Drug Topics - February 2009 - (Page 44)

Continuing Education NEW MOLECULAR ENTITIES & BIOLOGICS After oral administration, systemic exposure is decreased by about 50 percent when etravirine is taken in the fasting state; therefore, it should always be taken after a meal. Ertravirine is primarily metabolized by CYP3A4, CYP2C9, and CYP2C19. Precautions: While rashes observed in clinical trials were typically mild to moderate and self-resolving, severe and potentially life-threatening skin reactions have occurred on rare occasions. In this case, immediate discontinuation of treatment is required. Both fat redistribution and immune reconstitution syndrome can occur. Drug interactions: Etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19; therefore, inducers/inhibitors of these enzymes can be expected to alter etravirine concentrations. Ertravirine is an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19; alteration in concentrations of drugs metabolized via these pathways can be expected. Etravirine should not be administered with PIs without low-dose ritonavir (i.e., unboosted PIs) because of signiﬁcant alterations in PI concentrations. Concomitant etravirine and boosted tipranivir, fosamprenavir, or atazanavir therapy should be avoided due to signiﬁcant alterations in PI and/or etravirine concentrations. Adverse effects: The most common adverse events (incidence > 10 percent) of any intensity occurring at a higher rate than placebo were rash and nausea. Dosage and availability: The recommended dose of etravirine is 200 mg taken twice daily after a meal. The tablet may be dispersed in a glass of water if the patient is unable to swallow. Patient counseling: Inform patients that etravirine helps to control HIV infection. Reinforce the importance of using this drug in combination with other anti-HIV medications. Review the patient’s medication proﬁle and look for drug-drug interactions. Ask patients about any non-prescription medications, vitamins, and herbal supplements they are taking, including St. John’s wort. Instruct patients to take etravirine following a meal. Advise patients to read the patient package insert. Be available for questions. FESOTERODINE (Toviaz, Pﬁzer). FDA Rating: 1-S,T. Fesoterodine is a new muscarinic receptor antagonist that provides another treatment option for overactive bladder. Indications: Fesoterodine is indicated for the treatment of overactive bladder with symptoms of urinary incontinence, urinary urgency, and urinary frequency. Pharmacology and pharmacokinetics: Fesoterodine is a competitive muscarinic receptor antagonist. Muscarinic receptors play a role in the contraction of urinary bladder smooth muscle. Following oral administration, rapid metabolism by hydrolysis produces the active drug metabolite, 5-hydroxymethyl tolterodine. This metabolite is responsible for the antimuscarinic activity of fesoterodine. Fesoterodine is well absorbed following oral administration, with maximum concentrations reached after approximately 5 hours. No accumulation occurs after multiple doses are administered. Five-hydroxymethyl tolterodine is further metabolized in the liver into two inactive metabolites via the CYP2D6 and CYP3A4 pathways. The terminal half-life of the active metabolite is approximately 7 hours. Precautions: Fesoterodine is classiﬁed as a pregnancy category C medication. Contraindications include patients with urinary retention, gastric retention, or uncontrolled narrowangle glaucoma. Caution is advised in the presence of bladder outlet obstruction, mild-to-moderate renal or hepatic impairment, myasthenia gravis, and decreased gastrointestinal motility. Extreme heat can induce hyperthermia secondary to decreased sweating. Drug interactions: The active metabolite of fesoterodine is metabolized via the hepatic CYP2D6 and CYP3A4 pathways. More intense monitoring and/or dose reduction may be warranted when inhibitors of these pathways are co-administered (e.g., clarithromycin, itraconazole, and ketoconazole). Anticholinergic medications may increase the frequency and severity of blurred vision, constipation, dry mouth, and urinary retention. Adverse effects: The most commonly reported adverse effect during clinical trials was xerostomia (dry mouth). Other reported adverse effects include constipation, dyspepsia, nausea, upper abdominal pain, urinary tract infection, upper respiratory tract infection, dry eyes, urinary retention, cough, peripheral edema, back pain, insomnia, rash, and the need for increased liver function tests. Potential serious adverse effects included QT interval prolongation, chest pain, and diverticulitis. Fesoterodine is associated with a dose-dependent increase in heart rate. Dosage and availability: Fesoterodine is available as 4- and 8-mg extended-release tablets. The recommended starting dose is 4 mg given once daily. Based upon response and tolerability, the dose later may be increased to 8 mg once daily. Patients with severe renal insufﬁciency (CrCl < 30 mL/min) should not receive more than 4 mg/day. Use should be avoided in patients with severe hepatic impairment. Patient counseling: Patients should be instructed to take fesoterodine once daily without regard to meals. Fesoterodine should be taken whole; the tablet should not be crushed, chewed, or divided. If a dose is missed, therapy should resume the next day. LACOSAMIDE (Vimpat, Schwarz Biosciences). FDA Rating: 1-S,I,T. Lacosamide is an anticonvulsant created for use as adjunctive therapy for adults with uncontrolled partialonset seizures. Although other sodium-channel-blocking anticonvulsants are currently available, this agent targets sodium pathways in a new way. Indications: Lacosamide is indicated for the adjunctive treatment of partial-onset seizures in patients ≥17 years. Pharmacology and pharmacokinetics: In vitro studies show that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels and inhibits repetitive neuronal ﬁring. Lacosamide also binds to collapsing response mediator protein-2 (CRMP-2), a phosphoprotein expressed in the nervous system that is involved in neuronal differentiation and control of axonal outgrowth. W W W.D R U GTO P I C S .C O M 44 DRUG TOPICS Februar y 2009 http://WWW.DRUGTOPICS.COM

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Drug Topics - February 2009 Contents Health-System Edition Group Attempts to Resurrect Pain Care Act HSE Business Management HSE Clinical Letters Up Front Up Front in Depth Community Practice Niche Pharmacies Serve Special Populations Special Report Oral Oncology Drugs New Drugs Update 2008 Approvals OTC New Products Viewpoint

Drug Topics - February 2009

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