VA Class:AU350

AHFS Class:

• Anticholinergic Agents 28:36.08

Generic Name(s):

• Benztropine Mesylate

Benztropine mesylate is an antimuscarinic antiparkinsonian agent.

Parkinsonian Syndrome

Benztropine mesylate is used for the symptomatic management of all forms of parkinsonian syndrome including idiopathic parkinson disease and parkinsonism resulting from encephalitis (postencephalitic parkinsonism).200,201

Anticholinergic agents (e.g., benztropine, trihexyphenidyl) have been used as monotherapy or as adjunctive therapy to other antiparkinsonian agents in the management of parkinson disease.123,157,158 Levodopa (in combination with carbidopa) is currently the most effective drug for relieving motor symptoms of the disease.101,115,157 However, the effectiveness of levodopa decreases over time and most patients develop motor complications (e.g., motor fluctuations, dyskinesias) with long-term use.115,123,157 To avoid these complications, other antiparkinsonian agents may be initiated first to postpone the use of levodopa; this strategy is generally considered for younger patients who have mild and tolerable clinical manifestations.115,123,157 Some clinicians state that anticholinergic agents may be particularly useful for initial therapy in patients younger than 60 years of age with resting tremors as their only or most prominent parkinsonian symptom.115,123 Although the main indication for anticholinergic agents in patients with parkinson disease is to control tremors, evidence of a benefit is largely anecdotal and not supported by randomized controlled studies.123,157,158 In addition, these drugs are associated with adverse neuropsychiatric and cognitive effects, which are likely to be more severe in geriatric patients.158,159

For additional information on treatment options in parkinson disease, see Uses: Parkinsonian Syndrome, in Levodopa/Carbidopa 28:36.16.

Drug-induced Extrapyramidal Reactions

Benztropine is also used for the relief of antipsychotic agent-induced (e.g., phenothiazines) extrapyramidal symptoms (EPS), except for tardive dyskinesia.160,200,201

Anticholinergic agents (e.g., trihexyphenidyl, benztropine) have been used traditionally to restore the balance between acetylcholine and dopamine in patients with this condition; however, evidence supporting a benefit is either lacking or inconsistent and the drugs are associated with a variety of adverse effects.160,161,162 For these reasons, anticholinergic agents should generally be used cautiously and for the minimum duration necessary to control EPS.160,162

Administration

Benztropine mesylate is administered orally or by IM injection. Parenteral administration should be reserved for patients who cannot take oral medication or for emergency situations, such as acute dystonic reactions, when rapid response is desired. Although benztropine may also be administered IV, the manufacturer states that there is no clinically important difference in onset between IM or IV injection; therefore, IV administration of the drug is rarely necessary.

Dosage

Parkinsonian Syndrome

Dosage of benztropine mesylate should be individualized according to the age and weight of the patient and the type of parkinsonian syndrome being treated.200,201 Therapy should be initiated with a low dosage and then increased based on patient response and tolerability to the lowest effective dosage.200,201 The following dosage recommendations apply to both oral and parenteral therapy; however, oral administration is preferred whenever possible.200,201 (See Administration under Dosage and Administration.)

For the treatment of idiopathic or postencephalitic parkinsonian syndrome, the usual adult oral or parenteral dosage of benztropine mesylate is 1-2 mg daily (range: 0.5-6 mg daily).200,201 Benztropine therapy should be initiated at a low dosage and gradually increased by 0.5-mg increments at 5- or 6-day intervals to a maximum dosage of 6 mg daily or until optimum symptomatic relief is obtained.200,201 Patients with idiopathic parkinson disease may be initiated on a single daily dose of 0.5-1 mg at bedtime; while this dosage may be adequate in some patients, others may require a dosage of 4-6 mg daily.200,201 In patients with postencephalitic parkinsonism, the usual initial dosage of benztropine mesylate is 2 mg in a single daily dose or divided doses; sometimes a single dose of 2 mg is sufficient to control symptoms for 24 hours.200,201 In highly sensitive patients, a lower initial dose of 0.5 may be necessary.200,201 Younger patients with postencephalitic parkinsonian syndrome may tolerate larger initial doses and may require 2 mg 2 or 3 times daily for maintenance therapy. Older patients may be controlled with 1 or 2 mg daily.

For emergency situations when parenteral administration is necessary, an IM dose of 1-2 mg normally will provide quick relief; the dose may be repeated if parkinsonian symptoms return.200 (See Administration under Dosage and Administration.)

Geriatric patients and those with lower than average body weight generally cannot tolerate high dosages of the drug.200,201 In geriatric patients, dosage selection should start at the low end of the dosing range and the dosage should be increased only if needed and with close monitoring for adverse effects.200,201 (See Geriatric Precautions under Cautions.)

