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® Tecfidera Use in Multiple Sclerosis: A Patient Case Stefanie L. Drahuschak PharmD Candidate Class of 2014 University of Pittsburgh School of Pharmacy Walgreens Specialty Pharmacy March 12, 2014 Objectives 1) Review the basics of Multiple Sclerosis as a disease state. 2) Understand the important counseling points, adverse events, and dosing of Tecfidera®. 3) Apply the knowledge of MS and Tecfidera® to a specific patient case. Patient: CH 57 yo female No known drug allergies Diagnosis: Multiple Sclerosis ◦ ICD9 Code: 340 Patient: CH MS treatment history ◦ 2006 – 2010 Avonex® (interferon beta-1a) 30 mcg/0.5 mL ◦ 2010 – 2013 Copaxone® (glatiramer acetate) 20 mg/mL ◦ 2013 – present Tecfidera® (dimethyl fumarate) 120 mg PO BID x 7 days 240 mg PO BID thereafter Patient: CH Current Medications: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Tecfidera® 240 mg PO BID Prempro® 0.3/1.5 mg PO qday Simvastatin 80 mg PO qHS Sertraline 50 mg PO qday Amlodipine 10 mg PO qday HCTZ 25 mg PO qday Enalapril 20 mg PO qday Levothyroxine 100 mcg qAM Multiple Sclerosis MS is an inflammatory disease of the CNS The term multiple sclerosis refers to two characteristics of the disease: ◦ 1) Multiple areas of brain and spinal cord affected producing multiple neurologic symptoms ◦ 2) Characteristic plaques or sclerosed areas Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Epidemiology Usually diagnosed between 15-45 yo ~10,000 new cases diagnosed/yr in US Woman > men in 2:1 ratio Prevalence is higher the greater the distance from equator ◦ Inverse relationship between MS and vitamin D exposure? Occurs more frequently in whites of Scandinavian ancestry Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Clinical Presentation Primary S/Sx •Visual complaints/optic neuritis •Gait problems and falls •Parasthesias •Pain •Spasticity •Weakness •Sexual dysfunction •Ataxia •Speech difficulty •Psychological changes •Cognitive changes •Fatigue •Bowel/bladder dysfunction •Tremor Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL, Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Diagnosis Diagnosis of exclusion ◦ Sx can often be attributed to other neurological issues Occurrence of at least 2 episodes of neurologic disturbance reflecting distinct sites of damage in the CNS that cannot be explained by another mechanism Since 2010, McDonald criteria has been considered the gold standard for diagnosis Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. McDonald Criteria http://www.radiologyassistant.nl/en/p4556dea65db62/multiple-sclerosis.html Types of MS 1) Relapsing-Remitting MS (RRMS) ◦ Most common, about 85% initially diagnosed 2) Secondary-Progressive MS (SPMS) ◦ Symptoms worsen steadily over time 3) Primary-Progressive MS (PPMS) ◦ Only ~10% of patients 4) Progressive-Relapsing MS (PRMS) ◦ Rare (5%) Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Treatment Three broad categories ◦ 1) Symptomatic therapy ◦ 2) Treatment of acute attacks ◦ 3) Disease-modifying therapy Symptomatic Therapy Tx Gait problems ◦ Ampyra® (dalfampridine) Fatigue ◦ Modafinil (Provigil®) Depression ◦ SSRIs Sexual dysfunction ◦ Cialis®, Viagra® Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Tx of Acute Attacks When functional ability is affected, IV high-dose corticosteroids are used ◦ IV methylprednisolone MOA of corticosteroids is unknown, but suspected that steroids improve recovery by decreasing edema is the area of demyelination Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Disease-Modifying Therapy Interferons ◦ Betaseron® (IFN-beta1b) ◦ Avonex® (IFN-beta 1a) ◦ Rebif® (IFN-beta 1a) Copaxone® (glatiramer acetate) Tysabri® (natalizumab) Gilenya® (Fingolimod) Novantrone® (mitoxantrone) Tecfidera® (dimethyl fumarate) Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978. Tecfidera® Dimethyl fumarate Indication ◦ Tecfidera® is indicated for the treatment of patients with relapsing forms of multiple sclerosis Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Mechanism of Action Mostly unknown DMF and MMF activate the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway NRF2 pathway is involved in cellular response to oxidative stress Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Tecfidera® Dosing Initiation dose ◦ 120 mg PO BID x 7 days Maintenance dose ◦ 240 mg PO BID Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Tecfidera® Availability Hard, gelatin delayed release capsules of 120 or 240mg ◦ 120mg: “BG-12 120mg” on capsule ◦ 240mg: “BG-12 240mg” on capsule 30-day Starter Pack 7-day bottle of 120 mg capsules 30-day bottle of 240 mg capsules Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. ® Tecfidera http://www.empr.com/tecfidera-approved-a-first-line-oral-multiple-sclerosistreatment/article/286349/ Tecfidera® Administration Should be swallowed whole and intact Should NOT be crushed or chewed Capsule contents should NOT be sprinkled on food Can be without without regard to food Administration with food may reduce the incidence of flushing Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. ® Tecfidera Adverse Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Reactions Serious AE - Flushing Warmth, redness, itching, and/or burning sensation In clinical trials, 40% experienced Flushing generally began soon after initiation and improved over time Initiation dose is used to desensitize body to flushing Taking medication with food or premedicating with aspirin may help reduce incidence Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Serious AE: Lymphopenia Mean lymphocyte counts decreased by ~30% during the first year of treatment and then remained stable 4 weeks after d/c, lymphocyte counts increased but did not return to baseline Before tx, a baseline CBC should be conducted, then annually thereafter Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Pharmacokinetics Metabolism ◦ Extensively metabolized by esterases ◦ No involvement from CYP450 system Elimination ◦ Exhalation of CO2 is primary route – 60% ◦ Renal and fecal elimination are minor routes, accounting for 16% and 1%, respectively Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Use in Pregnancy Pregnancy Category C In animal studies, adverse effects on offspring survival, growth, sexual maturation, and neurobehavioral function were observed at clinically relevant doses Should only be used if benefit > risk Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Important Counseling Points Will be provided two strengths when starting therapy ◦ Do not crush, swallow whole Flushing and GI upset are most common reactions, especially initially ◦ Take with food, aspirin if needed Inform MD if you become pregnant Regular blood tests are important to monitor lymphocytes Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013. Patient CH: Assessment/Plan A: ◦ Since patient began Tecfidera® in 2013, no AE or change in disease state have been reported P: ◦ Continue Tecfidera® 240 mg PO BID ◦ Continue regular monitoring with MS specialist ◦ Add additional symptomatic treatment if necessary QUESTIONS?