Rhumatoid Arthritis/and Arava

[jimmym40]

My thai wife has rhumatoid arthritis and just started taking arava medication. Her side effects extreme and will discontinue taking arava. Just wondering if anyone here has this disease and/or taking this medication. And what physician special you are seeing.

[ZEAK]

My thai wife has rhumatoid arthritis and just started taking arava medication. Her side effects extreme and will discontinue taking arava. Just wondering if anyone here has this disease and/or taking this medication. And what physician special you are seeing.

Some info from one of my medical programs. Check out the section on nutrition.

Overview

Definition

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease. Main characteristics include symmetrical synovitis and joint erosion; extra-articular manifestations affect the lungs, eyes, heart, and blood vessels. RA affects approximately 1% of the population, striking women in a 3:1 ratio to men. The usual age of onset lies between 30 and 60, but the disease can strike at any age. Symptom severity and disease progression vary widely between individuals. Onset may be rapid or insidious.

Signs and Symptoms

Malaise, low-grade fever, weight loss, and stiffness in and about joints following inactivity

Morning stiffness lasts for more than one hour

Arthritis of more than three joints; specifically, proximal interphalangeal, metacarpophalangeal, wrist, elbow, knee, ankle, and metatarsophalangeal joints

At least one affected hand joint; specifically, wrist, metacarpophalangeal, or proximal interphalangeal joint

Extra-articular symptoms such as rheumatoid nodules, pleural effusion, pericarditis, lymphadenopathy, splenomegaly with leukopenia, vasculitis, normochromic, normocytic anemia, and elevated ESR.

Treatment Strategy

Treatment is typically aimed at relieving symptoms, preventing joint degradation, and preserving joint function. Traditional treatment involves a conservative approach using nonpharmacologic therapy and nonsteroidal anti-inflammatory drugs for up to a year before resorting to aggressive therapies. However, as substantial joint destruction can occur within two years of developing RA, the current recommendation is to treat RA earlier and more aggressively. Other general treatment strategies include the following.

Whole-body rest to reduce systemic inflammatory response and combat RA-associated fatigue

Articular rest such as joint relaxation techniques, assistive devices, and splints

Heat and cold treatment

Exercise to preserve joint motion, strength, endurance

Surgery (e.g., carpal tunnel release, resection of metatarsal heads, total hip or total knee arthroplasty) to address joint destruction, deformation, or refractory pain

Drug Therapies

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, ketoprofen, naproxen, tolmetin, diclofenac, and diflunisal reduce pain and inflammation. Gastrointestinal side effects are common and may include ulcers and bleeding. The recently FDA-approved celecoxib selectively inhibits cyclooxgenase-2 and has a reduced risk of gastrointestinal side effects. Many more "COX-2" drugs are expected to be approved shortly.

Disease-modifying antirheumatoid drugs (DMARDs) include gold salts (injectable or oral), antimalarials (e.g., hydroxychloroquine), penicillamine, and sulfasalazine. DMARDs also include immunosuppressive drugs such as methotrexate, azathioprine, and cyclophosphamide. Beneficial effects may not be apparent for weeks or months. Most DMARDs have serious side effects including gastrointestinal symptoms, thrombocytopenia, myelosuppression, proteinuria, and hepatotoxicity.

Costicosteroids (glucocorticoids) have both anti-inflammatory and immunosuppressive effects. Drugs such as prednisone (5 to 15 mg predinsone or equivalent daily, for short-term use) and methylprednisolone relieve symptoms quickly and may be given orally or by injection. Side effects include osteoporosis, mood changes, fluid retention and weight gain, and hypertension.

Some patients do not respond to individual DMARDs and better results may be achieved through drug combination. For example, a combination of methotrexate, hydroxychloroquine, and sulfasalazine may be more effective than methotrexate alone.

Experimental therapy options include the following.

Zileuton, a 5-lipoxygenase inhibitor, is under FDA review for treatment of mild synovitis

Oral Type II collagen

Minocycline

Recombinant human interleukin-1 receptor antagonist

Antibodies to TNF-alpha

Anti-CD4 monoclonal antibodies

Cyclosporine

Mycophenolate mofetil

Nutrition

The most common allergic foods are wheat, corn, and dairy. Elimination/challenge diets may identify whether these foods constitute a problem. Avoid foods completely for two weeks, then reintroduce the foods one at a time, every three days, and note symptoms. Citrus, chocolate, alcohol, red meat, flour products, spices, and carbonated drinks may also aggravate RA.

A vegetarian diet high in antioxidants may provide relief from the symptoms. This diet has high amounts of flavonoids (green tea [Camellia sinensis], blueberry , elderberry [sambucus nigra]) and low amounts of saturated fats.

A small percentage of people respond dramatically to a diet free of nightshades. They include peppers, eggplant, tomatoes, and white potatoes. A month-long trial is recommended.

Selenium levels are low in people who have RA. One clinical study demonstrated that selenium combined with vitamin E reduces RA symptoms. Dose is 50 to 75 mcg/day of selenium and 400 to 800 IU of vitamin E.

