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Drug Interactions between estazolam and Phyrago

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

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Interactions between your drugs

Moderate

estazolam dasatinib

Applies to: estazolam and Phyrago (dasatinib)

MONITOR: Coadministration with dasatinib may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by dasatinib, which is a time-dependent inhibitor of the isoenzyme. In a pharmacokinetic study of 54 healthy subjects, administration of simvastatin with a single 100 mg dose of dasatinib resulted in a 37% and 20% increase in simvastatin peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration without dasatinib. Other CYP450 3A4 substrates may be similarly affected.

MANAGEMENT: Caution is advised if dasatinib must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever dasatinib is added to or withdrawn from therapy.

References

  1. (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb

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Drug and food interactions

Major

dasatinib food

Applies to: Phyrago (dasatinib)

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. 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. Because dasatinib prolongs the QT interval, high plasma levels of dasatinib may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
  3. Cerner Multum, Inc. "Australian Product Information."

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Moderate

estazolam food

Applies to: estazolam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J (1979) "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol, 7, p. 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB (1984) "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol, 24, p. 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol, 4, p. 106-7
  6. Staak M, Raff G, Nusser W (1979) "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm, 17, p. 205-12
  7. Nichols JM, Martin F, Kirkby KC (1993) "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl), 112, p. 475-82
View all 7 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.

See also

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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.

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