Drug Topics - February 2009 - (Page 46)

Continuing Education NEW MOLECULAR ENTITIES & BIOLOGICS Ruﬁnamide is well absorbed, with peak concentrations attained after 4 to 6 hours. Renal excretion is the predominant route of elimination, with an approximate elimination half-life of 6 to 10 hours. Precautions: Ruﬁnamide is contraindicated in patients with Familial Short QT syndrome. As with other antiepileptics, ruﬁnamide increases the risk of suicidal thoughts and behaviors. As with other antiepileptic medications, ruﬁnamide should be tapered to discontinuation to avoid the risk of increased seizure frequency. Ruﬁnamide is in pregnancy category C. Drug interactions: Ruﬁnamide metabolism occurs partly through carboxylesterases. Drugs inducing the activity of carboxylesterases (such as carbamazepine and phenobarbital) may increase the clearance of ruﬁnamide. The effectiveness of hormonal contraceptives may be decreased with concurrent use of ruﬁnamide; additional non-hormonal contraception may be warranted. Adverse effects: Most reactions experienced by patients were mild to moderate and transient. The most commonly reported adverse effects (<10 percent) were headache, dizziness, fatigue, drowsiness, and nausea. Dosage and availability: In adults, ruﬁnamide should be initiated at 400 to 800 mg/day, divided into 2 doses. Further increases of 400 to 800 mg every 2 days may be made up to a target dose of 3200 mg/day. Dosage adjustments are not needed in patients with severe renal impairment. Use should be avoided in those with severe hepatic impairment. Patient counseling: Patients should be advised to watch for any changes in moods, behaviors, thoughts, or feelings. Patients who are concurrently taking hormonal contraceptives should be advised to use precaution, as the effectiveness of these medications may be compromised by ruﬁnamide. This medication should not be abruptly discontinued; it should be gradually reduced in dose as prescribed by a physician. Ruﬁnamide should be administered with meals and may be taken whole, as half-tablets, or crushed. SILODOSIN (Rapaﬂo, Watson). FDA Rating: 1-S,C. Silodosin is an agent similar to tamsulosin. It is used for the treatment of benign prostatic hyperplasia (BPH). Indication: Silodosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. Pharmacology and pharmacokinetics: Silodosin is a selective antagonist of post-synaptic alpha-1a adrenoreceptors found in the prostate. The blockage of these receptors results in the relaxation of these smooth muscle tissues and an improvement in urine ﬂow and reduction of BPH symptoms. Following oral administration, silodosin reaches a maximum concentration in a mean time of about 2.6 hours. Its half-life is roughly 13.3 hours. A meal with moderate fat resulted in decreased concentrations of silodosin; however, on the basis of safety and efﬁcacy studies conducted in the presence of food intake, it is recommended that this medication be taken with a meal. Silodosin is extensively metabolized in the liver. Precautions: Silodosin should be used cautiously among patients with orthostatic hypotension, vertigo, or syncope, par- ticularly during initiation of therapy. Carcinoma of the prostate and BPH result in many of the same symptoms; to rule out the presence of carcinoma, patients should be encouraged to obtain medical examination before starting silodosin. Drug interactions: Silodosin is extensively metabolized by CYP3A4 hepatic enzymes and is a P-glycoprotein substrate. Drugs that inhibit CYP3A4 (such as ketoconazole, clarithromycin, and protease inhibitors) or P-glycoprotein (such as cyclosporine) may cause increases in silodosin plasma concentrations. Patients receiving concurrent antihypertensive therapy and phosphodiesterase-5 inhibitors (such as sildenaﬁl) are at an increased risk of orthostatic hypertension. Adverse effects: The most commonly reported adverse effect of silodosin therapy is retrograde ejaculation with reduced or no semen. This is reversible upon discontinuation of therapy. Other reported reactions include dizziness, diarrhea, headache, nasopharyngitis, and nasal congestion. Dosage and availability: The recommended dose of silodosin is 8 mg taken once daily with a meal. Patients with moderate renal impairment (CrCl 30 to 50 mL/min) should receive a reduced dose of 4 mg once daily with a meal. Silodosin is contraindicated among patients with severe renal impairment (CrCl < 30 mL/min). Elderly patients may be more sensitive to the effects of silodosin and dosage should be adjusted on the basis of clinical response. Patient counseling: Explain that the most common side effect of therapy is orgasm with reduced or no semen. Inform the patient that this side effect is reversible upon discontinuation of the drug. Patients should be instructed to take silodosin once daily with a meal. TETRABENAZINE (Xenazine, Biovail). FDA Rating: 1P,O,T. Tetrabenazine is a novel dopamine-depleting agent used in the treatment of involuntary movements seen in patients with Huntington’s disease. Tetrabenazine is the ﬁrst approved treatment for any Huntington’s disease-related symptom. Indication: Tetrabenazine is indicated for the treatment of chorea associated with Huntington’s disease (Huntington’s Chorea). Pharmacology and pharmacokinetics: Tetrabenazine is a centrally acting, reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. It inhibits the human vesicular monoamine transporter type 2 (VMAT2), resulting in decreased uptake of monoamines in synaptic vesicles and depletion of monoamine stores. The net result is reduction in symptoms associated with hyperkinetic movement disorders (e.g., Huntington’s disease). Peak concentrations of primary metabolites are seen within 1 to 1.5 hours of a dose being taken. The primary metabolites are subsequently metabolized into another active metabolite whose peak concentration arises within 2 hours of administration. Tetrabenazine is metabolized hepatically to an extensive degree, and the metabolites are mainly excreted renally. Precautions: Tetrabenazine is contraindicated in patients with inadequately treated depression, as it is believed that the W W W.D R U GTO P I C S .C O M 46 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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