Zinc (45 mg/day) and manganese (45 mg/day) have both been found to be low in persons with RA.

Omega-3 fatty acids suppress the production of inflammatory compounds produced by white blood cells. Dose is 1,000 to 1,500 IU/day.

Bromelain is a proteolytic enzyme that when taken away from food is an anti-inflammatory (when taken with meals, it acts as a digestive enzyme). Dose is 2,000 to 2,500 mg bid.

Quercetin stabilizes mast cells, found in increased numbers in the synovial membranes of affected joints. Dose is 250 to 500 mg tid away from food.

[ZEAK]

My thai wife has rhumatoid arthritis and just started taking arava medication. Her side effects extreme and will discontinue taking arava. Just wondering if anyone here has this disease and/or taking this medication. And what physician special you are seeing.

Pick up some Glucosamine at a health food store. It rebuilds the cartilage in the joints. Takes about 3 months to start working. Also, there is a nasal spray that is calcium and vitamin D that helps a lot. Best of luck.

[ZEAK]

My thai wife has rhumatoid arthritis and just started taking arava medication. Her side effects extreme and will discontinue taking arava. Just wondering if anyone here has this disease and/or taking this medication. And what physician special you are seeing.

This is the info on Arava.

Pronunciation

(le FLU no mide)

U.S. Brand Names

Arava™

Generic Available

No

Pharmacological Index

Antimetabolite

Use

Treatment of active rheumatoid arthritis to reduce signs and symptoms and to retard structural damage as evidenced by x-ray erosions and joint space narrowing

Pregnancy Risk Factor

X

Pregnancy/Breast-Feeding Implications

Has been associated with teratogenic and embryolethal effects in animal models at low doses. Leflunomide is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be excluded prior to initiating treatment. Following treatment, pregnancy should be avoided until the drug elimination procedure is completed.

Contraindications

Pregnancy/breast-feeding; known hypersensitivity to leflunomide or any component

Warnings/Precautions

Hepatic disease (including seropositive hepatitis B or C patients) may increase risk of hepatotoxicity; immunosuppression may increase the risk of lymphoproliferative disorders or other malignancies; women of childbearing potential should not receive leflunomide until pregnancy has been excluded, patients have been counseled concerning fetal risk and reliable contraceptive measures have been confirmed. Caution in renal impairment. Not recommended for patients with severe immune deficiency, bone marrow dysplasia or uncontrolled infection. Has been associated with rare pancytopenia; use with caution in patients with a prior history of significant hematologic abnormalities. Discontinue if evidence of bone marrow suppression occurs, and begin procedure for accelerated removal (cholestyramine and activated charcoal, see Toxicology/Overdose). The use of live vaccines is not recommended. Leflunomide will increase uric acid excretion.

Adverse Reactions

>10%:

Gastrointestinal: Diarrhea (17%)

Respiratory: Respiratory tract infection (15%)

1% to 10%:

Cardiovascular: Hypertension (10%), chest pain (2%), palpitation, tachycardia, vasculitis, vasodilation, varicose vein, edema (peripheral)

Central nervous system: Headache (7%), dizziness (4%), pain (2%), fever, malaise, migraine, anxiety, depression, insomnia, sleep disorder

Dermatologic: Alopecia (10%), rash (10%), pruritus (4%), dry skin (2%), eczema (2%), acne, dermatitis, hair discoloration, hematoma, herpes infection, nail disorder, subcutaneous nodule, skin disorder/discoloration, skin ulcer, bruising

Endocrine & metabolic: Hypokalemia (1%), diabetes mellitus, hyperglycemia, hyperlipidemia, hyperthyroidism, menstrual disorder

Gastrointestinal: Nausea (9%), abdominal pain (5%), dyspepsia (5%), weight loss (4%), anorexia (3%), gastroenteritis (3%), stomatitis (3%), vomiting (3%), cholelithiasis, colitis, constipation, esophagitis, flatulence, gastritis, gingivitis, melena, candidiasis (oral), enlarged salivary gland, tooth disorder, xerostomia, taste disturbance

Genitourinary: Urinary tract infection (5%), albuminuria, cystitis, dysuria, hematuria, vaginal candidiasis, prostate disorder, urinary frequency

Hematologic: Anemia

Hepatic: Abnormal LFTs (5%)

Neuromuscular & skeletal: Back pain (5%), joint disorder (4%), weakness (3%), tenosynovitis (3%), synovitis (2%), arthralgia (1%), paresthesia (2%), muscle cramps (1%), neck pain, pelvic pain, increased CPK, arthrosis, bursitis, myalgia, bone necrosis, bone pain, tendon rupture, neuralgia, neuritis

Ocular: Blurred vision, cataract, conjunctivitis, eye disorder

Respiratory: Bronchitis (7%), cough (3%), pharyngitis (3%), pneumonia (2%), rhinitis (2%), sinusitis (2%), asthma, dyspnea, epistaxis, lung disorder

Miscellaneous: Infection (4%), accidental injury (5%), allergic reactions (2%), diaphoresis

<1%: Anaphylaxis, urticaria, eosinophilia, thrombocytopenia, leukopenia, pancytopenia, Stevens-Johnson syndrome, toxic epidermal necrolysis

Overdosage/Toxicology

There is no human experience with overdosage. Leflunomide is not dialyzable. Cholestyramine and/or activated charcoal enhance elimination of leflunomide's active metabolite (MI). In cases of significant overdose or toxicity, cholestyramine 8 g every 8 hours for 1-3 days may be administered to enhance elimination. Plasma levels are reduced by approximately 40% in 24 hours and 49% to 65% after 48 hours of cholestyramine dosing.

