Dose and Administration

Neonatal Abstinence Syndrome

1. 2.2-3mg/kg/24 hours (given in divided doses every 6 hours) PO or IM  ¹.
2. Use full dosage for 2-4 days. Reduce dosage by approximately 20% every 2-3 days according to neonatal abstinence score sheet, if clinical condition permits ².

Indications

1. Neonatal abstinence syndrome. Used as a second line drug or alternative to morphine. Indications for starting treatment are according to the neonatal abstinence clinical score sheet.
2. In terminal care situations where sedation is needed and secretions are a problem.

Contraindications & Precautions

1. Contraindicated in pre-existing CNS depression ³.
2. Use with caution, or not at all, with impaired liver, kidney, cardiovascular, cerebrovascular and respiratory function.
3. Use cautiously with hypothyroidism, acute infections, jaundice and leucopenia ^3,4.

Clinical Pharmacology

Chlorpromazine is a phenothiazine neuroleptic (antipsychotic) agent ³. It inhibits dopamine, has strong sedative effects to which tolerance may develop rapidly, strong anticholinergic, antiemetic and adrenergic blocking activity, moderate extrapyramidal effects and weak ganglionic block, antihistaminic and antiserotonergic activity ^{3, 6}. Chlorpromazine has been used in neonatal opioid abstinence syndrome for sedation and to reduce irritability, tremors and gastrointestinal symptoms ^1,7. Its sedative effect is prompt and effective.

After oral administration it is readily, but erratically absorbed. Extensive metabolism occurs in the gut wall and during the first-pass through the liver, hence peak plasma concentrations are much lower following oral administration than IM.

There may be some enterohepatic recycling. The metabolic pathways are hydroxylation and conjugation with glucuronic acid, N-oxidation, oxidation of a sulphur atom, and dealkylation ^3,6. (The adult half life = 30 hours). Plasma protein binding is 95-98% (primarily to albumin). There is wide distribution into body tissues and fluids. After crossing the blood/brain barrier concentrations achieved in the brain are higher than those in plasma. Excretion of active and inactive metabolites occurs in the urine and the bile-elimination of metabolites may be prolonged. Elimination (adults) is biphasic with a rapid initial phase and a prolonged secondary phase; elimination rate from the brain is unknown ^{3, 6, 8}.

Possible Adverse Effects

1. Pain and irritation at site of injection ³.
2. Sedation (tolerance develops rapidly), convulsions (rarely).
3. Tachycardia ECG changes, hypotension, cardiac arrhythmias.
4. Haemolytic anaemia, aplastic anaemia, agranulocytosis, mild leucopenia (high dose, long term).
5. Gastro-intestinal: Constipation
6. Jaundice: photosensitisation.
7. Hyperglycaemia.
8. Hypo/hyperthermia.
9. Extra pyramidal effects.
10. Possible suppression of cough and gag reflex.
11. Skin sensitisation and rashes ^3,4.

Special Considerations & Drug Interactions

1. CNS depressant effect may be enhanced with other CNS depressant drugs, e.g. sedatives, opiates ³. Infants should be monitored for apnoea.
2. Avoid abrupt withdrawal of the drug ⁴.
3. Largactil injection contains sodium sulphate which may cause an allergic reaction, e.g., anaphylaxis and/or asthmatic episodes in susceptible patients ⁶.
4. Largactil Forte Suspension contains the additives sodium benzoate, sorbitol (adverse effect = diarrhoea), propylene glycol and povidone K30.
5. Chlorpromazine may cause severe contact dermatitis in sensitised personnel. Nursing staff should avoid skin contact with the drug at administration times ^{3, 4, 6}.