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Drug Interactions between apalutamide and tinidazole

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

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Interactions between your drugs

Moderate

tinidazole apalutamide

Applies to: tinidazole and apalutamide

MONITOR: Coadministration with apalutamide may decrease the plasma concentrations of drugs that are substrates of the metabolic enzymes CYP450 3A4, CYP450 2C19, CYP450 2C9, and uridine diphosphate glucuronosyltransferase (UGT), as well as substrates of the membrane transporters organic anion transporting polypeptide (OATP) 1B1, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). According to the prescribing information, coadministration of apalutamide with single oral doses of sensitive CYP450 substrates resulted in a 92% decrease in the systemic exposure (AUC) of midazolam, a CYP450 3A4 substrate; 85% decrease in the AUC of omeprazole, a CYP450 2C19 substrate; and 46% decrease in the AUC of S(-) warfarin, a CYP450 2C9 substrate. These results indicate strong induction of CYP450 3A4 and 2C19 by apalutamide, and weak induction of CYP450 2C9. Coadministration of apalutamide with single oral doses of transporter substrates resulted in a 30% decrease in the AUC of fexofenadine, a P-gp substrate, and 41% decrease in the AUC of rosuvastatin, a BCRP/OATP1B1 substrate. These results suggest that apalutamide is a weak inducer of membrane transporters. Apalutamide may also induce UGT according to the prescribing information; however, no pharmacokinetic data from studies with UGT substrates are available.

MANAGEMENT: Caution is advised when apalutamide is used concomitantly with drugs that are substrates of CYP450 3A4, CYP450 2C19, CYP450 2C9, UGT, OATP1B1, P-gp and/or BCRP, particularly sensitive substrates or those with a narrow therapeutic range. Substitution for these medications is recommended when possible, or monitor for potential loss of therapeutic efficacy if coadministration is required. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a CYP450 inducer like apalutamide and for any dosage adjustments that may be required.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2018) "Product Information. Erleada (apalutamide)." Janssen Biotech, Inc.

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Drug and food interactions

Moderate

tinidazole food

Applies to: tinidazole

GENERALLY AVOID: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.

References

  1. Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
  2. Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
  3. Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
  4. Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
  5. (2002) "Product Information. Flagyl (metronidazole)." Searle
  6. Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
  8. Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
  9. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
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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