Sirolimus

What is sirolimus?

Sirolimus is a type of medicine called an immunosuppressant. An immunosuppressant decreases the body’s immune response. It is used to prevent rejection of transplanted organs, such as the kidney, heart and liver. It is also used to prevent and treat graft-versus-host disease (GVHD) in stem cell transplant patients. Sirolimus may also be used to treat other conditions.

You may hear sirolimus called rapamycin or by its brand name, Rapamune®. Sirolimus comes in tablet and liquid forms.

Before giving sirolimus to your child

Tell your doctor if your child has ever reacted to sirolimus or any other medicines.

Talk with the doctor or pharmacist if your child has any of the following conditions. Precautions may need to be taken with this medicine if your child has:

• kidney or liver problems
• infection or recent exposure to infections (such as chickenpox)
• high cholesterol

Make sure your doctor has a complete list of your child’s medicines.

How should you give your child this medicine?

• Give your child sirolimus exactly as your doctor or pharmacist tells you to, even if your child seems well.
• Talk to your child's doctor before you stop giving this medicine for any reason.
• Give your child sirolimus at the same times every day. Your doctor or pharmacist will tell you how often to give your child sirolimus.
• You may give sirolimus with food. Try to keep the type and amount of food the same. Changes in your child's diet may change how sirolimus is absorbed.
• Use the same drink (such as water, orange juice or apple juice) with each dose of sirolimus. DO NOT give GRAPEFRUIT, GRAPEFRUIT JUICE, pomelos or tangelos while your child is taking sirolimus.
• If you are giving tablets, your child should swallow the tablet whole. The tablet should NOT be cut, crushed or chewed.

If you are giving the liquid by mouth

• Put about 40 to 60 mL (3 to 4 tablespoons) of water, orange juice or apple juice into a glass.
• Measure sirolimus using the amber (brown) oral syringe. Squirt the measured amount of sirolimus gently into the glass.
• Stir the contents for about a minute, then give to your child to drink.
• Put another 40 mL (about 3 tablespoons) of water, orange juice or apple juice into the same glass, stir, and then give your child to drink.

It is best to use large volumes of liquid to dilute sirolimus, as instructed above. However, if your child is very young or cannot tolerate large volumes, you can use smaller volumes to dilute the dose. The amount can be calculated by multiplying your child’s dose by 10 mL. (See examples below.)

Example 1: If your child's dose is 0.8 mg:

• 0.8 mg X 10 mL = 8 mL
• Add at least 8 mL of water, orange juice or apple juice into a glass.
• Measure sirolimus using the brown oral syringe.
• Squirt the measured amount of sirolimus gently into the glass.
• Stir the contents for about a minute, then give it to your child to drink.
• Put another 8 mL of water, orange juice or apple juice into the same glass. Stir, then give it to your child to drink.

Example 2: If your child's dose is 1.2 mg:

• 1.2 mg X 10 mL = 12 mL
• Add at least 12 mL of water, orange juice or apple juice into a glass.
• Measure sirolimus using the brown oral syringe.
• Squirt the measured amount of sirolimus gently into the glass.
• Stir the contents for about a minute, then give it to your child to drink.
• Put another 12 mL of water, orange juice or apple juice into the same glass. Stir the contents for about a minute, then give it to your child to drink.

If you are giving the liquid by enteral (feeding) tube

Please remember that sirolimus is a very thick liquid and can block enteral (feeding) tubes. It needs to be diluted to prevent this from happening.

• Add at least 20 mL of water into a glass.
• Measure sirolimus using the brown syringe. Squirt the measured amount of sirolimus gently into the glass.
• Stir the contents for about a minute, then draw up the entire volume into a syringe.
• Give this amount into the enteral tube.
• Put 10 mL of water into the same glass. Stir the contents for about a minute, then draw up in a syringe and give this amount into the enteral tube.
• Flush with an extra 10 mL of water to make sure the sirolimus has traveled through the enteral tube.

What should you do if your child misses a dose?

Give the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose. Give the next dose at the regular time. Do not give your child two doses to make up for one missed dose.

If your child vomits

• If your child vomits a dose within 30 minutes of taking sirolimus, give another dose.
• If it is within 30 minutes to an hour, give half the dose.
• If it is longer than an hour, do not give another dose, but make a note that the dose was vomited.
• Do not repeat the dose more than once.

What are the possible side effects of sirolimus?

Your child may have some of these side effects while they take sirolimus. Check with your child's doctor if your child continues to have any of these side effects, and they do not go away, or they bother your child:

• upset stomach
• vomiting (throwing up)
• diarrhea (loose, watery stools)
• sores in the mouth or throat
• headache
• fatigue
• muscle, joint or back pain
  
• prolonged time for wound to heal
• acne

Call your child's doctor during office hours if your child has any of these side effects:

• unusual tiredness or weakness
• yellowing of the skin or eyes
• frequent urge to urinate (pee)
  
• decrease in the amount of urine being made

Most of the following side effects are not common, but they may be a sign of a serious problem. Call your child's doctor right away or take your child to Emergency if your child has any of these side effects:

• fever, chills
• cough or sore throat
• blood in urine, difficulty urinating or pain with urination
• severe headache
• seizures
• confusion
• shortness of breath or trouble breathing
• chest pain
• fast or irregular heartbeat
• swelling of hands, feet, ankles or lower legs
• severe stomach pain
• skin rash
• unusual bruising or bleeding

What safety measures should you take when your child is using sirolimus?

