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Drug Interactions between aspirin/citric acid/sodium bicarbonate and selpercatinib

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

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Interactions between your drugs

Major

sodium bicarbonate selpercatinib

Applies to: aspirin/citric acid/sodium bicarbonate and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When selpercatinib was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

References

  1. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Moderate

aspirin sodium bicarbonate

Applies to: aspirin/citric acid/sodium bicarbonate and aspirin/citric acid/sodium bicarbonate

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. Berg KJ (1977) "Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics." Eur J Clin Pharmacol, 12, p. 111-6
  2. Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT (1982) "Diuresis or urinary alkalinisation for salicylate poisoning?" Br Med J (Clin Res Ed), 285, p. 1383-6
  3. Balali-Mood M, Prescott LF (1980) "Failure of alkaline diuresis to enhance diflunisal elimination." Br J Clin Pharmacol, 10, p. 163-5
  4. Berg KJ (1977) "Acute effects of acetylsalicylic acid in patients with chronic renal insufficiency." Eur J Clin Pharmacol, 11, p. 111-6
  5. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
View all 5 references

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Drug and food interactions

Major

selpercatinib food

Applies to: selpercatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When selpercatinib was coadministered with multiple doses of itraconazole, a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of selpercatinib with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem, fluconazole, or verapamil is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. 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. Increased exposure to selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).

MANAGEMENT: Patients should limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Moderate

aspirin food

Applies to: aspirin/citric acid/sodium bicarbonate

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

aspirin food

Applies to: aspirin/citric acid/sodium bicarbonate

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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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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