Drugs used in rheumatic diseases and gout

Drugs used in rheumatic diseases and gout

 

Non-steroidal anti-inflammatory drugs

In regular full dosage NSAIDs have both a lasting analgesic and an anti-inflammatory effect which makes them particularly useful for the treatment of continuous or regular pain associated with inflammation. Therefore, although paracetamol often gives adequate pain control in osteoarthritis, NSAIDs are more appropriate than paracetamol or the opioid analgesics in the inflammatory arthritides (e.g. rheumatoid arthritis) and in some cases of advanced osteoarthritis. NSAIDs can also be of benefit in the less well defined conditions of back pain and soft-tissue disorders.

Differences in anti-inflammatory activity between NSAIDs are small, but there is considerable variation in individuals’ tolerance to these drugs and their response to them. About 60% of patients will respond to any NSAID; of the others, those who do not respond to one may well respond to another. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. If appropriate responses are not obtained within these times, another NSAID should be tried.

NSAIDs reduce the production of prostaglandins by inhibiting the enzyme cyclo­oxygenase. They vary in their selectivity for inhibiting different types of cyclo­oxygenase; selective inhibition of cyclo-oxygenase-2 improves gastro-intestinal tolerance. A number of other factors also determine susceptibility to gastro­intestinal effects and a NSAID should be chosen on the basis of the incidence of gastro-intestinal and other side-effects.

Cyclo-oxygenase-2 selective inhibitors are associated with an increased risk of thrombotic events (e.g. myocardial infarction and stroke) and should not be used in preference to non-selective NSAIDs except when specifically indicated (i.e. for patients at a particularly high risk of developing gastroduodenal ulceration or bleeding) and after assessing their cardiovascular risk.

 

CELECOXIB:

Indications: Symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient’s overall risks. Celecoxib is not indicated for use in children..

Contraindications: Known hypersensitivity to sulphonamides. Active peptic ulceration or gastrointestinal (GI) bleeding. Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors. In pregnancy and in women of childbearing potential unless using an effective method of contraception. Breast feeding. Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score 10). Patients with estimated creatinine clearance <30 ml/min. Inflammatory bowel disease. Congestive heart failure (NYHA II-IV). Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

Dose and Administration: As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient’s need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis. Osteoarthritis: The usual recommended daily dose is 200 mg taken once daily or in two divided doses. Rheumatoid arthritis: The initial recommended daily dose is 200 mg taken in two divided doses. The dose may, if needed, later be increased to 200 mg twice daily. Ankylosing spondylitis: The recommended daily dose is 200 mg taken once daily or in two divided doses. The maximum recommended daily dose is 400 mg for all indications.

 

DICLOFENAC SODIUM:

Indications: Musculoskeletal disorders, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout, pain due to trauma. Chronic juvenile arthritis.

Contraindications: Aspirin/anti-inflammatory induced allergy. Active peptic ulcer. Proctitis. Last trimester of pregnancy. Intravenous only: Cerebrovascular bleeding, bleeding tendency, high risk of surgically-induced haemorrhage, asthma, moderate to severe renal impairment, hypovolaemia, dehydration.

Dose and Administration: Orally, 75 – 150 mg daily in two or three divided doses. Injection: Treatment should not exceed two days. Continue treatment if necessary with tablets or suppositories. By intramuscular injection, 75 mg intragluteal injection; maximum total daily dose, 150 mg. By intravenous injection, treatment of postoperative pain, 75 mg by intravenous infusion over 30 minutes to two hours. Repeat if necessary after 4 – 6 hours; maximum dose, 150 mg in 24 hours. Prevention of post-operative pain, 25 – 50 mg by intravenous infusion over 15 minutes to 1 hour, then continuous intravenous infusion of 5 mg/ hour; maximum 150 mg in 24 hours. child 1–12 years, juvenile arthritis, by mouth or by rectum, 1–3 mg/kg daily in divided doses. child 6–12 years, postoperative pain, by rectum, 1–2 mg/kg daily in divided doses.

 

DICLOFENAC POTASSIUM:

Indications: Rheumatic disease, musculoskeletal disorders, acute gout, postoperative pain, Migraine.

Contraindications: Aspirin/anti-inflammatory induced allergy. Active peptic ulcer. Proctitis. Last trimester of pregnancy. Intravenous only: Cerebrovascular bleeding, bleeding tendency, high risk of surgically-induced haemorrhage, asthma, moderate to severe renal impairment, hypovolaemia, dehydration.

