Meta Information
ID:rapamycin
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
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:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
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/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
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:
Broad-Spectrum Metabolic Enzyme Inducers
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:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors
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:
/condition/hepatic-impairment
Target name:
Hepatic 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:
/biomarker/lipid-panel
Target name:
Lipid Panel
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
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:
/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:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A high-fat meal increases the absorption of rapamycin.
Actionable advice:
At healthspan doses and regimens, rapamycin is expected to be more effective when taken with some fat-containing foods.
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 (effective 2026-03-10)
Action type:
informational_none
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/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/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:
/class/ace-inhibitors
Target name:
ACE Inhibitors
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:
/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:
/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:
/condition/renal-impairment
Target name:
Renal Impairment
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:
/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/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
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:
/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
Target id:
/intervention/everolimus
Target name:
Everolimus
Severity:
major
Interaction type:
contraindicated
Nature:
absolute
Description:
Both drugs are mTOR inhibitors; using them together causes excessive toxicity and is irrational.
Actionable advice:
These should not be used together; they are alternatives.
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:
Pharmacological inference: everolimus is itself an mTOR inhibitor, so combining it with rapamycin is duplicative - additive immunosuppression and toxicity with no added benefit (pharmacologically irrational). Class-level/contraindicated.
Label source:
Class inference
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/class/mtor-inhibitors
Target name:
mTOR Inhibitors
Severity:
major
Interaction type:
contraindicated
Nature:
absolute
Description:
Combining mTOR inhibitors is redundant and leads to excessive toxicity and side effects.
Actionable advice:
This should not be combined with other mTOR inhibitors.
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:
Pharmacological inference: stacking two mTOR inhibitors is redundant and additively increases toxicity (stomatitis, cytopenias, metabolic, infection risk) without benefit. Class-level/contraindicated.
Label source:
Class inference
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/dronedarone
Target name:
Dronedarone
Severity:
major
Interaction type:
contraindicated
Nature:
absolute
Description:
Dronedarone strongly increases rapamycin levels, leading to a high risk of severe toxicity.
Actionable advice:
Combination is contraindicated; do not use together.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.
Label source:
Rapamune (sirolimus) FDA label, Sec. 7 Drug Interactions - sirolimus is a CYP3A4/P-gp substrate, so CYP3A4/P-gp INHIBITORS raise its blood levels. (dronedarone is a CYP3A4/P-gp inhibitor.)
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/dasatinib
Target name:
Dasatinib
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Both drugs interfere with each other's metabolism, increasing levels and risk of toxicity.
Actionable advice:
This combination should be avoided, or doses adjusted carefully.
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: dasatinib is a CYP3A4 substrate (and weak inhibitor), so mutual CYP3A4 competition can raise sirolimus exposure; additive cytopenias/fluid retention also possible. Label-grounded (CYP3A4) mechanism, compound not individually named.
Label source:
Class inference
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/class/p-glycoprotein-inducers
Target name:
P-glycoprotein Inducers
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Description:
These drugs increase rapamycin removal from the body, severely reducing its effectiveness.
Actionable advice:
This combination should be avoided; it may cause treatment failure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.
Label source:
Rapamune (sirolimus) FDA label, Sec. 7 Drug Interactions - sirolimus is a CYP3A4/P-gp substrate, so CYP3A4/P-gp INDUCERS lower its blood levels and efficacy.
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/cbd
Target name:
CBD
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
CBD significantly increases rapamycin blood levels, raising the risk of serious toxicity.
Actionable advice:
Requires significant rapamycin dose reduction.
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: cannabidiol inhibits CYP3A4 (and P-gp), and the sirolimus label states CYP3A4/P-gp inhibitors raise sirolimus levels - so CBD can increase exposure/toxicity. Label-grounded mechanism; CBD not individually named.
Label source:
Class inference
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/class/p-glycoprotein-inhibitors
Target name:
P-glycoprotein Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
These drugs block rapamycin removal, increasing its absorption and blood levels.
Actionable advice:
Requires rapamycin dose reduction and monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.
Label source:
Rapamune (sirolimus) FDA label, Sec. 7 Drug Interactions - sirolimus is a CYP3A4/P-gp substrate, so CYP3A4/P-gp INHIBITORS raise its blood levels.
