Disease-modifying antirheumatic drugs (DMARDs)

Drugs in this class include azathioprine (Imuran), cyclosporine (Sandimmune, Neoral), gold salts (Ridaura, Solganal, Aurolate, Myochrysine), hydroxychloroquine (Plaquenil), leflunomide (Arava), methotrexate (Rheumatrex), penicillamine (Cuprimine), and sulfasalazine (Azulfidine).

• How DMARDs work: This group includes a wide variety of agents that work in many different ways. They all interfere with the immune processes that promote inflammation.

• Who should not use this medication: Pregnant or breastfeeding women should not use azathioprine; additionally, people with the following conditions should not use this drug:
  
  
  • Allergy to azathioprine
  
  
  
  • Alcoholism
  
  
  
  • Preexisting bone marrow or blood toxicities
  
  
  
• Use: Azathioprine is taken orally up to 3 times daily. If the response is inadequate, the dose may be gradually increased after 6-8 weeks. Take with food to decrease stomach irritation.



• Drug or food interactions: Use of other immunosuppressant drugs increases the risk for infection and increases toxicity to bone marrow or blood cells. Many drug interactions exist. Contact a doctor or pharmacist before beginning new prescription or over-the-counter medications.



• Side effects: Immunosuppressant drugs are not safe during pregnancy. They may also cause bone marrow or blood cell toxicity. People with impaired kidney or liver function may need lower doses.

• Who should not use this medication: People receiving psoralen-PUV-A or UV-B radiation should not take cyclosporine because of an increased cancer risk. Additionally, persons with the following conditions should not take this drug:
  
  
  • Allergy to cyclosporine
  
  
  
  • Uncontrolled hypertension
  
  
  
  • Cancer
  
  
  
• Use: Cyclosporine is taken orally in daily doses. Take it at the same time of day and with the same food. High-fat meals may decrease absorption, while milk may slightly increase absorption.



• Drug or food interactions: Patients must tell their doctor what medications they are currently taking, because many drugs interact with cyclosporine. Grapefruit juice may increase the level of cyclosporine in the blood, causing increased side effects. Cyclosporine may increase the risk of severe muscle and kidney toxicity of cholesterol-lowering medications known as statins (lovastatin [Mevacor], atorvastatin [Lipitor], simvastatin [Zocor], Pravastatin [Pravachol]).




• The following drugs may decrease the level of cyclosporine in the blood, thereby decreasing effectiveness:

  • Antiseizure drugs - Carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital (Barbita, Luminal)
  
  
  
  • Antituberculosis drugs - Isoniazid (INH), rifampin (Rifadin, Rimactane)
  
  
  
  The following drugs increase cyclosporine side effects:
  
  
  • Antibiotics - Azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin (E.E.S., Ery-Tab, E-Mycin), gentamicin (Garamycin)
  
  
  
  • Antifungals - Itraconazole (Sporanox), ketoconazole (Nizoral), fluconazole (Diflucan), voriconazole (VFEND), amphotericin B (Fungizone, Amphotec, Abelcet)
  
  
  
  • Antivirals - Acyclovir (Zovirax)
  
  
  
  • Cardiovascular medications - Nicardipine (Cardene), verapamil (Calan, Isoptin, Covera-HS)
  
  
  
• Side effects: To guard against problems, blood pressure and kidney and liver function are monitored on a regular basis, as is the level of cyclosporine in the blood. Cyclosporine may increase the risk of infection or lymphoma.

• Who should not use this medication: Persons with the following conditions should not take gold salts:
  
  
  • Allergy to gold products or other heavy metals
  
  
  
  • Severe colitis
  
  
  
  • Pulmonary fibrosis
  
  
  
  • Exfoliative dermatitis
  
  
  
  • Bone marrow disease resulting in low blood cell counts
  
  
  
  • Blood cell disease
  
  
  
  • Lupus
  
  
  
• Use: Gold pills are taken every day or every other day. The injectable forms may be taken by injection every 1-2 weeks for the first 5-6 months, and then decreased to monthly injections.



• Drug or food interactions: Gold salts may increase bone marrow toxicity when used with other drugs that depress bone marrow function. When used with penicillamine (Cuprimine), gold salts may increase the risk for skin rash, bone marrow toxicity, and decreased blood cell counts.



• Side effects: Gold salts must be used with caution in people with liver or kidney disease and in those with a history of bone marrow disease or severe hypertension. Skin rash and irritation are common side effects. Gold salts may cause the following:
  
  
  • Decreased appetite
  
  
  
  • Mouth soreness
  
  
  
  • Diarrhea
  
  
  
  • Eye infection
  
  
  
  • Renal toxicity with edema
  
  
  
  • Pulmonary toxicity
  
  
  
  • Blood cell toxicity
  
  
  
  • Bone marrow toxicity

• Who should not use this medication: People with allergy to hydroxychloroquine or related drugs (for example, chloroquine [Aralen]), and those with a history of vision changes caused by the drug or related drugs should not take them.



• Use: Hydroxychloroquine is taken orally in varying doses. Take with food or milk.



