Drug Interaction Report
4 potential interactions and/or warnings found for the following 2 drugs:
- ivacaftor / lumacaftor
- bupivacaine / dexamethasone / epinephrine
Interactions between your drugs
dexAMETHasone ivacaftor
Applies to: bupivacaine / dexamethasone / epinephrine, ivacaftor / lumacaftor
MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. In study subjects, administration of a single 150 mg dose of ivacaftor with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased ivacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 89%, respectively, compared to administration of ivacaftor alone. When lumacaftor/ivacaftor was coadministered with rifampin, lumacaftor pharmacokinetics were minimally affected, but ivacaftor Cmax and AUC decreased by an average of 50% and 57%, respectively. No pharmacokinetic data are available for elexacaftor or tezacaftor, but decreased exposures are expected according to prescribing information.
MANAGEMENT: The potential for diminished pharmacologic effects of ivacaftor-containing medications should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.
References (5)
- (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
- (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
- (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2023) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals, SUPPL-40
dexAMETHasone lumacaftor
Applies to: bupivacaine / dexamethasone / epinephrine, ivacaftor / lumacaftor
MONITOR: Coadministration with lumacaftor may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4, 2B6, 2C19, 2C8, and/or 2C9. Lumacaftor is a potent inducer of CYP450 3A4 in vivo. Coadministration of lumacaftor with ivacaftor, a sensitive CYP450 3A4 substrate, decreased ivacaftor systemic exposure (AUC) by approximately 80%. In vitro, lumacaftor is an inducer of several other CYP450 isoenzymes including CYP450 2B6, 2C19, 2C8 and 2C9, although inhibition of the latter two isoenzymes has also been observed in vitro. Drugs that are substrates of CYP450 2C8 and 2C9 (e.g., sulfonylureas and other hypoglycemic agents, warfarin) may demonstrate decreased or increased exposures.
MANAGEMENT: Caution is advised when lumacaftor/ivacaftor is prescribed with drugs that undergo metabolism by CYP450 3A4, 2B6, 2C19, 2C8 and/or 2C9, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lumacaftor/ivacaftor is added to or withdrawn from therapy.
References (4)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
- Cerner Multum, Inc. (2015) "Canadian Product Information."
Drug and food interactions
ivacaftor food
Applies to: ivacaftor / lumacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.
ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.
References (4)
- (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
- (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
- (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
EPINEPHrine food
Applies to: bupivacaine / dexamethasone / epinephrine
MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.
References (7)
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
- Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
- (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
Therapeutic duplication warnings
No duplication 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.
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. |
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