Dose and Administration: Rheumatic disease, musculoskeletal disorders, acute gout, postoperative pain, 75–150 mg daily in 2–3 divided doses; child over 14 years, 75–100 mg daily in 2–3 divided doses. Migraine, 50 mg at onset, repeated after 2 hours if necessary then after 4–6 hours; max. 200 mg in 24 hours.

 

ETORICOXIB:

Indications: pain and inflammation in osteoarthritis and in rheumatoid arthritis; acute gout.

Contraindications: inflammatory bowel disease; uncontrolled hypertension; breast-feeding, ischaemic heart disease, cerebrovascular disease, peripheral arterial disease, and moderate or severe heart failure.

Dose and Administration: Osteoarthritis, adult and child over 16 years, 60 mg once daily. Rheumatoid arthritis, adult and child over 16 years, 90 mg once daily. Acute gout, adult and child over 16 years, 120 mg once daily for max. 8 days.

 

IBUPROFEN:

Indications: pain and inflammation in rheumatic disease (including juvenile idiopathic arthritis) and other musculoskeletal disorders; mild to moderate pain including dysmenorrhoea; postoperative analgesia; migraine; dental pain; fever and pain in children; post-immunisation pyrexia.

Contraindications: Gastrointestinal Hemorrhage, Post-operative from CABG Surgery, Pregnancy, Alcoholism, Blood Coagulation Disorder, Disease of Cardiovascular System, Duodenal Ulcer, Gastric Ulcer, Gastrointestinal Ulcer, Increased Cardiovascular Event Risk, Peptic Ulcer, Stomatitis.

Dose and Administration: adult and child over 12 years, initially 300–400 mg 3–4 times daily; increased if necessary to max. 2.4 g daily; maintenance dose of 0.6–1.2 g daily may be adequate. child 3–6 months (body-weight over 5 kg), 50 mg 3 times daily (max. 30 mg/kg daily in 3–4 divided doses); child 6 months– 1 year, 50 mg 3–4 times daily (max. 30 mg/kg daily in 3–4 divided doses); child 1–4 years, 100 mg 3 times daily (max. 30 mg/kg daily in 3–4 divided doses); child 4–7 years, 150 mg 3 times daily (max. 30 mg/kg daily in 3–4 divided doses); child 7–10 years, 200 mg 3 times daily (up to 30 mg/kg daily (max. 2.4 g) in 3–4 divided doses); child 10–12 years, 300 mg 3 times daily (up to 30 mg/kg daily (max. 2.4 g) in 3–4 divided doses). Rheumatic disease in children (including juvenile idiopathic arthritis), child 3 months–18 years (body-weight over 5 kg), 30–40 mg/kg (max. 2.4 g) daily in 3–4 divided doses; in systemic juvenile idiopathic arthritis up to 60 mg/kg (max. 2.4 g) daily [unlicensed] in 4–6 divided doses.

 

INDOMETHACIN:

Indications: Ankylosing Spondylitis, Bursitis, Gout, Osteoarthritis, Rheumatoid Arthritis, Shoulder Bursitis, Shoulder Tendonitis, Synovitis, Tendonitis, Tenosynovitis, Bartter’s Syndrome, Dysmenorrhea, Fever, Nephrogenic Diabetes Insipidus, Pericarditis, Premature Labor, Renal Colic, Twin Reversal Arterial Perfusion Syndrome.

Contraindications: Post-operative from CABG Surgery, Pregnancy, Blood Coagulation Disorder, Depression, Disease of Cardiovascular System, Esophageal Dysmotility, Gastrointestinal Hemorrhage, Gastrointestinal Ulcer, Increased Cardiovascular Event Risk, Parkinsonism, Renal Disease, Tobacco Smoker.

Dose and Administration: By mouth, rheumatic disease, 50–200 mg daily in divided doses, with food; child not recommended. Acute gout, 150–200 mg daily in divided doses. Dysmenorrhoea, up to 75 mg daily.

 

MEFENAMIC ACID:

Indications: pain and inflammation in rheumatoid arthritis and osteoarthritis; postoperative pain; mild to moderate pain; dysmenorrhoea and menorrhagia.

Contraindications: Post-operative from CABG Surgery, Pregnancy, Blood Coagulation Disorder, Chronic Heart Failure, Disease of Cardiovascular System, Disease of Liver, Gastrointestinal Hemorrhage, Gastrointestinal Ulcer, Increased Cardiovascular Event Risk, Peptic Ulcer, Renal Disease, Tobacco Smoker.

Dose and Administration: adult over 18 years, 500 mg 3 times daily. child 12–18 years, acute pain including dysmenorrhoea, menorrhagia, 500 mg 3 times daily.

