THERAPEUTICS

Brands

• Gengraf, Neoral, Sandimmune, Cicloral

Generic?

• Yes

Class

• Immunosuppressant

Commonly Prescribed for

(FDA approved in bold)

• Prophylaxis of organ rejection in patients with allogenic kidney, liver, and heart transplants

• Rheumatoid arthritis

• Psoriasis

• Myasthenia gravis (MG)

• Neuromyelitis optica

• Acute disseminated encephalomyelitis

• Leukemia refractory to routine treatment

• Aplastic anemia

• Ulcerative colitis

How the Drug Works

• It binds to cyclophilin thus inhibiting the phosphatase activity of calcineurin, with a resultant decrease in activation of nuclear factor of activated T-lymphocytes (NFATs). It also blocks the activation of JNK and p38 signaling pathways. Overall, it inhibits lymphokine (e.g., interleukin 2) production and release, and reduces T-lymphocyte (especially T-helper cell) activation

How Long Until It Works

• Most patients with MG improve 1–2 months after starting treatment, but maximum improvement takes 6 or more months

If It Works

• Decrease dose of corticosteroids. Gradually reduce to the minimum dose needed to maintain clinical improvement

If It Doesn't Work

• Consider alternative disease-modifying therapy or thymectomy

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Often used with corticosteroids (prednisone), especially in the initial stages of treatment

Tests

• Obtain baseline CBC, magnesium, potassium, uric acid, lipids, blood urea nitrogen, and creatinine. Measure trough levels 1 month after starting to determine dosing. Measure creatinine every 2–4 weeks for the first few months, then monthly, and then every 2–3 months when stable or when new medications are added. Measure CBC, uric acid, potassium, and lipids every 2 weeks for the first 3 months, then monthly. Monitor blood pressure frequently (at least monthly)

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Uncertain

Notable AEs

• Hypertension, hirsutism, cramps, diarrhea, infection, hypomagnesemia

• Tremor, convulsions, paresthesias

Life-Threatening or Dangerous AEs

• Renal failure. Elevations of blood urea nitrogen and creatinine are common and are dose related. Nephrotoxicity occurs in over 20% of patients

• Thrombocytopenia and microangiopathic hemolytic anemia

• Hyperkalemia

• Hepatotoxicity, usually in first month of therapy