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Modafinil (Provigil)
by Erowid
Listed below are some of the known interactions between Modafinil and other chemicals, plants or pharmaceutical medications. This is not a comprehensive list.

Birth Control Pills
Decreased Effectiveness The prescribing information for Modafinil products clearly states there is an interaction with hormonal contraceptives, but provides no information about how this is known. The mechanism is that Modafinil upregulates (increases effectiveness of) the enzyme CYP3A4/5, which is involved in the metabolism of the contraceptive hormones and thus breaks them down more quickly. We have only been able to find a single paper that looked at the issue in humans and it showed that daily 400 mg doses of Modafinil for a month significantly reduced the levels of the hormone estradiol and norgestimate in the 16 women studied. There is no direct research showing actual increases in impregnation rates and it is unclear whether less frequent or lower doses of Modafinil would have clinically significant effects on hormonal birth control. Some physicians have recommended increased doses of birth control as a solution. anxiety, shivering, tremor, serotonin syndrome Tentative
Case Report
Robertson 2002
Robertson 2000
Opiates/Methadone Decreased Effectiveness Methadone is metabolized by several liver enzymes in the CYP2* cluster, with CYP3A4 being an important metabolizer. Because modafinil up-regulates CYP1A2, CYP2B6, and CYP3A4/5, the action of methadone may be substantially shortened. Erowid also received one experience report from a reported methadone user who found that they had to redose with methadone every few hours to avoid opiate-withdrawal after taking large doses (> 1000 mg) of modafinil. anxiety, shivering, tremor, serotonin syndrome Tentative Wang 2003
Erowid 2004
If you have a positive or negative drug interaction to report, please let us know! Submit an interaction.
Erowid's interactions information is a summary of data gathered from first hand reports, research, and other resources. This page is intended to collect drug-drug and biology-drug interactions and is not exhaustive: other dangerous or medically important interactions may exist that are not listed here. Drug effects may vary dramatically from one person to another and from one experience to another based on a variety of factors such as body chemistry, age, gender, physical health, dose, and form of material.

  1. Anonymous. Experience 34028: Quick Sickness. Erowid Experience Vaults. 2004.
  2. Robertson P, Hellriegel ET, Arora S, Nelson M. Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002;71(1):46-56.
  3. Robertson P, DeCory HH, Madan A, Parkinson A. In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000;28(6):664-71.
  4. Wang JS, DeVane CL. Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Drug Metab Dispos. 2003;31(6):742-7.