Akineton

Antimuscarinic antiparkinsonian agent.a b

Administration

Oral Administration

Administer orally 1–3 times daily.a b

Dosage

Available as biperiden hydrochloride, dosage expressed in terms of the salt.a

Adjust dosage carefully according to individual requirements and response.b

Adults

Initially, 2 mg 3–4 times daily; if tolerance develops, or dosage is inadequate, titrate dose to maximum of 16 mg daily in 3–4 divided doses.b

Usual dosage: 2 mg 1–3 times daily.a b

Prescribing Limits

Adults

Maximum 16 mg daily.a b

Special Populations

No special population dosage recommendations at this time.a

Storage

Oral

25°C (may be exposed to 15–30°C).a Protect from light.a b

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of biperiden in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of biperiden in geriatric patients. However, elderly men are more likely to have age-related prostate problems, which may require caution for patients receiving biperiden.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Potassium

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Tiotropium

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Betel Nut

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bowel blockage or
• Glaucoma, narrow-angle or
• Megacolon (colon is enlarged)—Should not be used in patients with these conditions.

• Enlarged prostate or
• Epilepsy (seizures) or
• Glaucoma or
• Heart rhythm problems—Use with caution. May make these conditions worse.

It is important that your doctor check your progress at regular visits to allow changes in your dose and to check for any unwanted effects.

If you develop any unusual or strange thoughts and behavior while receiving biperiden, be sure to discuss it with your doctor. Some changes that have occurred in people receiving this medicine are like those seen in people who drink too much alcohol. Other changes might be confusion, worsening of depression, visual hallucinations (seeing things that are not there), suicidal thoughts, and unusual excitement, nervousness, or irritability.

Biperiden may cause drowsiness, trouble with controlling movements, or trouble with thinking or seeing clearly. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates or medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Anxiety
• chest pain or discomfort
• chills
• cold sweats
• confusion
• confusion about identity, place, and time
• decrease in frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• disturbed behavior
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• dry mouth
• false or unusual sense of well-being
• hyperventilation
• irregular heartbeats
• irregular, twisting uncontrolled movement of the face, hands, arms, or legs
• irritability
• nervousness
• painful urination
• restlessness
• shaking
• shortness of breath
• slow or irregular heartbeat
• trouble sleeping
• unusual tiredness

Get emergency help immediately if any of the following symptoms of overdose occur:

• Change in consciousness
• chest pain or discomfort
• convulsions
• decreased awareness or responsiveness
• decreased secretions of the mouth, pharynx, nose, or bronchi
• delusions of persecution, mistrust, suspiciousness, or combativeness
• dizziness
• dry mouth
• enlarged pupils
• face is warm or hot to touch
• fainting
• fast, slow, pounding, or irregular heartbeat or pulse
• foul-smelling breath
• holding false beliefs that cannot be changed by fact
• lightheadedness
• loss of consciousness
• loss of memory
• no breathing
• redness to face
• seeing, hearing, or feeling things that are not there
• severe sleepiness
• shakiness and unsteady walk
• trouble sitting still
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual excitement, nervousness, or restlessness
• warm, dry skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• difficulty having a bowel movement (stool)
• drowsiness
• nausea
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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.

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 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 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 was 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 LD50in dogs is 340 mg/kg. Chronic toxicity studies in both rat and dog have been reported.

There are no data on the excretion of biperiden into human milk. The effects in the nursing infant are unknown. The manufacturer recommends that caution be used when administering biperiden to nursing women.