Full Prescribing Info
Each tablet contains ciclosporin.
Ciclosporin (Arpimune) is a cyclic undecapeptide isolated from the fungus species Beauveria nivea. It is a powerful immunosuppressant with a specific action on T-lymphocytes.
Pharmacotherapeutic Group: Antineoplastic/immunosuppressant.
Pharmacology: Pharmacodynamics/Pharmacokinetics: Ciclosporin (Arpimune) is widely distributed throughout the body. Distribution in the blood is concentration-dependent with between 41 and 58% in erythrocytes and 10 to 20% in leucocytes; the remainder is found in plasma, about 90% protein-bound, mostly to lipoproteins. Because of the wide distribution, into blood cells whole blood concentrations are higher than and not compatible with plasma concentrations; where peak plasma concentrations are reported to be approximately 1 nanogram/mL for each mg of oral ciclosporin (Arpimune) whole blood concentrations for each mg range from about 1.4 to 2.7 nanograms/mL. Ciclosporin (Arpimune) is reported to cross the placenta and to be distributed into breast milk.
Clearance from the blood is biphasic. The terminal elimination half-life of an oral dose is reported to range from about 5 to 20 hours. Clearance in children is more rapid.
Ciclosporin (Arpimune) is extensively metabolized in the liver and primarily excreted in feces via the bile. About 6% of a dose is reported to be excreted in urine, less than 0.1% unchanged.
Used in immunosuppression for prophylactic treatment of organ transplants, ciclosporin (Arpimune) exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0- or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T1-helper cell is the main target, although the T1-suppressor cell may also be suppressed. It also inhibits lymphokine production and release including interleukin-2.
Usually in combination with corticosteroids (often with other immunosuppressants), in organ and tissue transplantations for the prophylaxis of graft rejection; in severe forms of atopic dermatitis, psoriasis or rheumatoid arthritis and in nephrotic syndrome.
Dosage/Direction for Use
Solid Organ Transplantation: Initiated 4-12 hrs prior to transplantation at a dose of 10-15 mg/kg, given in 2 divided doses. This dose is continued as 2 divided doses postoperatively for 1-2 weeks. In patients with stable graft function, the dose is then gradually reduced until a maintenance dose of 2-6 mg/kg/day is reached.
Bone Marrow Transplantation: First dose should be administered on the day before transplantation, preferably as an IV infusion. In patients on oral therapy, the dosage is 12.5 mg/kg/day, given in 2 divided doses for at least 3 months and preferably for 6 months before ciclosporin is withdrawn slowly.
Rheumatoid Arthritis: Initiation of therapy should take place over a period of 12 weeks. For the first 6 weeks, the recommended dose is 2.5 mg/kg/day, given orally in 2 divided doses. The daily dose can be increased gradually to a maximum of 4 mg/kg/day, if the clinical effects are insufficient.
Psoriasis: The recommended initial dose is 2.5 mg/kg orally in 2 divided doses. The daily dose may be gradually increased if there is no improvement after 1 month to a maximum of 5 mg/kg.
Atopic Dermatitis: The recommended daily dose range is 2.5-5 mg/kg orally in 2 divided doses for a maximum of 8 weeks.
Nephrotic Syndrome: An oral dose of 5 mg/kg/day in adults or 6 mg/kg/day in children (taken as 2 divided doses) is recommended for function of remission, except in patients with permitted levels of kidney failure in whom starting dose must not exceed 2.5 mg/kg/day.
There is a minimal experience with ciclosporin (Arpimune) overdose. Forced emesis and gastric lavage ca be of value up to two hours after administration of ciclosporin (Arpimune). Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal. Oral doses of ciclosporin (Arpimune) up to 10 g (about 150 mg/kg) have been tolerated with relatively minor clinical consequences, such as vomiting, drowsiness, headache, tachycardia, and in a few patients, moderately severe, reversible impairment of renal function. General supportive measure and symptomatic treatment should be followed in all cases of overdose. Ciclosporin (Arpimune) is dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral dosage at which half of experimental animals are estimated to dieis 31 and 39 times and >54 times the human maintenance dose for transplant patients (6 mg/kg: corrections based on body surface area) in mice, rats, and rabbits.
Ciclosporin (Arpimune) is contraindicated in patients with hypersensitivity to ciclosporin or to any of the ingredients of the formulation. Rheumatoid arthritis patients with abnormal renal function, uncontrolled hypertension, or malignancies should not receive ciclosporin (Arpimune). Psoriasis patients who are treated with ciclosporin (Arpimune)should not receive concomitant PUVA or UVB therapy, methothrexate or other immunosuppressive agents, coal tar or radiation therapy. Psoriasis patients with abnormal renal function, uncontrolled hypertension or malignancies should not receive ciclosporin.
Special Precautions
Regular monitoring of renal and hepatic function, blood pressure, serum lipids and serum electrolytes chiefly potassium and magnesium is required. Monitoring plasma ciclosporin concentrations is mandatory in transplant patients. Dosage adjustment may frequently be necessary in patients with renal impairment. Care is required in patients with hyperuricemia, and IV formulations should be given cautiously to those who have previously received parenteral drugs formulated in polyoxylated castor oil, or those with history of allergic reactions. Should not be used to treat atopic dermatitis, psoriasis or rheumatoid arthritis in patients with persistently raised creatinine, uncontrolled hypertension, uncontrolled infections or malignancy. Ciclosporin may increase the risk of benign intracranial hypertension.
Use In Pregnancy & Lactation
Use with caution if benefits outweigh risks. Take into consideration alcohol content of various cyclosporine formulations. Lactation: Excreted in milk, women should not breast-feed while receiving the drug.
Adverse Reactions
Nephrotoxicity, hypertension, gastrointestinal disturbances, hepatotoxicity, hypertrichosis, gum hyperplasia, tremor, headache, hyperlipidemia, electrolyte disturbances, hyperuricemia, paresthesia, muscle cramps and myalgia.
Drug Interactions
Statins, potassium-sparing diuretics, amlodipine, nifedipine, vaccines.
Store at temperatures not exceeding 30°C.
Shelf-Life: 36 months.
ATC Classification
L04AD01 - ciclosporin ; Belongs to the class of calcineurin inhibitors. Used as immunosuppressants.
Soft-gel cap 25 mg x 50's. 100 mg x 50's.
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