Periodic dosage adjustment may be required in patients receiving benztropine with levodopa-carbidopa to maintain optimum symptomatic relief.200,201 When benztropine is given to replace or supplement other antiparkinsonian drugs, the change should be gradual, with the dosage of the previous medication reduced as the dosage of benztropine is increased.200,201

Drug-Induced Extrapyramidal Reactions

For the symptomatic relief of antipsychotic agent-induced extrapyramidal reactions (except tardive dyskinesia), the recommended oral or parenteral dosage of benztropine mesylate is 1-4 mg once or twice daily.160,200,201 Dosage must be individualized according to the patient's response and tolerance. For the symptomatic relief of extrapyramidal disorders that develop shortly after initiation of antipsychotic (e.g., phenothiazines) therapy, 1-2 mg 2 or 3 times daily usually provides relief within 1 or 2 days.200,201 Since acute extrapyramidal symptoms are generally transient, the need for benztropine should be reevaluated after 1-2 weeks of therapy.200,201

For the relief of an acute dystonic reaction, 1-2 mg of benztropine mesylate may be given IM, followed by 1-2 mg orally twice daily to prevent recurrence.200,201

Adverse Effects

Adverse reactions to benztropine are mainly extensions of its anticholinergic (see Cautions: Adverse Effects, in the Antimuscarinics/Antispasmodics General Statement 12:08.08) and antihistaminic effects. Dryness of the mouth, blurred vision, mydriasis, nausea, nervousness, tachycardia, or skin rash may occur. In high dosage or in particularly susceptible patients, mental confusion and excitement, weakness and inability to move certain muscle groups, and, occasionally, urinary retention and/or difficulty in urination may result. Constipation, numbness of the extremities, listlessness, depression, vomiting, paralytic ileus, hyperthermia, fever, heat stroke, and visual hallucinations have also been reported. Adjustment of dosage will usually overcome most adverse effects of benztropine, but in the event of severe reactions, such as excitement or vomiting, the drug should be withdrawn and later resumed at a lower dosage.

Precautions and Contraindications

Benztropine should be used with caution or may be contraindicated in patients with conditions in which anticholinergic effects are undesirable. The usual precautions and contraindications associated with antimuscarinics should be observed with benztropine. For a complete discussion of the precautions and contraindications associated with antimuscarinics, see Cautions: Precautions and Contraindications, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.

Since benztropine has cumulative effects, continuous supervision of patients receiving the drug is advised, especially for those with a tendency toward tachycardia, or with prostatic hypertrophy. Patients with mental disorders receiving benztropine for control of drug-induced extrapyramidal effects should also be carefully observed, especially at the beginning of therapy or during dosage adjustment, since worsening of mental symptoms or toxic psychosis can occur.

Patients receiving benztropine concomitantly with phenothiazines or other drugs with anticholinergic effects should be warned to promptly report any adverse GI effects, since paralytic ileus, sometimes fatal, has occurred during concomitant therapy with these drugs.

Benztropine should not be used in patients with tardive dyskinesia, since the drug generally does not relieve signs and symptoms of this condition and may aggravate them. Benztropine is also contraindicated in patients with hypersensitivity to the drug or other components of the tablet or parenteral preparation.

Pediatric Precautions

Benztropine is contraindicated in children younger than 3 years of age and should be used with caution in older children because of the drug's adverse anticholinergic effects.

Geriatric Precautions

Because of the risk of adverse effects and the availability of more effective treatments, some experts recommend that use of benztropine should be avoided in geriatric patients.157,159

Pregnancy

Pregnancy

Safe use of benztropine during pregnancy has not been established.

Concomitant administration of benztropine with other drugs having anticholinergic effects may increase the risk of adverse anticholinergic effects. Concomitant administration of an anticholinergic antiparkinsonian agent (e.g., benztropine) with phenothiazines and/or tricyclic antidepressants may cause paralytic ileus, hyperthermia, or heat intolerance, effects that occasionally have been fatal. Patients who are receiving benztropine concomitantly with phenothiazines, haloperidol, or other drugs with anticholinergic or antidopaminergic activity should notify their clinicians promptly if adverse GI effects, fever, or heat intolerance occurs.

Pharmacology

The anticholinergic effect of benztropine is about equal to that of atropine. The antihistaminic activity of benztropine is similar to that of pyrilamine maleate. Benztropine does not produce as much central stimulation as does trihexyphenidyl. The effects of the drug are cumulative and may not be evident until 2 or 3 days after treatment is begun.

Chemistry and Stability

Chemistry

Benztropine mesylate is a synthetic, tertiary amine antimuscarinic antiparkinsonian agent. The drug resembles both atropine and diphenhydramine in chemical structure and exhibits anticholinergic, antihistaminic, and local anesthetic properties. Benztropine mesylate occurs as a white, odorless, slightly hygroscopic, crystalline powder and is very soluble in water and freely soluble in alcohol. Benztropine mesylate injection has a pH of 5-8.

Stability

Benztropine mesylate tablets should be stored in well-closed containers. Benztropine mesylate tablets and injection should be stored at controlled room temperature (20-25°C).200,201

Additional Information

For further information on pharmacology, cautions, acute toxicity, and drug interactions of benztropine, see the Antimuscarinics/Antispasmodics General Statement 12:08.08.

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