Chlorpromazine is a classic antipsychotic medicine used to treat psychotic episodes, severe agitation and severe nausea/vomiting. It is one of the most widely used mental health drugs worldwide for its efficacy and low cost.
Also known as: Largactil, Thorazine
Combining chlorpromazine with midazolam increases the risk of profound sedation, hypotension and respiratory depression.
Additive CNS depression plus inhibition of midazolam metabolism (CYP3A4/2D6) by chlorpromazine.
Level of consciousness, blood pressure and respiratory rate.
Sedation unresponsive to stimuli, slow breathing, hypotension.
Avoid the combination outside monitored settings; reduce the midazolam dose; use only in a clinical setting with airway support.
DailyMed — Thorazine (chlorpromazine) label, CNS depression; EMC-UK — Midazolam SmPC: https://www.medicines.org.uk/emc/product/5682
Combining chlorpromazine with lithium can cause confusion, a lowered seizure threshold and, rarely, encephalopathy.
Lithium lowers the seizure threshold; chlorpromazine may alter neurological response and mask lithium toxicity signs.
Serum lithium, tremor, level of consciousness.
Coarse tremor, confusion, vomiting, ataxia.
Monitor serum lithium and neurological status; consider dose adjustment in combination.
DailyMed — Lithium Carbonate label, antipsychotic interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b839ff4b-f62d-41ab-a823-550a756d58ec
Efavirenz may reduce chlorpromazine levels through enzyme induction, reducing its therapeutic effect.
Efavirenz induces CYP3A4 and CYP2D6, accelerating chlorpromazine metabolism.
Psychotic symptom control, extrapyramidal effects.
Psychotic symptom relapse after starting the antiretroviral.
Monitor clinical response; consider chlorpromazine dose adjustment if efficacy is lost.
DailyMed — Sustiva (efavirenz) label, Drug Interactions (CYP3A4 induction): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
Alcohol potentiates sedation and lowers the seizure threshold with chlorpromazine (Prontuário 10.1 — phenothiazine antipsychotics).
Avoid alcohol during treatment (site monograph).
Prontuário Terapêutico INFARMED, 10.1 (l. 30138 — "besides alcohol … potentiate sedative effects"); site monograph.
Chlorpromazine blocks D2 and worsens Parkinson's extrapyramidal symptoms.
Avoid; if antipsychotic needed, prefer atypicals under supervision.
Prontuário Terapêutico INFARMED (phenothiazines — Parkinson's disease).
Chlorpromazine prolongs QT — contraindicated with pre-existing long QT or with QT-prolonging drugs.
Baseline ECG and at high doses; review all QT prolongers.
Site monograph (chlorpromazine — caution with QT prolongers).
Phenothiazines are not safe in porphyria — risk of acute crisis.
Confirm porphyria diagnosis before prescribing.
Prontuário Terapêutico INFARMED, 10.1 (porphyria — antihistamines/phenothiazines not safe).
Chlorpromazine lowers the seizure threshold — caution in epileptics.
Maintain antiepileptics; monitor for seizures.
Prontuário Terapêutico INFARMED (phenothiazines — seizure threshold).
Phenothiazine with extensive pregnancy experience (nausea, psychosis): no consistent evidence of teratogenicity at usual doses. Risks to monitor in the 3rd trimester/delivery: neonatal depression, jaundice, transient extrapyramidal symptoms in the newborn.
Use only if clearly necessary, at the lowest effective dose; avoid high doses in the 3rd trimester (risk of neonatal symptoms).
Excreted into milk; Annex 2 refers to "Antipsychotics": possible drowsiness and lethargy in the infant (documented pattern for chlorpromazine). Prefer an alternative when breastfeeding; if used, monitor infant sedation.
Prontuário Terapêutico INFARMED — Annex 2 (chlorpromazine, under "Antipsychotics"; l. 42424); Annex 1: no specific entry (historical use in pregnancy nausea). EMC-UK (MHRA) — Chlorpromazine SmPC.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Phenothiazine typical antipsychotic with a broad receptor profile (D2 > alpha-1 ≈ M1 ≈ H1), explaining both efficacy and the side-effect burden; still essential in public health for robustness and cost.
Potent antagonism of mesolimbic/mesocortical D2 receptors (antipsychotic, antiemetic at the vomiting centre) with additive antagonism: alpha-1 (orthostatic hypotension), M1 (dry mouth, mydriasis, retention), H1 (sedation) and 5-HT2. Prolongs QT (hERG blockade) and lowers the seizure threshold.
Variable oral absorption (32–50% first pass; IM doubles exposure); peak 2–4 h (oral) / 15–30 min (IM). High protein binding (> 95%) and large tissue depots — effects persist after stopping.
Hepatic oxidation, N-demethylation and conjugation (CYP2D6 and CYP1A2; polymorphism alters exposure); > 100 metabolites described, mostly inactive. Excretion: urine (metabolites) and bile.
16–30 h (plasma), prolonged in the elderly and liver disease; tissue depots extend the effect (clinical tail for weeks).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
