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Sirolimus oral


Oral formulations of sirolimus.

Drugs List

  • RAPAMUNE 1mg tablets
  • RAPAMUNE 1mg/ml oral solution
  • RAPAMUNE 2mg tablets
  • RAPAMUNE 500microgram tablets
  • sirolimus 1mg tablets
  • sirolimus 1mg/ml oral solution sugar-free
  • sirolimus 2mg tablets
  • sirolimus 500microgram tablets
  • Therapeutic Indications


    Renal transplant rejection - prevention
    Sporadic lymphangioleiomyomatosis (S-LAM)

    Prophylaxis of organ rejection in adult patients at low or moderate immunological risk receiving a renal transplant.

    Sporadic lympangioleiomyomatosis (S-LAM) with moderate lung disease or declining lung function.


    Patients should receive the same dose when switching between oral solutions and tablet formulations. Verification that the sirolimus trough concentration levels remains within the recommended target ranges should be carried out 1 to 2 weeks later. When switching between different tablet strengths, verification of trough concentrations is recommended.

    Due to manufacturing differences multiples of the 500 microgram tablets are not a suitable substitute for other tablet strengths.


    Prophylaxis of organ rejection
    Initial therapy (2 to 3 months post-transplantation)
    Loading dose: 6mg loading dose, administered as soon as possible after transplantation.
    Initial dose: 2mg once daily.

    The dose should then be individualised to obtain whole blood trough levels of 4 to 12 nanograms/ml. Sirolimus therapy should be optimised with a tapering regimen of steroids and ciclosporin microemulsion.

    Maintenance therapy
    Sirolimus dose should be adjusted to obtain whole blood trough levels of 12 to 20 nanograms/ml (while ciclosporin should be progressively discontinued over 4 to 8 weeks). Maximum dose per day should not exceed 40mg. Sirolimus should be given with corticosteroids.

    In patients for whom ciclosporin withdrawal is either unsuccessful or cannot be attempted, the combination of ciclosporin and sirolimus should not be maintained for more than 3 months post-transplantation. In such patients, when clinically appropriate, sirolimus should be discontinued and an alternative immunosuppressive regimen instituted.

    Sporadic lymphangioleiomyomatosis (S-LAM)
    Initial dose: 2mg once daily.

    Measure sirolimus whole blood trough concentrations in 10 to 20 days, and adjust dosage to maintain concentrations between 5 and 15 nanograms/ml. After adjustment, patients should continue on the new maintenance dose for 7 to 14 days before further adjusting the dose. Once a stable dose is achieved, perform therapeutic drug monitoring every 3 months.

    Patients with Hepatic Impairment

    In patients with severe hepatic impairment, it is recommended that the maintenance dose of sirolimus be reduced by approximately 50%.

    Therapeutic Drug Monitoring

    If patients have switched between the tablet and oral solution formulations, it is recommended that a trough concentration be taken 1 or 2 weeks after switching formulations to confirm that the trough concentration is within the recommended target range.

    Target whole blood trough concentrations
    Prophylaxis of organ rejection
    Initial therapy (in combination with ciclosporin): 4 to 12 nanograms per ml.
    Maintenance therapy (following discontinuation of ciclosporin therapy): 12 to 20 nanograms/ml.

    Adjustments in sirolimus dosage should be based on more than a single trough level obtained more than 5 days after a previous dose change.

    Sporadic lymphangioleiomyomatosis (S-LAM)
    5 to 15 nanograms/ml.

    After adjustment, patients should continue on the new maintenance dose for 7 to 14 days before further adjusting the dose.


    Children under 18 years

    Precautions and Warnings

    Body mass index above 30kg per square metre
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    Hereditary fructose intolerance
    Lactose intolerance

