Trihexyphenidyl

Trihexyphenidyl is indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

• Dosage should be individualized
• The initial dose should be low and then increased gradually, especially in patients over 60 years of age.Whether trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts
• Postencephalitic patients, who are usually more prone to excessive salivation, may prefer to take it after meals and may, in addition, require small amounts of atropine which, under such circumstances, is sometimes an effective adjuvant
• If trihexyphenidyl tends to dry the mouth excessively, it may be better to take it before meals, unless it causes nausea
• If taken after meals, the thirst sometimes induced can be allayed by mint candies, chewing gum or water
• Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided
• Abrupt withdrawal of treatment may result in neuroleptic malignant syndrome (NMS) (See WARNINGS )
• Idiopathic Parkinsonism As initial therapy for parkinsonism, 1 mg of trihexyphenidyl hydrochloride may be administered the first day
• The dose may then be increased by 2 mg increments at intervals of three to five days, until a total of 6 to 10 mg is given daily
• The total daily dose will depend upon what is found to be the optimal level
• Many patients derive maximum benefit from this daily total of 6 to 10 mg, but some patients, chiefly those in the postencephalitic group, may require a total daily dose of 12 to 15 mg. …

• Safety and effectiveness
• In pediatric patients have not been established. (See also ADVERSE REACTIONS )

Sensitivity to the actions of parasympatholytic drugs may increase with age, particularly over the age of 60; therefore, elderly patients generally should be started on low doses of trihexyphenidyl and observed closely. Trihexyphenidyl has been shown to cause some cognitive dysfunctions in the elderly, including confusion and memory impairment. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION ).

• Trihexyphenidyl 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 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
• Since this medication may increase the susceptibility to heat stroke (gastrointestinal (GI) problems, fever, heat intolerance), use with caution during hot weather. …

• Trihexyphenidyl is contraindicated in patients with hypersensitivity to trihexyphenidyl or to any of the other ingredients
• Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma
• Blindness after long-term use due to narrow angle glaucoma has been reported

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with trihexyphenidyl 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. …

Patients to be treated with trihexyphenidyl 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 ). …

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 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. …

Pregnancy Teratogenic Effects Pregnancy Category C Animal reproduction studies to evaluate teratogenic and embryotoxic potential have not been conducted with trihexyphenidyl. It is also not known whether trihexyphenidyl can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Trihexyphenidyl should be given to a pregnant woman only if clearly needed.

The mean oral LD 50 of trihexyphenidyl has been reported to be 365 mg/kg (range, 325 to 410 mg/kg) in mice and 1660 mg/kg (1420 to 1940 mg/kg) in rats. At a dose of 40 mg/kg, dogs have exhibited emesis, restlessness followed by drowsiness, equilibrium disturbances, and mydriasis. In humans, doses up to 300 mg (5 mg/kg) have been ingested without fatalities or sequelae. However, rare cases of death associated with trihexyphenidyl overdosages taken in conjunction with other CNS-depressant agents have been reported or in patients with a compromised respiratory condition. …

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

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