trihexyphenidyl

Trihexyphenidyl is a synthetic antispasmodic medication used in the treatment of all forms of Parkinsonism, and drug-induced movement (extrapyramidal) disorders. Trihexyphenidyl is typically used as an adjuvant to levodopa, a dopamine drug used to treat Parkinsonism. Parkinsonism is characterized by symptoms such as tremor, muscle rigidity, slow movements, and impaired balance, posture and gait. Parkinsonism may be caused by Parkinson’s disease, brain diseases, impaired blood flow to the brain, or use of certain drugs.

Trihexyphenidyl is an anticholinergic antiparkinson agent that works by inhibiting the parasympathetic nervous system and by also directly relaxing the smooth muscles in the body. The parasympathetic system is part of the autonomous system that regulates the ‘rest and digest’ period, as opposed to the sympathetic system that regulates the ‘fight or flight’ response. Trihexyphenidyl relaxes the muscles and reduces the tremors, muscle spasms, stiffness and weak muscle control associated with Parkinsonism.

Trihexyphenidyl directly relaxes the smooth muscles and in addition, works by modifying the activity of acetylcholine, a chemical (neurotransmitter) in the nervous system that regulates muscle contractions and glandular secretions, by stimulating two types of receptors known as muscarinic and nicotinic receptors. Trihexyphenidyl binds with high affinity to M1 subtype of muscarinic receptors and prevents their stimulation by acetylcholine, reducing the symptoms caused by overstimulation of the parasympathetic nervous system.

The FDA-approved uses of trihexyphenidyl include:

• Treatment of all forms of parkinsonism, including postencephalitic, arteriosclerotic and idiopathic, as an adjuvant to levodopa
• Treatment of extrapyramidal disorders caused by drugs such as dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

• Do not use trihexyphenidyl in patients with hypersensitivity to any component of the trihexyphenidyl formulations.
• Do not use trihexyphenidyl in patients with narrow angle glaucoma (angle closure glaucoma), an eye condition that impairs eye fluid draining, leading to excessive intraocular pressure and optic nerve damage. Use of anticholinergic drugs such as trihexyphenidyl can precipitate angle closure in patients with narrow angle glaucoma.
  • Evaluate patients with gonioscopy to measure the drainage angles in the eye and intraocular pressure before starting treatment with trihexyphenidyl and monitor closely during treatment.
  • Prolonged use of trihexyphenidyl in patients with narrow angle glaucoma has resulted in blindness.
  • If a patient develops blurred vision during therapy, evaluate for narrow angle glaucoma.
• Anticholinergic drugs, including trihexyphenidyl, can impair the ability to perspire and maintain optimum body temperature. Use trihexyphenidyl with caution in conditions that pose a high risk for lack of sweating (anhidrosis) and consequent high body temperature (hyperthermia) that can be fatal. Risk factors, particularly when concurrently used with other drugs, include:
  • Hot weather
  • Alcoholism
  • Presence of a central nervous system disease
  • Manual work in a hot environment
• Dose reduction or discontinuation of trihexyphenidyl has been associated with a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS).
  • Symptoms include high temperature, muscle rigidity, altered mental status, and signs of autonomic instability such as irregular pulse or blood pressure, excessive sweating, high heart rate (tachycardia) and heart rhythm disturbances (dysrhythmias).
  • Diagnosis of NMS may be complicated by the possibility of other medical conditions with similar symptoms. Exercise caution.
• Monitor closely when using trihexyphenidyl in patients with heart, kidney or liver disorders, or high blood pressure (hypertension).
• Use trihexyphenidyl with caution in patients with any of the following conditions:
  • Glaucoma
  • Gastrointestinal or genitourinary tract obstructive diseases
  • Advanced age with possible prostate enlargement
• Trihexyphenidyl has atropine-like properties, although undesirable side effects such as tachycardia, arrhythmia and heart attack (myocardial infarction) are less frequent and less severe. Closely monitor patients on prolonged treatment with trihexyphenidyl for any untoward reactions.
• Antiparkinsonism agents such as trihexyphenidyl do not alleviate symptoms of tardive dyskinesia, a type of movement disorder that results from prolonged use of antipsychotic drugs or after discontinuation of these drugs. In some instances, tardive dyskinesia may be exacerbated by the use of antiparkinsonism agents.
  • Do not use trihexyphenidyl to treat tardive dyskinesia, but if tardive dyskinesia is a comorbidity with parkinsonism, it may relieve some of the parkinsonism symptoms.
  • Do not use trihexyphenidyl as a preventive treatment for drug-induced parkinsonism during antipsychotic therapy. It can increase the risk for tardive dyskinesia.
• Patients with narrowed arteries (arteriosclerosis) or with a history of idiosyncrasy to other drugs may have symptoms such as agitation, confusion, disturbed behavior, nausea or vomiting with trihexyphenidyl treatment.
  • Start treatment with a smaller initial dose and increase gradually in such patients.
  • Discontinue treatment for a few days and restart with a lower dose in patients who develop severe reactions.
• Trihexyphenidyl can produce stimulation and euphoria and has a potential for abuse. Use with cannabinoids, barbiturates, opioids and alcohol can have additive effects. Indiscriminate use can cause psychiatric disturbances.
• Concurrent use with other central nervous system (CNS) depressants or alcohol can increase the sedative effects. Caution patients to avoid alcohol and CNS depressants.
• Abrupt withdrawal of trihexyphenidyl can aggravate Parkinson's symptoms. Wean off gradually when discontinuing treatment.

