Indications
Main indications
- Psoriasis : (FDA-approved for ttt of psoriasis in adults(At 2.5 and 5 mg/kg/d for 12 to 16 weeks).
- Severe psoriasis – Recalcitrant psoriasis: 5 mg/kg daily in two divided doses to be be reduced by 1 mg/kg daily every other week.
- Stable moderate and severe ps : 2.5–3 mg/kg dailyto be increased by 0.5 to 1 mg/kg/day every other week until clinical improvement is seen or a maximum dose of 4–5 mg/kg/day.
- Hand and foot psoriasis.
- Psoriasis in Patients with major life events (such as a wedding).
Off-label indications
- Severe atopic dermatitis : 2.5–5 mg/kg daily for 6 wks in children from 2 to 16 years of age.
- Pyoderma gangrenosum.
- Chronic idiopathic urticaria : 4 mg/kg daily.
- Lichen planus.
- Bullous dermatoses : Pemphigus – Pemphigoid- Epidermolysis bullosa acquisita-Linear IgA bullous dermatosis.
- Autoimmune connective tissue diseases: Dermatomyositis-Lupus erythematosus-Scleroderma.
- Neutrophilic dermatoses : Behçet’s disease – Pyoderma gangrenosum.
- Alopecia : Alopecia areata – Lichen planopilaris.
- Granulomatous dermatoses : Granuloma annulare-Sarcoidosis.
- Disorders of keratinization : Pityriasis rubra pilaris.
- Photosensitivity dermatoses : Chronic actinic dermatitis.
- Others : (Eosinophilic cellulitis-Kimura’s disease-Morphea-Prurigo nodularis-Papular erythroderma of Ofuji-
- Persistent papular acantholytic dermatosis-Purpura pigmentosa chronica-Reiter’s syndrome-Scleromyxedema).
Dosage
- 3–5 mg/kg/d divided into 2 BID.
Baseline Monitoring
Examination
- Complete history and physical examination.
- Two baseline blood pressures at least a day apart.
Lab
- Serum creatinine levels (two baseline creatinine values at least a day apart)
- Baseline renal evaluation – BUN, urinalysis with microscopic examination (optional).
- CBC, ALT, AST, γ‐glutamyl transferase (γ‐GT), bilirubin.
- Fasting lipid profile – triglycerides, cholesterol, HDL, cholesterol.
- Consider PPD.
- Pregnancy test if indicated.
Patients with a low muscle mass may have signifcant nephrotoxicity even though their serum creatinine remains within the normal range, so baseline values should always be considered.
Follow Up Monitoring
Examination
- Re-evaluate the patient every 2 weeks for 1–2 months, then every 4–6 weeks while on cyclosporine.
- Blood pressure checked at each visit.
Lab
Every 2 weeks for the first 1–2 months, then monthly while on cyclosporine.
- Renal functions – serum creatinine, BUN, urinalysis.
- Liver function tests.
- Lipids – triglycerides, cholesterol.
- Serum CsA level in selected pts.
Side effects
- Renal dysfunction.
- Hypertension.
- Neurologic (Tremor- Headache – Paresthesia – hyperesthesia).
- Hypertrichosis.
- Gingival hyperplasia.
- Nausea, abdominal discomfort, Diarrhea.
- Myalgia, lethargy, Arthralgia.
- Hyperkalemia -Hyperuricemia -Hypomagnesemia-Hyperlipidemia.
Contraindications
- Absolute
- Signifcantly decreased renal function.
- Uncontrolled hypertension.
- Hypersensitivity to CsA.
- Clinically cured or persistent malignancy (except nonmelanoma skin cancers).
- Cutaneous T-cell lymphoma.
- Relative
- Age <18 years or >64 years.
- Controlled hypertension.
- Planning to receive a live attenuated vaccination.
- Medications that interfere with CsA metabolism or potentiate renal dysfunction.
- Active infection or evidence of immunodefciency.
- Concomitantly receiving phototherapy, methotrexate, or other immunosuppressive agents.
- Unreliable patients.
Pregnancy and lactation
- Pregnancy Category C.
- The manufacturer recommends avoiding cyclosporin in pregnancy unless the benefits to the mother outweighs the risks.
- potential risks to the fetus.
- Excreted in breast milk, do not use with breast feeding.
Drug interactions
- Drugs that increase cyclosporine drug levels – CYP 3A4 inhibition
- Antifungals: ketoconazole, itraconazole, fluconazole, vorinconazole.
- Diuretics: furosemide, thiazides, carbonic anhydrase inhibitors.
- Calcium channel antagonists: diltiazem, nicardipine, verapamil.
- Corticosteroids: high-dose methylprednisolone.
- Antiemetics: metoclopramide.
- Antibiotics: macrolides, fluoroquinolones.
- Antiarrhythmics: amiodarone.
- Antimalarials: hydroxychloquine, chloroquine.
- Anti-HIV drugs: ritonavir, indinavir, saquinavir, nelfinavir.
- SSRIs: fluoxetine, sertraline.
- Others: Allopurinol, bromocriptine, danazol, amphotericin B, oral contraceptives.
- Drugs that reduce cyclosporine drug levels – CYP 3A4 induction
- AntiTB : Rifampin, rifabutin.
- Antibacterial : Nafcillin.
- Anticonvulsants: Carbamazepine, phenobarbital, phenytoin, valproic acid.
- Others : Octreotide, ticlopidine.
- Drugs + cyclosporine >> potentiate renal toxicity
- Antibiotics : Aminoglycosides Tobramycin, gentamicin, Trimethoprim/sulfamethoxazole, vancomycin.
- Antivirals: acyclovir.
- Antifungals: Amphotericin B, ketoconazole.
- NSAID : Indomethacin, naproxen, diclofenac.
- H2 antihistamines : Cimetidine, ranitidine.
- Immunosuppressants: Tacrolimus, melphalan.
- Medications whose levels increase when taken concomitantly with cyclosporine
- Calcium channel blockers: diltiazem, nicardipine, verapimil \n
- Erectile dysfunction drugs: sildenafil, tadalafil, vardenafil \n
- Statins: atorvastatin, lovastatin, simvastatin \n
- Benzodiazepines: midazolam, triazolam \n
- Others: prednisolone, digoxin, colchicine, digoxin, diclofenac, bosentan.
- Methotrexate + cyclosporine = each drug can reduce the elimination of the other.
- Grapefruit juice is also a CYP450 inhibitor and should be avoided while taking cyclosporin.
Drug info
- CsA induced HTN is usually mild and is generally reversible after dose reduction or discontinuation of CsA.
- The initial dosage of CsA for the treatment of psoriasis should depend on the clinical state of the patient being treated.
- If there is insufficient response after 3 months on the maximum dose of 5 mg/kg daily, CsA should be discontinued.
- For obese patients, the ideal body weight should be used to calculate the starting dosage of CsA.
- Cyclosporine is best used on a short-term basis (<6–12 months) to control flares of psoriasis relatively quickly and to provide an alternative to the patient’s current regimen.
- Calcium channel blockers of the dihydropyridine class are the recommended first-line antihypertensive agents.
- Use during pregnancy should be considered only in exceptional patients for whom the potential benefits dramatically outweigh the risks
Precautions
- Grapefruit juice affects the metabolism of CsA and should be avoided.
- Serum creatinine is kept within 25% of the patient’s baseline creatinine level.
- Blood pressure and serum creatinine should be measured before conversion from sandimmune to neoral, in addition to 2, 4, and 8 weeks thereafter.