• Drug or food interactions: Hydroxychloroquine may increase the risk of liver toxicity when administered with other drugs toxic to the liver, such as acetaminophen (Tylenol). Hydroxychloroquine may increase levels of digoxin and metoprolol in the blood.



• Side effects: Annual eye examinations are required to monitor for possible vision changes. Hydroxychloroquine must be used with caution in individuals with the following conditions:
  
  
  • Liver disease
  
  
  
  • Alcoholism
  
  
  
  • G-6-PD deficiency
  
  
  
  • Kidney impairment
  
  
  
  • Psoriasis
  
  
  
  • Porphyria
  
  
  
  • Blood disorders

• Who should not use this medication: People with the following conditions should not use leflunomide:
  
  
  • People with allergy to leflunomide
  
  
  
  • Women who are pregnant or breastfeeding
  
  
  
  • Sexually active men who are not using contraception
  
  
  
  • Alcoholism
  
  
  
  • Immune deficiency syndromes
  
  
  
  • Liver failure
  
  
  
• Use: Leflunomide is taken as an oral tablet.



• Drug or food interactions: Cholestyramine (Questran) reduces the amount of leflunomide in the blood, thereby decreasing effectiveness. This medication is used to more rapidly eliminate leflunomide from the body if serious side effects are experienced. Rifampin (Rifadin, Rimactane) may increase leflunomide’s risk of toxicity. Leflunomide may increase the level of warfarin (Coumadin) in the blood and the risk for bleeding. Some vaccinations are not recommended while taking leflunomide.



• Side effects: Effective birth control is essential while taking leflunomide. This drug may cause birth defects if it is taken by the mother during pregnancy or by the father during the time of conception. Individuals with kidney or liver disease may need lower doses. Leflunomide may cause high blood pressure or worsen preexisting high blood pressure. Common side effects include stomach pain and diarrhea.

• Who should not use this medication: People with the following conditions should not take methotrexate:
  
  
  • Allergy to methotrexate
  
  
  
  • Alcoholism
  
  
  
  • Liver or kidney failure
  
  
  
  • Immune deficiency syndromes
  
  
  
  • Low blood cell counts
  
  
  
  • Pregnancy
  
  
  
• Use: Methotrexate is taken orally or as an injection once per week. It is the major DMARD to treat RA and the standard to which other treatments are compared.



• Drug or food interactions: NSAIDs (Motrin, Advil, Aleve, aspirin) may increase toxicity. Folic acid deficiency may worsen side effects of methotrexate. To lessen GI toxicity, daily administration of low dose folic acid (1-2 mg) is recommended.



• Side effects: To guard against problems, kidney and liver function are monitored on a regular basis, as are blood cell counts. Methotrexate may cause toxic effects on blood, kidneys, liver, lungs, and gastrointestinal and nervous systems.

• Who should not use this medication: People with the following conditions should not use penicillamine:
  
  
  • Allergy to penicillamine
  
  
  
  • Aplastic anemia or agranulocytosis
  
  
  
  • Pregnancy
  
  
  
• Use: Penicillamine is taken orally at least 1 hour before or 2 hours after meals. Penicillamine may take many months before a benefit is seen. It is rarely used to treat RA today.



• Drug or food interactions: Penicillamine may increase bone marrow toxicity when used with other drugs that depress bone marrow function. When used with gold salts (auranofin [Ridaura], aurothioglucose [Solganal]) or hydroxychloroquine (Plaquenil), penicillamine may increase the risk for skin rash, bone marrow toxicity, and decreased blood cell counts. Vitamins containing iron, sucralfate, or antacids should not be taken within 2 hours of taking penicillamine, since they decrease its absorption.



• Side effects: Penicillamine must be used with caution in individuals who are allergic to penicillin or who have kidney impairment. Penicillamine may decrease blood cell counts. Common side effects include nausea, vomiting, stomach pain, and diarrhea. Sense of taste may be impaired. Contact a doctor if any of the following occur:
  
  
  • Wheezing or breathing troubles
  
  
  
  • Unexplained fever
  
  
  
  • Sore throat
  
  
  
  • Unusual bleeding or bruising
  
  
  
  • Vision changes
  
  
  
  • Rash
  
  
  
  • Itching
  
  
  

• Who should not use this medication: People with the following conditions should not use sulfasalazine:
  
  
  • Allergy to sulfa drugs, aspirin, or aspirinlike products (NSAIDs)
  
  
  
  • Active peptic ulcer disease
  
  
  
  • Severe kidney failure
  
  
  
• Use: Sulfasalazine is taken orally in varying doses with food.



• Drug or food interactions: Sulfasalazine may decrease warfarin (Coumadin) absorption, thereby decreasing warfarin effectiveness. Sulfasalazine may increase the risk of bleeding when administered with other drugs that alter blood coagulation (for example, heparin [Hep-Lock]).



• Side effects: Sulfasalazine may cause the following:
  
  
  • Toxicity to blood cells
  
  
  
  • Nausea
  
  
  
  • Vomiting
  
  
  
  • Abdominal cramping
  
  
  
  • Constipation