Meta Information
ID:mtor-inhibitors
Name:
Schema Version:AIM-2.0
Interactions
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Strong CYP3A4 inhibitors block the primary metabolic enzyme for mTOR inhibitors, leading to dangerously high drug levels and increased risk of toxicity.
Actionable advice:
Avoid using strong CYP3A4 inhibitors with mTOR inhibitors unless under strict medical supervision with dose adjustments.
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit and Grapefruit Juice
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Grapefruit contains furanocoumarins that irreversibly inhibit the CYP3A4 enzyme in the gut, dramatically increasing mTOR inhibitor absorption and blood levels.
Actionable advice:
Completely avoid grapefruit and its juice while taking mTOR inhibitors.
Target id:
/dietary/grapefruit-pomelo
Target name:
Seville Oranges, Pomelos, Starfruit
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Similar to grapefruit, these fruits contain compounds that inhibit the CYP3A4 enzyme, which can significantly increase mTOR inhibitor levels.
Actionable advice:
Completely avoid Seville oranges, pomelos, and starfruit while taking mTOR inhibitors.
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
Description:
These agents speed up the metabolism and clearance of mTOR inhibitors by inducing the CYP3A4 enzyme, leading to sub-therapeutic drug levels and loss of efficacy.
Actionable advice:
Avoid using strong enzyme inducers with mTOR inhibitors as they can render the treatment ineffective.
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Description:
St. John's Wort is a potent inducer of the CYP3A4 enzyme and P-glycoprotein, which significantly reduces the concentration and effectiveness of mTOR inhibitors.
Actionable advice:
Do not take St. John's Wort while using mTOR inhibitors.
Target id:
/class/live-vaccines
Target name:
Live Attenuated Vaccines
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
mTOR inhibitors suppress the immune system, which can lead to a reduced vaccine response or, more dangerously, a disseminated infection from the live virus or bacteria in the vaccine.
Actionable advice:
Avoid receiving any live vaccines while on mTOR inhibitor therapy.
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
mTOR inhibitors are contraindicated in pregnancy due to the risk of fetal harm. Effective contraception is required for women of childbearing potential.
Actionable advice:
Do not take mTOR inhibitors if you are pregnant, and use effective birth control during treatment.
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
It is not known if mTOR inhibitors are excreted in human milk, but due to the potential for serious adverse reactions in the infant, breastfeeding is not recommended.
Actionable advice:
Do not breastfeed while taking mTOR inhibitors.
Target id:
/condition/hepatic-impairment
Target name:
Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
mTOR inhibitors are extensively metabolized by the liver; impaired liver function can lead to significantly higher drug levels and increased toxicity.
Actionable advice:
Dose reduction is required for individuals with moderate to severe hepatic impairment.
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Co-administration significantly increases the risk of nephrotoxicity (kidney damage). Cyclosporine also inhibits CYP3A4/P-gp, dramatically increasing sirolimus levels.
Actionable advice:
Avoid co-administration unless part of a specific transplant protocol with rigorous monitoring and dose adjustments.
Target id:
/procedure/major-surgery
Target name:
Major Surgery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
168
Hours after target:
336
Description:
mTOR inhibitors can impair wound healing and increase the risk of surgical complications like fluid collections (seromas) and wound dehiscence.
Actionable advice:
Discontinue use at least 1-2 weeks before and after major surgery, as directed by your physician.
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
major
Interaction type:
requirement
Nature:
absolute
Description:
A high-fat meal can significantly increase the absorption and peak concentration of sirolimus, but this effect can be variable. Consistency is key to stable drug levels.
Actionable advice:
Always take your dose in a consistent manner relative to food, either always with a high-fat meal or always without one.
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel (Cholesterol, Triglycerides)
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Description:
mTOR inhibitors frequently cause hypercholesterolemia and especially hypertriglyceridemia, which requires regular monitoring.
Actionable advice:
Regularly monitor your lipid panel, as management with diet, exercise, or medication may be necessary.
