Disclosure Outline Tocilizumab Tocilizumab

11/6/2011

Disclosure

Pharmaceutical Advances in • Own stock in Pfizer and Johnson & Johnson Treatments in Rheumatic Diseases

Kam Nola, PharmD, MS Lipscomb University College of Pharmacy Associate Professor & Vice-Chair Department of Pharmacy Practice Nashville, TN

November 7, 2011

New Molecular Entities Outline January 2010 – October 2011 • New molecular entities • Tocilizumab (Actemra®) approved January 2010 • Label changes • Collagenase clostridium histolyticum (Xiaflex®) • New combinations approved February 2010 • No recalls to review for 2011 • Pegloticase (Krystexxa®) approved September • Drug shortages 2010 • Belimumab (Benlysta®) approved March 2011

Tocilizumab Tocilizumab

• Indication • Dose – with a DMARD or as monotherapy – Rheumatoid arthritis (RA) – adults with moderate – RA – 4 mg/kg every 4 weeks up to 8 mg/kg based on to severely active RA who have had an inadequate clinical response response to one or more TNF-inhibitor – Dose not to exceed 800 mg per infusion – Systemic JIA – – Systemic Juvenile Idiopathic Arthritis (JIA) – • Patients <30 kg then 12 mg/kg every 2 weeks patients 2 years of age or older with active • Patients >30 kg then 8 mg/kg every 2 weeks systemic JIA – IV drip infusion over 1 hour; do not push or bolus • Do not start in patients with: • Mechanism – Absolute neutrophil count <2000 per m3 or – Interleukin-6 receptor inhibitor – Platelets <100,000 per m3 or – ALT or AST more than 1.5 times the upper limit of normal

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Tocilizumab Collagenase Clostridum Histolyticum

• Warnings/Precautions • Indication – Serious infection – Treatment of Dupuytren’s contracture in adults – GI perforation with a palpable cord – Lab changes • Mechanism – Hypersensitivity – Lysis of collagen deposits, enzymatic disruption of • Adverse effects the cord – Upper respiratory tract infection, nasopharyngitis • Dose – Headache, hypertension, increased ALT – Injection procedure • Monitoring (see above) • 0.25 mL for cords affecting a MP joint – Labs • 0.20 mL for cords affecting a PIP joint – Infection – Finger extension procedure

Collagenase Clostridum Histolyticum Peglioticase

• Warnings/Precautions • Indication – Treatment of chronic gout in patients refractory to – Tendon rupture conventional therapy, – Allergic reactions – NOT indicated for asymptomatic hyperuricemia – Patients with abnormal bleeding – ecchymosis, • Mechanism contusion – Uric acid specific enzyme – Catalyzing oxidation of uric acid to allantoin • Adverse effects • Dose – Edema, contusion, injection site reaction, pain – 8 mg IV infusion every 2 weeks • Monitoring • Not for patients with glucose-6-phosphate dehydrogenase deficiency (G6PD)

Peglioticase Belimumab

• Warning/Precautions • Indication – Anaphylaxis – Adults with active, autoantibody positive, systemic – Infusion reactions – pre-medicate with antihistamines lupus erythematosus on standard therapy and corticosteroids – NOT for active severe lupus nephritis or severe active – Gout flares initially CNS lupus – Congestive heart failure exacerbation • Mechanism • Adverse effects – B-lymphocyte-stimulator (BLyS) specific inhibitor – Gout flares, infusion reactions, nausea, contusion, nasopharyngitis, constipation, chest pain, anaphylaxis, • Dose vomiting – 10 mg/kg every 2 weeks for the first 3 doses then • Monitoring every 4 weeks – IV infusion over 1 hour

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Belimumab Label Changes 2011

• Warnings/Precautions • Febuxostat – safety updates; January 2011 – Serious infection • Rituximab – updates to warnings and – Hypersensitivity reaction, including anaphylaxis precautions; January 2011 – Depression • Infliximab – updates to warnings, precautions, • Adverse effects and adverse reactions; February 2011 – Nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, • Tocilizumab – approved for the treatment of depression, migraine, pharyngitis systemic juvenile idiopathic arthritis, April • Monitoring 2011

Label Changes 2011 New Combinations

• Azathioprine – updates to boxed warning, • Naproxen and esomeprazole (Vimovo®) – for warnings, and adverse reactions; May2011 the treatment of arthritis in patients at risk for • Abatacept – subcutaneous injection approved, NSAID-associated ulcers, April 2010 indication includes JIA; August/September 2011 • Ibuprofen and famotidine (Duexis®) – • Duloxetine – updates to warnings and approved for the relief of rheumatoid arthritis precautions, added pregnancy registry; April and and osteoarthritis and prevention of gastric September 2011 ulcers, April 2011 • Various NSAID changes to warnings, precautions, and adverse effects

Drug Shortages Drug Shortages

• www.ashp.org/shortages – Current shortages – Resolved shortages – Drugs no longer available • http://www.fda.gov/Drugs/DrugSafety/DrugS hortages/default.htm

Collins T. The Rheumatologist, October 2011.

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Supply Chain Example Summary

• 2010-2011 has seen new molecular entities in rheumatology – First product for systemic lupus erythematosus in years – Expansion of products available to treat JIA – Combinations of older products • Challenges have been drug shortages that promise to continue