modafinil

Last edited 02/2020 and last reviewed 11/2020

Modafinil is a stimulant drug unrelated to amphetamines, originally licensed for treating patients with narcolepsy. In the UK, the licensed indications for modafinil have been broadened to include "excessive sleepiness associated with chronic pathological conditions, including narcolepsy, obstructive sleep apnoea/hypopnoea syndrome and moderate to severe chronic shift work sleep disorder" (1)

• the drug's mode of action is not known
• there is no evidence of dependency or tolerance with short-term use
• side-effects include headache and dry mouth which are usually transient
• modafinil does not reduce symptoms of cataplexy
• modafinil is contraindicated in patients with moderate to severe hypertension
• modafinil increases the metabolism of oral contraceptives, so the summary of product characteristics recommends the use of an oral contraceptive containing at least 50µg of ethinylestradiol, or alternative or concomitant contraceptives (1)

A review (1) concerning managing excessive sleepiness in adults concluded ".. licensed indications for modafinil have recently been extended to encompass excessive sleepiness associated with any chronic disease (including so-called "shift work sleep disorder"). However, there is little published evidence to justify such indiscriminate use. Of particular concern is the 'medicalisation' of sleepiness associated with shift work..."

Modafinil has been discouraged during pregnancy because of a lack of safety data. In June 2019, the manufacturer alerted health care professionals that an interim analysis of postmarketing surveillance data detected major malformations among 15% of children exposed to modafinil during pregnancy compared with 3% in the background population (2)

• Danish Health Registry analysis (49 pregnancies exposed to modafinil and 828,644 unexposed) found that modafinil was associated with significantly more congenital defects than no exposure (OR 3.4, 95% CI 1.5-7.4), or methylphenidate exposure (3.0, 1.2-7.4)

The summary of product characteristics must be consulted before prescribing this drug.

Reference:

1. Drug and Therapeutics Bulletin 2004; 42(7):52-6.
2. NICE (January 29th 2020). Medicines Awareness Service: Daily. First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations