Rapamune

1-Active Ingredient:
Sirolimus

2-Concentration:
-oral solution contains 1 mg/ 1 ml Sirolimus
-tablet contains 1 mg or 2 mg Sirolimus

3-Dosage form:
-oral solution
-tablets

4-Indication:
For the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants

5-Side effect:
-immunosuppresion
-increased susceptibility to infection and the possible development of lymphoma and the other malignancies, particularly of the skin
-over suppression of the immune system can also increase susceptibility to infection including opportunistic infection
-fatal infection
-sepsis
-deterioration of renal function (with long term admenstration)

6-Contraindication:
It’s contraindicated in patients with hypersensitivity to Sirolimus or its derivatives or any component of the drug product

7-Precautions:
*general
-its intended only for oral administration
-lumphocele occurred significantly more often in a dose related fashion in patients treated with rapamune so appropriate operative measures should be considered to minimize this application
*lipids
-rapamune use in renal transplant patients was associated with increased serum cholesterol and triglycerides that may require treatment
*renal function
Patients treated with cyclosporine and rapamune were noted to have higher erum creatinine levels and lower glomerular filtration rates compared with patients treated with cyclosporine and placebo or azathioprine controls.
*calcineurin inhibitor- induced hemolytic uremic syndrome
The concomitant use of Sirolimus with a calcineurin inhibitor may increase the risk of calcineurin inhibitor- induced HUS/TTP/TMA
*concomitant use of angiotensin- converting enzyme (ACE) inhibitors
In rare cases the concomitant administration of Sirolimus and ACE inhibitors has resulted in angioneurotic edema type reaction
*antimicrobial prophylaxis
-cases of pneumocystis crainii pneumonia have been reported in patients not receiving antimicrobial prophylaxis so it should be administered for a year after transplantation
-cytomegalovirus prophylaxis is recommended for 3 months after transplantation
*intestinal lung disease
Cases of intestinal lung disease, some fetal , with no identified infectious etiology have occurred in patients receiving immunosuppressive regimen sometimes it has resolved by discontinuation or dose reduction. The risk increase by increasing concentration
*pregnancy
- Sirolimus was embryo/feto toxic in rates at dosage of 0.1 mg/ kg
-embryo/feto toxicity was manifested as mortality and reduced fetal weight
*lactation
- Sirolimus is excreted in trace amounts in milk of lacting rats, it’s not known whether its excreted in human milk or not
-the safety profiles of Sirolimus in infants are not known
*pediatric use
-the safety and efficacy of rapamune in pediatric patients below the age of 13 years have not been established
*geriatric use
-clinical studies of rapamune oral solution or tablet didn’t include sufficient numbers of patients aged 65 years or over to determine whether safety and efficacy differ in this population from younger people.

8-Dose:
It is recommended that rapamune oral solution and tablets be used initially in regimen with cyclosporine and corticosteroid for 2 to 4 months after transplantation in patients at low to moderate immunological risk

9-Over dose:
General supportive measures should be followed in all cases of overdose based on the poor aquoues solubility and the high erythrocyte and plasma protein binding of Sirolimus, it is anticipated that Sirolimus is not dialyzable to any extent. in mice and rats the acute oral lethal dose was greater than 800 mg/kg

10-Storage:
*oral solution:
-should be protected from light
-Refrigerated at 2 – 4 C
-once the bottle opened the continents should be used within one month
*tablets:
-should be stored at 20-25 C-use cartons to protect blister cards and strips from light
-dispense in a tight light resistant containers

11-Package:
Tablets: box containing 10 strips each contain 10 tablets

12-produced by:
Wyeth pharmaceuticals

13-Price:
-oral solution: 169 £
-tablets: 90 £