Target id:
/biomarker/complete-blood-count
Target name:
Complete Blood Count (CBC)
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Description:
mTOR inhibitors can suppress bone marrow, leading to anemia (low red blood cells), leukopenia (low white blood cells), and thrombocytopenia (low platelets).
Actionable advice:
Obtain a baseline and periodic CBC to monitor for hematologic side effects.
Target id:
/condition/immunocompromised
Target name:
Immunocompromised State
Severity:
major
Interaction type:
adverse
Nature:
absolute
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:
Use with extreme caution in immunocompromised individuals and monitor closely for signs of infection.
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors (e.g., Diltiazem, Verapamil, Erythromycin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Moderate CYP3A4 inhibitors slow the metabolism of mTOR inhibitors, leading to elevated drug levels and an increased risk of side effects.
Actionable advice:
Use with caution and monitor for side effects; dose adjustments may be necessary under medical guidance.
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
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.
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors (e.g., Lisinopril, Ramipril)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Concurrent use of mTOR inhibitors and ACE inhibitors has been associated with an increased risk of angioedema (swelling of the face, lips, and throat).
Actionable advice:
Monitor for signs of angioedema if taking these medications together and seek immediate medical attention if it occurs.
Target id:
/class/nephrotoxic-agents
Target name:
Other Kidney-Damaging Agents (e.g., NSAIDs, Aminoglycosides)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
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:
Use caution and avoid concurrent use of other nephrotoxic drugs when possible; ensure adequate hydration.
Target id:
/class/statins
Target name:
Statins
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Concurrent use with mTOR inhibitors may increase the risk of myopathy and rhabdomyolysis (severe muscle breakdown), especially with statins metabolized by CYP3A4.
Actionable advice:
Monitor for muscle pain or weakness. Using a statin not metabolized by CYP3A4 (like pravastatin or rosuvastatin) may be safer.
Target id:
/class/herbal-cyp3a4-inhibitors
Target name:
Herbal CYP3A4 Inhibitors (e.g., Quercetin, Berberine, Piperine)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Certain herbal supplements can inhibit the CYP3A4 enzyme, potentially increasing the levels and side effects of mTOR inhibitors.
Actionable advice:
Avoid taking supplements known to inhibit CYP3A4, or discuss with your doctor as dose adjustments may be needed.
Target id:
/biomarker/fasting-glucose
Target name:
Fasting Glucose and HbA1c
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Description:
mTOR inhibitors can cause hyperglycemia (high blood sugar) and new-onset diabetes by inducing insulin resistance.
Actionable advice:
Monitor blood glucose levels and HbA1c periodically, especially if you have pre-existing diabetes or risk factors.
Target id:
/biomarker/advanced-renal-function-panel
Target name:
Renal Function Panel (Creatinine, eGFR)
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Description:
mTOR inhibitors can be associated with proteinuria and a decline in kidney function, especially when used with other nephrotoxic agents.
Actionable advice:
Monitor kidney function with periodic blood and urine tests.
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Liver Function Panel (ALT, AST)
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Description:
Although uncommon, mTOR inhibitors can cause elevations in liver enzymes, indicating potential liver stress or damage.
Actionable advice:
Monitor liver function tests periodically during treatment.
Target id:
/condition/renal-impairment
Target name:
Pre-existing Kidney Disease
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Description:
Patients with pre-existing renal impairment, particularly with proteinuria, may be at higher risk for worsening kidney function while on mTOR inhibitors.
Actionable advice:
Monitor renal function and proteinuria closely if you have pre-existing kidney disease.
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets (e.g., Warfarin, Aspirin, Clopidogrel)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Description:
mTOR inhibitors can cause thrombocytopenia (low platelet count), which may increase the risk of bleeding when combined with blood-thinning medications.
Actionable advice:
Monitor for signs of bleeding or easy bruising and have your platelet count checked regularly.