Tricyclic antidepressant Pregnancy: Safety in pregnancy has not been established and there is evidence of harmful effects in animals at high doses; administration in pregnancy and during breast-feeding is not advised unless there are compelling medical reasons. Withdrawal symptoms, respiratory depression and agitation have been reported in neonates whose mothers took tricyclic antidepressants during the last trimester. Lofepramine is excreted in breast milk. (SPC 4.6)

Lofepramine

Brand names: Gamanil, Lomont

Lofepramine is a tricyclic antidepressant used in the treatment of depression, generally regarded as having a more favourable side-effect and toxicity profile than older tricyclics.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: The usual dose is 70 mg twice daily (140 mg daily) or three times daily (210 mg daily), depending upon patient response

Route: Oral

Frequency: Twice or three times daily

No separate maximum dose is stated in the SPC beyond the 70 mg three times daily (210 mg daily) regimen. Elderly: elderly patients may respond to lower doses in some cases. Paediatric population: not recommended. eMC SPC section 4.2.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to lofepramine, dibenzazepines, or any of the excipients
Mania
Severe liver impairment and/or severe renal impairment
Heart block or cardiac arrhythmias
The recovery phase following a myocardial infarction
Untreated narrow angle glaucoma
Prostatic hypertrophy with urinary retention; patients at risk of paralytic ileus
Acute alcoholic, hypnotic, analgesic and psychotropic drug poisoning, and acute deliria
With or within 2 weeks of cessation of therapy with monoamine oxidase inhibitors

Side effects

Antimuscarinic and gastrointestinal - dry mouth, constipation, nausea, vomiting, diarrhoea; urinary hesitancy and retention
Cardiac - tachycardia, cardiac conduction disorders, QT prolongation, arrhythmias including ventricular arrhythmias or torsades de pointes; increase in cardiac insufficiency; hypotension
Nervous system - dizziness, headache, paraesthesia, tremor; rarely drowsiness, convulsions and taste impairment
Visual disturbances including blurred vision, mydriasis and disturbance of accommodation; induction of glaucoma
Psychiatric - sleep disturbance, agitation, confusion, nightmares, hallucinations, hypomania, mania, psychoses, delirium; suicidal ideation and behaviour reported during therapy or early after discontinuation
Hepatobiliary - increases in liver enzymes, sometimes progressing to clinical hepatitis and jaundice, usually within the first 3 months; rarely bone marrow depression and SIADH with hyponatraemia

Interactions

Monoamine oxidase inhibitors - must not be given with or within 2 weeks of stopping an MAOI (SPC 4.3)
Amiodarone - concomitant use should be avoided (SPC 4.3)
Terfenadine - concomitant use should be avoided (SPC 4.3)
Thyroid preparations / hyperthyroidism - caution, as aggravation of unwanted cardiac effects may occur (SPC 4.4)
Alcohol withdrawal or withdrawal of other drugs with anticonvulsant properties - lofepramine may lower the convulsion threshold; use with extreme caution (SPC 4.4)

Clinical monograph

How it works

It inhibits the reuptake of noradrenaline and serotonin and is metabolised partly to desipramine, increasing monoamine availability at synapses.

Prescribing in practice

Although less toxic in overdose than some older tricyclics, it can still cause antimuscarinic and cardiac effects and should be used with caution in cardiovascular disease.
It has been associated with abnormal liver function tests, so caution is advised in hepatic impairment.
Use with caution in the elderly and in those at risk of urinary retention or angle-closure glaucoma.

Monitoring

Monitor mood and suicidal ideation, antimuscarinic and cardiovascular effects, and liver function where clinically indicated.

Counselling the patient

Explain that antidepressant benefit may take several weeks to develop.
Do not stop the medicine suddenly because of withdrawal effects.
Report worsening mood, suicidal thoughts or difficulty passing urine.

Evidence & guidelines

Lofepramine is an established tricyclic antidepressant available in the UK and is recognised as relatively safer in overdose than older agents in current prescribing references.

Reference: NICE NG222; Maudsley; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

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