Sirolimus

Vascular anomalies refer to a group of conditions where blood or lymphatic vessels develop abnormally. These include venous, lymphatic and combined malformations. Some vascular anomalies may cause pain, swelling, bleeding, or problems with movement and daily activities.

• What is sirolimus?
  Sirolimus is a medicine that controls abnormal blood vessel growth. It blocks a pathway in the body (called mTOR) that is often overactive in people with vascular anomalies. Sirolimus is not a cure, but it can help reduce symptoms and improve quality of life for many patients.
  
  
• Who might benefit from sirolimus?
  Sirolimus is most helpful for people with slow-flow vascular malformations, especially lymphatic malformations and some venous malformations. It can reduce pain, bleeding, oozing, and sometimes the size of the malformation. It is often used when other treatments, like surgery or sclerotherapy, are not possible or have not worked well.
  
  
• How is sirolimus taken?
  Sirolimus is usually taken by mouth and is usually started at a dose of 0.8 mg/m²/dose twice a day. Doctors will check blood levels and adjust the dose to keep sirolimus at a safe and effective level, often between 5- 15 ng/mL, depending on age and condition.
  
  
• How long does it take to see results?
  Most people start to notice improvement in symptoms – such as less pain, swelling, or bleeding – within the first month of starting sirolimus. In many cases, doctors see measurable changes in the size of the vascular anomaly or improvements in quality of life by 3 to 6 months. Some patients may continue to improve over the first year of treatment, and benefits can last as long as the medicine is continued. If sirolimus is stopped, symptoms may come back after several months.
  
  
• What screening and monitoring blood tests are required before starting and while on sirolimus?
  Before starting sirolimus, certain evaluations are needed to make sure it is safe and to help prevent side effects. These tests help your doctor check your health and evaluate for potential problems that sirolimus can cause.
  
  Blood tests and evaluations before starting sirolimus include:
  
  • Full blood count (FBC): This test checks your red and white blood cells and platelets. Sirolimus can lower these blood indices, hence it is important to have these baseline numbers evaluated.
    
  • Kidney function tests: These include creatinine and urea to make sure your kidneys are working well.
    
  • Liver function tests: These check for healthy liver function, since sirolimus is processed by the liver.
    
  • Fasting cholesterol and triglyceride levels: Sirolimus can raise cholesterol and triglycerides.
    
  • Blood pressure measurement: High blood pressure can result from sirolimus, so it should be checked before treatment. Blood pressure monitoring will also be performed during treatment.
    
  • Urine test: Checking for protein or other signs of kidney problems.
    
  
  If any of these tests are abnormal, your doctor may need to treat the problem first or monitor you more closely while you are taking sirolimus. After starting sirolimus, these tests will be regularly repeated to ensure sirolimus is taken safely and working well. Your sirolimus blood levels will also be monitored to keep the dose in the target range.
  
  
• What are possible side effects?
  Most people tolerate sirolimus well, but the most common are mouth sores (oral ulcers), infections, stomach upset, and rashes. Serious side effects are rare but can include lung or blood abnormalities. Doctors will closely monitor these with regular check-ups and blood tests.
  
  
• Medications and foods that may interact with sirolimus
  Some medicines and foods can change how sirolimus works in the body. These interactions may make sirolimus less effective or increase its side effects. It is important to tell your doctor about all medicines, supplements or herbal remedies that you may be taking.
  
  Medicines that can increase sirolimus levels (higher risk of experiencing more side effects):
  
  • Antibiotics and antifungals: erythromycin, clarithromycin, ketoconazole, voriconazole, itraconazole, clotrimazole, fluconazole
    
  • Heart medicines: nicardipine, diltiazem, verapamil
    
  • Others: danazol, bromocriptine, letermovir, protease inhibitors (for HIV or hepatitis C, e.g. ritonavir, indinavir)
    
  • Cannabidiol products
    
  
  Medicines that can lower sirolimus levels (higher risk of decreased efficacy):
  
  • Certain antibiotics: rifampin
    
  • Seizure medicines: carbamazepine, phenytoin, phenobarbital
    
  • Herbal products: St. John’s Wort
  
  Other important interactions:
  
  • Grapefruit and grapefruit juice can increase sirolimus levels and should be avoided.
    
  • Cyclosporine (an immunosuppressant) may increase sirolimus levels if given concurrently; sirolimus should be taken 4 hours after cyclosporine.
    
  
  If you need to take any of these medicines or products, your doctor may need to change your sirolimus dose or monitor your blood levels more closely. Never start or stop any medicine or supplement without talking to your doctor.
  
  As sirolimus reduces the immune system of the body, live vaccines should be avoided. Non-live vaccines can be given. Please inform the doctors that you are on sirolimus before having any vaccines.
  
  In patients at higher risk of infections, prophylactic antibiotics (e.g. oral Bactrim) may be started together with sirolimus to reduce the risk of infections.
  
  
• What happens if sirolimus is stopped?
  Symptoms may return if sirolimus is stopped, and some patients may need to restart treatment. Long-term studies show that sirolimus can be used safely for several years but require regular monitoring.
  
  
• Other treatment options
  Treatment for vascular anomalies may also include observation, sclerotherapy or surgery. Sirolimus or other targeted therapies are often considered when these options are not sufficient or not possible.

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