What is Rapamune?
Rapamune is a medicine containing the active substance sirolimus, available as an oral solution (1 mg / ml) and as triangular tablets (white: 1 mg; yellow: 2 mg).
What is Rapamune used for?
Rapamune is used in the prevention of kidney transplant rejection in adult patients, with the risk of low or moderate rejection. The use of Rapamune is recommended in combination with ciclosporin and corticosteroids (other anti-rejection drugs) for a period of 2-3 months. After this time, Rapamune can be used in maintenance therapy in combination with corticosteroids, but only if the treatment with ciclosporin can be stopped.
The medicine can only be obtained with a prescription.
How is Rapamune used?
Rapamune treatment must be started and then managed by a transplant specialist.
Rapamune is given as a starting dose of 6 mg as soon as possible after the transplant, followed by 2 mg once a day for 2-3 months. Sirolimus levels should be monitored in the patient's blood by adjusting the dose to obtain adequate levels (4 to 12 ng / ml). Rapamune should be taken four hours after each dose of ciclosporin. Rapamune intake should be regular, with or without food.
After this period, Rapamune can be used as a "maintenance therapy" in patients who can discontinue cyclosporine. In these cases the dose of ciclosporin should be eliminated progressively over 4-8 weeks, while the dose of Rapamune increased to obtain blood levels of sirolimus of about 12-20 ng / ml. On average, the dose of Rapamune has quadrupled.
The available information on the safety and efficacy of Rapamune in patients under the age of 18 is insufficient to be able to recommend the medicine in this age group.
How does Rapamune work?
The active ingredient contained in Rapamune is sirolimus, an immunosuppressive agent that acts by inhibiting a particular protein called the "specific rapamycin target for mammals" (mTOR). Once inside the body, sirolimus binds to a protein found in cells and produces a "complex" that blocks mTOR. Given that mTOR is involved in multiplication
of activated T lymphocytes (white blood cells responsible for the attack on the transplanted organ), Rapamune reduces the number of these globules, therefore the risk of rejection.
What studies have been carried out on Rapamune?
Rapamune has been the subject of two main studies involving a total of 1 295 kidney transplant patients, with the risk of low to moderate rejection. The first study (719 patients) compared a dose of Rapamune in oral solution with azathioprine (another anti-rejection medicine), while the second study (576 patients) compared a dose of Rapamune in an oral solution with a placebo (a dummy treatment ). The medicines have been used in addition to cyclosporin and corticosteroids. Efficacy was measured by observing the number of failed treatments (due to rejection or loss of the new kidney or death) after six months.
Two studies examined Rapamune as a maintenance therapy for up to five years out of a total of 765 patients who had responded to an initial treatment of 2-3 months and who were able to stop taking ciclosporin.
Another study compared the effectiveness of the oral solution and the tablets.
What benefit has Rapamune shown during the studies?
Rapamune was more effective than placebo and as effective as azathioprine in combined use with ciclosporin and corticosteroids. In the first study, 19% of patients for whom the approved dose of Rapamune was added failed treatment after six months (53 out of 284), compared with 32% of those patients for whom azathioprine was added ( 52 out of 161). In the second study the failure rate was lower among patients in whom Rapamune was added (30%; 68 out of 277) compared to patients in whom placebo was added (48%, 62 out of 130).
Use studies as maintenance therapy have shown that long-term care with Rapamune is effective in contributing to the survival of the new kidney, with an improvement in its function and blood pressure, after stopping cyclosporin.
The other study showed that the oral solution and the tablets are equally effective in preventing rejection.
What is the risk associated with Rapamune?
The most common side effects associated with Rapamune (seen in more than 1 patient in 10) are urinary tract infection (the organs through which urine flows), thrombocytopenia (low platelet count), anemia (low red blood cell count), hypokalaemia (low levels of potassium in the blood), hypophosphataemia (low levels of phosphate in the blood), hypercholesterolemia (high levels of cholesterol in the blood), hyperglycaemia (high blood sugar levels), hypertriglyceridemia (high levels of triglycerides in the blood, a type of fat), headache, lymphocele (fluid accumulation around the kidney), hypertension (high blood pressure), abdominal pain, diarrhea, constipation, nausea, acne (pimples), arthralgia (joint pain), peripheral edema ( swelling, usually in the legs), pyrexia (fever), pain, increased lactate dehydrogenase in the blood (index of tissue destruction) and increased blood levels of creatinine (a marker of kidney problems). By reducing the activity of the immune system, Rapamune can also increase the risk of cancer, especially lymphomas and skin cancer. For the full list of all side effects reported with Rapamune, see the Package Leaflet.
Rapamune should not be used in patients who may be hypersensitive (allergic) to sirolimus or any of the other components.
Caution is recommended when administering Rapamune concomitantly with other medicinal products. For more information, see the package leaflet.
Why has Rapamune been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits associated with Rapamune outweigh the risks in preventing organ rejection in adult patients undergoing kidney transplantation with low to moderate immunological risk and therefore recommended the granting of the marketing authorization for Rapamune.
More information on Rapamune:
On 14 March 2001, the European Commission issued a marketing authorization for Rapamune, valid throughout the European Union, to Wyeth Europa Ltd. The marketing authorization was renewed on 14 March 2006.
For the full version of the Rapamune evaluation (EPAR), click here.
Last update of this summary: 11-2008.
