Dosing Tips

• Onset of action of the intramuscular acetate formulation following a single injection is generally 2–4 hours; duration of action is generally 2–3 days

• Zuclopenthixol acetate is not intended for long-term use, and should not generally be used for longer than 2 weeks; patients requiring treatment longer than 2 weeks should be switched to a depot or oral formulation of zuclopenthixol or another antipsychotic

• When changing from zuclopenthixol acetate to maintenance treatment with zuclopenthixol decanoate, administer the last injection of acetate concomitantly with the initial injection of decanoate

• The peak of action for the decanoate is usually 4–9 days, and doses generally have to be administered every 2–3 weeks

• Treatment should be suspended if absolute neutrophil count falls below 1,000/mm³

Overdose

• Sedation, convulsions, extrapyramidal symptoms, coma, hypotension, shock, hypo/hyperthermia

Long-Term Use

• Zuclopenthixol decanoate is intended for maintenance treatment

• Some side effects may be irreversible (e.g., tardive dyskinesia)

Habit Forming

• No

How to Stop

• Slow down-titration of oral formulation (over 6–8 weeks), especially when simultaneously beginning a new antipsychotic while switching (i.e., cross-titration)

• Rapid oral discontinuation may lead to rebound psychosis and worsening of symptoms

• If antiparkinson agents are being used, they should be continued for a few weeks after zuclopenthixol is discontinued

Pharmacokinetics

• Metabolized by CYP450 2D6 and CYP450 3A4

• For oral formulation, elimination half-life approximately 20 hours

• For acetate, rate-limiting half-life approximately 32 hours

• For decanoate, rate-limiting half-life approximately 17–21 days with multiple doses

Drug Interactions

• Theoretically, concomitant use with CYP450 2D6 inhibitors (such as paroxetine and fluoxetine) or with CYP450 3A4 inhibitors (such as fluoxetine and ketoconazole) could raise zuclopenthixol plasma levels and require dosage reduction

• Theoretically, concomitant use with CYP450 3A4 inducers (such as carbamazepine) could lower zuclopenthixol plasma levels and require dosage increase

• CNS effects may be increased if used with other CNS depressants

• If used with anticholinergic agents, may potentiate their effects

• Combined use with epinephrine may lower blood pressure

• Zuclopenthixol may block the antihypertensive effects of drugs such as guanethidine, but may enhance the actions of other antihypertensive drugs

• Using zuclopenthixol with metoclopramide or piperazine may increase the risk of extrapyramidal symptoms

• Zuclopenthixol may antagonize the effects of levodopa and dopamine agonists

• Some patients taking a neuroleptic and lithium have developed an encephalopathic syndrome similar to neuroleptic malignant syndrome

Other Warnings/Precautions

• If signs of neuroleptic malignant syndrome develop, treatment should be immediately discontinued

• Use with caution in patients with epilepsy, glaucoma, urinary retention

• Decanoate should not be used with clozapine because it cannot be withdrawn quickly in the event of serious adverse effects such as neutropenia

• Possible antiemetic effect of zuclopenthixol may mask signs of other disorders or overdose; suppression of cough reflex may cause asphyxia

• Use only with great caution if at all in Parkinson’s disease or Lewy body dementia

• Observe for signs of ocular toxicity (pigmentary retinopathy and lenticular and corneal deposits)

• Avoid undue exposure to sunlight

• Avoid extreme heat exposure

• Do not use epinephrine in event of overdose as interaction with some pressor agents may lower blood pressure

Do Not Use

• If patient is taking a large concomitant dose of a sedative hypnotic

• If patient is taking guanethidine or a similar acting compound

• If patient has CNS depression, is comatose, or has subcortical brain damage

• If patient has acute alcohol, barbiturate, or opiate intoxication

• If patient has angle-closure glaucoma

• If patient has pheochromocytoma, circulatory collapse, or blood dyscrasias

• In case of pregnancy

• If there is a proven allergy to zuclopenthixol

ZUCLOPENTHIXOL: SPECIAL POPULATIONS

Renal Impairment

• Use with caution

Hepatic Impairment

• Use with caution

Cardiac Impairment

• Use with caution

Elderly

• Some patients may tolerate lower doses better

• Maximum acetate dose 100 mg

• Although conventional antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events