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Drug Interactions between ifosfamide and LiproZonePak

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

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Interactions between your drugs

Major

lidocaine topical prilocaine topical

Applies to: LiproZonePak (lidocaine / prilocaine topical) and LiproZonePak (lidocaine / prilocaine topical)

Some of the medication in prilocaine topical is absorbed through the skin into the bloodstream and may cause interactions with other medications such as lidocaine topical. When used together, this combination may increase the risk of methemoglobinemia, a condition that can lead to oxygen deprivation in tissues and vital organs due to reduced oxygen-carrying capacity of the blood. Individuals may be more susceptible to developing methemoglobinemia during treatment with these medications if they are very young (especially neonates and infants) or have anemia, diseases of the heart or lungs, blood circulation disorders, liver cirrhosis, shock, sepsis, and certain genetic predispositions such as NADH cytochrome-b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency, and hemoglobin M. In addition, excessive use of prilocaine topical such as application of large doses or on larger than recommended areas, as well as use on inflamed or abraded areas or broken skin, can increase absorption and result in high blood levels of the medication. Close medical supervision is necessary when medications that can cause methemoglobinemia are used together. Signs and symptoms of methemoglobinemia may be delayed by several hours after treatment with prilocaine topical. Patients (or their caregivers) should seek immediate medical attention if they develop a gray discoloration of the skin, mouth, or nail bed; nausea; headache; dizziness; lightheadedness; fatigue; shortness of breath; rapid or shallow breathing; a rapid heartbeat; palpitation; anxiety; or confusion. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Moderate

ifosfamide lidocaine topical

Applies to: ifosfamide and LiproZonePak (lidocaine / prilocaine topical)

Some of the medication in lidocaine topical may be absorbed into the bloodstream following local application. When present in sufficient concentrations in the blood, local anesthetics such as lidocaine topical may cause methemoglobinemia, a rare condition that can lead to oxygen deprivation in tissues and vital organs due to reduced oxygen-carrying capacity of the blood. The risk is increased when combined with other medications that can also induce methemoglobinemia such as ifosfamide. Individuals may be more susceptible to developing methemoglobinemia during treatment with these medications if they are very young (especially neonates and infants) or have anemia, diseases of the heart or lungs, blood circulation disorders, liver cirrhosis, shock, sepsis, and certain genetic predispositions such as NADH cytochrome-b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency, and hemoglobin M. In addition, use of topical anesthetics on inflamed or abraded areas or broken skin, as well as excessive use such as application of large doses or on larger than recommended areas, can increase absorption and result in high blood levels of the medication. Topical anesthetics that are applied to mucous membranes such as inside the mouth, nose, or throat (e.G., for sore throat; for numbing prior to dental procedures or scoping of the lungs or gastrointestinal tract) may also be absorbed to a significant extent. Close medical supervision is necessary when medications that can cause methemoglobinemia are used together. Do not exceed the recommended dose or frequency and duration of use when treated with products that contain local anesthetics, including some over-the-counter preparations. Signs and symptoms of methemoglobinemia may be delayed by several hours after treatment with topical anesthetics. Patients (or their caregivers) should seek immediate medical attention if they develop a gray discoloration of the skin, mouth, or nail bed; nausea; headache; dizziness; lightheadedness; fatigue; shortness of breath; rapid or shallow breathing; a rapid heartbeat; palpitation; anxiety; or confusion. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Drug and food interactions

Moderate

ifosfamide food

Applies to: ifosfamide

Consumer information for this interaction is not currently available.

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

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.