zuclopenthixol

Absorption: Well absorbed following oral administration; slowly absorbed from IM sites.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ metoprolol concentrations and an ↑ risk of adverse effects; metabolites do not have antipsychotic activity; minimal amounts excreted unchanged in urine.

Half-Life: PO: 20 hr.

Time/Action Profile ⬆ ⬇

(antipsychotic effect)

ROUTE	ONSET	PEAK	DURATION
PO	within hours	4 hr (plasma concentrations)	8–24 hr
IM ( acuphase)	2–4 hr	8 hr (sedation)	2–3 days
IM ( depot)	within 3 days	3–7 days (plasma concentrations)	2–4 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Narrow-angle glaucoma.

Use Cautiously in:

Electrolyte abnormalities, concurrent use of diuretics or drugs affecting QT interval, or history of cardiovascular disease (↑ risk of serious arrhythmias);
Intestinal pathology or brain lesions (antiemetic effect may mask symptoms);
History of seizures (may ↓ seizure threshold);
Parkinson disease (may cause deterioration);
Risk factors/history of stroke;
Renal impairment;
Hepatic impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety and effectiveness not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of stroke, cognitive decline, and mortality in older adults with dementia.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, hypotension, tachycardia, THROMBOEMBOLISM

Derm: ↑sweating, photosensitivity

EENT: abnormal vision accommodation

Endo: hyperprolactinemia, hyperglycemia

F and E: ↑thirst

GI: constipation, dry mouth, diarrhea, vomiting

GU: ↓libido, abnormal urination

Hemat: anemia, granulocytopenia

Metab: weight gain

MS: myalgia

Neuro: dizziness, extrapyramidal symptoms, fatigue, sedation, NEUROLEPTIC MALIGNANT SYNDROME, tardive dyskinesia, syncope, weakness

Interactions ⬆ ⬇

Drug-drug:

↑risk of CNS depression with other CNS depressants, including alcohol, some antihistamines, some antidepressants, anxiolytics, barbiturates, benzodiazepines, and sedative/hypnotics.
CYP2D6 inhibitors may ↑ levels and risk of toxicity.
Diuretics, lithium, class Ia and III antiarrhythmics , some antipsychotics (including thioridazine), macrolides, and fluoroquinolones↑ risk of QT interval prolongation and serious arrhythmias; avoid concurrent use.
↑risk of anticholinergic adverse reactions with other anticholingeric drugs.
↑risk of hypotension with antihypertensives and diuretics.
Concurrent use with tricyclic antidepressants may result in altered metabolism and effects of both.
↑risk of extrapyramidal symptoms with metoclopramide.
May ↓ effectiveness of levodopa and dopamine agonists.

Route/Dosage ⬆ ⬇

PO (Adults ): Acute psychoses: 10–50 mg/day in 2–3 divided doses initially; may ↑ by 10–20 mg/day every 2–3 days; titrate according to response. Usual dose range is 20–60 mg/day; doses >100 mg/day are not recommended. Dose should be ↓ to lowest dose needed to control symptoms (20–40 mg/day). After maintenance dose is established, give as a single daily dose.
IM (Adults ): Acuphase: 50–150 mg; may be repeated every 2–3 days if necessary; some patients may need an additional dose 1–2 days after 1st injection only; care must be taken to avoid overmedicating due to delay in absorption and antipsychotic effects. Max dose = 400 mg or 4 injections. Acuphase is not meant for long-term use; duration should not >2 wk. If dose >2 mL, divide dose and give in 2 different sites. If PO maintenance is needed, initiate 2–3 days following the last dose of Acuphase. If depot is used for maintenance, may be given concurrently with the last injection of Acuphase. Suggested transfer regimen to PO dosing: If Acuphase dose was 50 mg, then oral dose could be 20 mg/day; if Acuphase dose was 100 mg, then oral dose could be 40 mg/day; if Acuphase dose was 150 mg, then oral dose could be 60 mg/day. Suggested transfer regimen to depot dosing: If Acuphase dose was 50 mg, then depot dose could be 100 mg IM every 2 wk. If Acuphase dose was 100 mg, then depot dose could be 200 mg IM every 2 wk. If Acuphase dose was 150 mg, then depot dose could be 300 mg IM every 2 wk.
IM (Adults ): Depot: Usual maintenance dose is 150–300 mg every 2–4 wk; regimens should be individualized according to response; care must be taken not to overmedicate due to delayed/prolonged absorption and effects. If dose >2 mL, divide dose and give in 2 different sites.

Availability ⬆ ⬇

Tablets (contain castor oil): 10 mg; 25 mg
Zuclopenthixol acetate injection (Acuphase) (contains medium-chain triglycerides): 50 mg/mL
Zuclopenthixol decanoate injection (Depot) (contains medium-chain triglycerides): 200 mg/mL

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) before and periodically during therapy.
Observe carefully when administering oral medication to ensure that medication is actually taken and not hoarded.
Assess weight and BMI initially and during therapy.
Assess fluid intake and bowel function. ↑ fiber and fluids in the diet help minimize constipation.
Monitor for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling, masklike face, shuffling gait, rigidity, tremors; dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. ↓ in dose or discontinuation of medication may be necessary. Benztropine or diphenhydramine may be used to control these symptoms.
Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Report immediately; may be irreversible.
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, arrhythmias, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Report immediately.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

Monitor CBC and liver function tests every 6 mo and periodically as needed during treatment. May ↑ AST, ALT, and alkaline phosphatase.
- Monitor blood glucose before and periodically during therapy. May cause hyperglycemia.
- Monitor serum prolactin before and periodically during therapy. May ↑ prolactin.

Implementation ⬆ ⬇

PO: Administer before or after meals.
IM: Administer deep in large muscle. A test dose may be ordered for 1st administration.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. If a dose is missed, omit and take next dose as scheduled. Discontinuation should be gradual.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Caution patient to report these symptoms immediately to health care provider.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Medication may cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, visual disturbances, dark-colored urine, or clay-colored stools occur.
Advise patient to avoid sun exposure and to wear protective clothing and sunscreen when outdoors.
Advise patient to notify health care provider of medication regimen before treatment or surgery.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding or planning to breastfeed. Infants exposed in the 3rd trimester may exhibit extrapyramidal and withdrawal reactions, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