Meta Information
ID:mtor-inhibitors
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 inhibitors block the primary enzyme that metabolizes rapamycin, leading to dangerously high drug levels and increased risk of severe toxicity.
Actionable advice:
Strong CYP3A4 inhibitors should not be used at all while taking rapamycin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit and Grapefruit Juice (Contains)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit contains compounds that are potent inhibitors of the CYP3A4 enzyme in the gut wall, dramatically increasing rapamycin absorption and blood levels.
Actionable advice:
Grapefruit and its juice should not be consumed at any time while on rapamycin therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because grapefruit juice inhibits the CYP3A4-mediated metabolism of sirolimus, it must not be taken with sirolimus
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
informational_none
Target id:
/class/broad-spectrum-inducers
Target name:
Strong CYP3A4/P-gp Inducers (e.g., Rifampin, Carbamazepine, Phenytoin)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs (e.g., rifampin) speed up the activity of the CYP3A4 enzyme, causing rapamycin to be cleared from the body too quickly, rendering it ineffective.
Actionable advice:
Strong CYP3A4 inducers should not be used, as they will eliminate the effects of rapamycin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort is a potent inducer of the CYP3A4 enzyme, which significantly accelerates rapamycin metabolism and can lead to a complete loss of therapeutic effect.
Actionable advice:
St. John's Wort supplements should not be taken while using rapamycin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Drugs and other agents that could decrease sirolimus concentrations: Carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort (Hypericum perforatum)
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/class/live-vaccines
Target name:
Live Attenuated Vaccines
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin suppresses the immune system, which can allow the weakened virus or bacteria in a live vaccine to cause a serious, widespread infection.
Actionable advice:
All live vaccines should be avoided while on rapamycin and for a period after stopping.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The use of live vaccines should be avoided during treatment with sirolimus; live vaccines may include, but are not limited to, the following: measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid.
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin can cause harm to a developing fetus and is contraindicated during pregnancy.
Actionable advice:
Rapamycin should not be taken during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Based on animal studies and the mechanism of action, sirolimus can cause fetal harm when administered to a pregnant woman
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if rapamycin passes into breast milk, but due to the potential for serious adverse reactions in a nursing infant, it is contraindicated.
Actionable advice:
Rapamycin should not be taken while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
There is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Since rapamycin is extensively metabolized by the liver, liver dysfunction can lead to significantly higher drug levels and toxicity.
Actionable advice:
Requires dose reduction and careful monitoring in individuals with impaired liver function.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The maintenance dose of sirolimus should be reduced in patients with hepatic impairment
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
adjust_with_prescriber
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Co-administration with other potent immunosuppressants like cyclosporine or tacrolimus greatly increases the risk of over-immunosuppression, leading to severe infections and potential kidney toxicity.
Actionable advice:
Co-administration should be avoided unless under the strict supervision of a transplant specialist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The concomitant use of sirolimus with a calcineurin inhibitor may increase the risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/procedure/major-surgery
Target name:
Major Surgery
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
168
Hours after target:
336
Description:
Rapamycin can impair wound healing and increase the risk of post-surgical complications like fluid collections (lymphoceles).
Actionable advice:
Rapamycin should be discontinued at least 1-2 weeks before and after major surgery, as directed by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
There have been reports of impaired or delayed wound healing in patients receiving sirolimus, including lymphocele and wound dehiscence
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
moderate
Interaction type:
informational
Nature:
conditional
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A high-fat meal increases the level of rapamycin while it decreases the level of everolimus. Thus the exposure effect of a high-fat meal is strictly dependent on the specific drug and cannot be generalized at a class-level.
Actionable advice:
At healthspan doses and regimens, rapamycin is expected to be more effective when taken with some fat-containing foods. Everolimus is not commonly used as a healthspan intervention.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
a high-fat meal (861.8 kcal, 54.9% kcal from fat) increased the mean total exposure (AUC) of sirolimus by 23 to 35%, compared with fasting.
Label source:
FDA sirolimus prescribing information
Source url:
Exact phrase from label:
In healthy subjects, a high-fat meal (containing approximately 1000 calories and 55 grams of fat) reduced systemic exposure to AFINITOR 10 mg (as measured by AUC) by 22% and the peak blood concentration C max by 54%.
Label source:
FDA everolimus (AFINITOR) prescribing information — Effect of Food
Action type:
informational_none
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel (Cholesterol, Triglycerides)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin frequently causes hypercholesterolemia and hypertriglyceridemia by altering lipid metabolism.
Actionable advice:
Regular monitoring of your lipid panel (cholesterol, triglycerides) is required while on therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Any patient who is administered sirolimus should be monitored for hyperlipidemia.
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/biomarker/complete-blood-count
Target name:
Complete Blood Count (CBC)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin can suppress bone marrow function, potentially leading to anemia (low red blood cells), leukopenia (low white blood cells), and thrombocytopenia (low platelets).
