Clinical Uses and Dosages of Cyclosporine
Cyclosporine is primarily used for severe dermatological conditions, organ transplantation, and certain autoimmune disorders, with recommended dosages ranging from 2.5-5 mg/kg/day depending on the indication, with careful monitoring required to minimize nephrotoxicity and hypertension. 1, 2
Dermatological Indications
Psoriasis: FDA-approved for severe, recalcitrant plaque psoriasis. Initial dose of 2.5 mg/kg/day divided twice daily, with potential increases of 0.5 mg/kg/day every 2 weeks to a maximum of 4 mg/kg/day. Treatment should be discontinued if no response after 6 weeks at maximum dose. 3, 2
Atopic Dermatitis: Used off-label in the US (approved in EU) for severe, refractory cases at 3-5 mg/kg/day divided twice daily. 2, 1
Acute Generalized Exanthematous Pustulosis (AGEP): Used for severe cases at 3-5 mg/kg/day divided twice daily. 4
Nephrology Indications
Nephrotic Syndrome: Used in minimal change disease and membranous glomerulonephritis at 3-5 mg/kg/day. 2
Idiopathic Glomerular Disease: Dosage of 3-5 mg/kg/day with careful monitoring of renal function. 2
Hematology Indications
- Immune Thrombocytopenia: Used at 3-6 mg/kg/day with monitoring of trough drug levels. Response rates at 1 month range from 37.8% to 56.7%. 2
Rheumatology Indications
- Rheumatoid Arthritis: Initial dose of 2.5 mg/kg/day divided twice daily, with potential increases of 0.5-0.75 mg/kg/day after 8 and 12 weeks to a maximum of 4 mg/kg/day if insufficient response. 3
Administration Guidelines
- Cyclosporine should be given on an empty stomach or before meals. 2
- The microemulsion formulation (Neoral) is preferred over the original formulation (Sandimmune) due to more consistent absorption. 2
- For oral solution, dilute with room temperature orange or apple juice (avoid grapefruit juice). 3
- Once-daily dosing may be as effective as twice-daily dosing with the microemulsion formulation. 2
Monitoring Requirements
Pre-treatment: Complete physical examination, blood pressure, baseline serum creatinine, BUN, CBC, serum magnesium, potassium, uric acid, lipids, and pregnancy test if indicated. 2, 1
During treatment:
Treatment Duration and Strategies
- Short courses (up to 6 months) are recommended to minimize long-term risks. 2, 1
- Intermittent therapy is safer than continuous treatment. 2
- For psoriasis, once control is achieved, taper to lowest effective dose. 3
- Long-term treatment beyond 1 year is not recommended due to increased risk of nephrotoxicity. 2, 3
Major Adverse Effects
Nephrotoxicity: Most common adverse effect. Reversible in short-term treatment (19-24% of patients), but risk of irreversible damage increases after 2 years of treatment. 2
Hypertension: Common adverse effect that may require dose reduction or treatment with calcium channel blockers. 2, 1
Other adverse effects: Gingival hyperplasia (6.6%), hypertrichosis, tremor, paresthesia, GI effects (nausea, vomiting, diarrhea), hyperlipidemia, and increased risk of infections. 2
Contraindications
- Abnormal renal function 2
- Uncontrolled hypertension 2
- History of malignancy 2
- Prior extensive PUVA treatment (>200 treatments) or radiation therapy 2
- Hypersensitivity to cyclosporine 2
Important Drug Interactions
- Avoid drugs that interfere with CYP3A4 metabolism, which can increase or decrease cyclosporine levels. 2, 1
- Avoid concurrent use with nephrotoxic drugs like aminoglycosides, amphotericin, and NSAIDs. 1
- St. John's Wort decreases cyclosporine concentration. 2
- Grapefruit juice increases cyclosporine concentration. 2, 3
Clinical Pearls
- Bioavailability varies between different cyclosporine formulations; avoid switching between brands without careful monitoring. 2
- Combining with topical treatments may allow for lower cyclosporine doses and better maintenance of remission. 2, 1
- For severe, unstable disease, start at the higher end of the dosage range (5 mg/kg/day). 2, 4
- For less urgent cases, start at a lower dose (2.5-3 mg/kg/day) and increase if necessary. 2, 1