October, 2009 Vol. 58

MILNACIPRAN (SAVELLA™)

(Savella™) is a serotonin/norepinephrine reuptake inhibitor approved for the treatment of fibromyalgia. The exact mechanism of how milnacipran confers its ability to improve symptoms of fibromyalgia is unknown.

Dosing involves tapering on to and off of the medication; with a starting dose of 12.5 mg by mouth daily and taper up to 50 mg by mouth twice daily. Maximum daily dose is 100 mg twice daily. Safety and effectiveness of milnacipran for fibromyalgia has not been established in pediatric patients less than 17 years of age.
No dosing adjustment is necessary in mild renal impairment, CrCl greater or equal to 30 mL/min. In severe renal impairment (CrCl, 5 to 29 mL/min), reduce maintenance dose by 50%. End-stage renal disease, CrCl less than 5 mL/min use not recommended.
Milnacipran is contraindicated in patients with narrow angle glaucoma or concomitant use with MAOI or use of MAOI within the preceding 14 days before milnacipran initiation or within 5 days after milnacipran discontinuation. Caution with concomitant use with other serotonergic drugs due to risk of serotonin syndrome, also with epinephrine and norepinephrine which may lead to paroxysmal hypertension and arrhythmia.
Adverse effects are generally reported as mild to moderate and decreasing over continued therapy. Nausea is most frequently reported, also reported as greater than 5% include dry mouth, hyperhydrosis, headache, hot flush and constipation.

Decision: Milnacipran (Savella™) tablets are approved for addition to formulary.

MICAFUNGIN (MYCAMINE™) INJECTION

Micafungin (Mycamine™) is an echinocandin antifungal agent indicated for:
Treatment of patients with candidemia, disseminated candidiasis, Candida peritonitis and esophageal candidiasis.
Prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation.

Micafungin has been studied in over 3500 subjects in 41 clinical trials and is found to have a safety profile comparable to fluconazole and caspofungin.
Micafungin is dosed at 100-150 mg daily and should be administered by intravenous infusion over 1 hour; no loading dose is required. No dose adjustments are required based on race or gender, in patients with mild-to-moderate hepatic insufficiency, or in patients with severe renal dysfunction.
Potential drug-drug interactions with micafungin have been well studied in 14 studies. In these studies, no interaction that altered the pharmacokinetics of micafungin was observed.
Adverse events included possible histamine-mediated symptoms (including rash, pruritus, facial swelling and vasodilatation). The most common treatment-emergent adverse reactions included diarrhea, nausea, vomiting, pyrexia, hypokalemia, thrombocytopenia, and headache.

Decision: Micafungin (Mycamine™) injection is approved for addition to formulary and caspofungin (Cancidas™) removed from the formulary.

DRONEDARONE (MULTAQ™) TABLETS

Dronedarone (Multaq™), previously reviewed in the September P and T News, is an antiarrhythmic indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. The dosing is simple, one 400 mg tablet orally twice a day with breakfast and supper.
Dronedarone does come with a Black Box Warning and a long list of drug-drug interactions. A review of the patient's history, recent ECG, current labs, and complete medication (including herbals and nutraceuticals) list should be done prior to prescribing.

Decision: Dronedarone (Multaq) tablets are approved for addition to formulary. As part of the review process and to assist in risk mitigation, a "Multaq Order Sheet" has been developed and is required for use at both hospitals.

LISDEXAMFETAMINE (VYVANSE™) TABLETS

Lisdexamfetamine (Vyvanse™) is designed as a capsule for once-a-day oral administration and is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

The efficacy in the treatment of ADHD was established on the basis of two controlled trials in children aged 6 to 12 and one controlled trial in adults who met DSM-IV-TR® criteria for ADHD.
After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug's activity. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the pre-synaptic neuron and increase the release of these monoamines into the extra-neuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.
Dosage should be individualized according to the therapeutic needs and response of the patient. In children 6 to12 years of age or adults who are either starting treatment for the first time or switching from another medication, 30 mg once daily in the morning is the recommended dose. Daily dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals. The maximum recommended dose is 70 mg/day; doses greater than 70 mg/day have not been studied in children under 6 years of age or over 12 years of age. Vyvanse may be taken with or without food.
Most common adverse effects, and comparable to dextroampetamine are decreased appetite and insomnia. Less common are irritability, nervousness, dry mouth, headache, sweating, upper GI pain and vomiting. Lisdexamfetamine is contraindicated with advanced arteriosclerosis, symptomatic cardiovascular disease, and moderate to severe hypertension or administration of an MAOI with the past 14 days