Actionable advice:
Periodic monitoring of a complete blood count (CBC) is necessary to screen for hematologic side effects.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/condition/immunocompromised
Target name:
Immunocompromised State
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
mTOR inhibitors are immunosuppressants and can increase the risk and severity of infections, including opportunistic infections, in individuals who are already immunocompromised.
Actionable advice:
This should be used with extreme caution in immunocompromised individuals, and close monitoring for signs of infection is important.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
WARNING: IMMUNOSUPPRESSION
Label source:
Action type:
monitor
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors (e.g., Diltiazem, Verapamil, Erythromycin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Moderate CYP3A4 inhibitors significantly slow the metabolism of rapamycin, which can cause toxic accumulation of the drug in the body.
Actionable advice:
Moderate CYP3A4 inhibitors should not be used; if unavoidable, this requires significant dose reduction and close medical monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Exercise caution when using sirolimus with drugs or agents that are modulators of CYP3A4 and P-gp. The dosage of sirolimus and/or the co-administered drug may need to be adjusted
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
avoid
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Food affects the absorption of mTOR inhibitors. To ensure predictable and stable blood levels, the drug should be taken consistently, either always with food or always without food.
Actionable advice:
Establish a routine and always take your dose consistently with or without food.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
administered orally once daily, consistently with or without food
Label source:
Action type:
informational_none
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors (e.g., Lisinopril, Ramipril)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
An increased risk of angioedema (rapid swelling of the skin, throat, and tongue) has been reported when rapamycin is taken with ACE inhibitors.
Actionable advice:
It is worth watching out for any signs of swelling, particularly of the face and airways, when using this combination.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The concomitant use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme (ACE) inhibitors, may increase the risk of developing angioedema.
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/class/nephrotoxic-agents
Target name:
Other Kidney-Damaging Agents (e.g., NSAIDs, Aminoglycosides)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
mTOR inhibitors can be nephrotoxic on their own, and this risk is amplified when combined with other drugs known to harm the kidneys.
Actionable advice:
Caution is warranted, and concurrent use of other nephrotoxic drugs is best avoided when possible; adequate hydration helps.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caution should be exercised when using agents (e.g., aminoglycosides and amphotericin B) that are known to have a deleterious effect on renal function
Label source:
Action type:
avoid
Target id:
/class/statins
Target name:
Statins
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combination of rapamycin and statins may increase the risk of myopathy and rhabdomyolysis (severe muscle breakdown).
Actionable advice:
This is best used with caution, and it is important to promptly report any unexplained muscle pain, tenderness, or weakness.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The concomitant administration of sirolimus and HMG-CoA reductase inhibitors resulted in adverse reactions such as CPK elevations (3%), myalgia (6.7%) and rhabdomyolysis (<1%).
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/class/herbal-cyp3a4-inhibitors
Target name:
Herbal CYP3A4 Inhibitors (e.g., Quercetin, Berberine, Piperine)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain herbal supplements can inhibit the CYP3A4 enzyme, potentially increasing the levels and side effects of mTOR inhibitors. [class-derived from: rapamycin_systemic_healthspan]
Actionable advice:
Supplements known to inhibit CYP3A4 are best avoided, or discussed with a doctor as dose adjustments may be needed.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/biomarker/fasting-glucose
Target name:
Fasting Glucose and HbA1c
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
mTOR inhibitors can cause hyperglycemia (high blood sugar) and new-onset diabetes by inducing insulin resistance.
Actionable advice:
Blood glucose levels and HbA1c are best monitored periodically, especially with pre-existing diabetes or risk factors.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Hyperglycemia, hypercholesterolemia and hypertriglyceridemia have been reported
Label source:
Action type:
monitor
Target id:
/biomarker/advanced-renal-function-panel
Target name:
Renal Function Panel (Creatinine, eGFR)
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
mTOR inhibitors can be associated with proteinuria and a decline in kidney function, especially when used with other nephrotoxic agents.
Actionable advice:
Kidney function should be monitored with periodic blood and urine tests.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor renal function prior to treatment and periodically thereafter
Label source:
Action type:
monitor
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Liver Function Panel (ALT, AST)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Although uncommon, mTOR inhibitors can cause elevations in liver enzymes, indicating potential liver stress or damage.
Actionable advice:
Liver function tests should be monitored periodically during treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The maintenance dose of sirolimus should be reduced in patients with hepatic impairment
Label source:
Action type:
monitor
Target id:
/condition/renal-impairment
Target name:
Renal Impairment (Cleared)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While not cleared by the kidneys, rapamycin can be nephrotoxic, and its use may worsen kidney function, especially when combined with other kidney-harming drugs.
Actionable advice:
This is best used with caution in individuals with pre-existing kidney disease, and it is a good idea to monitor renal function regularly.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Dosage adjustment is not required in patients with renal impairment
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets (e.g., Warfarin, Aspirin, Clopidogrel)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin can cause thrombocytopenia (low platelets), which may modestly increase the risk of bleeding when combined with drugs that thin the blood.
