Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
100 mg tablets
Approved indication: narcolepsy
Australian Medicines Handbook section 16.8.3
In addition to disturbing sleep, narcolepsy is associated with excessive sleepiness during the day. A multiple sleep latency test can help to confirm the diagnosis.1 Treatment of daytime sleepiness may require the use of psychostimulants. Modafinil now offers an alternative to dexamphetamine and methylphenidate.
The mechanism of action of modafinil is unclear. It does not bind with receptors for noradrenaline, dopamine or serotonin.
Patients take a single dose in the mornings. This is rapidly absorbed with the peak plasma concentration being achieved within four hours. Modafinil is eliminated mainly by metabolism, with most of the metabolites being excreted in the urine. Cytochrome P450 3A4 may be involved in the metabolism so there is a potential for interactions with inducers and inhibitors of this enzyme. Modafinil may also induce its own metabolism.
Two clinical trials compared different doses (200 mg and 400 mg) of modafinil with placebo.2,3 Several tests such as the Epworth sleepiness scale1 were used to assess the outcomes. Both doses of modafinil improved the patients' symptoms, but not all of the changes were significantly greater than placebo.3
During these trials approximately 5% of patients withdrew because of adverse effects. Common adverse reactions while taking modafinil included headache, nausea and nervousness. Like other stimulants, modafinil has some euphoric effects so there is the possibility that it could be abused.
While the 400 mg dose is well tolerated it has no significant advantage over the 200 mg dose. Approximately 60% of patients will improve with 200 mg daily (38% of patients will improve with a placebo). Some of the significant improvements may be of questionable clinical relevance. For example, patients can stay awake for five minutes if they are taking a placebo and for eight minutes if they are taking modafinil. Continuous treatment may result in reduced plasma concentrations of modafinil when it induces it own metabolism. As the double-blind clinical trials only lasted for nine weeks it is not known if modafinil is effective in long-term treatment of narcolepsy. It has no role in patients complaining of a general tiredness or lack of energy.
- Southcott AM. Sleep studies. Aust Prescr 1998;21:40-3.
- US Modafinil in Narcolepsy Multi center Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43:88-97.
- US Modafinil in Narcolepsy Multi center Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000;54:1166-75.