Ciprofloxacin with Alfentanil Interaction Details

Brand Names Associated with Ciprofloxacin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

Increased ALfentanil exposure and an increased risk of respiratory depression

Interaction Summary

The concomitant use of ALfentanil with CYP3A4 inhibitors may increase ALfentanil concentrations resulting in increased or prolonged opioid effects. Concurrent use may also increase the risk of respiratory depression. If concomitant use is necessary, closely monitor patients for respiratory depression and sedation, and consider decreasing the dose of ALfentanil as necessary. If the CYP3A4 inhibitor is being discontinued, consider increasing ALfentanil dose and closely monitor patients for opioid withdrawal. During a study with healthy volunteers, intravenously and orally administered fluconazole decreased ALfentanil metabolism and increased alfentanil subjective effects and respiratory depression . During another study, dilTIAZem was shown to increase the half-life of ALfentanil by 50%. ALfentanil is metabolized by cytochrome P450 3A enzymes, which are inhibited by dilTIAZem .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

The concomitant use of ALfentanil with CYP3A4 inhibitors may increase ALfentanil concentrations resulting in increased or prolonged opioid effects. Concurrent use may also increase the risk of respiratory depression. If concomitant use is necessary, closely monitor patients for respiratory depression and sedation, and consider decreasing the dose of ALfentanil as necessary. If the CYP3A4 inhibitor is being discontinued, consider increasing ALfentanil dose and closely monitor patients for opioid withdrawal.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of ALfentanil

Literature Reports

A) A study observed a reduction in clearance and distribution volume as well as prolongation of half-life of ALfentanil following concomitant treatment with fluconazole .

B) The effects of IV and oral fluconazole on the pharmacokinetics of ALfentanil were studied in 9 healthy volunteers using a randomized, double-blind, placebo-controlled, cross-over study design. Three phases, at 4-week intervals, were studied and consisted of either oral fluconazole 400 mg and IV saline, oral placebo and IV fluconazole 400 mg, or oral placebo and IV saline. Sixty minutes after the oral administration of fluconazole or placebo, IV ALfentanil 20 mcg/kg was infused over 2 minutes. Intravenous fluconazole decreased the clearance of ALfentanil by approximately 60% (3.1 mL/min/kg vs. 1.3 mL/min/kg) while oral fluconazole decreased the clearance by 55% (3.1 mL/min/kg vs. 1.4 mL/min/kg). The half-life of ALfentanil was prolonged by the presence of IV and oral fluconazole (1.5 hours vs 2.7 hours and 2.5 hours, respectively). Fluconazole also increased ALfentanil-induced subjective effects and respiratory depression. Overall, the route of fluconazole administration had no significant effect on the magnitude of the interaction with ALfentanil. Because ALfentanil is intravenously administered, it bypasses the presystemic metabolism in the intestinal wall and liver so its pharmacokinetics are not dependent on the fluconazole route of administration .

C) A double-blind, randomized, placebo-controlled study of 30 patients undergoing coronary artery bypass surgery was conducted to determine the effects of dilTIAZem on midazolam and ALfentanil pharmacokinetics. Two hours prior to surgery, patients received dilTIAZem 60 mg orally or placebo. DilTIAZem (0.1 mg/kg/hr) or placebo (saline) infusions were initiated prior to anesthesia and continued until the next morning. Anesthesia was induced with 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 started at the beginning of induction and were maintained until skin closure. From the induction time to 23 hours post-operatively, dilTIAZem increased the area under the concentration-time curve (AUC) of midazolam by 15% and ALfentanil by 24%. When evaluating the data from the end of surgery to 23 hours post-op, the AUCs of midazolam and ALfentanil were increased by 24% and 40%, respectively. The mean half-life of midazolam and ALfentanil was increased by 43% and 50%, respectively, when compared to the placebo group. In patients receiving dilTIAZem, extubation was 2.5 hours later on average than the placebo controls. These results indicate that dilTIAZem inhibits the cytochrome P450 3A enzymes which are responsible for midazolam and ALfentanil metabolism .

Ciprofloxacin Overview

• Ciprofloxacin is used to treat or prevent certain infections caused by bacteria such as pneumonia; gonorrhea (a sexually transmitted disease); typhoid fever (a serious infection that is common in developing countries); infectious diarrhea (infections that cause severe diarrhea); and infections of the skin, bone, joint, abdomen (stomach area), and prostate (male reproductive gland), Ciprofloxacin is also used to treat or prevent plague (a serious infection that may be spread on purpose as part of a bioterror attack) and inhalation anthrax (a serious infection that may be spread by anthrax germs in the air on purpose as part of a bioterror attack). Ciprofloxacin may also be used to treat bronchitis, sinus infections, or urinary tract infections but should not be used for bronchitis and sinus infections, or certain types of urinary tract infections if there are other treatment options. Ciprofloxacin extended-release (long-acting) tablets are used to treat kidney and urinary tract infections; however, some types of urinary tract infections should only be treated with ciprofloxacin extended release tablets if no other treatment options are available. Ciprofloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.

• Antibiotics such as ciprofloxacin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.