Chemical formula: C₁₅H₁₅NO₂S Molecular mass: 273.35 g/mol PubChem compound: 4236
Modafinil interacts in the following cases:
Results from clinical interaction studies suggest that the largest effects may be on substrates of CYP3A4/5 that undergo significant presystemic elimination, particularly via CYP3A enzymes in the gastrointestinal tract. Examples include ciclosporin, HIV-protease inhibitors, buspirone, triazolam, midazolam and most of the calcium channel blockers and statins. In a case report, a 50% reduction in ciclosporin concentration was observed in a patient receiving ciclosporin in whom concurrent treatment with modafinil was initiated.
A number of tricyclic antidepressants and selective serotonin reuptake inhibitors are largely metabolised by CYP2D6. In patients deficient in CYP2D6 (approximately 10% of a Caucasian population) a normally ancillary metabolic pathway involving CYP2C19 becomes more important. As modafinil may inhibit CYP2C19, lower doses of antidepressants may be required in such patients.
The effectiveness of steroidal contraceptives may be impaired due to induction of CYP3A4/5 by modafinil. Alternative or concomitant methods of contraception are recommended for patients treated with modafinil. Adequate contraception will require continuation of these methods for two months after stopping modafinil.
Co-administration of potent inducers of CYP activity, such as carbamazepine and phenobarbital, could reduce the plasma levels of modafinil.
Substances that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol and omeprazole may have reduced clearance upon co-administration of modafinil and may thus require dosage reduction.
Due to a possible inhibition of CYP2C19 by modafinil and suppression of CYP2C9 the clearance of phenytoin may be decreased when modafinil is administered concomitantly. Patients should be monitored for signs of phenytoin toxicity, and repeated measurements of phenytoin plasma levels may be appropriate upon initiation or discontinuation of treatment with modafinil.
Due to possible suppression of CYP2C9 by modafinil the clearance of warfarin may be decreased when modafinil is administered concomitantly. Prothrombin times should be monitored regularly during the first 2 months of modafinil use and after changes in modafinil dosage.
Modafinil is associated with the onset or worsening of anxiety. Patients with major anxiety should only receive treatment with modafinil in a specialist unit.
Modafinil is associated with the onset or worsening of psychotic symptoms or manic symptoms (including hallucinations, delusions, agitation or mania). Patients treated with modafinil should be carefully monitored for the appearance or worsening of psychotic or manic symptoms. If psychotic or manic symptoms occur, discontinuation of modafinil may be required.
There is limited amount of data from the use of modafinil in pregnant women.
Studies in animals have shown reproductive toxicity.
Modafinil is not recommended for use during pregnancy and in women of childbearing potential not using effective contraception. As modafinil may reduce the effectiveness of oral contraception alternative additional methods of contraception are required.
Available pharmacodynamic/toxicological data in animals have shown excretion of modafinil/metabolites in milk.
Modafinil should not be used during breast feeding.
No data on fertility are available.
Patients with abnormal levels of sleepiness who take modafinil should be advised that their level of wakefulness may not return to normal. Patients with excessive sleepiness, including those taking modafinil should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity. Undesirable effects such as blurred vision or dizziness might also affect ability to drive.
The following adverse reactions have been reported in clinical trials and/or post-marketing experience. The frequency of adverse reactions considered at least possibly related to treatment, in clinical trials involving 1561 patients taking modafinil were as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to ≤1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be estimated from the available data).
The most commonly reported adverse drug reaction is headache, affecting approximately 21% of patients. This is usually mild or moderate, dose-dependent and disappears within a few days.
Uncommon: pharyngitis, sinusitis
Uncommon: eosinophilia, leucopenia
Uncommon: minor allergic reaction (e.g. hayfever symptoms)
Not known: Angioedema, urticaria (hives). Hypersensitivity reactions (characterised by features such as fever, rash, lymphadenopathy and evidence of other concurrent organ involvement), anaphylaxis
Common: decreased appetite
Uncommon: hypercholesterolaemia, hyperglycaemia, diabetes mellitus, increased appetite
Common: nervousness, insomnia, anxiety, depression, abnormal thinking, confusion, irritability
Uncommon: sleep disorder, emotional lability, decreased libido, hostility, depersonalisation, personality disorder, abnormal dreams, agitation, aggression, suicidal ideation, psychomotor hyperactivity
Rare: hallucinations, mania, psychosis
Not known: delusions
Very common: headache
Common: dizziness, somnolence, paraesthesia
Uncommon: dyskinesia, hypertonia, hyperkinesia, amnesia, migraine, tremor, vertigo, CNS stimulation, hypoaesthesia, incoordination, movement disorder, speech disorder, taste perversion
Common: blurred vision
Uncommon: abnormal vision, dry eye
Common: tachycardia, palpitation
Uncommon: extrasystoles, arrhythmia, bradycardia
Common: vasodilatation
Uncommon: hypertension, hypotension
Uncommon: dyspnoea, increased cough, asthma, epistaxis, rhinitis
Common: abdominal pain, nausea, dry mouth, diarrhoea, dyspepsia, constipation
Uncommon: flatulence, reflux, vomiting, dysphagia, glossitis, mouth ulcers
Uncommon: sweating, rash, acne, pruritus
Not known: serious skin reactions, including erythema multiforme, Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS).
Uncommon: back pain, neck pain, myalgia, myasthenia, leg cramps, arthralgia, twitch
Uncommon: abnormal urine, urinary frequency
Uncommon: menstrual disorder
Common: asthenia, chest pain
Uncommon: peripheral oedema, thirst
Common: abnormal liver function tests, dose related increases in alkaline phosphatase and gamma glutamyl transferase have been observed.
Uncommon: abnormal ECG, weight increase, weight decrease
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