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Drug Interactions between acetaminophen / codeine and pirtobrutinib

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

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Interactions between your drugs

Moderate

codeine pirtobrutinib

Applies to: acetaminophen / codeine and pirtobrutinib

MONITOR: Coadministration with pirtobrutinib may increase the plasma concentrations of drugs that are substrates of CYP450 2C8, 2C19, 3A4, P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP). The peak plasma concentration (Cmax) and systemic exposure (AUC) of repaglinide, a CYP450 2C8 substrate, increased by 98% and 130%, respectively, and the Cmax and AUC of omeprazole, a CYP450 2C19 substrate, increased by 49% and 56%, respectively, when administered with pirtobrutinib. The Cmax and AUC of oral midazolam, a CYP450 3A4 substrate, increased by 58% and 70%, respectively, while exposure to IV midazolam was not significantly affected, when administered with pirtobrutinib. The Cmax and AUC of digoxin, a P-gp substrate, increased by 51% and 17%, respectively, when administered with a single pirtobrutinib dose (200 mg), and 55% and 35%, respectively, when administered with multiple pirtobrutinib doses (200 mg daily). The Cmax and AUC of rosuvastatin, a BCRP substrate, increased by 146% and 140%, respectively, when administered with pirtobrutinib. The risk of adverse reactions related to these substrates may be increased.

MANAGEMENT: Caution is advised if pirtobrutinib is used concomitantly with substrates of CYP450 2C8, 2C19, 3A4, P-gp, and/or BCRP, particularly sensitive substrates or those with a narrow therapeutic range. 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. Jaypirca (pirtobrutinib)." Lilly, Eli and Company

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Moderate

acetaminophen pirtobrutinib

Applies to: acetaminophen / codeine and pirtobrutinib

MONITOR: Coadministration with pirtobrutinib may increase the plasma concentrations of drugs that are substrates of CYP450 2C8, 2C19, 3A4, P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP). The peak plasma concentration (Cmax) and systemic exposure (AUC) of repaglinide, a CYP450 2C8 substrate, increased by 98% and 130%, respectively, and the Cmax and AUC of omeprazole, a CYP450 2C19 substrate, increased by 49% and 56%, respectively, when administered with pirtobrutinib. The Cmax and AUC of oral midazolam, a CYP450 3A4 substrate, increased by 58% and 70%, respectively, while exposure to IV midazolam was not significantly affected, when administered with pirtobrutinib. The Cmax and AUC of digoxin, a P-gp substrate, increased by 51% and 17%, respectively, when administered with a single pirtobrutinib dose (200 mg), and 55% and 35%, respectively, when administered with multiple pirtobrutinib doses (200 mg daily). The Cmax and AUC of rosuvastatin, a BCRP substrate, increased by 146% and 140%, respectively, when administered with pirtobrutinib. The risk of adverse reactions related to these substrates may be increased.

MANAGEMENT: Caution is advised if pirtobrutinib is used concomitantly with substrates of CYP450 2C8, 2C19, 3A4, P-gp, and/or BCRP, particularly sensitive substrates or those with a narrow therapeutic range. 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. Jaypirca (pirtobrutinib)." Lilly, Eli and Company

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Drug and food interactions

Major

pirtobrutinib food

Applies to: pirtobrutinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pirtobrutinib, which is primarily metabolized by CYP450 3A4. 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 pirtobrutinib (200 mg single dose) was administered with itraconazole, a potent CYP450 3A4 inhibitor, pirtobrutinib systemic exposure (AUC) increased by 49%. Concomitant use of diltiazem or verapamil, moderate CYP450 3A4 inhibitors, is predicted to increase pirtobrutinib AUC by 20% and 30%, respectively. 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 pirtobrutinib may increase the risk of infection, bruising, bleeding, fatigue, musculoskeletal pain, diarrhea, edema, and dyspnea.

MANAGEMENT: It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with pirtobrutinib.

References

  1. (2023) "Product Information. Jaypirca (pirtobrutinib)." Lilly, Eli and Company

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Major

acetaminophen food

Applies to: acetaminophen / codeine

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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Moderate

codeine food

Applies to: acetaminophen / codeine

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 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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