 

MELOXICAM:

Indications: pain and inflammation in rheumatic disease; exacerbation of osteoarthritis (short-term); ankylosing spondylitis.

Contraindications: Acute Gastrointestinal Ulcer with Perforation, Coronary Artery Bypass Graft, Post-operative from CABG Surgery, Pregnancy, Alcoholism, Blood Coagulation Disorder, Cerebrovascular Accident, Chronic Heart Failure, Disease of Cardiovascular System, Gastrointestinal Hemorrhage, Gastrointestinal Ulcer, Increased Cardiovascular Event Risk, Myocardial Infarction, Peptic Ulcer, Severe Renal Disease, Tobacco Smoker.

Dose and Administration: By mouth, osteoarthritis, 7.5 mg daily, increased if necessary to max. 15 mg once daily. Rheumatoid arthritis, ankylosing spondylitis, 15 mg once daily, may be reduced to 7.5 mg daily; elderly 7.5 mg daily.

 

NAPROXEN:

Indications: pain and inflammation in rheumatic disease (including juvenile idiopathic arthritis) and other musculoskeletal disorders; dysmenorrhoea; acute gout.

Contraindications: Post-operative from CABG Surgery, Pregnancy, Alcoholism, Anemia, Body Fluid Retention, Cerebrovascular Accident, Chronic Heart Failure, Disease of Cardiovascular System, Disease of Liver, Edema, Esophageal Dysmotility, Gastrointestinal Hemorrhage, Gastrointestinal Perforation, Gastrointestinal Ulcer, Hypertension, Hypovolemia, Increased Cardiovascular Event Risk, Myocardial Infarction, Renal Disease, Thromboembolic Disorder, Tobacco Smoker.

Dose and Administration: Rheumatic disease, 0.5–1 g daily in 1–2 divided doses; child (over 5 years), juvenile idiopathic arthritis, 10 mg/kg daily in 2 divided doses. Acute musculoskeletal disorders and dysmenorrhoea, 500 mg initially, then 250 mg every 6–8 hours as required; max. dose after first day 1.25 g daily; child under 16 years not recommended. Acute gout, 750 mg initially, then 250 mg every 8 hours until attack has passed; child under 16 years not recommended.

 

PIROXICAM:

Indications: pain and inflammation in rheumatic disease (including juvenile idiopathic arthritis) and other musculoskeletal disorders; acute gout.

Contraindications: Post-operative from CABG Surgery, Pregnancy, Acute Hepatic Failure, Alcoholism, Blood Coagulation Disorder, Body Fluid Retention, Cerebrovascular Accident, Chronic Heart Failure, Debilitation, Disease of Cardiovascular System, Drug-Induced Hepatitis, Edema, Gastrointestinal Hemorrhage, Gastrointestinal Perforation, Gastrointestinal Ulcer, Hypertension, Increased Cardiovascular Event Risk, Myocardial Infarction, Severe Renal Disease, Thrombotic Disorder, Tobacco Smoker.

Dose and Administration: By mouth, rheumatic disease, initially 20 mg daily, increased if necessary to 30 mg daily in single or divided doses; child (over 6 years), juvenile idiopathic arthritis, under 15 kg, 5 mg daily; 16–25 kg, 10 mg; 26–45 kg, 15 mg; over 46 kg, 20 mg. Acute musculoskeletal disorders, 40 mg daily in single or divided doses for 2 days, then 20 mg daily for 7–14 days. Acute gout, 40 mg initially, then 40 mg daily in single or divided doses for 4–6 days. child not recommended.

 

TENOXICAM:

Indications: pain and inflammation in rheumatic disease and other musculoskeletal disorders.

Contraindications: Post-operative from CABG Surgery, Pregnancy, Acute Hepatic Failure, Alcoholism, Blood Coagulation Disorder, Body Fluid Retention, Cerebrovascular Accident, Chronic Heart Failure, Debilitation, Disease of Cardiovascular System, Drug-Induced Hepatitis, Edema, Gastrointestinal Hemorrhage, Gastrointestinal Perforation, Gastrointestinal Ulcer, Hypertension, Increased Cardiovascular Event Risk, Myocardial Infarction, Severe Renal Disease, Thrombotic Disorder, Tobacco Smoker.

Dose and Administration: Rheumatic disease, 20 mg daily; Acute musculoskeletal disorders, 20 mg daily for 7 days (max. 14 days); child not recommended.

 

LORNOXICAM:

Indications: Short-term treatment of moderate postoperative pain, such as pain after dental surgery. Treatment of pain associated wih acute lumbo-sciatia. Symptomatic treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis.

