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;
Concurrent use of other drugs known to prolong QT interval;
Pedi: Safety and effectiveness not established; not recommended.

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 hypokalmia, hypomagnesemia, genetic predisposition, cardiovascular disease history (including bradycardia), recent MI, HF, or arrhythmias;
Known/suspected glaucoma;
History of seizures (may ↓ seizure threshold);
Parkinson's disease (may worsen symptoms);
Geri: Consider age-related in renal, cardiac, and hepatic function;
OB: Use only if expected benefit outweighs potential risks to infant;
Lactation: Safe use not established; low levels in breast milk are not expected to affect infant if therapeutic doses are used.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: dizziness, NEUROLEPTIC MALIGNANT SYNDROME

EENT: blurred vision

CV: extrapyramidal symptoms, tachycardia, hypotension, QT INTERVAL PROLONGATION, sedation, tardive dyskinesia, THROMBOEMBOLISM

GI: constipation, dry mouth, excess salivation, hepatotoxicity

GU: ↓libido, urinary retention

Derm: photosensitivity reactions, rash, sweating

Endo: glucose intolerance, hyperprolactinemia, menstrual irregularity

Hemat: agranulocytosis, granulocytopenia, neutropenia

Metab: weight change

MS: osteoporosis (long term use)

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 (including quinidine, amiodarone, and sotalol), some antipsychotics (including thioridazine), some macrolides (including erythromycin), and some fluoroquinolones (including moxifloxacin); concurrent use should be avoided.
Concurrent use of diuretics and other drugs affecting electrolytes may ↑ risk of QT interval prolongation and serious arrhythmias.
↑risk of anticholinergic adverse reactions, including paralytic ileus when used concurrently with other anticholinergics or drugs with anticholinergic side effects.
May ↓ metabolism and ↑ effects 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 may be ↓.
IM (Adults ): Initiate with a 5–20 mg test dose (use 5 mg dose in elderly/frail/cachectic patients) as 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 decreased in the first wk following depot injection. Guidelines for conversion from PO to depot IM injection: daily oral dose (mg) × 4 = dose of depot injection (mg) given every 2 wk or daily oral dose (mg) × 8 = depot injection (mg) given every 4 wk.

Availability ⬆ ⬇

Tablets (flupentixol dihydrochloride): 0.5 mg; 3 mg; 5 mg
Depot 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), ECG, pulse, and respiratory rate before and frequently during the period of dose adjustment. May cause QT 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. 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 periodically 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.
- May cause false-positive pregnancy tests.

Implementation ⬆ ⬇

PO: Initially, take tablets 3 times daily, without regard to food. Dose will increase for first few days until desired results. Maintenance dose is usually taken in morning.
- When converting to IM doses, PO dose is usually continued in decreasing doses for first wk.
IM: Inject deep IM preferably into gluteus maximus. Solution is a yellow viscous oil, aspirate prior to injection to ensure dose is not injected IV. Do not administer solutions that are discolored, hazy, or contain particulate matter.
- For large doses or pain with large volume, flupentizol decanoate BP 10% (100 mg/mL) may be used instead of flupentixol decanoate BP 2% (20 mg/mL).

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; abrupt discontinuation may cause withdrawal symptoms (nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, myalgias, paraesthesias, insomnia, restlessness, anxiety, agitation, vertigo, feelings of warmth and coldness, tremor). Symptoms begin within 1 to 4 days of withdrawal and abate within 7 to 14 days. Advise patient to read Patient Information leaflet prior to starting therapy and with each Rx refill in case of changes.
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.
Caution patient to avoid concurrent use of alcohol and other CNS depressants.
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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