Cathy Sochasky, BScPharm (FCSHP) Drug Information Pharmacist Health Sciences Centre Dept. of Pharmacy

OBJECTIVES To discuss the various medications used to treat the arthritic symptoms of scleroderma. To review the potential adverse effects/interactions associated with these medications. To understand the importance of monitoring while on these medications for their effectiveness and potential risks. 2

Introduction to Scleroderma Chronic multisystem autoimmune disease Also termed “systemic sclerosis” Sclera – “hard” Derma – “skin” Cause unknown Symptoms, extent of skin/organs affected varies between patients. No one specific medication to fully control underlying disease process. Many medications used to manage specific conditions/ symptoms of this disease. 3

Diagnosis Complex, often based on clinical symptoms Physical exam (hands, knees, joints) Investigations (lab results, X-rays) 2 Types: localized (skin), systemic (lung, kidney, blood vessels & heart) 4

Initial Symptoms Musculoskeletal almost always present in ScD; degree and type varies Arthritic-like which include non-specific muscle pain (flu-like), joint stiffness/puffiness, impaired hand function May resemble rheumatoid-like polyarthritis or carpal tunnel syndrome in early stages 5

Management of Musculoskeletal Symptoms – What are the Goals and Therapeutic Options? Goals: 1. Control of pain and joint inflammation 2. Immunosuppression – maintenance 3. Prevention of organ damage (organ specific tx) – skeletal muscles, GI tract, kidney, lungs) 6

Management of Musculoskeletal Symptoms – What are the Goals and Therapeutic Options? cont’d Treatment: - Combination drug treatment for rapid control of the inflammation with maintenance treatment (localized). - May require organ specific treatment (systemic) 7

Medications Non Steroidal Anti-Inflammatory Drugs (NSAIDs) Analgesics Corticosteroids Disease Modifying Anti-Rheumatic Modifying Drugs (DMARDs) – methotrexate Others (azathioprine, mycophenolate, cyclophosphamide) 8

Non Steroidal Anti-Inflammatory Drugs Ibuprofen (Motrin®, Advil®) Naproxen (Naprosyn®) Diclofenac (Voltaren®) Celecoxib (Celebrex®) Ketorolac (Toradol®) Action:- Reduce inflammation & relieve pain - No difference in effectiveness between these meds demonstrated in studies - However, some patients do respond better to one than another. - Similar action, should not combine 9

Comparative Dosage Table – Common NSAIDs 10 MedicationOral Effective Dosage Range Diclofenac (Voltaren) Immediate release50 mg three to four times daily Diclofenac (Voltaren) Enteric coated50 mg twice to three times daily or 75 mg twice daily Diclofenac (Voltaren) Extended-release75 to 100 mg once or twice daily Ibuprofen (Motrin)300 mg four times daily; or 400, 600 or 800 mg three to four times daily, not to exceed 3200 mg daily Ketoprofen (Orudis)150 to 300 mg daily, given in 3 to 4 divided doses Naproxen (Naprosyn)250 to 500 mg twice daily, not to exceed 1500 mg/day Naproxen Sodium (Anaprox)275 mg twice daily Sulindac (Clinoril)150 mg twice daily, not to exceed 400 mg daily Tolmetin (Tolectin)400 mg three times daily, not to exceed 1800 mg daily. Control is usually achieved at doses of 200 to 600 mg daily three times daily

To take with food or milk – Does it matter? Most mfrs say to take NSAIDs with food or milk. Rationale – protective effect to stomach (FACT: never been studied to prove it) Food can delay onset of its effect (only important if immediate relief needed) Taking an NSAID on an empty stomach is not a risk for GI bleeding to occur. 11

Adverse Effects of NSAIDs 1. GASTROINTESTINAL - Nausea, vomiting, heartburn - Ulcers, bleeding, perforation What are the risk factors for GI bleeding/perforation? Long duration of use High doses ≥ 60 years old History of ulcers/bleeding Concomitant use of alcohol, corticosteroid and/or blood thinners 12

Recommendation All patients with ≥ 1 of the above risks should: Use a low NSAID dose Take NSAID intermittently Avoid if possible If NSAID used, add a protective agent (omeprazole, pantoprazole) or use celecoxib 13

What are the symptoms of GI bleeding? Can occur without warning Black, tarry stools Dark specks or blood in vomit Weakness, short of breath, pale skin, stomach pain 14 Adverse Effects of NSAIDs cont’d

2. Cardiac Toxicity Due to their mechanism of action and possibly due to blood pressure elevating effects If high blood pressure (BP), should have BP checked prior to and after 1-4 weeks of NSAID use. Note: Pain can increase BP, therefore NSAID use may also lower BP. Risk may be less with naproxen. 15 Adverse Effects of NSAIDs cont’d

3. Kidney effects Concern re: Scleroderma renal crisis (kidney failure due to hypertension) Monitoring kidney function, blood pressure and electrolytes important in 1 st 1-3 weeks and then every 3-6 months if prolonged use. 16 Adverse Effects of NSAIDs cont’d

Other Analgesics Acetaminophen (with & without codeine) May be useful for mild arthritic-like pain Does not relieve redness, stiffness or swelling Large doses may lead to liver damage Recommend no greater than 3-4 g/day (i.e. 6-8 Tylenol extra strength) Avoid taking multiple meds that contain acetaminophen eg. OTC cough/cold meds 17

Corticosteroids (e.g. oral prednisone, topical, injections- Depo Medrol®) Rapid effect on inflammation Used initially for its possible beneficial effect on inflammation for arthritis, myositis, puffy hands, skin & lung disease Used in low doses (≤ 7.5 mg) for short periods, often in combination Concerns: limited data, side effects (increased risk of renal crisis, serious infections) 18

DMARD- Methotrexate (oral, inj) immunosuppressive used in early stages of skin, muscle and joint involvement often in combination with steroids Advantages: weekly dosing, low cost, long standing safety profile Disadvantages: GI symptoms (nausea, flu-like, oral ulcers, fatigue), drug interactions, frequent blood monitoring Dosing: Oral dose titrated to maximum of mg once a week. (Inj used if not tolerating or oral not effective) Continue 2 mos, up to 4-6 mos 19

Hydroxychloroquine- an oral alternative if intolerance or contraindication to MTX e.g. liver disease ARE SERIOUS INFECTIONS A RISK WITH MTX? Not really an issue with the low doses of this drug May be due to disease itself or use of steroids 20 DMARD

DRUG INTERACTIONS 1. NSAIDs + MTX not a problem with low doses ( mg/wk) Concern with higher doses like 150 mg 2. NSAIDs + gingko (herb) Case reports-potential for increased bleeding; use with caution or avoid 21

DRUG INTERACTIONS cont’d 3. NSAIDs and SSRI antidepressants (e.g. citalopram, sertraline, fluoxetine) increase in upper GI bleeding, main concern in those already at risk of bleeding alternatives: acetaminophen, celecoxib or switch to different class of antidepressant or add a drug that protects stomach (e.g. PPI) report to doctor any evidence of bleeding or if going to surgery 22

DRUG INTERACTIONS cont’d 4. MTX and trimethoprim (Septra) Avoid this antibiotic (may affect white blood cells) 5. NSAIDs + BP medications (captopril, valsartan) NSAID may reduce effect of BP medication greatest risk first month dosage adj, monitoring kidney function (esp with diuretics) and BP 23

WEBSITES FOR PATIENT EDUCATION ON ARTHRITIS

QUESTIONS?? 25