Skip to main content

Drug Interactions between CodiCLEAR DH and difelikefalin

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

HYDROcodone difelikefalin

Applies to: CodiCLEAR DH (guaifenesin / hydrocodone) 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

  1. (2021) "Product Information. Korsuva (difelikefalin)." Cara Therapeutics, Inc.
  2. (2022) "Product Information. Korsuva (difelikefalin)." Otsuka Canada Pharmaceutical Inc
  3. (2022) "Product Information. Kapruvia (difelikefalin)." Vifor Fresenius Medical Care Renal Pharma UK Ltd

Switch to consumer interaction data

Drug and food interactions

Major

HYDROcodone food

Applies to: CodiCLEAR DH (guaifenesin / hydrocodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc

Switch to consumer interaction data

Moderate

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

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. 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.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer