Trihexyphenidyl Hydrochloride 2 mg Tablet, 1,000-count — NDC 63850-0021-3 (Billing 63850-0021-03)

WARNINGS Patients to be treated with trihexyphenidyl HCl should have a gonioscope evaluation prior to initiation of therapy and close monitoring of intraocular pressures. The use of anticholinergic drugs may precipitate angle closure with an increase in intraocular pressure. If blurring of vision occurs during therapy, the possibility of narrow angle glaucoma should be considered.

Blindness has been reported due to aggravation of narrow angle glaucoma (see CONTRAINDICATIONS and ADVERSE REACTIONS ). Trihexyphenidyl HCl should be administered with caution in hot weather, especially when given concomitantly with other atropine-like drugs to the chronically ill, alcoholics, those who have central nervous system disease, or those who do manual labor in a hot environment. Anhidrosis may occur more readily when some disturbance of sweating already exists.

If there is evidence of anhidrosis, the possibility of hyperthermia should be considered. Dosage should be decreased so that the ability to maintain body heat equilibrium via perspiration is not impaired. Severe anhidrosis and fatal hyperthermia have occurred with the use of anticholinergics under the conditions described above.

Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with dose reduction or discontinuation of trihexyphenidyl. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated.

In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.

ADVERSE REACTIONS Minor side effects, such as dryness of the mouth, blurred vision, dizziness, mild nausea or nervousness, will be experienced by 30 to 50 percent of all patients. These sensations, however, are much less troublesome with trihexyphenidyl HCl than with belladonna alkaloids and are usually less disturbing than unalleviated parkinsonism. Such reactions tend to become less pronounced, and even to disappear, as treatment continues.

Even before these reactions have remitted spontaneously, they may often be controlled by careful adjustment of dosage form, amount of drug, or interval between doses. Isolated instances of suppurative parotitis secondary to excessive dryness of the mouth, skin rashes, dilatation of the colon, paralytic ileus, and certain psychiatric manifestations such as delusions, hallucinations, and paranoia, all of which may occur with any of the atropine-like drugs, have been reported rarely with trihexyphenidyl HCl. Potential side effects associated with the use of any atropine-like drugs, including trihexyphenidyl HCl, include cognitive dysfunctions, including confusion and memory impairment; constipation, drowsiness, urinary hesitancy or retention, tachycardia, dilation of the pupil, increased intraocular pressure, choreiform movements, weakness, vomiting, and headache.

Exacerbation of parkinsonism with abrupt treatment withdrawal has been reported. Neuroleptic malignant syndrome with abrupt treatment withdrawal has been reported ( see WARNINGS , Neuroleptic Malignant Syndrome ). The occurrence of angle-closure glaucoma in patients receiving trihexyphenidyl HCl has been reported (blindness has been reported in some cases).

Paradoxical sinus bradycardia, dry skin, and cycloplegia have been reported. In addition to adverse events seen in adults, the following adverse events have been reported in the literature in pediatric patients: hyperkinesia, psychosis, forgetfulness, weight loss, restlessness, chorea, and sleep alterations.

Drug Interactions Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl HCl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with trihexyphenidyl HCl may cause increased sedative effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications.

Prophylactic administration of anticholinergic agents, such as trihexyphenidyl, as a prevention of drug-induced parkinsonism during neuroleptic therapy is not recommended. There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics ( see PRECAUTIONS , General ) . The usual dose of either trihexyphenidyl or levodopa may need to be reduced during concomitant therapy, since concomitant administration may increase drug-induced involuntary movements ( see DOSAGE AND ADMINISTRATION ).

PRECAUTIONS General Patients with cardiac, liver, or kidney disorders, or with hypertension, should be closely monitored. Since trihexyphenidyl HCl has atropine-like properties, patients on long-term treatment should be carefully monitored for untoward reactions. Since trihexyphenidyl HCl has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy.

Incipient glaucoma may be precipitated by parasympatholytic drugs such as trihexyphenidyl HCl. Tardive dyskinesia may appear in some patients on long-term therapy with antipsychotic drugs or may occur after therapy with these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them.

However, parkinsonism and tardive dyskinesia often coexist in patients receiving chronic neuroleptic treatment, and anticholinergic therapy with trihexyphenidyl HCl may relieve some of these parkinsonism symptoms. Trihexyphenidyl HCl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson's disease. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting.

Such patients should be allowed to develop a tolerance through the initial administration of a small dose and gradual increase in dose until an effective level is reached. If a severe reaction should occur, administration of the drug should be discontinued for a few days and then resumed at a lower dosage. Psychiatric disturbances can result from indiscriminate use (leading to overdosage) to sustain continued euphoria.

( See DRUG ABUSE AND DEPENDENCE .) Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided ( see DOSAGE AND ADMINISTRATION ). Information for Patients Trihexyphenidyl HCl may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. Patients should be cautioned about operating machinery, including automobiles, until they are reasonably certain that trihexyphenidyl HCl therapy does not adversely affect their ability to engage in such activities.

Because of increased sedative effects, patients should be cautioned to avoid the use of alcohol or other CNS depressants while taking trihexyphenidyl HCl. Since this medication may increase the susceptibility to heat stroke (gastrointestinal (GI) problems, fever, heat intolerance), use with caution during hot weather. ( See WARNINGS .) Patients should be advised to report the occurrence of Gl problems, fever, or heat intolerance promptly since paralytic ileus, hyperthermia, or heat stroke may occur.

If GI upset occurs, trihexyphenidyl HCl may be taken with food. Patients should have close monitoring of intraocular pressure. ( See WARNINGS .) Drug Interactions Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl HCl, and thus, an abuse potential exists.

Concurrent use of alcohol or other CNS depressants with trihexyphenidyl HCl may cause increased sedative effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications. Prophylactic administration of anticholinergic agents, such as trihexyphenidyl, as a prevention of drug-induced parkinsonism during neuroleptic therapy is not recommended.

There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics ( see PRECAUTIONS , General ) . The usual dose of either… [Excerpted — this section continues on DailyMed.]

DRUG ABUSE AND DEPENDENCE Although trihexyphenidyl HCl is not classified as a controlled substance, the possibility of abuse should be borne in mind due to its stimulant and euphoriant properties.