Names and pronunciation
(pi-tol′i-sant) Wakix
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Drug reference
(pi-tol′i-sant) Wakix
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Func. class.: Narcolepsy agent
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Chem. class.: Histamine receptor modulator
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ACTION: Selective antagonist/inverse agonist of the histamine-3 (H3) receptor; activation of histaminergic neurons increases histamine release, which promotes wakefulness, attention, and memory; regulates the release of other neurotransmitters involved in wake promotion, including dopamine, noradrenaline, and acetylcholine
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USES: Excessive daytime sleepiness in adults with narcolepsy
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CONTRAINDICATIONS Hypersensitivity, severe hepatic disease P PRECAUTIONS Alcoholism, bradycardia, CAD, cardiac disease, children, breastfeeding, contra- ception requirement, diabetes mellitus, females, geriatrics, heart failure, hepatic disease, hypertension, hypocalcemia, hy- pokalemia, hypomagnesemia, long QT syndrome, MI, malnutrition, poor me- tabolizers, pregnancy, QT prolongation, renal disease, thyroid disease
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SIDE EFFECTS CNS: Headache, insomnia, anxiety, hallucinations, irritability, cataplexy GI: Nausea, abdominal pain, anorexia, dry mouth INTEG: Rash RESP: URI MS: MS pain CV: Increased heart rate
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INTERACTIONS Increased: cardiac dysrhythmia risk— drugs that prolong the QT interval (class Ia, III antidysrhythmics); avoid using together Increased: pitolisant effect—CYP2D6 inhibitors (buPROPion, PARoxetine, FLUoxetine); reduce dose by half Decreased: pitoisant effect—CYP3A4 inducers (carBAMazepine, phenytoin, rifAMPin); increase dose to double Decreased: pitolisant effect—hista- mine-1 receptor antagonists (diphenhy drAMINE, imipramine, clomiPRAMINE); avoid using together Decreased: CYP3A4 substrates (mid- azolam, hormonal contraceptives, cyclo- SPORINE)—use alterative contraception
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DOSAGE AND ROUTES • Adults PO Initially, 8.9 mg daily in the morning on awakening for 1 wk; then in- crease to 17.8 mg daily for 1 wk; after that, the dose may be adjusted based on effi- cacy response and tolerability; max: 35.6 mg/day; limit to 17.8 mg/day in CYP2D6 poor metabolizers; up to 8 wks may be necessary
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Available forms: Tablets 4.45, 17.8 mg
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Administer: • Give each dose in the morning on patient wakening
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Assess: • Narcolepsy: assess for trouble staying awake baseline and after 1 wk, 2 wk • Hepatic/renal disease: monitor LFTs, serum bilirubin, BUN, creatinine baseline and periodically
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Evaluate: • Therapeutic response: ability to stay awake
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • If a dose is missed, skip the missed dose and administer the next dose the following day in the morning on wakening • Report to healthcare provider if inabil- ity to stay awake continues • Pregnancy/breastfeeding: identify if pregnancy is planned to suspected; if using hormonal contraceptives, an alter- native method should be used during and for 21 days after last dose; do not use in pregnancy; encourage to enroll in the WAKIX pregnancy registry if patient be- comes pregnant; to enroll or obtain infor- mation from the registry, call 1-800-833- 7460; present in breast milk
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PHARMACOKINETICS Protein binding is 91%-96%, metabolized by CYP2D6 and to a lesser extent by CYP3A4; inactive metabolites are further metabolized or conjugated with glycine or glucuronic acid, excreted 90% urine (<2% unchanged), 2.3% feces; half-life 7.5-24.2 hours, absorption 90%; peak 2-5 hr; increased in hepatic/renal disease
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• Adults PO Initially, 8.9 mg daily in the morning on awakening for 1 wk; then in- crease to 17.8 mg daily for 1 wk; after that, the dose may be adjusted based on effi- cacy response and tolerability; max: 35.6 mg/day; limit to 17.8 mg/day in CYP2D6 poor metabolizers; up to 8 wks may be necessary
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