers (e.g., meperidine), potassium tablets/capsules, tricyclic antidepressants (e.g., amitriptyline, doxepin).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., risperidone, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain anticholinergics or drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: unusually fast/slow heartbeat, slow/shallow breathing, unconsciousness, seizures, loss of coordination, fever, hot/dry/flushed skin, widened pupils, change in vision, change in the amount of urine, confusion, hallucinations.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.