Belumosudil and Alfentanil: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 15, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Alfentanil
No brand names on recordBelumosudil
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Let me walk you through this one. Alfentanil is a strong opioid pain medicine, and belumosudil (Rezurock) can slow down the liver enzyme that breaks alfentanil down. When that enzyme is blocked, alfentanil can build up in your body and its effects can become stronger or last longer.
The main worry is breathing that becomes too slow or shallow, along with extra drowsiness. This matters most if the Rezurock is started after you are already on a steady alfentanil dose. The good news is that your care team can manage this by adjusting your dose and watching you more closely. Please talk with your doctor or pharmacist before making any changes yourself.
Effect: Belumosudil, a CYP3A4 inhibitor, is expected to reduce alfentanil clearance, increasing alfentanil exposure (AUC) and raising the risk of increased or prolonged opioid effects, including respiratory depression.
- Mechanism: Inhibition of CYP3A4-mediated metabolism of alfentanil (not a prodrug; effect is potentiated).
- Direction: Increased alfentanil effect.
- Evidence/onset: Probable; onset unspecified. Comparator diltiazem prolonged alfentanil half-life by ~50%.
- Management: If co-use is necessary, consider alfentanil dose reduction until stable effects achieved. Monitor for sedation and respiratory depression. On discontinuation of belumosudil, exposure falls; monitor at frequent intervals for reduced efficacy or withdrawal and consider increasing alfentanil.
What happens
Increased ALfentanil exposure and an increased risk of respiratory depression
Interaction Deep Dive
Taking ALfentanil together with CYP3A4 inhibitors can raise ALfentanil exposure, which may lead to greater or more prolonged opioid effects. Such effects may be intensified when ALfentanil and a CYP3A4 inhibitor are used together, especially if the inhibitor is introduced after the patient has reached a stable ALfentanil dose. Once a CYP3A4 inhibitor is stopped and its effects wane, ALfentanil exposure will fall, which can diminish opioid efficacy or trigger a withdrawal syndrome in patients who have become physically dependent on ALfentanil. Should combined use be required, consider lowering the ALfentanil dose until stable drug effects are reached. Discontinuing a CYP3A4 inhibitor may produce ALfentanil exposure below what is expected, decreased efficacy, or possibly a withdrawal syndrome in a patient who has developed physical dependence on ALfentanil. When a CYP3A4 inhibitor is being withdrawn, monitor patients closely at frequent intervals and consider raising the ALfentanil dose1. In a separate study, dilTIAZem was found to lengthen the half-life of ALfentanil by 50%. ALfentanil undergoes metabolism by cytochrome P450 3A enzymes, and dilTIAZem inhibits these enzymes4.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of ALfentanil
How to manage this interaction
Your care team can manage this combination safely with a few steps:
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your alfentanil dose may need to be adjusted and individualized by your team, often lowered, until your response is steady.
- Your team may monitor you more closely for excess drowsiness or slowed breathing, especially when belumosudil is first added.
- If belumosudil is later stopped, your team may watch you closely and consider increasing alfentanil, since its effect can drop and withdrawal is possible.
Tell your pharmacist or doctor right away about unusual sleepiness, confusion, or slow/shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A study noted decreased clearance and volume of distribution, along with an extended half-life of ALfentanil, when it was given together with fluconazole 2.
b) The impact of both intravenous and oral fluconazole on ALfentanil pharmacokinetics was investigated in 9 healthy volunteers through a randomized, double-blind, placebo-controlled, cross-over study. Three phases were conducted at 4-week intervals, comprising either oral fluconazole 400 mg with IV saline, oral placebo with IV fluconazole 400 mg, or oral placebo with IV saline. IV ALfentanil 20 mcg/kg was infused over 2 minutes beginning sixty minutes after the oral administration of fluconazole or placebo. Intravenous fluconazole lowered ALfentanil clearance by roughly 60% (3.1 mL/min/kg vs. 1.3 mL/min/kg), whereas oral fluconazole reduced clearance by 55% (3.1 mL/min/kg vs. 1.4 mL/min/kg). ALfentanil half-life was extended in the presence of both IV and oral fluconazole (1.5 hours vs 2.7 hours and 2.5 hours, respectively). Fluconazole additionally heightened ALfentanil-induced subjective effects and respiratory depression. In general, the route by which fluconazole was administered did not significantly alter the extent of the interaction with ALfentanil. Since ALfentanil is given intravenously, it avoids presystemic metabolism in the intestinal wall and liver, so its pharmacokinetics do not depend on the route of fluconazole administration 3.
c) A double-blind, randomized, placebo-controlled study involving 30 patients undergoing coronary artery bypass surgery was carried out to assess the effects of dilTIAZem on the pharmacokinetics of midazolam and ALfentanil. Two hours before surgery, patients were given either dilTIAZem 60 mg orally or placebo. Infusions of dilTIAZem (0.1 mg/kg/hr) or placebo (saline) were started before anesthesia and continued until the following morning. Anesthesia was induced using midazolam 0.1 mg/kg, ALfentanil 50 mcg/kg, and propofol. Continuous infusions of midazolam 1 mcg/kg/min and ALfentanil 1 mcg/kg/min were begun at the start of induction and continued until skin closure. From induction through 23 hours after surgery, dilTIAZem raised the area under the concentration-time curve (AUC) of midazolam by 15% and of ALfentanil by 24%. When assessing the data from the end of surgery to 23 hours post-op, the AUCs of midazolam and ALfentanil rose by 24% and 40%, respectively. The mean half-life of midazolam and ALfentanil increased by 43% and 50%, respectively, compared with the placebo group. Among patients given dilTIAZem, extubation occurred on average 2.5 hours later than in the placebo controls. These findings indicate that dilTIAZem inhibits the cytochrome P450 3A enzymes responsible for the metabolism of midazolam and ALfentanil 4.
Common questions
Can I take Belumosudil and Alfentanil together?
Belumosudil can raise alfentanil levels and increase the risk of dangerously slow breathing, so your care team may lower the alfentanil dose and monitor you closely, especially when belumosudil is started or stopped. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Belumosudil and Alfentanil interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Belumosudil and Alfentanil interaction managed?
Your care team can manage this combination safely with a few steps: Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your alfentanil dose may need to be adjusted and individualized by your team, often lowered, until your response is steady. Your team may monitor you more closely for excess drowsiness or slowed breathing, especially when belumosudil is fi… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Belumosudil or Alfentanil need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: Alfentanil HCl intravenous injection, alfentanil HCl intravenous injection. Rising Pharma Holdings, Inc (per FDA), East Brunswick, NJ, 2025.
- Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023. DailyMed
- Palkama VJ, Isohanni MH, Neuvonen PJ, et al: The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998; 87:190-194. DOI
- Ahonen J, Olkkola KT, Salmenpera M, et al: Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting. Anesthesiology 1996; 85:1246-1252. PubMed
Keep reading about Alfentanil
Keep reading about Belumosudil
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