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/amiodarone
Target name:
Amiodarone
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Amiodarone increases rapamycin levels in the blood, raising the risk of toxicity.
Actionable advice:
Requires rapamycin dose reduction and monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.
Label source:
Rapamune (sirolimus) FDA label, Sec. 7 Drug Interactions - sirolimus is a CYP3A4/P-gp substrate, so CYP3A4/P-gp INHIBITORS raise its blood levels. (amiodarone is a CYP3A4/P-gp inhibitor.)
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/class/nephrotoxic-agents
Target name:
Nephrotoxic Agents (NSAIDs, ACEi, ARBs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Combining with other drugs harmful to kidneys increases the risk of kidney damage.
Actionable advice:
Kidney function should be monitored closely.
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: sirolimus can add to nephrotoxicity (notably potentiating calcineurin-inhibitor renal injury) and impair renal recovery, so combining with other nephrotoxic agents increases kidney-damage risk. Established class effect.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/berberine
Target name:
Berberine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Berberine can increase rapamycin blood levels, raising the risk of side effects.
Actionable advice:
Berberine inhibits CYP3A4/P-gp and can raise sirolimus levels. If combined, your prescriber should lower the sirolimus dose and check a sirolimus trough level.
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: berberine inhibits CYP3A4 and P-gp; per the sirolimus label, CYP3A4/P-gp inhibitors raise sirolimus levels, so co-use can increase exposure/toxicity. Label-grounded mechanism; compound not individually named.
Label source:
Class inference
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/class/arbs
Target name:
Angiotensin Receptor Blockers (ARBs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Increased risk of angioedema, a serious swelling reaction, when taken together.
Actionable advice:
Swelling of the face, lips, or tongue should be watched for closely.
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: like ACE inhibitors, ARBs combined with mTOR inhibitors may raise angioedema risk (lower than with ACE inhibitors). Caution.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/curcumin-and-piperine
Target name:
Curcumin and Piperine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Piperine increases rapamycin absorption, raising blood levels and side effect risk.
Actionable advice:
Piperine inhibits CYP3A4/P-gp and can raise sirolimus levels. If combined, your prescriber should lower the sirolimus dose and check a sirolimus trough level.
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: piperine is a potent CYP3A4/P-gp inhibitor (and curcumin modulates these), so this combination can raise sirolimus absorption/levels per the label's CYP3A4/P-gp interaction. Label-grounded mechanism.
Label source:
Class inference
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/piperine
Target name:
Piperine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Piperine increases rapamycin absorption, raising blood levels and side effect risk.
Actionable advice:
Piperine inhibits CYP3A4/P-gp and can raise sirolimus levels. If combined, your prescriber should lower the sirolimus dose and check a sirolimus trough level.
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: piperine inhibits CYP3A4 and P-gp and enhances absorption of co-administered drugs; per the sirolimus label, CYP3A4/P-gp inhibitors raise sirolimus levels. Label-grounded mechanism; compound not individually named.
Label source:
Class inference
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/quercetin
Target name:
Quercetin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Quercetin can increase rapamycin blood levels, raising the risk of side effects.
Actionable advice:
Quercetin can inhibit CYP3A4/P-gp and modestly raise sirolimus levels. If combined, monitor a sirolimus trough level and have your prescriber adjust the dose if it rises.
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: quercetin inhibits CYP3A4/P-gp in vitro; per the sirolimus label, CYP3A4/P-gp inhibitors raise sirolimus levels, so a modest increase is plausible. Low-certainty, label-grounded mechanism.
Label source:
Class inference
Action type:
adjust_with_prescriber
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/milk-thistle
Target name:
Milk Thistle (Silymarin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Milk thistle may increase rapamycin blood levels, potentially increasing its side effects.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for side 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: silymarin (milk thistle) has mild, inconsistent CYP3A4/P-gp-modulating activity; a small rise in sirolimus levels is possible but the effect is weak. Low-certainty, label-grounded mechanism.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Rapamycin may slightly increase digoxin levels, potentially increasing its side effects.
Actionable advice:
Digoxin levels should be monitored if used together.
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: digoxin is a P-gp substrate; competition for P-gp with sirolimus could slightly raise digoxin levels. Narrow-therapeutic-index drug - monitor. Mechanistic, modest.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/potassium
Target name:
Potassium
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Rapamycin can increase potassium levels; combining with supplements may lead to hyperkalemia.
