modafinil (Provigil, Sparlon)
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Introduction
DEA-controlled substance: class 4. (racemic mixture)
Indications
- narcolepsy[8]
- hypersomnia (safe in children 6-15 years)
- somnolence[11]
- fatigue in patients with multiple sclerosis[10]
- depression[3]
- adjunctive therapy for obstructive sleep apnea[5]
- shift-work sleep disorder
Contraindications
- avoid in patients with:
- left ventricular hypertrophy
- ischemic heart disease
- clinically significant mitral valve prolapse
- pregnancy:
- increased risk for congenital malformations when used during 1st trimester[12]
pregnancy category = c/d/x?
Dosage
- narcolepsy: 200 mg PO QAM
- hypersomnolence: 200-300 mg PO QD
- multiple sclerosis: 200 mg PO QAM
Reduce dosage 50% with liver impairment
Pharmacokinetics
- time to peak concentration: 2-4 hours
- absorption not affected by food
- protein binding is 60%
- elimination 1/2life is 7-15 hours
- metabolized in the liver by cyt P450 2C19[3]
- steady-state levels reached after 2-4 days
- allow 1-2 weeks for clinical effect
elimination via liver
1/2life = 7-14 hours
protein binding = 60 %
Adverse effects
- headache
- nausea
- hypersalivation
- nervousness
- anxiety
- insomnia
- euphoria
- skin rash
- serious rash, including Stevens-Johnson syndrome[8]
- rare cases of toxic epidermal necrolysis
- drug rash with eosinophilia & systemic symptoms (rare)[8]
- hypertension (rare)
- tachycardia (rare)
- tolerance & dependence have NOT been reported
- anorexia[7]
- psychiatric symptoms[8]
- hypersensitivity reactions[8]
- angioedema & multi-organ hypersensitivity reactions
Drug interactions
- modafinil inhibits cyt P450 2C19[3]
- may increase levels of drugs metabolized by cyt P450 2C19
- modafinil induces cyt P450 3A4
- may diminish levels of drugs metabolized by cyt P450 3A4
- interactions with antidepressants
Mechanism of action
- unknown
- does NOT bind to adrenergic, dopamine, serotonin, histamine-3, GABA, benzodiazepine or adenosine receptors
- binds to dopamine reuptake site & causes an increase in extracellular dopamine
More general terms
More specific terms
Additional terms
- cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19)
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
References
- ↑ Micromedex
- ↑ Prescriber's Letter 7(7):41 2000
- ↑ 3.0 3.1 3.2 3.3 Prescriber's Letter 8(3):16 2001
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 Journal Watch 22(2):17, 2002 Pack et al, Am J Respir Crit Care Med 164:1675, 2001
- ↑ Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, Arora S, Schwartz JR, Niebler GE, Dinges DF; U.S. Modafinil in Shift Work Sleep Disorder Study Group. Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med. 2005 Aug 4;353(5):476-86. Erratum in: N Engl J Med. 2005 Sep 8;353(10):1078. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16079371
Basner RC. Shift-work sleep disorder--the glass is more than half empty. N Engl J Med. 2005 Aug 4;353(5):519-21. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16079378 - ↑ 7.0 7.1 Prescriber's Letter 13(2): 2006 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220214&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Morgenthaler TI et al, Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007, 30:1705 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18246980
- ↑ FDA MedWatch Updates to the WARNINGS section of the prescribing information http://www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil
Prescriber's Letter 14(12): 2007 Safety Warning with Modafinil Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=231210&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 10.0 10.1 Medical Knowledge Self Assessment Program (MKSAP) 16 American College of Physicians, Philadelphia 2012
- ↑ 11.0 11.1 Deprecated Reference
- ↑ 12.0 12.1 Damkier P, Broe A. First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations. JAMA. 2020;323(4):374-376. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31990303 https://jamanetwork.com/journals/jama/article-abstract/2759460