Drug Topics - February 2009 - (Page 42)

Continuing Education NEW MOLECULAR ENTITIES & BIOLOGICS of initiation of the infusion. The initial phase half-life is about 1 minute, and accounts for 85 percent to 90 percent of elimination. The terminal half-life is approximately 15 minutes. Most patients see a full reversal of drug effect within 5 to 15 minutes following discontinuation. Clevidipine is highly protein bound (>99 percent), with metabolism occurring primarily in the blood and tissues by means of esterases. Current studies show that elimination is not affected by either renal or hepatic dysfunction. Precautions: Clevidipine has been assigned a pregnancy category C rating. Clevidipine is an oil-in-water emulsion and should not be used by patients with a hypersensitivity to egg yolks or soybean oil. Any unused portion of the drug should be discarded 4 hours after stopper puncture to prevent contamination. Clevidipine is contraindicated in patients with severe aortic stenosis and should be used cautiously in patients with heart failure, pancreatitis, hyperlipidemia, and other disorders of lipid metabolism. Patients who have not made a transition to alternate hypertensive therapy should be monitored closely for rebound hypertension for a minimum of 8 hours. Drug Interactions: Clevidipine is unlikely to inhibit CYP450 enzymes at clinically relevant concentrations. No drug interaction studies have been conducted, but the potential for drug interactions is thought to be low. Adverse effects: The most common adverse reactions (<2 percent) reported were headache, nausea, and vomiting. Isolated cases of acute renal failure and atrial ﬁbrillation were reported during clinical trials. Hypotension and tachycardia are potential adverse effects when the dose is titrated upward. Dosage and availability: Clevidipine is supplied as a sterile, milky white injectable emulsion. The intravenous infusion should be initiated at a rate of 1 to 2 mg/hour. The drug is then titrated to achieve desired blood pressure by initially doubling doses at short intervals (90 seconds). As blood pressure approaches goal, the dose should be adjusted less frequently (every 5 to 10 minutes) with smaller increases in the dose. Patient counseling: Patients should be informed that clevidipine is an antihypertensive agent used in acute settings to tightly control blood pressure. The medication is an infusion administered by a healthcare professional in a hospital or clinical setting. DESVENLAFAXINE (Pristiq, Wyeth). FDA rating: 1S,T (T = tablet). Desvenlafaxine is a new selective serotonin and norepinephrine reuptake inhibitor (SNRI) with activity similar to venlafaxine. It provides another option for the treatment of major depressive disorder (MDD). Indication: Desvenlafaxine is indicated for the treatment of MDD in adults. Pharmacology and pharmacokinetics: Desvenlafaxine is a potent and selective SNRI whose clinical efﬁcacy is thought to be related to the potentiation of these neurotransmitters in the central nervous system. The absolute oral bioavailability of desvenlafaxine is about 80 percent. It is metabolized primarily by conjugation and to a lesser extent by CYP3A4. Approximately 45 percent is excreted unchanged in the urine. Elimination is signiﬁcantly correlated with creatinine clearance. Precautions: Desvenlafaxine should not be used by patients with a hypersensitivity to desvenlafaxine or any excipients in the formulation. Because desvenlafaxine is the major metabolite of venlafaxine, patients with a hypersensitivity to venlafaxine also should not receive desvenlafaxine. Concomitant monoamine oxidase inhibitor (MAOI) and desvenlafaxine therapy is contraindicated due to the risk of serotonin syndrome. Desvenlafaxine should not be started within 14 days of stopping an MAOI; an MAOI should not be started within 7 days of stopping desvenlafaxine. An increased risk of suicidal thinking and behavior has been detected in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders; therefore, patients on desvenlafaxine should be monitored for clinical worsening and suicide risk. Hypertension should be controlled in patients before initiating treatment because sustained elevated blood pressure has occurred in trials. Caution should be observed in patients with lipid metabolism disorders, because cholesterol and triglyceride elevation have been detected in trials. Drug interactions: Desvenlafaxine should be administered cautiously with other serotonergic drugs due to the potential for serotonin syndrome. Although CYP3A4 is a minor metabolic pathway, concomitant use of potent CYP3A4 inhibitors may result in higher concentrations. Adverse effects: The most commonly observed adverse reactions in studies were nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and speciﬁc male sexual function disorders. Dosage and availability: The recommended dose of desvenlafaxine is 50 mg once daily with or without food. No additional beneﬁt has been seen with a higher dose. The dose should be reduced for patients with moderate to severe renal impairment or end-stage renal disease. Desvenlafaxine is available as 50- and 100-mg extended-release tablets. Patient counseling: Inform patients that desvenlafaxine is used to treat depression. Ask patients whether they have ever had an allergic reaction to venlafaxine. Inform patients, family members, or caregivers of the potential risk of suicidal thoughts or actions during the ﬁrst few months of treatment in young adults. Instruct them to watch closely for any unusual changes in behavior or mood and to notify their healthcare provider immediately if any are observed. Review the patient’s medication proﬁle and look for drug-drug interactions. Instruct patients to read the medication guide and be available to answer questions. Inform patients that they should have their blood pressure monitored while receiving this therapy. Advise patients that serum lipid measurements may be needed, because total LDL, cholesterol and triglyceride elevations may occur while on treatment. DIFLUPREDNATE (Durezol, Sirion Therapeutics). FDA rating: 1-P,H (H = ophthalmic solution). Diﬂuprednate is a new ophthalmic corticosteroid for use after ophthalmic W W W.D R U GTO P I C S .C O M 42 DRUG TOPICS Februar y 2009 http://WWW.DRUGTOPICS.COM

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Drug Topics - February 2009

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