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Drug Interactions between Cassipa and quizartinib

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

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Interactions between your drugs

Major

buprenorphine quizartinib

Applies to: Cassipa (buprenorphine / naloxone) and quizartinib

GENERALLY AVOID: Quizartinib can cause dose- and concentration-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death. In a clinical study where 265 patients with newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML) were treated with quizartinib (38% for >=6 months; 30% for >1 year) in combination with chemotherapy, 2.3% had a Fridericia-corrected QT interval (QTcF) greater than 500 ms and 10% had a QTcF increase from baseline greater than 60 ms. Overall, QT prolongation of any grade occurred in 14% of the quizartinib patients (compared to 4.1% of patients treated with placebo and chemotherapy), and 4% required dose reductions of quizartinib due to QT prolongation. The study excluded patients with a QTcF >=450 ms or other risk factors for QT prolongation or arrhythmic events. Based on an analysis of the exposure-response relationship, quizartinib is predicted to produce a median increase of 18 and 24 ms in the QTcF at steady-state peak plasma concentration during maintenance therapy at the 26.5 mg and 53 mg dose levels, respectively. Across premarketing clinical trials, torsade de pointes arrhythmia was reported in approximately 0.2%, cardiac arrest in 0.6% (including 0.4% with a fatal outcome), and ventricular fibrillation in 0.1% of the total 1,081 patients with AML treated with quizartinib. These severe cardiac events occurred predominantly during the induction phase. 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, hypomagnesemias). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of quizartinib with other drugs that can prolong the QT interval should generally be avoided. If concomitant use is required, more frequent monitoring with electrocardiograms (ECGs) is recommended to guide continued treatment. All patients treated with quizartinib should have ECGs performed as well as potassium and magnesium serum levels measured prior to initiation of treatment, at regular intervals during treatment, and when clinically indicated such as following dose escalation or during episodes of diarrhea or vomiting. Do not initiate quizartinib or escalate the dose if QTcF interval is greater than 450 ms. In addition, hypokalemia and hypomagnesemia should be corrected before and during treatment. If QTcF increases to greater than 480 ms during treatment, reduce the dose, interrupt therapy, or permanently discontinue quizartinib as clinically appropriate in accordance with the prescribing information. 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. Quizartinib should be permanently discontinued in patients who experience torsade de pointes, polymorphic ventricular tachycardia, or QT prolongation with signs or symptoms of life-threatening arrhythmia.

References

  1. (2023) "Product Information. Vanflyta (quizartinib)." Daiichi Sankyo, Inc.

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Drug and food interactions

Major

buprenorphine food

Applies to: Cassipa (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.