Gramune ®
(Ciclosporin)

Prescribing Information:

Special Note:
Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Gramune® (Ciclosporin). Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.
Composition: Gramune® Soft Gelatin Capsules (Ciclosporin) are available in 25mg, 50mg and 100mg strengths.

Indications:
Gramune® (Ciclosporin) is an immunosuppressive agent used to prevent organ rejection in kidney, liver, bone marrow, or heart transplant patients. It is always to be used with adrenal corticosteroids. The drug may also be used in the treatment of chronic rejection in patients previously treated with other Immunosuppressive agents.

Transplantation:
-Organ transplantation: prevention of rejection of kidney, liver heart, lung and pancreas.
-Bone marrow: Prevention of graft rejection. Prevention and treatment of graft versus host disease (GVHD).

Non - Transplantation:
- Psoriasis: severe case in which alternative therapies are ineffective or inappropriate.
- Atopic dermatitis: severe cases in which alternative therapies are ineffective or inappropriate.
- Rheumatoid Arthritis: severe cases in which standard treatment are ineffective or inappropriate.

Dosage and Administration:

Adults:
The initial oral dose of Gramune® (Ciclosporin) should be given 4-12 hours prior to transplantation as a single dose of 12 - 15 mg/kg. Although a daily single dose of 14-18 mg/kg was used in most clinical trials, few centers continue to use the highest dose, most favoring the lower end of the scale. Maintenance dosing of 5 to 10 mg per kg body weight per day.

Adjunct therapy with adrenal corticosteroids is recommended.
A dosage schedule based on the patient's weight started with 2.0 mg/kg/day for the first 4 days tapered to 1.0 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose.

OR

an initial dose of 200 mg tapered by 40 mg/day until reaching 20 mg/day. After 2 months at this dose, a further reduction to 10 mg/day was made. Adjustments in dosage of prednisone must be made according to the clinical situation

Pediatric:
In pediatric usage, the same dose and dosing regimen may be used as in adults although in several studies, children have required and tolerated higher doses than those used in adults.

Adverse Effects:
-Genitourinary: Renal dysfunction, Glomerular capillary thrombosis.
-Cardiovascular: Hypertension, Myocardial infarction. Cramps.
-Skin: Hirsutism, Pruritus, acne.
-Central Nervous system: Anxiety, tremor, convulsions, confusion, depression, headache,
-Gastrointestinal: Anorexia, diarrhea, gastritis, constipation, gum hyperplasia, nausea vomiting, peptic ulcer, upper Gl bleeding, Abdominal discomfort, Hepatatoxicity, pancreatitis.
-Autonomic Nervous System: Paresthesia, flushing.
-Respiratory: Sinusitis.
-Hematopoietic: Leukopenia, Lymphoma, hematuria, thrombocytopenia.
-Miscellaneous: Gynecomastia, allergic reaction, anemia conjunctivitis, edema, fever, brittle, fingemails, hearing loss, hiccups, hyperglycemia, muscle pain, tinnitus, hair breaking, joints pain, lethargy, mouth sores, night sweats, swallowing, difficulty, tingling, visual disturbance, weakness, weight loss.

Precautions:

General:
- Patients with malabsorption may have difficulty in achieving therapeutic levels of Ciclosporin with soft gelatin capsules.
- Mild to moderate hypertension is a common side effect of Ciclosporin therapy and the incidence decreases over time. Antihypertensive therapy may be required. However, since Ciclosporin may cause Hyperkalemia, Potassium sparing diuretics should not be used.

Pregnancy:
Ciclosporin proved to be without any embroyolethal or teratogenic effects however, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:
Ciclosporin passes into breast milk of mothers receiving treatment with Gramune® (Ciclosporin) and therefore should not breast-feed.

Pediatric Use:
Although no adequate and well-controlled studies have been conducted in children, patients as young as 6 months of age have received the drug with no unusual adverse effects.

Overdosage:
There is a minimal experience with overdosage. Because of the slow absorption of Gramune® (Ciclosporin) soft gelatin capsules, forced emesis would be of value up to 2 hours after administration. Transient hepatotoxicity and nephrotoxicity may occur, which should be resolved following drug withdrawal.

Storage:
- Preserve in sealed containers, protect from light.
- Store at 10O "C -30O "C

Presentation
25mg, 100mg box containing 50 soft gelatin capsules of Ciclosporin and 50mg box containing 30 soft gelatin capsules.

Available at all leading pharmacies in Pakistan on prescription only.
For further queries.
Tel: +92 21 34123535, 34123636, 0346-3636201
UAN: +92 21 111-graton (472-866)
Fax: +92 21 34937304
Email: info@gratonpharma.com
Web: www.gratonpharma.com