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Wakefulness-Promoting Agent (Narcolepsy / OSAHS / Shift Work) Pregnancy: Avoid — insufficient safety data. Animal studies show skeletal abnormalities. CYP3A4 induction reduces hormonal contraception efficacy — particular concern. Use effective non-hormonal contraception during treatment.

Modafinil

Brand names: Provigil

Adult dose

Dose: 200 mg once daily in the morning. Range: 200–400 mg/day
Route: Oral
Frequency: Once daily (morning for narcolepsy/OSAHS; 1 hour before work shift for shift work)
Max: 400 mg/day
Narcolepsy: 200–400 mg daily (morning or split 200 mg morning + 200 mg noon). OSAHS (adjunct to CPAP): 200 mg once daily. Shift Work Sleep Disorder (SWSD): 200 mg 1 hour before night shift. Schedule 4 (Part 1) Controlled Drug — prescription requirements apply. Source: BNF 90; NICE TA212.

Paediatric dose

Dose: Not licensed under 18 years in UK for narcolepsy. Off-label use possible under specialist guidance N/A/kg
Route: Oral
Frequency: Once daily
Max: N/A
Not licensed for paediatric narcolepsy in UK (unlike some countries). Specialist use only under strict supervision. Source: BNF for Children 2024.

Dose adjustments

Renal

Severe renal impairment: reduce dose to 100 mg daily — reduced clearance of modafinil acid metabolite.

Hepatic

Severe hepatic impairment: reduce dose to 100 mg daily — significantly increased modafinil exposure.

Paediatric weight-based calculator

Not licensed for paediatric narcolepsy in UK (unlike some countries). Specialist use only under strict supervision. Source: BNF for Children 2024.

Clinical pearls

  • MHRA 2007 SJS warning — the critical safety alert: rash within the first 3 months of modafinil treatment — even a mild rash — must be treated with urgency. Stop modafinil immediately if rash develops. SJS and TEN have been reported. MHRA restricts use to narcolepsy, OSAHS, and SWSD — off-label use for cognitive enhancement or fatigue states (MS, cancer) is outside the licence.
  • Mechanism — not amphetamine: modafinil inhibits dopamine reuptake transporter (DAT) selectively in the hypothalamic wake-promoting centre (tuberomammillary nucleus). Does not cause the generalised catecholamine surge of amphetamines. Wakefulness without euphoria or significant CV stimulation — explains lower abuse potential. Orexin system is partially involved.
  • Contraceptive interaction — commonly missed: CYP3A4 induction lowers ethinylestradiol levels by 20–30%. All women on combined OCP must use additional contraceptive (barrier method) during modafinil AND for 2 months after stopping. Document this counselling. Progestogen-only pills may also be affected — recommend non-hormonal contraception.
  • OSAHS use — adjunct only: modafinil does not treat the underlying apnoea — CPAP remains the primary treatment. Modafinil is for residual excessive daytime sleepiness in patients who are CPAP-compliant but still sleepy. It is not a substitute for CPAP. NICE TA212 approved for this indication.
  • Narcolepsy with cataplexy — sodium oxybate is preferred: for narcolepsy with prominent cataplexy, sodium oxybate (Xyrem) is more effective than modafinil as it treats both cataplexy and EDS. Modafinil does not treat cataplexy. Combined use is an option for EDS on sodium oxybate background. Source: BNF 90; NICE TA212; MHRA Drug Safety Update 2007 (SJS/TEN).

Contraindications

  • History of hypersensitivity reactions including SJS (MHRA 2007 warning — rare but serious SJS/TEN reported with modafinil)
  • Uncontrolled hypertension or cardiac arrhythmia
  • History of left ventricular hypertrophy or mitral valve prolapse with CNS stimulants

Side effects

  • Headache (most common — 15–35%)
  • Nausea, dry mouth, anorexia
  • Insomnia (take in the morning — avoid doses after noon)
  • Hypertension, tachycardia (mild sympathomimetic effect)
  • Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (rare — MHRA 2007 safety alert: rash within first 3 months; stop immediately if severe rash develops)
  • Psychiatric symptoms (anxiety, agitation, hallucinations — especially at higher doses or with bipolar disorder)
  • Dependence potential (Schedule 4 Part 1 — lower than amphetamines but not zero)

Interactions

  • Combined oral contraceptives (oestrogen-containing): modafinil is a CYP3A4 inducer — reduces contraceptive efficacy. MHRA requires additional contraceptive method during treatment and for 2 months after stopping
  • Warfarin: modafinil inhibits CYP2C9 — may increase INR; monitor closely
  • Ciclosporin: CYP3A4 induction reduces ciclosporin levels — monitor trough levels
  • Phenytoin, carbamazepine: reduced levels due to CYP induction — monitor levels
  • MAO inhibitors: additive sympathomimetic effects — avoid

Monitoring

  • Blood pressure and heart rate at baseline and after dose changes
  • Skin surveillance (rash monitoring — first 3 months: monthly review or sooner if any rash)
  • Sleep diary and Epworth Sleepiness Scale (ESS) at 4 weeks and 3 months
  • Psychiatric symptoms (anxiety, mood changes — especially in bipolar disorder)
  • Contraceptive method (document additional contraception in women on hormonal contraception)

Reference: BNFc; BNF 90; NICE TA212 (modafinil for OSAHS); MHRA Drug Safety Update 2007 (SJS); MHRA SPC Provigil. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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