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Drug Interactions between crizotinib and Suboxone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

buprenorphine crizotinib

Applies to: Suboxone (buprenorphine / naloxone) and crizotinib

GENERALLY AVOID: Crizotinib can cause prolongation of the QT interval, which pharmacokinetic/pharmacodynamic modeling indicate may be concentration-dependent. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials done in adults on crizotinib (250 mg twice daily) QTcF (Fridericia corrected QT interval) prolongation greater than or equal to 500 msec was observed in 34 of 1619 (2.1%) and an increase from baseline QTcF greater than or equal to 60 msec was observed in 79 of 1585 patients (5%). In clinical studies of pediatric patients (dosed according to body surface area), a prolonged QT interval was observed in approximately 4% of patients. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Concomitant use of crizotinib with drugs that prolong the QT interval should generally be avoided. ECG and serum electrolytes, including potassium, magnesium, and calcium, should be monitored before starting crizotinib therapy and periodically during treatment according to the manufacturer's labeling. Electrolytes should be replaced as clinically indicated. Crizotinib should not be started if baseline QTc (QT corrected for heart rate) is greater than 500 msec. Likewise, treatment should be interrupted in patients who develop a QTc greater than 500 msec on at least 2 separate ECGs. Once the QTc has recovered to baseline or less than 481 msec, crizotinib can be resumed at the next lower dosage recommended in the manufacturer's labeling. Crizotinib should be permanently discontinued if the patient has a QTc greater than 500 msec or a change greater than or equal to 60 msec from baseline with torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of a serious arrhythmia. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. (2022) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group, SUPPL-33
  2. (2022) "Product Information. Xalkori (crizotinib)." Pfizer Australia Pty Ltd, pfpxalkc11122
  3. (2023) "Product Information. Xalkori (crizotinib)." Pfizer Ltd, XI 36_1

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Drug and food interactions

Major

crizotinib food

Applies to: crizotinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.

References

  1. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group

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Major

buprenorphine food

Applies to: Suboxone (buprenorphine / naloxone)

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. (2002) "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc
  2. Kilicarslan T, Sellers EM (2000) "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry, 157, p. 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P (1998) "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction, 93, p. 1385-92
  4. Tracqui A, Kintz P, Ludes B (1998) "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol, 22, p. 430-4
  5. Reynaud M, Tracqui A, Petit G, Potard D, Courty P (1998) "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry, 155, p. 448-9
  6. Kintz P (2002) "A new series of 13 buprenorphine-related deaths." Clin Biochem, 35, p. 513-6
  7. Martin HA (2011) "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs, 37, p. 200-2
  8. Hakkinen M, Launiainen T, Vuori E, Ojanpera I (2012) "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol, 68, p. 301-9
  9. Substance Abuse and Mental Health Services Administration (US) (2013) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 http://www.ncbi.nlm.nih.gov/books/NBK64245/
  10. Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ (2013) "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend, 132, p. 580-6
  11. Ferrant O, Papin F, Clin B, et al. (2011) "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int, 204, e8-11
  12. Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I (2004) "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction, 99, p. 978-88
  13. Kintz P (2001) "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int, 121, p. 65-9
  14. Sekar M, Mimpriss TJ (1987) "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia, 42, p. 567-8
  15. Gueye PN, Borron SW, Risede P, et al. (2002) "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci, 65, p. 107-14
  16. US Food and Drug Administration (2016) FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf
View all 16 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.