    Administration of live vaccines is not recommended
    Cytomegalovirus prophylaxis recommended for 3 months following transplant
    Afro-Caribbean or black patients may show reduced response
    Prophylaxis for Pneumocystis carinii required for 12 months post transplant
    Treatment to be initiated and supervised by a specialist
    May contain polysorbate
    Oral solution contains alcohol
    Some formulations contain lactose
    Some formulations contain sucrose
    Some products contain arachis (peanut) oil, soya or soya derivative
    500microgram tablets are not bioequivalent with other tablet strengths
    Take at the same time in respect to food as absorption may be affected
    Consider immunosuppressant adjustment in the event of PML
    Monitor for protein in urine
    Monitor hepatic function
    Monitor renal function during concurrent administration with ciclosporin
    Monitor serum lipids
    Monitor whole blood levels closely in hepatic impairment
    Monitor whole blood levels to adjust dose
    Consider changes to immunosuppressive regime if creatinine rises
    Consider immunosuppressant adjustment if BK virus nephropathy develops
    Delayed graft function: Sirolimus may delay recovery of renal function
    Immunosuppressive drugs may increase risk of malignancy
    May reduce effectiveness of vaccinations during treatment
    Oversuppression of immune system may increase susceptibility to infection
    Treatment may adversely affect wound healing
    Dose adjustment required when ciclosporin progressively discontinued
    Combination treatment with ciclosporin should not exceed 3 months
    Advise patient not to take St John's wort concurrently
    Advise patient grapefruit products may increase plasma level
    May cause impaired fertility
    Female: Contraception required during and for 3 months after treatment
    Advise patient on appropriate sun protection methods
    Advise patient to avoid exposure to sunlight and UV rays during treatment

    Sirolimus is associated with increased serum cholesterol and triglycerides. Patients should be monitored for hyperlipidaemia and if hyperlipidaemia is detected, subsequent interventions such as diet, exercise and lipid-lowering agents should be initiated. The risk/benefit should be considered in patients with established hyperlipidaemia before initiating an immunosuppressive regimen and continued therapy should be re-evaluated in patients with severe refractory hyperlipidaemia.

    There is limited information indicating that black renal transplant recipients (predominantly African-American) require higher doses and trough levels of sirolimus to achieve the same efficacy as observed in non-black patients. Currently, the efficacy and safety data are too limited to allow specific recommendations for use of sirolimus in black recipients.

    Pregnancy and Lactation


    Sirolimus is contraindicated in pregnancy.

    At the time of writing there is no adequate data for the use of sirolimus in pregnant women.

    Studies in animals have shown reproductive toxicity but not teratogenicity. The potential risk for humans is unknown. Briggs concludes that if sirolimus is used during pregnancy or in the case of inadvertent exposure, close monitoring of the embryo / foetus for developmental toxicity is warranted.

    The effect of concurrent therapies must also be considered.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Sirolimus is contraindicated in breastfeeding.

    At the time of writing there is not adequate data to support use in breastfeeding. The low molecular weight and long half life suggest excretion into breast milk will occur. The effects of potential exposure on a nursing infant are unknown but consideration should be given to the carcinogenic properties of sirolimus.

    Following administration of radio labelled sirolimus, radioactivity is excreted in the milk of lactating rats.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Abdominal pain
    Acute hepatic necrosis (sometimes fatal)
    Altered liver function tests
    Alveolar proteinosis
    Anaphylactic reaction
    Anaphylactoid reaction
    Anastomotic disruption
    Bacterial infection
    BK virus associated with nephropathy
    Bronchiolitis obliterans
    Cytomegalovirus infection
    Deep vein thrombosis (DVT)
    Epstein-Barr virus
    Exfoliative dermatitis
    Fascial dehiscence
    Focal segmental glomerulosclerosis
    Fungal infection
    Haemolytic uraemic syndrome
    Herpes simplex
    Herpes zoster
    Hypersensitivity reactions
    Impaired fertility
    Impaired healing
    Impairments of sperm parameters
    Increase in lactate dehydrogenase
    Increase in serum ALT/AST
    Increased risk of skin cancer
    Increased susceptibility to development of lymphoma and other malignancies
    Increased susceptibility to infection
    Interstitial lung disease
    Lymphoproliferative disorders
    Mycobacterial infection
    Nephrotic syndrome
    Pericardial effusion
    Peripheral oedema
    Pleural effusion
    Progressive multifocal leukoencephalopathy (PML)
    Pulmonary embolism
    Pulmonary fibrosis
    Pulmonary haemorrhage
    Serum creatinine increased
    Thrombotic thrombocytopenic purpura
    Urinary tract infections
    Vasculitis (allergic)
    Viral infection


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: January 2016

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    NICE Evidence Services Available at: Last accessed: 11 January 2016

    Summary of Product Characteristics: Rapamune. Wyeth Pharmaceuticals Ltd. Revised October 2018.

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