Promune
Global Market size:
Innovators information :
Generic Name : Cyclosporin
Brand Name : Sandimmune
Company : Novartis
Strengths : 25 / 50 & 100 mg
Dosage Form : Capsule
Packing : Pack of 50’s
Composition :
Promune 25
Each soft gelatin capsule contains
Cyclosporine ……………………………………………………………………………………………………. 25 mg
Promune 50
Each soft gelatin capsule contains
Cyclosporine ……………………………………………………………………………………………………. 50 mg
Promune 100
Each soft gelatin capsule contains
Cyclosporine ……………………………………………………………………………………………………. 100 mg
Product Source : Inhouse
Clinical Pharmacology :
Indication and Dosage :
Solid organ transplantation
A starting dose of 10-15 mg/kg should be given in two divided doses a maximum of 12 hours preceding transplantation and continued daily for 1-2 weeks post operatively. Dosage should then be gradually reduced until a maintenance dose of 2-6 mg/kg/day (depending on blood cyclosporine levels) is reached. The total daily requirement should always be taken in two divided doses.
In renal graft recipients doses at the lower end of this range (i.e <3-4 mg/kg/day), which result in trough blood levels below 50-100 mg/ml are associated with an increased level of rejection.
If PROMUNE is given in conjunction with other immunosuppressive agents (e.g. corticosteroids or as a part of a 3 or 4 drug regiment), lower doses (e.g. 3-6 mg/kg/day orally initially may be given).
Bone Marrow Transplantation
The first dose should be administered on the day before transplantation, preferably as an i.v. infusion. Patients started on oral therapy should initially be given 12.5-15 mg/kg/day beginning on the day before transplantation. The maintenance dose of approx. 12.5 mg/kg/day should be given for 3-6 (preferably 6) months before being tapered off to zero by one year after transplantation. Higher oral doses or administration by i.v. infusion may be required in patients with gastrointestinal disturbances.
The total daily requirement should always be taken in two divided doses (morning and evenings). GVHD should respond to reinstitution of therapy if it develops after cyclosporine is withdrawn.
Guidelines have been developed for the conversion from conventional oral formulations of cyclosporine to the microemulsion formulations in patients who have received solid organ or bone marrow transplants. An initial weight for weight conversion is recommended with subsequent dose titration for cyclosporine required. Dosage reduction on changing formulation may be required in patients who absorbed cyclosporine poorly from the conventional oral formulations in order to reduce the elevated trough concentrations obtained using the microemulsion formulation.
Before the conversion to microemulsion formulation is initiated, cyclosporine trough concentration, serum creatinine concentration and blood pressure should be measured. These measurements should be repeated 4 to 7 days after converting to the microemulsion formulation and at regular intervals for the first two months after conversion as necessary.
Rheumatoid arthritis
For the first 6 weeks of treatment the recommended dose is 2.5 to 3.5 mg/kg/day given orally in 2 divided doses. If the clinical effect is considered insufficient the daily dose may be then increased gradually to a maximum of 5 mg/kg, subject to the conditions listed below. Treatment should be withdrawn if no response is apparent after 3 months. For maintenance treatment the dose must be titrated individually on the basis of tolerance.
Kidney function monitoring:
PROMUNE may cause impairment of kidney function and a reliable baseline value for serum creatinine should therefore be established prior to treatment. Serum creatinine and blood pressure determinations should be performed at weekly intervals during the first 4 weeks of treatment and at monthly intervals thereafter or more frequently if dosage is increased, an NSAID is added to regimen or the dose of the existing NSAID is increased. In case where the creatinine exceeds the baseline value by 20-30% at more than one measurement the dose should be reduced by 25-50% even if the value by 20-30% at more than one measurement the dose should be reduced by 25-50% even if the values remain within the normal range.
If blood pressure significantly exceeds the baseline value appropriate antihypertensive therapy should be initiated and the dose reduced or withdrawn if normalisation does not follow.
Psoriasis
To induce remission the recommended initial dosage is (oral) is 2.5 mg/kg daily in two divided doses, increasing if there is no improvement after 4 weeks by 0.5-1 mg/kg per month up to a maximum of 5 mg/kg/day. Treatment should be withdrawn if there is no improvement in the lesions after 4 weeks at 5 mg/kg/day or if evidence of renal dysfunction is noted. A starting dose of 5 mg/kg/day is justified in patients whose conditions require rapid improvement.
