Drug Interactions between Cassipa and difelikefalin
This report displays the potential drug interactions for the following 2 drugs:
- Cassipa (buprenorphine/naloxone)
- difelikefalin
Interactions between your drugs
buprenorphine difelikefalin
Applies to: Cassipa (buprenorphine / naloxone) and difelikefalin
MONITOR: The central nervous system (CNS) adverse effects of difelikefalin (e.g., dizziness, somnolence, mental status changes, gait disturbances) may be potentiated by the concomitant use of opioids. In two clinical trials, 17% of hemodialysis patients receiving difelikefalin reported at least one CNS side effect, compared to 12% of patients who received placebo. When patients were analyzed by age, the incidence of somnolence was found to be higher in difelikefalin-treated patients 65 years of age or older (7%) than in those less than 65 years old (2.8%).
MONITOR: Concomitant use of difelikefalin with opioids may increase the risk of hyperkalemia. In clinical trials, the incidence of hyperkalemia was 4.7% in patients who received difelikefalin versus 3.5% in placebo-treated patients. Additionally, 2.8% of difelikefalin-treated subjects had potassium levels greater than 7 mmol/L, compared to 1.0% in the placebo group. In subjects also receiving opioids, the incidence of hyperkalemia was almost doubled in the difelikefalin group (11.7%) compared to the placebo group (6.2%). The clinical relevance of these findings is unknown, as a causal relationship has not been established.
MANAGEMENT: Caution is advised during coadministration of difelikefalin with opioids. Patients should be monitored for increased adverse CNS effects, particularly in patients 65 years of age and older. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. In addition, more frequent monitoring of serum potassium levels may be required. Patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, convulsion, weak pulse, and a slow or irregular heartbeat.
References
- (2021) "Product Information. Korsuva (difelikefalin)." Cara Therapeutics, Inc.
- (2022) "Product Information. Korsuva (difelikefalin)." Otsuka Canada Pharmaceutical Inc
- (2022) "Product Information. Kapruvia (difelikefalin)." Vifor Fresenius Medical Care Renal Pharma UK Ltd
Drug and food interactions
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
- (2002) "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc
- Kilicarslan T, Sellers EM (2000) "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry, 157, p. 1164-6
- Reynaud M, Petit G, Potard D, Courty P (1998) "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction, 93, p. 1385-92
- 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
- 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
- Kintz P (2002) "A new series of 13 buprenorphine-related deaths." Clin Biochem, 35, p. 513-6
- Martin HA (2011) "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs, 37, p. 200-2
- 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
- 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/
- 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
- Ferrant O, Papin F, Clin B, et al. (2011) "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int, 204, e8-11
- 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
- Kintz P (2001) "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int, 121, p. 65-9
- Sekar M, Mimpriss TJ (1987) "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia, 42, p. 567-8
- 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
- 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
difelikefalin food
Applies to: difelikefalin
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
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.
See also
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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