Savella Milnacipran

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Savella - Milnacipran

• Manufacturer Forest Pharmaceutics, Inc.
• FDA Approval Date 01/16/2009

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Savella - Milnacipran Clinical Application

• Indications
• Fibromyalgia
• Place in therapy
• Alternative treatment for patients who have
  uncontrolled fibromyalgia
• Potential to become first line

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Savella - Milnacipran Clinical Application

• Contraindications
• Uncontrolled narrow-angle Glaucoma
• Concomitant use with MAOIs
• Must wait 14 days before starting milnacipran if
  patient is on on MAOI
• Black Box Warnings
• Increased risk of Suicidality

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Savella - Milnacipran Clinical Application

• Warnings/Precautions
• Elevated BP/HR
• Serotonin Syndrome
• Seizures
• Hepatotoxicity
• Discontinuation
• Hyponatremia
• Abdominal Bleeding
• Urogenital issues in Males

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Savella - MilnacipranDrug Facts

• Pharmacology
• SNRI
• Mechanism unknown in FM
• Affinity for NE 3x greater
• than Serotonin
• No significant affinity to
• histamine, DA, muscurinic
• receptors

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Savella - MilnacipranDrug Facts

• Pharmacokinetics
• A 85-90 bioavailablity
• D Vd 400L, PB 13
• M renal metabolism with minimal CYP450
  metabolism
• E Urine (55 unchanged drug)
• T1/2 6-8 hrs

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Savella - Milnacipran Drug Interactions

• Drug Interactions Object Drugs
• Serotonergic Drugs
• Increased risk for serotonin syndrome
• Alpha/Beta-agonists
• Paroxysmal hypertension/arrhythmias
• Digoxin IV
• Postural hypotension/tachycardia
• Clomipramine
• Euphoria and postural hypotension

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Savella - Milnacipran Drug Interactions

• Drug Interactions Precipitant Drugs
• Lithium
• Serotonin syndrome
• MAOIs

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Savella - Milnacipran Adverse Effects

• Common Adverse Effects
• Nausea (37) 20
• Headache (18) 14
• Constipation (16) 4
• Hot Flush (12) 2
• Dizziness (10) 6

• Hyperhydrosis (9) 2
• Palpitations (7) 2
• Vomiting (7) 2
• Increased HR (6) 1
• Hypertension (5) 2

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Savella - Milnacipran Monitoring Parameters

• Efficacy Monitoring
• Improvement in pain/sxs associated with FM
• Toxicity Monitoring
• Sign/Sxs of Serotonin Syndrome
• BP, HR, renal fx, mental status changes
• Intraocular pressure in glaucoma pts

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Savella - Milnacipran Prescription Information

• Dosing
• Initial
• Day 1 12.5 mg once
• Day 2-3 25 mg/day (12.5 mg twice daily)
• Day 4-7 50 mg/day (25 mg twice daily)
• After Day 7 100 mg/day (50 mg twice daily)
• Usual
• 100 mg/day (50 mg twice daily)
• Taper upon discontinuation
• Max
• 200 mg/day

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Savella - Milnacipran Prescription Information

• Renal Dosing Adjustments
• CrCl lt 30 ml/min decrease dose by 50
• Not recommended in end stage renal failure
• Hepatic Dosing Adjustments
• None

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Savella - Milnacipran Prescription Information

• Cost

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Savella - Milnacipran Clinical Trial Information

• Safety and Efficacy of milnacipran in treatment
  of fibromyalgia
• Treatments placebo vs. 100 mg vs. 200 mg
• Primary Outcomes
• Treatment of FM ( 30 pain improvement, very
  much improved/much improved on PGIC, 6pt
  improvement in physical fx using PCS score)
• Treatment of pain associated with FM

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Savella - Milnacipran Clinical Trial Information
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Savella - Milnacipran Clinical Trial Information
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Savella - Milnacipran Summary

• 3rd approved alternative to treat fibromyalgia
• Milnacipran has been available as an
  antidepressant in Europe for over 10 years
• Dosed twice daily
• Low potential for drug-drug interactions
• No direct head-to-head studies comparing other
  treatments for fibromyalgia

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Savella - Milnacipran References

• www.savella.com
• Savella package insert. Forest Pharmaceuticals,
  Inc. Jan. 2009.
• Mease PJ The Efficacy and Safety of Milnacipran
  for Treatment of Fibromyalgia. A Randomized,
  Double-blind, Placebo-controlled Trial. Journal
  of Rheumatology 200936(2)