Sirolimus weakens your child's immune system, so it increases your child's chances of getting an infection. You and your child can take the following precautions to prevent infections:

• Avoid people with infections, such as a cold or the flu.
• Avoid places that are crowded with large groups of people.
• Be careful when brushing or flossing your child's teeth.
• You and your child should not touch your child's eyes or inside the nose without washing hands first.

Your child's health-care team will review with you what to do in case of fever.

Your child's health-care team may prescribe medicine(s) to prevent certain types of infection.

Sirolimus may make your child's skin more likely to sunburn. Make sure your child covers their skin and head with clothing and a hat when outside. Your child should also use sunscreen (a cream that protects the skin from the sun). Look for a sunscreen that says it protects against the sun's ultraviolet rays, called UVA and UVB rays. The sunscreen should have a sun protection factor, called SPF, of at least 30. Ask your pharmacist to help you pick the right sunscreen. Your child should not use tanning lamps or tanning beds.

Your child may NOT have grapefruits, grapefruit juice, pomelos or tangelos for the entire time your child is taking sirolimus. These products may make the sirolimus level in your child's blood go up and increase the chance of having certain side effects. Read the ingredients of mixed fruit juices to make sure that they do not contain grapefruit juice, pomelo juice or tangelo juice.

Drug interactions

It is important to check with your child's doctor or pharmacist before giving your child any other medicines. These include prescription, over the counter, herbal, homeopathic, or natural remedies, supplements, or treatments. Tell your child's doctor or pharmacist if your child takes any other medicines and that your child is taking sirolimus.

There are some medicines that should not be taken together with sirolimus, or in some cases the dose of sirolimus or the other medicine may need to be adjusted. It is important that you tell your doctor and pharmacist if your child takes any other medicines, including:

• macrolide antibiotics (such as clarithromycin or azithromycin)
• antifungals (such as fluconazole or voriconazole)
• cholesterol medications (such as atorvastatin)
• other immunosuppressants
• anti-seizure medicines (such as phenytoin, carbamazepine or phenobarbital)
• HIV medicines (such as ritonavir)
• cisapride
• calcium channel blockers (such as diltiazem)

If your child is also taking cyclosporine, space the sirolimus dose from cyclosporine by at least 4 hours. If your child is also taking tacrolimus, both medicines can be taken at the same time.

Vaccinations

Your child should not receive any immunizations (vaccines) without your child's doctor's approval. Your child or anyone else in your household should not get the oral polio vaccine while your child is being treated with sirolimus. Tell your child's doctor if anyone in your household has recently received the oral polio vaccine. Your child should avoid contact with anyone who has recently received this vaccine. Other live vaccines that your child should not get include measles, mumps and rubella (MMR), varicella (chickenpox) vaccine, yellow fever, rotavirus and the live flu vaccine. Other family members in your household can still get these live vaccines.

Fertility

There is a chance that sirolimus may cause birth defects if it is taken at the time of conception or if it is taken during pregnancy. Sirolimus may also impair male fertility and may greatly decrease your child's ability to father a child of their own. This is usually reversible after sirolimus is stopped. If your child is sexually active, it is best that they use a form of birth control while receiving sirolimus. Tell the doctor right away if your child may be pregnant or would like to become pregnant.

After your child stops taking sirolimus

After your child stops receiving sirolimus, it may still cause side effects. These delayed effects may include certain types of cancer. Your child's doctor will be able to give you more details about this.

Check with your doctor immediately if any of the following signs occur, even after sirolimus treatment has stopped:

• yellow eyes or skin
  
• blood in urine or stools
• black tarry bowel movements
• unusual bleeding or bruising
• stomach, lower back, or side pain
• cough or a hoarse voice
• diarrhea

What other important information should you know about sirolimus?

• Keep a list of all medicines your child is taking and show the list to the doctor or pharmacist.
• Tell the doctor or dentist that your child is taking sirolimus before your child has any operation, even on the teeth, or an emergency treatment.
• Keep all appointments at the clinic or doctor's office so that the doctor can check your child's response to sirolimus. The doctor may need to change the dose so that your child is getting the right amount. The doctor may order blood tests to check for liver or kidney problems, blood cell counts and/or cholesterol levels.
• Blood levels of sirolimus are checked routinely. On days that your child is having a level checked, do not give the morning dose until the blood has been drawn.
• Make sure you always have enough sirolimus to last through weekends, holidays and vacations. Call your pharmacy at least two days before your child runs out of medicine to order refills.
• Keep sirolimus protected from light. If giving the liquid form to your child, use the amber (brown) coloured syringe to measure each dose.
• Keep sirolimus tablets at room temperature in a cool, dry place. Do NOT store it in the bathroom or kitchen.
• Keep sirolimus liquid in the refrigerator. Once opened, contents should be used within 30 days.
• Do not keep any medicines that are out of date. Check with your pharmacist about the best way to throw away outdated or leftover medicines.

Gardez le sirolimus hors de la vue et de la portée de votre enfant. Conservez-le sous clé dans un endroit sécuritaire. Si votre enfant ingère trop de sirolimus, téléphonez à votre centre antipoison local à l'un des numéros suivants. Ces appels sont gratuits.

• Composez le 1-800-POISON-X, ou 1-844-764-7669, de n'importe où au Canada sauf au Québec.
• Composez le 1-800-463-5060 si vous habitez au Québec.