Sirolimus

How Does Sirolimus Work?

Sirolimus works by inhibiting mTOR (mechanistic target of rapamycin), a protein inside immune cells that acts as a master regulator of cell growth and proliferation. When sirolimus enters immune cells, it binds to a protein called FKBP-12. The resulting sirolimus-FKBP12 complex then binds to and blocks mTOR, preventing immune cells (particularly T-cells and B-cells) from dividing in response to signals from cytokines like interleukin-2 (IL-2).

This mechanism is fundamentally different from calcineurin inhibitors like tacrolimus and cyclosporine, which prevent T-cell activation upstream. Sirolimus acts downstream by arresting the cell cycle in the G1 phase, preventing progression to S phase where cell division would occur. This makes sirolimus particularly valuable for patients who need to reduce or eliminate calcineurin inhibitor exposure — such as those with calcineurin inhibitor-induced nephrotoxicity — because sirolimus is significantly less damaging to kidney function.

In lymphangioleiomyomatosis, mTOR is pathologically overactive due to TSC2 gene mutations, driving uncontrolled proliferation of LAM cells in lung tissue. By inhibiting mTOR, sirolimus directly targets the molecular driver of disease progression, stabilizing lung function and slowing cyst formation. The mTOR pathway is also a key regulator of cellular aging, which is why sirolimus is being actively investigated in longevity research.

How Hard Is It to Find Sirolimus in Stock?

Sirolimus has a findability score of 72 out of 100, meaning it is generally available but can be intermittently difficult to locate at standard retail pharmacies. As of early 2026, sirolimus is not listed on the FDA's or ASHP's active drug shortage databases — a positive development compared to some years past. Multiple generic manufacturers (Zydus, Amneal, Teva, Glenmark) now produce sirolimus tablets, providing meaningful supply redundancy.

Despite adequate national supply, many patients encounter stocking gaps at their local retail pharmacy because sirolimus is a specialty medication with relatively low prescription volume. Pharmacies typically order it on demand rather than keeping it stocked. The oral solution (1 mg/mL) and 0.5 mg tablet strength are particularly prone to availability gaps. Patients in areas with fewer transplant centers may face more consistent stocking challenges.

To find sirolimus in stock near you without calling every pharmacy yourself, use medfinder. medfinder contacts pharmacies in your area to check availability and texts you the results. Specialty pharmacies and transplant center-affiliated pharmacies are also highly recommended for more consistent sirolimus supply, particularly for the oral solution formulation.

Who Can Prescribe Sirolimus?

Sirolimus is not a controlled substance and requires no special DEA certification to prescribe. Any licensed physician, nurse practitioner, or physician assistant can write a sirolimus prescription. However, because sirolimus requires therapeutic drug monitoring, complex drug interaction management, and coordination with a transplant or subspecialty program, it is typically initiated and managed by specialists.

• Transplant Nephrologists — primary prescribers for kidney transplant patients
• Transplant Surgeons — may initiate post-transplant immunosuppression
• Pulmonologists — prescribe for LAM, ideally those specializing in rare lung diseases
• Medical Oncologists — prescribe nab-sirolimus (Fyarro) for PEComa
• Nurse Practitioners and Physician Assistants — can prescribe within transplant or subspecialty programs

Telehealth follow-up appointments are available at many transplant centers for established patients on sirolimus, making prescription renewals and trough level reviews more convenient. New patients initiating sirolimus typically require an in-person assessment first.

Is Sirolimus a Controlled Substance?

No. Sirolimus is not a controlled substance and is not scheduled by the DEA. Any licensed prescriber — physician, nurse practitioner, or physician assistant — can legally prescribe sirolimus without any special DEA registration or triplicate prescription requirements.

Sirolimus prescriptions can be transferred between pharmacies without restriction, and prescriptions can be called in, faxed, or transmitted electronically like other non-controlled medications. Because sirolimus is a specialty medication requiring complex management (therapeutic drug monitoring, interaction screening), it is typically prescribed and managed by specialists rather than general practitioners, but this is based on clinical complexity — not legal restriction.

Common Side Effects of Sirolimus

Common side effects that many patients experience include:

• Mouth sores (mucositis)
• High cholesterol and triglycerides (hyperlipidemia)
• Fluid retention and edema
• Nausea, diarrhea
• Low blood counts (anemia, thrombocytopenia)
• Impaired wound healing
• High blood pressure
• Acne, elevated liver enzymes

Serious Side Effects (Seek Immediate Care)

• Serious infections (bacterial, viral, fungal, opportunistic) — boxed warning
• Lymphoma and skin cancers — boxed warning
• Interstitial lung disease / pneumonitis (new or worsening shortness of breath)
• Severe allergic reaction (angioedema) — facial swelling, difficulty breathing
• Not approved for liver or lung transplant patients — increased mortality risk

Final Thoughts on Sirolimus

Sirolimus (Rapamune) is one of the most pharmacologically interesting drugs in transplant medicine — originally discovered in soil bacteria from Easter Island, it has become a critical tool for kidney transplant recipients and the only oral treatment for LAM. Its mTOR-inhibiting mechanism distinguishes it from calcineurin inhibitors and provides a valuable alternative for patients who need to minimize kidney damage from tacrolimus or cyclosporine.

Access challenges are real but manageable. Generic sirolimus is produced by multiple manufacturers, keeping national supply stable. The primary challenge is stocking at retail pharmacies, which can be solved by using specialty pharmacies, mail-order supplies, and early refill practices. Cost can be dramatically reduced using GoodRx or SingleCare coupons for generic sirolimus (as low as $35/month) or through Pfizer's RxPathways program for brand Rapamune.

If you're having trouble locating sirolimus at your pharmacy, medfinder helps you find which pharmacies near you have it in stock — quickly, without the calls. Always take sirolimus exactly as prescribed, never miss doses without contacting your transplant team, and keep up with your scheduled blood level monitoring.