Leflunomide Brand Name– Arava
What is Leflunomide
Leflunomide is the first isoxazol derivative approved for the treatment of rheumatoid arthritis (RA).
Leflunomide was also the first agent for rheumatoid arthritis indicated for both symptomatic improvement and retardation of structural joint damage based on radiographic evidence of its disease modifying activity.
After 52 weeks of treatment in clinical trials, leflunomide showed similar improvements in tender and swollen joint counts, pain, and other symptoms when compared to methotrexate or sulfasalazine.
Leflunomide was significantly superior to placebo in time to progression of structural disease as evidenced by Sharp X-ray scores. Sharp scores were not consistently different between leflunomide and methotrexate.
Analysis of long-term studies will define whether or not leflunomide prevents RA-induced disability, but data are available to show that leflunomide subjectively improves functional daily activity and quality of life. Due to its unique mechanism of action, leflunomide efficacy may be additive to other antirheumatic agents, but certain drugs are not recommended for concurrent use (e.g., methotrexate).
Leflunomide has a fast onset of action (4 weeks) relative to other disease-modifying agents.
However, the long half-life of the drug (14—15 days) is problematic should adverse events like hepatotoxicity occur, and a drug elimination procedure is required for cases of pregnancy or significant overdose or toxicity to rapidly lower drug plasma levels (see Dosage).
Leflunomide is being evaluated for the treatment of systemic lupus erythematosus and for efficacy as an immunosupressant in organ transplantation.
Leflunomide received priority review and FDA approval in September 1998; at that time it was the first disease-modifying agent for RA approved in more than a decade.
In June 2003, leflunomide received an expanded indication for the improvement of physical function (e.g., ability to perform daily activities) in patients with rheumatoid arthritis.
Indications
- juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA)
- rheumatoid arthritis
For the treatment of active rheumatoid arthritis
Side Effects
- abdominal pain
- acne vulgaris
- agranulocytosis
- alopecia
- anaphylactoid reactions
- anemia
- angina
- angioedema
- anorexia
- anxiety
- arthralgia
- asthenia
- back pain
- blurred vision
- bone pain
- cataracts
- chest pain (unspecified)
- cholelithiasis
- cholestasis
- cirrhosis
- coagulopathy
- colitis
- conjunctivitis
- constipation
- contact dermatitis
- cough
- cystitis
- cystitis
- depression
- diabetes mellitus
- diarrhea
- dizziness
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- dysgeusia
- dyspepsia
- dyspnea
- dysuria
- ecchymosis
- elevated hepatic enzymes
- encephalopathy
- epistaxis
- erythema multiforme
- esophagitis
- fetal death
- fever
- flatulence
- gastritis
- gingivitis
- hair discoloration
- headache
- hematoma
- hematuria
- hepatic failure
- hepatic necrosis
- hepatitis
- hepatotoxicity
- hyperglycemia
- hyperhidrosis
- hyperlipidemia
- hypertension
- hyperthyroidism
- hypokalemia
- immunosuppression
- increased urinary frequency
- infection
- insomnia
- jaundice
- leukopenia
- maculopapular rash
- malaise
- melena
- menstrual irregularity
- migraine
- muscle cramps
- myalgia
- nausea
- neuritis
- neuropathic pain
- neutropenia
- oral ulceration
- palpitations
- pancreatitis
- pancytopenia
- paresthesias
- pelvic pain
- peripheral edema
- peripheral neuropathy
- pharyngitis
- pneumonitis
- proteinuria
- pruritus
- psoriasis
- pulmonary fibrosis
- rash
- rhinitis
- sinus tachycardia
- sinusitis
- skin discoloration
- skin ulcer
- Stevens-Johnson syndrome
- stomatitis
- synovitis
- tendon rupture
- teratogenesis
- thrombocytopenia
- toxic epidermal necrolysis
- urticaria