Contraindications: Allergy to lornoxicam or any of the excipients. Previous hypersensitivity reactions (symptoms like asthma, rhintis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin (acetylsalicylic acid). Active peetic ulceration or a history of recurrent peptic ulceration. Severe renal impairment (serum creatinine > 700 micromol/ml). Pregnancy and lactation. Patients under 18 years of age.

Dose and Administration: Postoperative pain/acute lumbo-sciatia, recommended daily dose, 8mg to 16mg taken before meals (daily doses above 8mg should be divided into two or more doses). Maximum single dose, 8mg; maximum daily dose, 16mg. Osteoarthritis/Rheumatoid arthritis, recommended daily dose, 12 mg taken before meals (4mg three times daily or 8mg in the morning and 4mg at night); maximum recommended daily dose for long-term treatment, 12mg.

 

AESCIN AMORPHOSED:

Indications: Swelling following injuries, headaches following concussion, for supportive treatment in cases of tendinitis (inflammation of tendon sheaths).

Contraindications: As a precaution, Aescin coated tablets should not be used during the first 3 months of pregnancy except under a doctor’s explicit instructions.

Dose and Administration: Unless otherwise directed, start with an initial dose of 2 coated tablets 3 times daily. As a maintenance dose and in milder cases, take 1-coated tablet 3 times daily with some liquid after meals.

Dosage for children: Take 1 coated tablet 2 – 3 times daily with some liquid after meals.

 

Drugs that suppress the rheumatic disease  process

Certain drugs such as those affecting the immune response can suppress the disease process in rheumatoid arthritis and psoriatic arthritis; gold, penicillamine, hydroxychloroquine, chloroquine, and sulfasalazine can also suppress the disease process in rheumatoid arthritis while sulfasalazine and possibly gold can suppress the disease process in psoriatic arthritis. Unlike NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs) can affect the progression of disease but may require 2–6 months of treatment for a full therapeutic response. Since in the first few months of treatment, the course of rheumatoid arthritis is unpredictable and the diagnosis uncertain, it is usual to start treatment with an NSAID alone. However, disease-modifying anti-rheumatic drugs should be initiated by specialists as soon as diagnosis, progression, and severity of the disease have been confirmed. Response to a disease-modifying anti-rheumatic drug may allow the dose of the NSAID to be reduced. Disease-modifying antirheumatic drugs can improve not only the symptoms of inflammatory joint disease but also extra-articular manifestations such as vasculitis. They reduce the erythrocyte sedimentation rate, C-reactive protein, and sometimes the titre of rheumatoid factor; some also retard erosive damage as judged radiologically. The choice of a disease-modifying antirheumatic drug should take into account co-morbidity and patient preference. Sulfasalazine, methotrexate, intramuscular gold and penicillamine are similar in efficacy. However, sulfasalazine or methotrexate are often used first because they may be better tolerated.

 

PENICILLAMINE:

Indications: Cystine Renal Calculi, Cystinuria, Rheumatoid Arthritis, Wilson’s Disease, Felty’s Syndrome, Heavy Metal Toxicity, Lead Toxicity, Rheumatoid Vasculitis.

Contraindications: Agranulocytosis, Aplastic Anemia, and Aplastic Anemia Secondary to Drugs, Lactating Mother, Pregnancy, Renal Disease, and Myasthenia Gravis.

Dose and Administration: Severe active rheumatoid arthritis, administered on expert advice, adult initially 125–250 mg daily for 1 month increased by similar amounts at intervals of not less than 4 weeks to usual maintenance of 500– 750 mg daily in divided doses; max. 1.5 g daily; if remission sustained for 6 months, reduction of daily dose by 125–250 mg every 12 weeks may be attempted; elderly initially up to 125 mg daily for 1 month increased by similar amounts at intervals of not less than 4 weeks; max. 1 g daily; child maintenance of 15–20 mg/kg daily (initial dose lower and increased at intervals of 4 weeks over a period of 3–6 months).

 

SODIUM AUROTHIOMALATE (GOLD INJECTION):

Indications: active progressive rheumatoid arthritis, juvenile idiopathic arthritis.

Contraindications: severe renal and hepatic disease; history of blood disorders or bone marrow aplasia, exfoliative dermatitis, systemic lupus erythematosus, necrotising enterocolitis, pulmonary fibrosis; acute porphyria.

Dose and Administration: By deep intramuscular injection, administered on expert advice.