Actionable advice:
Potassium levels should be monitored if combining.
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: FLAG - sirolimus is not a classic hyperkalemia-inducing drug, so the premise that it meaningfully raises potassium is weak; any additive effect with potassium supplements is minor/uncertain. Low-confidence row, consider revising.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/intervention/resveratrol
Target name:
Resveratrol
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Resveratrol may increase rapamycin blood levels, potentially increasing its side effects.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for side 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: resveratrol modulates CYP3A4/P-gp in vitro and could modestly raise sirolimus levels; human relevance is uncertain. Low-certainty, label-grounded mechanism.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0
Target id:
/condition/liver-transplant
Target name:
Liver Transplantation
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus use is not recommended in liver transplant patients. Combination with tacrolimus or cyclosporine has been associated with excess mortality, graft loss, and hepatic artery thrombosis (boxed warning).
Actionable advice:
Sirolimus is not recommended after liver transplant (higher risk of hepatic artery thrombosis and graft loss). The transplant team should use an alternative immunosuppressant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The safety and efficacy of sirolimus as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
avoid
Target id:
/condition/lung-transplant
Target name:
Lung Transplantation
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus use is not recommended in lung transplant patients due to reports of bronchial anastomotic dehiscence, often fatal (boxed warning).
Actionable advice:
Sirolimus should not be used as part of an immunosuppressive regimen in de novo lung transplant patients.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
avoid
Target id:
/intervention/cyclosporine
Target name:
Cyclosporine
Severity:
major
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cyclosporine substantially increases sirolimus blood concentrations. Co-administration requires staggered dosing — sirolimus 4 hours after cyclosporine.
Actionable advice:
Sirolimus should be taken 4 hours after cyclosporine oral solution or capsules. Sirolimus trough concentrations should be monitored and the dose adjusted accordingly.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
it is recommended that sirolimus be taken 4 hours after administration of cyclosporine oral solution (MODIFIED) and/or cyclosporine capsules (MODIFIED)
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
separate
Target id:
/intervention/tacrolimus
Target name:
Tacrolimus
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus combined with tacrolimus in de novo liver transplant patients was associated with excess mortality and graft loss.
Actionable advice:
The sirolimus + tacrolimus combination should be avoided in de novo liver transplant patients.
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 sirolimus in combination with tacrolimus was associated with excess mortality and graft loss
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
avoid
Target id:
/intervention/mycophenolate
Target name:
Mycophenolate Mofetil (MMF)
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In de novo renal transplant patients, sirolimus + MMF + steroids + IL-2 antagonist regimen had higher acute rejection rates than the cyclosporine-based control regimen.
Actionable advice:
It is important to talk to the transplant team about regimen selection; standard combinations include cyclosporine, MMF, steroids, and IL-2 receptor antagonist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
de novo renal transplant patients treated with sirolimus, mycophenolate mofetil (MMF), steroids, and an IL-2 receptor antagonist had significantly higher acute rejection rates
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/class/cyp3a4-inducers
Target name:
Strong CYP3A4/P-gp Inducers
Severity:
major
Interaction type:
pharmacokinetic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 and P-gp inducers (rifampin, rifabutin) substantially decrease sirolimus concentrations, risking rejection.
Actionable advice:
Concomitant use should be avoided, and alternative agents should be selected.
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 label: Sirolimus (Rapamune)
Action type:
avoid
Target id:
/dietary/grapefruit-juice
Target name:
Grapefruit Juice
Severity:
major
Interaction type:
pharmacokinetic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit juice inhibits CYP3A4-mediated metabolism of sirolimus.
Actionable advice:
Sirolimus should not be taken with grapefruit juice.
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 label: Sirolimus (Rapamune)
Action type:
avoid
Target id:
/intervention/cannabidiol
Target name:
Cannabidiol (CBD)
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabidiol may increase sirolimus blood levels. Therapeutic drug monitoring and dose reduction may be required.
Actionable advice:
Sirolimus levels should be monitored, it is worth watching out for toxicity, and a sirolimus dose reduction may be warranted.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The blood levels of sirolimus may increase upon concomitant use with cannabidiol
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
adjust_with_prescriber
Target id:
/intervention/verapamil
Target name:
Verapamil
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Verapamil can increase sirolimus concentrations, and sirolimus can increase verapamil concentrations. Both directions warrant monitoring.