- vasculitis
- vertigo
- vomiting
- weight loss
- xerostomia
Monitoring Parameters
- CBC with differential
- LFTs
- pregnancy testing
- serum electrolytes
Contraindications
- agranulocytosis
- alcoholism
- bone marrow suppression
- breast-feeding
- chemotherapy
- children
- contraception requirements
- diabetes mellitus
- eosinophilic pneumonia
- geriatric
- hepatic disease
- hepatitis
- hepatotoxicity
- hypertension
- immunosuppression
- infection
- jaundice
- male-mediated teratogenicity
- peripheral neuropathy
- pneumonitis
- pregnancy
- pregnancy testing
- pulmonary disease
- pulmonary fibrosis
- renal failure
- renal impairment
- reproductive risk
- sarcoidosis
- serious rash
- tuberculosis
- vaccination
Interactions
- Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
- Alogliptin; Pioglitazone
- Alosetron
- Alpelisib
- Amlodipine; Atorvastatin
- Aspirin, ASA; Pravastatin
- Atorvastatin
- Atorvastatin; Ezetimibe
- Azathioprine
- Bacillus Calmette-Guerin Vaccine, BCG
- Baricitinib
- Bosentan
- Cefaclor
- Charcoal
- Cholestyramine
- Cimetidine
- Ciprofloxacin
- Dichlorphenamide
- Dienogest; Estradiol valerate
- Doxercalciferol
- Dronabinol
- Drospirenone
- Drospirenone; Estradiol
- Drospirenone; Ethinyl Estradiol
- Drospirenone; Ethinyl Estradiol; Levomefolate
- Duloxetine
- Elagolix
- Elagolix; Estradiol; Norethindrone acetate
- Eluxadoline
- Estradiol; Levonorgestrel
- Estradiol; Norethindrone
- Estradiol; Norgestimate
- Ethanol
- Ethinyl Estradiol
- Ethinyl Estradiol; Desogestrel
- Ethinyl Estradiol; Ethynodiol Diacetate
- Ethinyl Estradiol; Etonogestrel
- Ethinyl Estradiol; Levonorgestrel
- Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
- Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
- Ethinyl Estradiol; Norelgestromin
- Ethinyl Estradiol; Norethindrone
- Ethinyl Estradiol; Norethindrone Acetate
- Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
- Ethinyl Estradiol; Norethindrone; Ferrous fumarate
- Ethinyl Estradiol; Norgestimate
- Ethinyl Estradiol; Norgestrel
- Ezetimibe; Simvastatin
- Fluvastatin
- food
- Fosphenytoin
- Furosemide
- Glimepiride; Pioglitazone
- Glimepiride; Rosiglitazone
- HMG-CoA reductase inhibitors
- Influenza Virus Vaccine
- Intranasal Influenza Vaccine
- Isoniazid, INH
- Isoniazid, INH; Pyrazinamide, PZA; Rifampin
- Isoniazid, INH; Rifampin
- Itraconazole
- Ketoconazole
- Lamivudine, 3TC; Zidovudine, ZDV
- Lesinurad
- Lesinurad; Allopurinol
- Leuprolide; Norethindrone
- Levonorgestrel
- Live Vaccines
- Loperamide
- Loperamide; Simethicone
- Lovastatin
- Lovastatin; Niacin
- Maraviroc
- Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
- Measles/Mumps/Rubella Vaccines, MMR
- Mestranol; Norethindrone
- Metformin; Pioglitazone
- Metformin; Repaglinide
- Metformin; Rosiglitazone
- Methotrexate
- Mitoxantrone
- Nanoparticle Albumin-Bound Paclitaxel
- Nateglinide
- Niacin; Simvastatin
- Nonsteroidal antiinflammatory drugs
- Norethindrone
- Norgestrel
- Oral Contraceptives
- Ozanimod
- Paclitaxel
- Penicillin G
- Penicillin G Benzathine
- Penicillin G Benzathine; Penicillin G Procaine
- Penicillin G Procaine
- Phenytoin
- Pioglitazone
- Pitavastatin
- Pravastatin
- Ramelteon
- Repaglinide
- Revefenacin
- Rifampin
- Riluzole
- Rimegepant
- Rituximab
- Rituximab; Hyaluronidase
- Rosiglitazone
- Rosuvastatin
- Rotavirus Vaccine
- Rubella Virus Vaccine Live
- Segesterone Acetate; Ethinyl Estradiol
- Selexipag
- Simvastatin
- Simvastatin; Sitagliptin
- Smallpox and Monkeypox Vaccine, Live, Nonreplicating
- Smallpox Vaccine, Vaccinia Vaccine
- Sulfasalazine
- Tacrine
- Talazoparib
- Terbinafine
- Teriflunomide
- Theophylline, Aminophylline
- Tizanidine
- Tolbutamide
- Topotecan
- Tucatinib
- Typhoid Vaccine
- Ubrogepant
- Varicella-Zoster Virus Vaccine, Live
- Warfarin
- Yellow Fever Vaccine, Live
- Zidovudine, ZDV
