Meta Information
ID:pde5-inhibitors
Name:
Schema Version:AIM-2.0
Interactions
Target id:
/class/nitrates
Target name:
Nitrate Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
PDE5 inhibitors potentiate the hypotensive effects of nitrates by increasing cGMP levels, leading to excessive vasodilation and a potentially life-threatening drop in blood pressure.
Actionable advice:
Absolutely avoid taking PDE5 inhibitors if you are using any form of nitrate medication (e.g., nitroglycerin).
Target id:
/intervention/riociguat
Target name:
Riociguat
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Both PDE5 inhibitors and riociguat (a soluble guanylate cyclase stimulator) increase cGMP levels, and their combined use can cause severe, symptomatic hypotension.
Actionable advice:
Do not take PDE5 inhibitors and riociguat together under any circumstances.
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Strong inhibitors of the CYP3A4 enzyme block the metabolism of PDE5 inhibitors, leading to dangerously high drug levels and an increased risk of severe side effects like hypotension and priapism.
Actionable advice:
Avoid co-administration, or use a significantly reduced starting dose of the PDE5 inhibitor as directed by a physician.
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
PDE5 inhibitors are primarily metabolized by the liver. Severe liver disease significantly impairs this process, leading to much higher drug levels and an increased risk of toxicity.
Actionable advice:
Use is not recommended or requires significant dose reduction under strict medical supervision in severe liver disease.
Target id:
/condition/renal-impairment
Target name:
Severe Kidney Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
The clearance of PDE5 inhibitors and their metabolites can be significantly reduced in severe kidney disease, leading to drug accumulation and increased risk of side effects.
Actionable advice:
Dose adjustments are required for patients with severe renal impairment; consult your physician.
Target id:
/class/alpha-blockers
Target name:
Alpha-Blockers
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Both alpha-blockers (often used for BPH or hypertension) and PDE5 inhibitors cause vasodilation, and their combined use can lead to an additive drop in blood pressure, causing dizziness or fainting.
Actionable advice:
Separate doses by at least 4 hours and start with the lowest effective dose of each medication.
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
PDE5 inhibitors have a mild systemic vasodilatory effect that can add to the blood pressure-lowering effects of other antihypertensive drugs, increasing the risk of hypotension.
Actionable advice:
Monitor blood pressure when starting or adjusting doses and be aware of potential dizziness.
Target id:
/dietary/alcohol-acute
Target name:
Alcohol
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Both alcohol and PDE5 inhibitors can lower blood pressure. Consuming them together, especially in large amounts, increases the risk of orthostatic hypotension (dizziness upon standing), headache, and increased heart rate.
Actionable advice:
Limit alcohol intake when using PDE5 inhibitors to minimize the risk of side effects.
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Grapefruit contains compounds that inhibit the CYP3A4 enzyme in the gut wall, which can significantly increase the absorption and blood levels of PDE5 inhibitors, raising the risk of side effects.
Actionable advice:
Avoid consuming grapefruit or grapefruit juice while using PDE5 inhibitors.
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Moderate inhibitors of the CYP3A4 enzyme can slow the metabolism of PDE5 inhibitors, leading to increased drug levels and a higher risk of side effects. Dose adjustment is often necessary.
Actionable advice:
Consult a physician, as a lower dose of the PDE5 inhibitor may be required.
Target id:
/class/broad-spectrum-inducers
Target name:
Metabolic Enzyme Inducers (e.g., St. John's Wort, Rifampin)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
Description:
These substances speed up the activity of the CYP3A4 enzyme, causing the body to break down and clear PDE5 inhibitors more quickly, which can significantly reduce their effectiveness.
Actionable advice:
Avoid using strong enzyme inducers with PDE5 inhibitors, as they may not work effectively.
Target id:
/condition/priapism-risk
Target name:
Conditions Predisposing to Priapism
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Individuals with conditions such as sickle cell anemia, multiple myeloma, or leukemia are at a higher risk of developing priapism (a prolonged, painful erection), a rare but serious side effect of PDE5 inhibitors.
Actionable advice:
Use with caution and under medical guidance if you have a condition that increases the risk of priapism.
Target id:
/condition/retinitis-pigmentosa
Target name:
Retinitis Pigmentosa
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
PDE5 inhibitors have a minor inhibitory effect on PDE6, an enzyme found in the retina. In patients with certain hereditary retinal disorders like retinitis pigmentosa, this can pose a risk to vision.
Actionable advice:
Use of PDE5 inhibitors is generally not recommended for individuals with retinitis pigmentosa.
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
A high-fat meal can delay the absorption of certain PDE5 inhibitors (especially sildenafil and vardenafil), resulting in a slower onset of action and potentially a less potent effect.
Actionable advice:
For fastest onset, take on an empty stomach or at least 2 hours away from a high-fat meal.
Target id:
/intervention/l-citrulline
Target name:
L-Citrulline or L-Arginine
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
0
Description:
These amino acids are precursors to nitric oxide (NO). Since PDE5 inhibitors work by prolonging the action of NO, combining them may enhance vasodilatory effects, though this could also slightly increase the risk of low blood pressure.
Actionable advice:
If combining, be mindful of potential additive effects like lightheadedness; consider taking the supplement about an hour before the medication.
Target id:
/intervention/dietary-nitrate
Target name:
Dietary Nitrates (e.g., Beetroot Juice, Leafy Greens)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Foods rich in nitrates can increase the body's production of nitric oxide, which may synergize with the mechanism of PDE5 inhibitors to improve vasodilation. This is distinct and much safer than pharmaceutical nitrates.
Actionable advice:
Consuming nitrate-rich foods as part of a healthy diet is generally safe and may be beneficial.
Target id:
/class/qt-prolonging-agents
Target name:
QT-Prolonging Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Some PDE5 inhibitors (e.g., vardenafil) can cause a small, dose-dependent prolongation of the QT interval. Combining with other drugs that have this effect could theoretically increase the risk of cardiac arrhythmias.
Actionable advice:
Use with caution if you are taking other medications known to prolong the QT interval; consult your doctor.