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Drug Interactions between glasdegib and pseudoephedrine / terfenadine

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

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Interactions between your drugs

Moderate

terfenadine glasdegib

Applies to: pseudoephedrine / terfenadine and glasdegib

GENERALLY AVOID: Glasdegib may cause dose-related prolongation of the QT interval. 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. The effect of glasdegib administration on corrected QT interval (QTc) was evaluated in 36 healthy study subjects. At therapeutic plasma concentrations for the recommended dose, achieved with a single 150 mg dose, the largest placebo and baseline-adjusted QTc interval change was 8 msec. At twice the therapeutic plasma concentration, achieved with a single 300 mg dose, the QTc change was 13 msec. In a clinical trial that had 98 evaluable patients treated with glasdegib 100 mg in combination with low-dose cytarabine, 5% of patients were found to have a QTc interval greater than 500 msec and 4% had a QTc increase from baseline greater than 60 msec. The clinical trial excluded patients with baseline QTc greater than 470 msec or a history of long QT syndrome or uncontrolled cardiovascular disease. 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). 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 glasdegib with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Patients should have electrocardiograms (ECGs) performed prior to initiation of treatment with glasdegib, approximately one week after initiation, and then once monthly for the next two months, although patients with risk factors may require more frequent and ongoing ECG monitoring. If QTc interval is greater than 500 msec at any time during treatment, interrupt and reduce glasdegib dosing in accordance with product labeling recommendations. Glasdegib should be permanently discontinued in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. ECGs should be monitored at least weekly for 2 weeks upon the resolution of QTC prolongation to less than or equal to 480 msec. Because hypokalemia and hypomagnesemia are risk factors for ventricular arrhythmias, electrolyte levels should also be obtained prior to and during treatment, and any abnormalities corrected as necessary. 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 (3)
  1. (2023) "Product Information. Daurismo (glasdegib)." Pfizer U.S. Pharmaceuticals Group
  2. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Ltd
  3. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Canada ULC

Drug and food interactions

Major

terfenadine food

Applies to: pseudoephedrine / terfenadine

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

References (17)
  1. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr (1992) "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther, 52, p. 231-8
  2. Zimmermann M, Duruz H, Guinand O, et al. (1992) "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J, 13, p. 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. (1991) "Torsades de pointes occurring in association with terfenadine use." JAMA, 266, p. 2375-6
  4. Monahan BP, Ferguson CL, Killeavy ES, et al. (1990) "Torsades de pointes occurring in association with terfenadine use." JAMA, 264, p. 2788-90
  5. Honig PK, Wortham DC, Zamani K, et al. (1993) "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA, 269, p. 1513-8
  6. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P (1993) "Torsades de pointes after terfenadine-itraconazole interaction." BMJ, 306, p. 186
  7. Cortese LM, Bjornson DC (1992) "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm, 11, p. 675
  8. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP (1994) "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med, 12, p. 636-8
  9. Zechnich AD, Haxby DG (1996) "Drug interactions associated with terfenadine and related nonsedating antihistamines." West J Med, 164, p. 68-9
  10. Honig PK, Wortham DC, Lazarev A, Cantilena LR (1996) "Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine." J Clin Pharmacol, 36, p. 345-51
  11. Woosley RL (1996) "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol, 36, p. 233-52
  12. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL (1996) "Grapefruit juice alters terfenadine pharmacokinetics resulting in prolongation of repolarization on the electrocardiogram." Clin Pharmacol Ther, 59, p. 383-8
  13. Hsieh MH, Chen SA, Chiang CE, et al. (1996) "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol, 54, p. 85-8
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  15. Rau SE, Bend JR, Arnold JMO, Tran LT, Spence JD, Bailey DG (1997) "Grapefruit juice terfenadine single-dose interaction: Magnitude, mechanism, and relevance." Clin Pharmacol Ther, 61, p. 401-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
Moderate

glasdegib food

Applies to: glasdegib

GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of glasdegib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. When glasdegib was coadministered with ketoconazole, a potent CYP450 3A4 inhibitor, glasdegib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.4- and 2.4-fold, respectively, compared to administration of glasdegib alone. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

When administered with a high-fat, high-calorie meal (800 to 1000 total calories, 500 to 600 fat calories, 250 carbohydrate calories, and 150 protein calories), glasdegib Cmax and AUC decreased by 31% and 16%, respectively.

MANAGEMENT: Glasdegib may be administered with or without food. Coadministration of grapefruit or grapefruit juice with glasdegib should preferably be avoided.

References (3)
  1. (2023) "Product Information. Daurismo (glasdegib)." Pfizer U.S. Pharmaceuticals Group
  2. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Ltd
  3. (2022) "Product Information. Daurismo (glasdegib)." Pfizer Canada ULC
Moderate

pseudoephedrine food

Applies to: pseudoephedrine / terfenadine

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)
  1. 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
  2. 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
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company

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

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