zuclopenthixol

Absorption: PO: well absorbed following oral administration; IM (depot and acuphase): slowly absorbed from IM sites.

Distribution: Enters breast milk.

Metabolism/Excretion: Mostly metabolized (partially by the CYP2D6 enzyme system), 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 hrs	4 hr (blood level)	8–24 hr
IM (acetate [Acuphase])	2–4 hr	8 hr (sedation)	2–3 days
IM (decanoate [Depot])	within 3 days	3–7 days (blood level)	2–4 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Treatment of dementia;
Narrow angle glaucoma;
Pedi: Safety and effectiveness not established, use not recommended.

Use Cautiously in:

Hepatic or renal impairment;
Electrolyte abnormalities, including hypokalemia, hypomagnesemia, concurrent diuretic therapy or drugs affecting QT interval or cardiovascular disease/history (↑ risk of serious arrhythmias);
Intestinal pathology or brain lesions (antiemetic effect may mask symptoms);
History of seizures (may ↓ threshold);
Parkinson's disease (may cause deterioration);
Risk factors/history of stroke;
Abrupt discontinuation (should be tapered);
Geri: Consider age-related in renal, hepatic, and cardiovascular function, concurrent disease states and drug therapies;
OB: Infants exposed in the third trimester may exhibit extrapyramidal and withdrawal reactions including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders; do not use in pregnancy unless expected benefit to the mother outweighs potential fetal risks;
Lactation: Enters breast milk; safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

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

EENT: abnormal vision accommodation

CV: arrhythmias, hypotension, tachycardia, THROMBOEMBOLISM

GI: constipation, dry mouth, diarrhea, thirst, vomiting

Derm: ↑sweating, photosensitivity reactions

Endo: hyperprolactinemia, hyperglycemia

GU: ↓libido, abnormal urination

Hemat: anemia, granulocytopenia

Metab: weight change

MS: myalgia

Interactions ⬆ ⬇

Drug-drug:

↑risk of CNS depression with other CNS depressants including alcohol, some antihistamines, some antidepressants, anxiolytics, barbiturates, benzodiazepines, and sedative/hypnotics.
↑levels and risk of toxicity with CYP2D6 inhibitors.
Concurrent use of diuretics, lithium, Class Ia and III antiarrhythmics including amiodarone, sotalol, and quinidine; some antipsychotics including thioridazine, some macrolides including erythromycin; and some fluoroquinolones including moxifloxacin↑ risk of QT interval prolongation and serious arrhythmias; concurrent use should be avoided.
↑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 ↓ beneficial effects of levodopa and dopamine agonists.

Route/Dosage ⬆ ⬇

PO (Adults ): Acute psychoses: 10–50 mg/day in 2–3 divided doses initially; may be ↑ 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 (usual range 20–40 mg/day). Once maintenance dose is established, may be given as a single daily dose.
IM (Adults ): Zuclopenthixol acetate [Acuphase]: 50–150 mg, may be repeated every 2–3 days if necessary, some patients may need an additional dose 1–2 days after first injection only; care must be taken to avoid overmedicating due to delay in absorption and antipsychotic effects. Maximum cumulative dose should not exceed 400 mg or four injections. Zuclopenthixol acetate (Acuphase) dose form is not meant for long-term use, duration should not exceed 2 wk. If injection volume exceeds 2 mL, dose should be divided and given in two sites. If oral maintenance is to be used, treatment with tablets should be initiated 2–3 days following the last dose of the Zuclopenthixol acetate (Acuphase) dose form; if Zucopenthixol decanoate (Depot) dose form is to be used for maintenance, may be given concurrently with the last injection of Zuclopenthixol acetate (Acuphase) dose form. Suggested transfer regimen to oral dosing: If Zuclopenthixol acetate (Acuphase) dose was 50 mg, then daily oral dose could be 20 mg; if Zuclopenthixol acetate (Acuphase) dose was 100 mg, then daily oral dose could be 40 mg; if Zuclopenthixol acetate (Acuphase) dose was 150 mg, then daily oral dose could be 60 mg. Suggested transfer regimen to Zuclopenthixol decanoate (Depot) dosing: If Zuclopenthixol acetate (Acuphase) dose was 50 mg, then IM dose of Zuclopenthixol decanoate (Depot) could be 100 mg every 2 wk; if Zuclopenthixol acetate (Acuphase) dose was 100 mg, then IM dose of Zuclopenthixol decanoate (Depot) could be 200 mg every 2 wk; if Zuclopenthixol acetate (Acuphase) dose was 150 mg, then IM dose of Zuclopenthixol decanoate (Depot) could be 300 mg every 2 wk.
IM (Adults ): Zuclopenthixol decanoate [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 injection volume exceeds 2 mL, dose should be divided and given in two sites.

Availability ⬆ ⬇

Zuclopenthixol hydrochloride 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. Increased bulk 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, mask-like 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. Reduction 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 cause ↑ AST, ALT, and alkaline phosphatase.
- Monitor blood glucose prior to and periodically during therapy. May cause hyperglycemia.
- Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

Implementation ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Instruct patient to take as directed. If a dose is missed, omit and take next dose as scheduled. Discontinuation should be gradual.
Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Caution patient to report these symptoms immediately to health care professional.
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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, visual disturbances, dark-colored urine, or clay-colored stools occur.
Instruct patient to avoid sun exposure and to wear protective clothing and sunscreen when outdoors.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding or planning to breastfeed.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