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Transcript
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
Medication
Oral Effective Dosage Range
Diclofenac (Voltaren) Immediate release 50 mg three to four times daily
Diclofenac (Voltaren) Enteric coated
50 mg twice to three times daily or 75 mg
twice daily
Diclofenac (Voltaren) Extended-release
75 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
10
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
Adverse Effects of NSAIDs
cont’d
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 1st 1-3 weeks and then every
3-6 months if prolonged use.
16
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 25-30 mg
once a week. (Inj used if not tolerating or oral not
effective) Continue 2 mos, up to 4-6 mos
19
DMARD
 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
DRUG INTERACTIONS
1. NSAIDs + MTX
 not a problem with low doses (7.5-15 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
 www.rheuminfo.com
 www.arthritis.ca
 www.rheumatology.org
 www.arthritis.org
 www.jointhealth.org
24
QUESTIONS??
25