Drug Interactions

Cytochrome P-450 2C9 enzyme inhibitor

Decreased effect: Administration of cholestyramine and activated charcoal enhance the elimination of leflunomide's active metabolite

Stability

Protect from light; store at 25°C (77°F)

Mechanism of Action

Inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects

Pharmacodynamics/Kinetics

Distribution: Vd: 0.13 L/kg

Metabolism: Hepatic, to A77 1726 (MI) which accounts for nearly all pharmacologic activity; further metabolism to multiple inactive metabolites

Bioavailability: 80%

Half-life: Mean 14-15 days; enterohepatic recycling appears to contribute to the long half-life of this agent, since activated charcoal and cholestyramine substantially reduce plasma half-life

Time to peak: 6-12 hours

Elimination: Urine 43%; Feces 48%

Usual Dosage

Adults: Oral: Initial: 100 mg/day for 3 days, followed by 20 mg/day; dosage may be decreased to 10 mg/day in patients who have difficulty tolerating the 20 mg dose. Due to the long half-life of the active metabolite, plasma levels may require a prolonged period to decline after dosage reduction.

Dosing adjustment in renal impairment: No specific dosage adjustment is recommended. There is no clinical experience in the use of leflunomide in patients with renal impairment. The free fraction of MI is doubled in dialysis patients. Patients should be monitored closely for adverse effects requiring dosage adjustment.

Dosing adjustment in hepatic impairment: No specific dosage adjustment is recommended. Since the liver is involved in metabolic activation and subsequent metabolism/elimination of leflunomide, patients with hepatic impairment should be monitored closely for adverse effects requiring dosage adjustment.

Guidelines for dosage adjustment or discontinuation based on the severity and persistence of ALT elevation secondary to leflunomide have been developed. For ALT elevations >2 times the upper limit of normal, dosage reduction to 10 mg/day may allow continued administration. Cholestyramine 8 g 3 times/day for 1-3 days may be administered to decrease plasma levels. If elevations >2 times but less than or equal to 3 times the upper limit of normal persist, liver biopsy is recommended. If elevations >3 times the upper limit of normal persist despite cholestyramine administration and dosage reduction, leflunomide should be discontinued and drug elimination should be enhanced with additional cholestyramine as indicated.

Elderly: Although hepatic function may decline with age, no specific dosage adjustment is recommended. Patients should be monitored closely for adverse effects which may require dosage adjustment.

Dietary Considerations

No interactions with food have been noted

Monitoring Parameters

Serum transaminase determinations at baseline and monthly during the initial phase of treatment; if stable, monitoring frequency may be decreased to intervals determined by the individual clinical situation

Mental Health: Effects on Mental Status

May cause dizziness, malaise, anxiety, depression, or insomnia

Mental Health: Effects on Psychiatric Treatment

May rarely cause leukopenia, caution with clozapine and carbamazepine

Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health: Effects on Dental Treatment

1% to 10% of patients may experience stomatitis (3%), gingivitis, candidiasis (oral), enlarged salivary gland, tooth disorder, dry mouth, and taste disturbance

Patient Information

Take as directed; do not increase dose without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Store medication away from light. You may experience diarrhea (buttermilk, boiled milk, or yogurt may help); nausea, vomiting, loss of appetite, and flatulence (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known). If diabetic, monitor blood sugars closely; this medication may alter glucose levels. Report chest pain, palpitations, rapid heartbeat, or swelling of extremities; persistent gastrointestinal problems; skin rash, redness, irritation, acne, ulcers, or easy bruising; frequency, painful or difficult urination, or genital itching or irritation; depression, acute headache, anxiety, or difficulty sleeping; weakness, muscle tremors, cramping or weakness, back pain, or altered gait; cough, cold symptoms, wheezing, or difficulty breathing; easy bruising/bleeding; blood in vomitus, stool, urine; or other unusual effects related to this medication. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant or have sex unless using appropriate barrier contraception while on this medication. This drug may cause severe fetal defects. Do not breast-feed.

[Ulysses G.]

Pick up some Glucosamine at a health food store. It rebuilds the cartilage in the joints.

This seems to work for me and I have considerably less pain than I did from pharmaceutical drugs.

Expensive in Thailand though.

[jimmym40]

Thanks so much Zeak for all the info provided and taking the time to respond.

For anyone who is taking or knows of anyone taking arava at the moment, we may have a 60 day supply, new unopened bottles of arava available. PM me if you can use.

Thanks again Zeak. We'll have to decide with her doc is my wife should discontinue the use.