Common side effects of trihexyphenidyl include:

• Mild nausea
• Dryness of mouth
• Dizziness
• Blurred vision
• Nervousness
• Confusion
• Memory impairment
• Drowsiness
• Weakness
• Headache
• Irregular, involuntary (choreiform) movements
• Constipation
• Vomiting
• Urinary hesitancy or retention
• Rapid heart rate (tachycardia)
• Dilation of pupils
• Increased intraocular pressure

Less common side effects of trihexyphenidyl include:

• Inflammation and infection of the parotid salivary gland (suppurative parotitis)
• Skin rashes
• Dilatation of the colon
• Paralysis of the intestinal muscles (paralytic ileus)
• Delusion
• Hallucinations
• Paranoia
• Paradoxical slowing of heart rate (sinus bradycardia)
• Paralysis of the ciliary muscles of the eye (cycloplegia)
• Angle closure glaucoma
• Loss of vision
• Aggravation of parkinsonism symptoms with abrupt drug withdrawal
• Neuroleptic malignant syndrome with abrupt withdrawal of the drug

Side effects in patients with arteriosclerosis or idiosyncrasy to other drugs include:

• Nausea
• Vomiting
• Confusion
• Agitation
• Disturbed behavior

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablets

• 2 mg
• 5 mg

Elixir

• 0.4 mg/mL

Adult:

Parkinson Disease

• Initial: 1 mg orally first day, then increase by 2 mg once every 3-5 days until reaching 6-10 mg/day
• Maintenance: 5-15 mg/day orally divided once every 6-8 hours
• Use SR product once stabilized on regular release product; when used with levodopa, generally use 3-6 mg/day in divided doses
• Do not crush SR product
• Monitor: Intraocular pressure (IOP)

Drug-induced Extrapyramidal Symptoms

• 1 mg/day orally initially; increase as necessary to maintenance range of 5-15 mg/day orally divided once every 6-8 hours

Geriatric:

• Nonanticholinergic antiparkinson agents should be considered first when treating Parkinson Disease (Beers Criteria)
• Not recommended for preventing extrapyramidal symptoms

Parkinsonism

• 5-15 mg/day orally divided once every 6-8 hours

Pediatric:

• Safety and efficacy not established

Addiction/Overdose

• Trihexyphenidyl is not classified as a controlled substance, but there is a possibility of abuse because of its properties that can produce stimulation and euphoria.
• Trihexyphenidyl overdose can cause peripheral symptoms such as warm, dry skin, facial flushing, reduced secretions in the nose, mouth, throat and airway, foul-smelling breath, dilated and sluggish pupils, irregular heart rhythm, rapid heart rate (tachycardia), decreased bowel sounds, elevated temperature and urinary retention.
• Neuropsychiatric symptoms of trihexyphenidyl overdose include confusion, anxiety, agitation, aggression, incoherence, disorientation, hallucinations, illusions, delirium, loss of memory, paranoia, hyperactivity, impaired balance, coordination and speech (ataxia), lip smacking and tasting movements, and seizures, which may progress to stupor, coma, paralysis, cardiorespiratory arrest and death.
• Trihexyphenidyl overdose may be treated with symptomatic and supportive care including:
  • Gastric lavage or other methods to eliminate unabsorbed drug
  • Administration of diazepam or a short-acting barbiturate if central nervous system (CNS) excitation is present
  • Respiratory support, if necessary
  • Vasopressin medications to increase blood pressure
  • Treatment for high temperature
  • Fluid replacement and maintenance of acid/base balance
  • Urinary catheterization, if required

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Trihexyphenidyl has no listed severe interactions with other drugs.
• Serious interactions of trihexyphenidyl include:
  • glucagon
  • glucagon intranasal
  • glycopyrronium tosylate topical
  • revefenacin
  • secretin
  • umeclidinium bromide/vilanterol inhaled
• Trihexyphenidyl has moderate interactions with at least 69 different drugs.
• Mild interactions of trihexyphenidyl include:
  • levodopa

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• No animal reproductive studies have been conducted with trihexyphenidyl. It is not known if trihexyphenidyl can cause fetal harm if used during pregnancy, or if it can affect reproductive capacity. Trihexyphenidyl should be used in pregnant women only if clearly needed.
• It is not known if trihexyphenidyl is present in breastmilk. The drug should be used with caution in nursing mothers, because many drugs are excreted in breastmilk. Trihexyphenidyl can suppress lactation and hence, should be used in breastfeeding women only if potential benefits to the mother justifies the potential risks to the breastfed infant.

• Take trihexyphenidyl exactly as prescribed. Take with food, if the medication causes stomach upset.
• Do not abruptly stop taking trihexyphenidyl, the drug should be gradually weaned off under your physician’s care.
• You will need regular eye tests, do not miss your appointments.
• Trihexyphenidyl may impair mental and physical abilities required for hazardous activities such as driving or operating heavy machinery. Avoid engaging in such activities until the drug effects can be determined.
• Avoid drinking alcohol and taking other central nervous system depressants while on treatment with trihexyphenidyl, they can increase its sedative effects.
• Use trihexyphenidyl with caution during hot weather because it can increase the risk for heat stroke. Drink adequate fluids and avoid exposure to heat.
• Report to your physician immediately if you have gastrointestinal problems, fever or heat intolerance.
• Store trihexyphenidyl safely out of reach of children.
• In case of overdose, seek immediate medical care or contact Poison Control.