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Drug Interactions between Codafen and ifosfamide / mesna

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

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Interactions between your drugs

Moderate

codeine ifosfamide

Applies to: Codafen (codeine / guaifenesin) and ifosfamide / mesna

MONITOR: Centrally-acting agents such as antiemetics, sedatives, narcotics, or antihistamines may add to the neurotoxic effects of ifosfamide. Administration of ifosfamide can cause CNS toxicity, which necessitates careful monitoring of the patient. Neurologic manifestations include somnolence, confusion, hallucinations, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma. There have also been reports of peripheral neuropathy. Ifosfamide neurotoxicity may occur within a few hours to a few days after initial administration and typically resolves within 48 to 72 hours of ifosfamide discontinuation. However, symptoms may persist for longer periods of time, and recovery has occasionally been incomplete. Fatal outcomes have been reported. There have also been reports of recurrence of CNS toxicity after several uneventful treatment courses.

MANAGEMENT: Due to the potential for additive effects, centrally-acting agents should be used with caution in combination with ifosfamide. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. If ifosfamide-induced encephalopathy occurs, both ifosfamide and non-essential concomitant CNS agents should be discontinued. Supportive therapy should be initiated and maintained until complete resolution of neurotoxicity.

References

  1. Simonian NA, Gilliam FG, Chiappa KH "Ifosfamide causes a diazepam-sensitive encephalopathy." Neurology 43 (1993): 2700-2
  2. "Product Information. Ifex (ifosfamide)." Bristol-Myers Squibb PROD (2001):

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Drug and food interactions

Moderate

ifosfamide food

Applies to: ifosfamide / mesna

GENERALLY AVOID: Grapefruit and/or grapefruit juice may reduce the efficacy of ifosfamide, whose anticancer effect is dependent on its activation to the 4-hydroxyifosfamide metabolite via CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4 metabolism by certain compounds present in grapefruit. There are no data available about the effects of grapefruit on ifosfamide. However, in a small study, 8 patients with incurable malignancies received ifosfamide 3 g/m2 by infusion with the potent CYP450 3A4 inhibitor ketoconazole 200 mg orally twice daily for 4 days starting 1 day before the ifosfamide infusion. Ketoconazole decreased the clearance of ifosfamide by 11%, decreased systemic exposure (AUC) of the active metabolite 4-hydroxyifosfamide by 30%, and increased the AUC of the inactive but potentially neurotoxic metabolite 2-dechloroethylifosfamide by 23%, as compared to control. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

GENERALLY AVOID: Alcohol may potentiate the neurotoxic effects of ifosfamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, ifosfamide therapy may cause gastrointestinal disorders and alcohol consumption may increase nausea and vomiting.

MANAGEMENT: Given the potential for reduced efficacy of ifosfamide and increased risk of neurotoxicity and nephrotoxicity it may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with ifosfamide. In addition, patients receiving ifosfamide should be warned of the increased risk of neurotoxicity, nausea and vomiting when used in combination with alcohol. Patients should avoid or limit the consumption of alcohol during treatment with ifosfamide.

References

  1. "Product Information. Ifosfamide (ifosfamide)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2019):
  2. Kerbusch T, jansen rlh, mathot raa, huitema adr, Jansen RNM, Rijswijk REN, Beijen JH "Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin" Clin Pharmacol and Therapeutic 70 (2001): 132-141
  3. "Product Information. Ifex (ifosfamide)." Baxter Pharmaceutical Products, Inc (2018):
  4. "Product Information. Holoxan (iFOSFamide)." Baxter Healthcare Pty Ltd (2018):
  5. "Product Information. Ifosfamide (ifosfamide)." Baxter Healthcare Ltd (2022):
  6. "Product Information. Ifex (ifosfamide)." Baxter Corporation (2018):
View all 6 references

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Moderate

codeine food

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