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Drug Interactions between ExeClear-C and lorlatinib

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

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Interactions between your drugs

Moderate

codeine lorlatinib

Applies to: ExeClear-C (codeine / guaifenesin) and lorlatinib

MONITOR: Coadministration of codeine with potent or moderate CYP450 3A4 inducers may result in lower codeine plasma concentrations, higher levels of the inactive metabolite norcodeine, and less metabolism via CYP450 2D6, resulting in lower morphine levels. This interaction may lead to reduced codeine efficacy and potentially initiate the onset of withdrawal symptoms in patients who are physically dependent. In addition, patients may be at an increased risk of CNS and/or respiratory-depressant effects from increased levels of codeine once concomitant therapy with the CYP450 3A4 inducer is ceased. This is particularly worrisome if the CYP450 3A4 inducer also possesses CNS- and/or respiratory-depressant effects. This interaction has also been reported with dihydrocodeine.

MANAGEMENT: The potential loss of efficacy of codeine or dihydrocodeine and onset of opioid withdrawal symptoms should be considered when used in combination with a potent or moderate CYP450 3A4 inducer. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. Some manufacturers of products containing codeine advise against the concomitant use of codeine with CYP450 3A4 inducers. If concomitant use is considered necessary, caution and close clinical and laboratory monitoring are recommended. Dosage adjustments may also be required whenever a CYP450 3A4 inducer is added to or withdrawn from therapy. Following discontinuation of a CYP450 3A4 inducer, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2015) "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc
  4. (2015) "Product Information. Acetaminophen-Codeine Phosphate (acetaminophen-codeine)." Qualitest Products Inc
  5. Cerner Multum, Inc. (2015) "Canadian Product Information."
  6. (2016) "Product Information. Tuzistra XR (chlorpheniramine-codeine)." Vernalis Pharmaceuticals Inc
  7. Caraco Y, Sheller J, Wood AJ (1997) "Pharmacogenetic determinants of codeine induction by rifampin: the impact on codeine's respiratory, psychomotor and miotic effects." J Pharmacol Exp Ther, 281, p. 330-6
View all 7 references

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Drug and food interactions

Major

lorlatinib food

Applies to: lorlatinib

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of lorlatinib. 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.

MANAGEMENT: Patients treated with lorlatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. If coadministration is unavoidable, some authorities recommend reducing the initial dosage of lorlatinib from 100 mg orally once daily to 75 mg orally once daily. In patients who have had a dosage reduction to 75 mg orally once daily due to adverse reactions, the lorlatinib dosage should be further reduced to 50 mg orally once daily upon initiation of a potent CYP450 3A4 inhibitor. After 3 plasma half-lives following discontinuation of the potent CYP450 3A4 inhibitor, the lorlatinib dosage may be increased to that used prior to initiation of the inhibitor.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2018) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group

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Moderate

codeine food

Applies to: ExeClear-C (codeine / guaifenesin)

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.

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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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