Actionable advice:
This is best used with caution, and it is worth monitoring for signs of unusual bruising or bleeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The most common (>= 30%) adverse reactions observed with sirolimus in clinical studies for organ rejection prophylaxis in recipients of renal transplantation are: peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia.
Label source:
Rapamune (sirolimus) FDA label, Sec. 6 Adverse Reactions. The label establishes thrombocytopenia as a common sirolimus effect; the additive bleeding risk with anticoagulants/antiplatelets is the class inference built on that labeled effect.
Action type:
monitor
Target id:
/biomarker/comprehensive-metabolic-panel
Target name:
Comprehensive Metabolic Panel
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
This test is essential for monitoring kidney function (BUN, creatinine), liver function (AST, ALT), and electrolytes, all of which can be affected by rapamycin.
Actionable advice:
Obtain a comprehensive metabolic panel (CMP) at baseline and periodically during treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Renal function should be closely monitored during the co-administration of sirolimus with cyclosporine
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/biomarker/hemoglobin-a1c
Target name:
Hemoglobin A1c
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin can impair glucose tolerance and insulin sensitivity, potentially leading to hyperglycemia or new-onset diabetes.
Actionable advice:
Fasting glucose and HbA1c should be monitored regularly to detect any changes in blood sugar control.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In a second study evaluating the safety and efficacy of conversion from tacrolimus to sirolimus 3 to 5 months post kidney transplant, a higher rate of adverse events, discontinuations due to adverse events, acute rejection, and new onset diabetes mellitus was observed following conversion to sirolimus.
Label source:
Rapamune (sirolimus) FDA label, Sec. 6.4 Conversion from Calcineurin Inhibitors. Hyperglycemia and diabetes mellitus are also listed as adverse reactions (Sec. 6.1, 6.7). FLAG: the label documents hyperglycemia/new-onset diabetes but does not use the phrase 'impaired insulin sensitivity'; that mechanism is from the longevity/mTOR literature, not the FDA label.
Action type:
monitor
Target id:
/condition/fasted-state
Target name:
Fasted State
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
2
Description:
Taking rapamycin in a fasted state (or with a light, low-fat meal) provides the most consistent and predictable absorption, which is crucial for stable dosing.
Actionable advice:
A dose is best taken consistently, either on an empty stomach or with a light, low-fat meal.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus tablets are to be administered orally once daily, consistently with or without food
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
separate
Target id:
/class/fibrates
Target name:
Fibrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Similar to statins, co-administration with fibrates can increase the risk of developing severe muscle toxicity (myopathy).
Actionable advice:
This is best used with caution, and it is a good idea to monitor for any signs of muscle pain or weakness.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
up to 90% of patients required treatment for hyperlipidemia and hypercholesterolemia with anti-lipid therapy (e.g., statins, fibrates).
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor
Target id:
/intervention/resistance-training
Target name:
Resistance Training
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
24
Hours after target:
48
Description:
Rapamycin inhibits mTORC1, a key signaling pathway for muscle protein synthesis, potentially blunting the muscle-building effects of resistance exercise for 1-2 days after dosing.
Actionable advice:
Schedule intense resistance training sessions at least 2 days after your weekly rapamycin dose.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established mTOR biology: rapamycin/sirolimus inhibits mTORC1, the central regulator of muscle protein synthesis, so it can blunt the hypertrophic response to resistance exercise (rapamycin-muscle-anabolism literature). This is a mechanistic/longevity inference, NOT a statement in the sirolimus FDA label, which does not address exercise.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/intermittent-fasting
Target name:
Intermittent Fasting
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
null
Description:
Both rapamycin and fasting inhibit the mTOR pathway, potentially leading to a synergistic effect on cellular autophagy and other longevity-related processes.
Actionable advice:
Consider taking your weekly rapamycin dose during your fasting window to enhance its effects.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: rapamycin (direct mTORC1 inhibition) and fasting/caloric restriction (nutrient-sensing mTOR downregulation) converge on reduced mTOR signalling and increased autophagy; an additive longevity effect is biologically plausible but unstudied as a combination and is not in the FDA label.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/spermidine
Target name:
Spermidine
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine is a natural polyamine that induces autophagy through a different mechanism than rapamycin, suggesting a potential for additive or synergistic cellular clean-up effects.
Actionable advice:
It may be beneficial to take spermidine on the same day as your rapamycin dose.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: spermidine induces autophagy via EP300/acetylation pathways distinct from mTOR, so co-use with rapamycin could be additive on autophagy. Plausible, longevity-research-level, not demonstrated clinically and not in the FDA label.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/potassium-elevators
Target name:
Potassium Elevators
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rapamycin can sometimes cause hyperkalemia (high potassium), and this risk may be increased when taken with other medications that also raise potassium levels (e.g., ACE inhibitors, ARBs, spironolactone).
Actionable advice:
It is a good idea to check serum potassium levels, especially when combining with other potassium-sparing agents.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Renal function should be closely monitored during the co-administration of sirolimus with cyclosporine
Label source:
FDA sirolimus prescribing information (effective 2026-03-10)
Action type:
monitor