flupentixol

Absorption: Flupentixol dihydrochloride: 40% absorbed following oral administration; Flupentixol decanoate: Slowly released from IM injection sites.

Distribution: Distributes to lungs, liver, and spleen; enter CNS; extensive tissue distribution.

Protein Binding: 99%.

Metabolism/Excretion: Mostly metabolized; metabolites do not have antipsychotic activity. Most metabolites are excreted in feces; some renal elimination.

Half-Life: Flupentixol dihydrochloride: 35 hr; Flupentixol decanoate: 3 wk.

Time/Action Profile ⬆ ⬇

(antipsychotic effect)

ROUTE	ONSET	PEAK	DURATION
PO	within 2–3 days	3–8 hr (blood level)	8 hr
IM (depot)	24–72 hr	4–7 days (blood level)	2–4 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to flupentixol or other thioxanthines (cross-sensitivity with phenothiazines may occur);
CNS depression due to any cause, including comatose states, cortical brain damage (known or suspected), or circulatory collapse;
Opiate, alcohol, or barbiturate intoxication;
Hepatic impairment, cerebrovascular insufficiency, or severe cardiovascular pathology.

Use Cautiously in:

Brain tumors or intestinal obstruction (may mask symptoms);
Patients exposed to extreme heat or organophosphorous insecticides;
Risk factors for/history of stroke;
Any risk factors for QT prolongation, including hypokalemia, hypomagnesemia, genetic predisposition, cardiovascular disease history (including bradycardia), recent MI, HF, or arrhythmias;
Known/suspected glaucoma;
History of seizures (may ↓ seizure threshold);
Parkinson disease (may worsen symptoms);
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: tachycardia, hypotension, QT interval prolongation, THROMBOEMBOLISM

Derm: photosensitivity, rash, sweating

EENT: blurred vision

Endo: glucose intolerance, hyperprolactinemia

GI: constipation, dry mouth, excess salivation, hepatotoxicity

GU: ↓libido, menstrual irregularities, urinary retention

Hemat: agranulocytosis, granulocytopenia, neutropenia

Metab: weight gain

MS: osteoporosis

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

Interactions ⬆ ⬇

Drug-drug:

↑CNS depression with other CNS depressants, including alcohol, some antidepressants, some antihistamines, anxiolytics, benzodiazepines, and sedative/hypnotics.
↑risk of QT prolongation and serious arrhythmias with class Ia and III antiarrhythmics, some antipsychotics (including thioridazine), macrolides, and fluoroquinolones; avoid concurrent use.
Diuretics and other drugs affecting electrolytes may ↑ risk of QT interval prolongation and serious arrhythmias.
Anticholinergic medications may ↑ risk of anticholinergic adverse reactions, including paralytic ileus.
May ↑ levels and risk of toxicity of tricyclic antidepressants.
↑risk of extrapyramidal symptoms with metoclopramide.
May ↓ effectiveness of levodopa and dopamine agonists.

Route/Dosage ⬆ ⬇

PO (Adults ): 1 mg 3 times daily initially; ↑ by 1 mg every 2–3 days until desired response; usual effective dose is 3–6 mg/day in divided doses (up to 12 mg/day has been used); if insomnia occurs, ↓ evening dose.
IM (Adults ): Initiate with a 5–20 mg test dose (use 5-mg dose in older adults) of the 2% injection. Patients previously treated with long-acting neuroleptic injections may tolerate initial doses of 20 mg. A 2nd 20-mg dose may be given 4–10 days later and then 20–40 mg every 2–3 wk depending on response. Oral flupentixol should be continued, but gradually ↓ in the 1st wk following depot injection. Guidelines for conversion from oral to depot IM injection: daily oral dose (mg) × 4 = dose of depot IM injection (mg) given every 2 wk or daily oral dose (mg) × 8 = depot IM injection (mg) given every 4 wk.

Availability ⬆ ⬇

Tablets (flupentixol dihydrochloride): 0.5 mg; 3 mg; 5 mg
Solution for depot IM injection (flupentixol decanoate: contains medium-chain triglycerides [coconut oil]): 20 mg/mL (2%); 100 mg/mL (10%)

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) before and periodically during therapy.
Monitor BP (sitting, standing, lying), HR, ECG, and respiratory rate before and frequently during the period of dose adjustment. May cause QT interval prolongation.
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 signs/symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

Monitor CBC and liver function tests periodically 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.
- May cause false-positive pregnancy tests.

Implementation ⬆ ⬇

PO: Initially, take tablets 3 times daily, without regard to food. Dose will ↑ for 1st few days until desired results. Maintenance dose is usually taken in morning.
- When converting to IM doses, PO dose is usually continued in ↓doses for 1st wk.
IM: Inject deep IM preferably into gluteus maximus. Solution is a yellow viscous oil; aspirate before injection to ensure dose is not injected IV. Do not administer solutions that are discolored, hazy, or contain particulate matter. Doses >2 mL should be administered as divided doses between two injection sites.
- For large doses or pain with large volume, flupentixol decanoate 10% (100 mg/mL) solution may be used instead of the 2% (20 mg/mL) solution.

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; abrupt discontinuation may cause withdrawal symptoms (nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, myalgias, paresthesias, insomnia, restlessness, anxiety, agitation, vertigo, feelings of warmth and coldness, tremor). Symptoms begin within 1–4 days of withdrawal and abate within 7–14 days.
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. Advise patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to avoid concurrent use of alcohol and other CNS depressants.
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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