LARGACTIL

What it is

Largactil is a major tranquilliser. The active ingredient is chlorpromazine hydrochloride, available in tablet strengths of 25 mg or 100 mg, as a syrup containing 5 mg per mL, and as an injection solution containing 50 mg per 2 mL.

Approved indications

— Treatment of acute functional psychosis (e.g. schizophrenia, mania or psychotic depression). — Long-term treatment of schizophrenia. — Short-term treatment of agitation and severe depression. — Severe behavioural disturbances in some children with mental retardation or autism, including the treatment of self-injurious and aggressive behaviour or overactivity. — In the management of terminal illness to enhance the effect of analgesics and to control nausea and vomiting. — Control of intractable hiccough.

Dosing overview

Dosage varies with the individual and the purpose for which the drug is used, with initial dosage being low with increases at frequent, regular intervals until the desired response has been obtained. For adults, a suitable initial oral dose for ambulant patients is 25 mg three times daily increased, if necessary, by 25 mg two or three times daily up to a total of 600–800 mg per day. The usual maintenance doses range from 25 to 100 mg three times daily, but higher doses are sometimes used in bed patients or in psychotic cases. The usual single dose for adults by deep intramuscular injection is 25 to 50 mg and this may be repeated as necessary three to four times in 24 hours. For children over 5 years of age, one third to one half of the appropriate adult dosage may be given; for younger children the oral dose may be calculated on the basis of 0.5 mg/kg bodyweight.

Key safety warnings

Acute withdrawal symptoms, including nausea, vomiting, headache, anxiety, agitation, dyskinesia, dystonia, disturbed temperature regulation, and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics, with relapse and the emergence of extrapyramidal reactions also reported; therefore, gradual withdrawal is advisable. Long-term usage of chlorpromazine can cause the development of tardive dyskinesia, which may be irreversible. Prolonged administration of any phenothiazine may result in tardive dyskinesia, particularly in the elderly and children. A potentially fatal syndrome called neuroleptic malignant syndrome has been reported in association with anti-psychotic drugs, characterised by muscular rigidity, fever, hyperthermia, altered consciousness and autonomic instability (e.g. tachycardia, labile blood pressure, profuse sweating, dyspnoea). It is imperative that treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome. Phenothiazines depress the mechanism for regulation of temperature, with severe hypothermia occurring during swimming in cold water or in patients receiving antipyretic therapy, and heat stroke occurring in hot weather. Agranulocytosis has been reported at an incidence of between 1:1,300 and 1:500,000, with most reported cases occurring between the fourth and tenth week of treatment; patients should be warned to report the sudden appearance of sore throat, fever or other signs of infection. Very rare cases of QT interval prolongation have been reported with chlorpromazine, which may potentiate QT interval prolongation increasing the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal. Severe liver toxicity, sometimes resulting in death, has been reported with chlorpromazine use, and patients or caregivers should be instructed to report immediately signs and symptoms such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a physician.

Contraindications

Largactil should never be used in circulatory collapse. Largactil should never be used in CNS depression, e.g. coma or drug intoxication. Largactil should never be used in hypersensitivity to chlorpromazine, other phenothiazines, or to any of the other ingredients of Largactil. Largactil should never be used in bone marrow depression. Largactil should never be used in phaeochromocytoma. Largactil should never be used in hepatic failure or active hepatic disease. Largactil should never be used in children younger than 1 year, due to a possible association between use of phenothiazine-containing products and Sudden Infant Death Syndrome (SIDS).

PBS listing

Largactil tablets of 25 mg are listed on the PBS as a single restricted item with an ex-manufacturer price of A$4.58. Largactil tablets of 100 mg are listed on the PBS as a single restricted item with an ex-manufacturer price of A$14.03. Largactil oral solution containing 25 mg per 5 mL in 100 mL bottles is listed on the PBS as a single restricted item with an ex-manufacturer price of A$10.65. Largactil injection containing 50 mg in 2 mL is listed on the PBS with two items, one restricted and one unrestricted, with an ex-manufacturer price of A$19.52.

Regulatory history

Largactil was first approved on 21 October 1991. The injection formulation (50 mg/2 mL ampoule) was first listed on the ARTG on 1991-10-21. The tablet formulations (25 mg and 100 mg) were first listed on the ARTG on 1995-04-26. The syrup formulation (5 mg/mL oral liquid) was first listed on the ARTG on 2005-05-02.