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Drug Interactions between Pharmore Paracetamol and pralsetinib

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

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Interactions between your drugs

Moderate

acetaminophen pralsetinib

Applies to: Pharmore Paracetamol (acetaminophen) and pralsetinib

MONITOR: Coadministration with pralsetinib may alter the plasma concentrations of drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5. In vitro studies indicate that pralsetinib is both an inhibitor as well as an inducer of CYP450 2C8, 2C9, 3A4, and 3A5. Therefore, pralsetinib may decrease clearance via inhibition or increase clearance via induction of these isoenzymes, resulting in increased or decreased plasma concentrations of agents that are metabolized by one or more of these isoenzymes. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if pralsetinib is used concomitantly with drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5, particularly sensitive substrates or those with a narrow therapeutic range. Some authorities recommend avoiding coadministration of pralsetinib with CYP450 2C8, 2C9, 3A4, and/or 3A5 substrates for which minimal concentration changes may lead to therapeutic failure or serious toxicities. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever pralsetinib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

References

  1. (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
  2. (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
  3. (2023) "Product Information. Gavreto (pralsetinib)." Genentech
  4. (2021) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
View all 4 references

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Drug and food interactions

Major

pralsetinib food

Applies to: pralsetinib

ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 to 8.5 hours.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pralsetinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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 pralsetinib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, constipation, hypertension, and pneumonia.

MANAGEMENT: Pralsetinib should be administered on an empty stomach, at least 2 hours after or 1 hour before a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with pralsetinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
  3. (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406

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Major

acetaminophen food

Applies to: Pharmore Paracetamol (acetaminophen)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA (1985) "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med, 145, p. 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA (1986) "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA, 255, p. 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med, 104, p. 399-404
  4. Thummel KE, Slattery JT, Nelson SD (1988) "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther, 245, p. 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA, 244, p. 251-3
  6. Kartsonis A, Reddy KR, Schiff ER (1986) "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med, 105, p. 138-9
  7. Prescott LF, Critchley JA (1983) "Drug interactions affecting analgesic toxicity." Am J Med, 75, p. 113-6
  8. (2002) "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical
  9. Whitcomb DC, Block GD (1994) "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA, 272, p. 1845-50
  10. Bonkovsky HL (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  11. Nelson EB, Temple AR (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  12. Zimmerman HJ, Maddrey WC (1995) "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology, 22, p. 767-73
View all 12 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.

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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.

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