Amitriptyline Hydrochloride

Source: UK SPC (eMC) for Amitriptyline 10 mg Film-Coated Tablets, §4.2 (https://www.medicines.org.uk/emc/product/10849/smpc). Not all dosage schemes can be achieved with all pharmaceutical forms/strengths — select the appropriate formulation/strength for the starting dose and subsequent increments. DEPRESSION: dosage should be initiated at a low level and increased gradually, noting clinical response and any evidence of intolerability. Elderly patients over 65 years and patients with cardiovascular disease — initially 10 mg to 25 mg daily, which may be increased up to 100 mg to 150 mg divided into two doses depending on individual response and tolerability; doses above 100 mg should be used with caution. The antidepressant effect usually sets in after 2 to 4 weeks and treatment must be continued for an appropriate length of time, usually up to 6 months after recovery, to prevent relapse. NEUROPATHIC PAIN, PROPHYLAXIS OF CHRONIC TENSION-TYPE HEADACHE AND MIGRAINE PROPHYLAXIS: patients should be individually titrated; recommended doses are 25 mg to 75 mg daily in the evening; the initial dose should be 10 mg to 25 mg in the evening, increased by 10 mg to 25 mg every 3 to 7 days as tolerated; the dose can be taken once daily or divided into two doses; the analgesic effect is normally seen after 2 to 4 weeks. Elderly over 65 and patients with cardiovascular disease — a starting dose of 10 mg to 25 mg in the evening is recommended. HEPATIC IMPAIRMENT: careful dosing and, if possible, a serum level determination is advisable. CYP2D6: consider a lower dose of amitriptyline if a strong CYP2D6 inhibitor (e.g. bupropion, quinidine, fluoxetine, paroxetine) is added; known poor metabolisers of CYP2D6 or CYP2C19 may have higher plasma concentrations of amitriptyline and nortriptyline — consider a 50% reduction of the recommended starting dose. DISCONTINUATION: when stopping therapy the drug should be gradually withdrawn over several weeks. PAEDIATRIC (not a per-kg dose, so not expressed as mg/kg): amitriptyline should NOT be used in children and adolescents aged less than 18 years for depression, neuropathic pain or headache prophylaxis, as safety and efficacy have not been established; it is contraindicated in children under 6 years of age. For NOCTURNAL ENURESIS the SPC gives children aged 6 to 10 years 10 mg to 20 mg (a suitable dosage form should be used for this age group) and children aged 11 years and above 25 mg to 50 mg daily, increased gradually, administered 1-1½ hours before bedtime; an ECG should be performed prior to initiating therapy to exclude long QT syndrome; the maximum treatment course should not exceed 3 months, with medical review every 3 months if repeated courses are needed. Verify any under-18 use against a children's formulary. §4.5 was not retrieved in this bundle — the interactions below come from §4.2, §4.3 and §4.4; verify the full §4.5.