 

CHLOROQUINE:

Indications: active rheumatoid arthritis (including juvenile idiopathic arthritis), systemic and discoid lupus erythematosus; malaria.

Contraindications: Hemolytic Anemia from Pyruvate Kinase and G6PD Deficiencies, Maculopathy, Retinal Disorder, Visual Field Defect.

Dose and Administration: Administered on expert advice, by mouth, chloroquine (base) 150 mg daily; max. 2.5 mg/kg daily, see recommendations above; child up to 3 mg/kg daily.

 

HYDROXYCHLOROQUINE SULPHATE:

Indications: active rheumatoid arthritis (including juvenile idiopathic arthritis), systemic and discoid lupus erythematosus; dermatological conditions caused or aggravated by sunlight.

Contraindications: Deficiency of Glucose-6-Phosphate Dehydrogenase, Hemolytic Anemia from Pyruvate Kinase and G6PD Deficiencies, Maculopathy, Retinal Disorder, Visual Field Defect.

Dose and Administration: Administered on expert advice, initially 400 mg daily in divided doses; maintenance 200–400 mg daily; max. 6.5 mg/kg daily (but not exceeding 400 mg daily), see recommendations above; child up to 6.5 mg/kg daily (max. 400 mg daily).

 

ADALIMUMAB:

Indications: Ankylosing Spondylitis, Crohn’s Disease in Remission, Juvenile Rheumatoid Arthritis, Plaque Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Severe Crohn’s Disease, Crohn’s Disease.

Contraindications: pregnancy; breast-feeding; Acute Tuberculosis, Blastomycosis, Coccidioidomycosis, Histoplasmosis, Lupus-Like Syndrome, Miliary Tuberculosis, Severe Infection.

Dose and Administration: By subcutaneous injection, rheumatoid arthritis, adult over 18 years, 40 mg on alternate weeks; if necessary increased to 40 mg weekly in patients receiving adalimumab alone. Psoriatic arthritis, ankylosing spondylitis, adult over 18 years, 40 mg on alternate weeks.

 

ETANERCEPT:

Indications: Ankylosing Spondylitis, Juvenile Rheumatoid Arthritis, Plaque Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis.

Contraindications: pregnancy; breast-feeding; Acute Tuberculosis, Blastomycosis, Coccidioidomycosis, Histoplasmosis, Lupus-Like Syndrome, Miliary Tuberculosis, Severe Infection.

Dose and Administration: By subcutaneous injection, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, adult over 18 years, 25 mg twice weekly or 50 mg once weekly. Polyarticular-course juvenile idiopathic arthritis, child 4–17 years, 400 micrograms/kg (max. 25 mg) twice weekly, with an interval of 3–4 days between doses. Plaque psoriasis, adult over 18 years, 25 mg twice weekly; max. treatment duration 24 weeks; discontinue if no response after 12 weeks

 

Gout and cytotoxic-induced hyperuricaemia

 

COLCHICINE:

Indications: acute gout, short-term prophylaxis during initial therapy with allopurinol and uricosuric drugs; prophylaxis of familial Mediterranean fever (recurrent polyserositis)

Contraindications: Acute Severe Gastrointestinal Disorder, Disorder of the Digestive System, Hemolytic Anemia from Pyruvate Kinase and G6PD Deficiencies, Aplastic Anemia, Cardiac Disease, Disease of Liver, Hemodialysis with High-Flux Membrane, Severe Hepatic Disease, Severe Renal Disease and pregnancy.

Dose and Administration: Treatment of gout, 500 micrograms 2–4 times daily until symptoms relieved, max. 6 mg per course; course not to be repeated within 3 days. Prevention of gout attacks during initial treatment with allopurinol or uricosuric drugs, 500 micrograms twice daily. Prophylaxis of familial Mediterranean fever, 0.5–2 mg daily.

 

ALLOPURINOL:

Indications: prophylaxis of gout and of uric acid and calcium oxalate renal stones; prophylaxis of hyperuricaemia associated with cancer chemotherapy.

Contraindications: Hypersensitivity Angiitis, Renal Disease with Moderate to Severe Function Impairment.

Dose and Administration: Initially 100 mg daily, preferably after food, then adjusted according to plasma or urinary uric acid concentration; usual maintenance dose in mild conditions 100–200 mg daily, in moderately severe conditions 300–600 mg daily, in severe conditions 700–900 mg daily; doses over 300 mg daily given in divided doses; child under 15 years, (in neoplastic conditions, enzyme disorders) 10–20 mg/kg daily (max. 400 mg daily).

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Pharmacist interested in improving the health outcome for every single case he meets.

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