Renal function should be monitored every two weeks during the first three months of therapy with cyclosporine and at regular intervals, depending on the dose, thereafter in patients whose serum creatinine concentration remains stable. If serum creatinine concentration increases to greater than 30% above baseline at more than one measurement the dose should be reduced by 25 to 50% even if the values within the normal range. Treatment should be discontinued if dosage reduction is not successful within 1 month. Treatment should also be discontinued if hypertension develops that cannot be controlled by dosage reduction or appropriate antihypertensive therapy. The daily dosage of cyclosporine should be titrated individually to the lowest effective level given as two divided doses for maintenance therapy.
PROMUNE is indicated in the treatment of patients with severe psoriasis in whom conventional therapy is ineffective or inappropriate. An accurate baseline status should be established by careful dermatological and physical examinations including measurements of blood pressure and renal function on at least 2 occasions prior to initiation of therapy. Development of malignancies especially those of the skin has been reported in psoriatic patients treated with cyclosporine as well as during treatment with conventional therapy. Dermatological malignancies and premalignant disorders such as mycosis fungoides should be excluded or treated before therapy with cyclosporine is started and it should be used if it is the only option for successful therapy.
Atopic dermatitis
The recommended daily dose range of PROMUNE is 2.5-5 mg/kg orally in two divided doses for a maximum of 8 weeks. If a starting dose of 2.5 mg/kg does not achieve a good initial response within 2 weeks, the dose may be increased rapidly to a maximum of 5 mg/kg/day. Rapid and adequate control of very severe disease is more likely with a starting dose of 5 mg/kg/day given orally in two divided doses.
PROMUNE is indicated in the treatment of patients aged more than 16 years with severe atopic dermatitis in whom conventional therapy is ineffective or inappropriate. An accurate baseline status should be established by physical examination, including measurements of blood pressure and renal function on at least two occasions, prior to the initiation of therapy.
Active herpes simplex infections should be allowed to clear and skin infections caused by Staphylococcus aureus should be controlled with appropriate antibacterial agents prior to initiating treatment with cyclosporine. Concomitant administration with erythromycin can increase the blood concentration of cyclosporine and the combination should be avoided if possible. If there is no alternative to erythromycin, blood concentrations of cyclosporine must be closely monitored.
Uveitis
5 mg/kg/day orally in two divided doses is recommended as the starting dose until inflammation subsides and visual acuity improves.
A systemic steroid (e.g. prednisone 0.2-0.5 mg/kg/day) may be added in order to accelerate remission or combat acute inflammatory episodes and/or if the latter alone proves insufficiently effective, cyclosporine microemulsion formulation should be withdrawn if there is no improvement after three months.
For maintenance treatment the dose should gradually be reduced to the lowest effective level, which should not exceed 5 mg/kg/day during periods of remission.
Cyclosporine may cause impairment of kidney function and a reliable baseline value for serum creatinine should therefore be established prior to treatment. This should be derived from at least 2 determinations, both indicating normal kidney function when used to ascertain creatinine clearance by means of a suitable formula. Serum creatinine and blood pressure determinations should be performed at weekly intervals during the 4 weeks of treatment and at monthly intervals thereafter, or more frequently if dosage is increased. The dose should be reduced by 25-50% if serum creatinine exceeds the baseline value by more than 30% - even if it is still within the normal range and cyclosporine withdrawn if there is no reduction within a month. In cases where creatinine exceeds the baseline value by 20-30% transient, non-renal increases must be eliminated by means of repeat determinations. If blood pressure significantly exceeds the baseline value appropriate antihypertensive therapy should be initiated and the dose reduced or withdrawn if normalization does not follow.
Nephrotic syndrome
An oral dose of 5 mg/kg/day in adults or 6 mg/kg/day in children (taken as two divide doses) is recommended for induction of remission, except in patients with permitted levels of kidney failure, in whom the starting dose must not exceed 2.5 mg/kg/day. (N.B. Serum creatinine levels of >200 µmol/L in adults and >140 µmol/L in children are contraindications.)
Patients (particularly steroid-resistant) who do not respond adequately to cyclosporine microemulsion formulation alone should be given a concomitant oral steroid low dosage.
Cyclosporine microemulsion formulation should be withdrawn if there is no improvement after three months treatment.
Dosage should be individually adjusted as a function of efficacy (proteinuria) and safety (primarily serum creatinine) but should not exceed 5 mg/kg/day in adults and 6 mg/kg/day in children. For maintenance the dosage should be gradually reduced to the lowest effective level.
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