Actionable advice:
Sirolimus trough and verapamil levels should be monitored, and dose adjustment may be warranted.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Drugs with concentrations that could increase when given with sirolimus: Verapamil
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
adjust_with_prescriber
Target id:
/intervention/pneumocystis-prophylaxis
Target name:
Pneumocystis (PJP) Prophylaxis
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
PJP cases have been reported in transplant patients not receiving prophylaxis. Standard transplant care requires PJP prophylaxis for 1 year post-transplant.
Actionable advice:
Receive antimicrobial PJP prophylaxis for 1 year following transplantation.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
antimicrobial prophylaxis for Pneumocystis carinii pneumonia should be administered for 1 year following transplantation
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/intervention/cmv-prophylaxis
Target name:
Cytomegalovirus (CMV) Prophylaxis
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CMV prophylaxis is recommended in transplant recipients on sirolimus, particularly those at increased risk.
Actionable advice:
Receive CMV prophylaxis for 3 months post-transplant, especially if at increased risk.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cytomegalovirus (CMV) prophylaxis is recommended for 3 months after transplantation
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/intervention/sun-uv-exposure
Target name:
Sunlight / UV Exposure
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Immunosuppression with sirolimus increases skin cancer risk. UV exposure should be limited.
Actionable advice:
Wear protective clothing and use high-SPF sunscreen; limit sun and UV exposure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/condition/wound-healing
Target name:
Wound Healing / Recent Surgery
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus is associated with fluid accumulation and impairment of wound healing.
Actionable advice:
Plan major surgery with the transplant team; expect delayed wound healing.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fluid Accumulation and Impairment of Wound Healing
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/condition/interstitial-lung-disease
Target name:
Interstitial Lung Disease / Pneumonitis
Severity:
major
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus can cause interstitial lung disease and non-infectious pneumonitis.
Actionable advice:
Sirolimus can cause pneumonitis. If you have interstitial lung disease, report new cough or breathlessness promptly; the drug may need to be stopped if pneumonitis is confirmed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Interstitial Lung Disease/Non-Infectious Pneumonitis
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
monitor
Target id:
/biomarker/proteinuria
Target name:
Proteinuria
Severity:
moderate
Interaction type:
monitoring
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus is associated with proteinuria, especially after conversion from a calcineurin inhibitor.
Actionable advice:
Urine protein should be monitored periodically.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Proteinuria
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
monitor
Target id:
/condition/male-fertility
Target name:
Male Fertility
Severity:
moderate
Interaction type:
adverse
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Azoospermia or oligospermia may occur in males taking sirolimus.
Actionable advice:
It is important to talk to a healthcare provider about fertility implications and sperm banking before therapy initiation.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Male Infertility: Azoospermia or oligospermia may occur
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Food (Consistent Dosing)
Severity:
minor
Interaction type:
pharmacokinetic
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A high-fat meal increases sirolimus exposure 23–35%. The label requires consistent dosing with or without food.
Actionable advice:
Sirolimus is generally best taken consistently with or without food — the same way each day.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
consistently with or without food
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
informational_none
Target id:
/condition/lymphangioleiomyomatosis
Target name:
Lymphangioleiomyomatosis (LAM)
Severity:
moderate
Interaction type:
requirement
Nature:
relative
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sirolimus inhibits the activated mTOR pathway in LAM cells and is FDA-indicated for the treatment of LAM in adults.
Actionable advice:
This is best used under specialist supervision, with monitoring of pulmonary function and trough levels.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sirolimus inhibits the activated mTOR pathway and thus the proliferation of LAM cells
Label source:
FDA label: Sirolimus (Rapamune)
Action type:
monitor
Target id:
/class/cns-depressants
Target name:
CNS Depressants
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
General caution when combined with other active therapeutic agents.
Actionable advice:
It is important to talk to a physician before combining this with other medications.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Generic placeholder row: the text is non-specific ('general caution') and there is no established CNS-depressant interaction for this agent. No validatable interaction claim - marked unvalidatable (candidate for removal).
Action type:
informational_none
Merged From
- rapamycin_systemic_disease
- rapamycin_systemic_healthspan