Zolpidem with Crizotinib Interaction Details
Brand Names Associated with Zolpidem
- Ambien®
- Ambien® CR
- Edluar®
- Intermezzo®
- Zolpidem
- Zolpimist®
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased zolpidem exposure
Interaction Summary
Concomitant use of zolpidem and a CYP3A inhibitor may increase the exposure and pharmacodynamic effects of zolpidem. Consider using another zolpidem tartrate immediate-release product for a lower zolpidem tartrate dose (5 mg). In a study of concomitant use with ketoconazole (strong CYP3A inhibitor), zolpidem Cmax and AUC increased and the half-life was prolonged. Additionally, there was an increase in the pharmacodynamic effects of zolpidem . In another study with concomitant ritonavir, the clearance of zolpidem was reduced . If zolpidem and a strong CYP3A inhibitor are coadministered, consider using a lower zolpidem dose .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of zolpidem and a CYP3A inhibitor may increase the exposure and pharmacodynamic effects of zolpidem. Consider using another zolpidem tartrate immediate-release product for a lower zolpidem tartrate dose (5 mg). Consider using a lower zolpidem dose if a strong CYP3A inhibitor is coadministered .
Mechanism Of Interaction
Inhibition of CYP3A-mediated metabolism of zolpidem
Literature Reports
A) Coadministration of a single dose of zolpidem tartrate 5 mg and ketoconazole (a potent CYP3A4 inhibitor) 200 mg twice daily for 2 days increased zolpidem Cmax by 30% and the total AUC by 70% compared to zolpidem alone and prolonged the half-life of zolpidem by 30%. Additionally there was an increase in the pharmacodynamic effects of zolpidem .
B) The zolpidem Cmax, total AUC, and half-life were significantly increased after pretreatment with fluvoxaMINE in a pharmacokinetic trial with 20 healthy male volunteers (22 to 30 years old). Participants were given a single dose of zolpidem 5 mg (day 1), followed by 6 days of fluvoxaMINE 100 mg/day (days 2 to 7), and a second dose of zolpidem 5 mg together with fluvoxaMINE 100 mg on day 8. The mean Cmax of zolpidem was 56.4 +/- 25.6 nanograms (ng)/mL on day 1 and 67.3 +/- 25.8 ng/mL after pretreatment with fluvoxaMINE (p=0.005; 90% CI, 1.10 to 1.37), and the zolpidem AUC(0 to infinity) increased by approximately 150% from 200.9 +/- 116.8 ng x hr/mL to 512 +/- 354.6 ng x hr/mL after pretreatment (p less than 0.0001; 90% CI, 2.14 to 2.71). The half-life was 2.24 +/- 0.8 hours with zolpidem alone compared with 4.99 +/- 2.92 hours with concomitant fluvoxaMINE (p less than 0.0001). Chronic use of concomitant zolpidem and fluvoxaMINE might lead to enhanced adverse effects associated with zolpidem .
C) Coadministration of a single dose of zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state levels in male subjects resulted in a 34% increase in zolpidem AUC(0 to infinity), but no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance .
D) Increased plasma concentrations and pharmacodynamic effects of zolpidem when coadministered with ketoconazole were demonstrated in a randomized, double-blind, 5-way crossover study of 12 healthy volunteers. The study involved five treatment protocols: (a) zolpidem placebo plus azole placebo, (b) 5 mg zolpidem plus azole placebo, (c) zolpidem plus ketoconazole, (d) zolpidem plus itraconazole, and (e) zolpidem plus fluconazole. The mean clearance of zolpidem was decreased from 422 mL/min for the (b) treatment group to 250 mL/min for the (c) treatment group. Changes also were noted in the elimination half-life (t1/2) from 1.86 to 2.41 hours, and AUC from 254 to 424 ng/mL/hr. The ketoconazole group also demonstrated pharmacodynamic changes as expressed by EEG beta amplitude increases and impairment of DSST (digit-symbol substitution test) scores, as well as slight impairment of delayed recall. There were no significant changes in kinetics or dynamics of zolpidem in the other azole treatment groups .
E) In a pharmacokinetic study (n=19), concomitant administration of single-dose zolpidem 5 mg and telaprevir 750 mg every 8 hours for 10 days resulted in decreases in zolpidem AUC and Cmax. The ratio estimate for zolpidem AUC and Cmax (with telaprevir to without telaprevir) was 0.53 and 0.58 , respectively .
F) A study involving 6 healthy male volunteers demonstrated that coadministration of ritonavir and zolpidem did not alter pharmacodynamic effects of zolpidem. Each patient received zolpidem 5 mg and 4 scheduled doses of ritonavir 200 mg. The results included a significant reduction in zolpidem clearance to 78% of control values. The elimination half-life was prolonged from 2 to 2.4 hours, which was not significant .
Zolpidem Overview
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Zolpidem is used to treat insomnia (difficulty falling asleep or staying asleep). Zolpidem belongs to a class of medications called sedative-hypnotics. It works by slowing activity in the brain to allow sleep.
Crizotinib Overview
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Crizotinib is used to treat certain types of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body. It is also used to treat a certain type of anaplastic large cell lymphoma (ALCL) that has returned or is unresponsive to other treatment(s) in certain adults and children 1 year of age and older. Crizotinib is also used to treat a certain type of inflammatory myofibroblastic tumor (IMT; type of cancer that occurs in mucosal tissues usually in the abdominal area, involving the lungs, bladder, stomach, uterus, liver, or intestines) that cannot be treated with surgery or that has not improved or has come back after previous treatment(s) in adults and children 1 year of age and older. Crizotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
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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:
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.