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Drug Interactions between cefmetazole and Kaletra

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

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Interactions between your drugs

Moderate

cefmetazole ritonavir

Applies to: cefmetazole and Kaletra (lopinavir / ritonavir)

GENERALLY AVOID: Ritonavir capsules, ritonavir oral solution, lopinavir-ritonavir oral solution, and tipranavir capsules all contain alcohol, which may produce a disulfiram-like reaction when coadministered with drugs that can inhibit aldehyde dehydrogenase (ALDH) such as nitroimidazoles (e.g., metronidazole, tinidazole), nitrofurans (e.g., furazolidone, nifurtimox), and cephalosporins with an N-methylthiotetrazole (NMTT) side chain that structurally resembles 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. The interaction is well established for disulfiram. However, data for other potential ALDH inhibitors such as metronidazole and cephalosporins are limited and conflicting.

MANAGEMENT: Until further information is available, use of ritonavir capsules, ritonavir oral solution, lopinavir-ritonavir oral solution, or tipranavir capsules with nitroimidazoles (including vaginal formulations), nitrofurans, and certain cephalosporins should be avoided if possible.

References

  1. Uri JV, Parks DB "Disulfiram-like reaction to certain cephalosporins." Ther Drug Monit 5 (1983): 219-24
  2. Kline SS, Mauro VF, Forney RB Jr, et al. "Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia." Antimicrob Agents Chemother 31 (1987): 1328-31
  3. Portier H, Chalopin JM, Freysz M, Tanter Y "Interaction between cephalosporins and alcohol." Lancet 08/02/80 (1980): 263
  4. Shimada J, Hayashi Y, Nakamura K "Cefmetazole: clinical evaluation of efficacy and safety in Japan." Drugs Exp Clin Res 11 (1985): 181-94
  5. Freundt KJ, Kitson TM "Inactivation of aldehyde dehydrogenase by a putative metabolite of cefamandole." Infection 14 (1986): 44-7
  6. Freundt KJ, Schreiner E, Christmann-Kleiss U "Cefamandole: a competitive inhibitor of aldehyde dehydrogenase." Infection 13 (1985): 91
  7. McMahon FG "Disulfiram-like reaction to a cephalosporin." JAMA 243 (1980): 2397
  8. Reeves DS, Davies AJ "Antabuse effect with cephalosporins." Lancet 2 (1980): 540
  9. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  10. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  11. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  12. Neu HC, Prince AS "Interaction between moxalactam and alcohol." Lancet June (1980): 1422
  13. Brown KR, Guglielmo BJ, Pons VG, Jacobs RA "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med 97 (1982): 621-2
  14. Umeda S, Arai T "Disulfiram-like reaction to moxalactam after celiac plexus alcohol block." Anesth Analg 64 (1985): 377
  15. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  16. Jones RO "Death following the ingestion of alcohol in an antabuse treated patient." Can Med Assoc J 60 (1949): 609-12
  17. van Ieperen L "Sudden death during disulfiram-ethanol reaction." S Afr Med J 66 (1984): 165
  18. Buening MK, et al. "Disulfiram-like reaction to beta-lactams." JAMA 245 (1981): 2047
  19. Foster TS, Raehl CL, Wilson HD "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm 37 (1980): 858-9
  20. Elenbaas RM "Drug therapy reviews: management of the disulfiram-alcohol reaction." Am J Hosp Pharm 34 (1977): 827-31
  21. "Product Information. MetroGel-Vaginal (metroNIDAZOLE topical)." Curatek Pharmaceuticals Ltd (2022):
  22. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  23. Cina SJ, Russell RA, Conradi SE "Sudden death due to metronidazole/ethanol interaction." Am J Forensic Med Pathol 17 (1996): 343-6
  24. "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation PROD (2001):
  25. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  26. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):
  27. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  28. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8
  29. McMahon FG, Ryan JR, Jain AK, LaCorte W, Ginzler F "Absence of disulfiram-type reactions to single and multiple doses of cefonicid: a placebo-controlled study." J Antimicrob Chemother 20 (1987): 913-8
  30. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
  31. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim (2005):
View all 31 references

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Drug and food interactions

Moderate

ritonavir food

Applies to: Kaletra (lopinavir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

lopinavir food

Applies to: Kaletra (lopinavir / ritonavir)

ADJUST DOSING INTERVAL: Food significantly increases the bioavailability of lopinavir from the oral solution formulation of lopinavir-ritonavir. Relative to fasting, administration of lopinavir-ritonavir oral solution with a moderate-fat meal (500 to 682 Kcal; 23% to 25% calories from fat) increased lopinavir peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 80%, respectively, whereas administration with a high-fat meal (872 Kcal; 56% from fat) increased lopinavir Cmax and AUC by 56% and 130%, respectively. No clinically significant changes in Cmax and AUC were observed following administration of lopinavir-ritonavir tablets under fed conditions versus fasted conditions. Relative to fasting, administration of a single 400 mg-100 mg dose (two 200 mg-50 mg tablets) with a moderate-fat meal (558 Kcal; 24.1% calories from fat) increased lopinavir Cmax and AUC by 17.6% and 26.9%, respectively, while administration with a high-fat meal (998 Kcal; 51.3% from fat) increased lopinavir AUC by 18.9% but not Cmax. Relative to fasting, ritonavir Cmax and AUC also increased by 4.9% and 14.9%, respectively, with the moderate-fat meal and 10.3% and 23.9%, respectively, with the high-fat meal.

MANAGEMENT: Lopinavir-ritonavir oral solution should be taken with meals to enhance bioavailability and minimize pharmacokinetic variability. Lopinavir-ritonavir tablets may be taken without regard to meals.

References

  1. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

cefmetazole food

Applies to: cefmetazole

GENERALLY AVOID: Some cephalosporins may occasionally induce a disulfiram-like reaction when coadministered with alcohol. The interaction has been reported for cefamandole, cefoperazone, cefotetan, and moxalactam. These agents contain an N-methylthiotetrazole (NMTT) side chain that may inhibit aldehyde dehydrogenase (ALDH) similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentration of acetaldehyde, the accumulation of which produces 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, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. Cefonicid contains a structurally similar side chain but did not produce elevations in blood acetaldehyde or a disulfiram reaction to ethanol in 15 healthy volunteers given single and multiple one gram doses of the drug.

MANAGEMENT: Patients receiving cephalosporins with the NMTT side chain should avoid the concomitant use of alcohol and alcohol-containing products.

References

  1. Kline SS, Mauro VF, Forney RB Jr, et al. "Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia." Antimicrob Agents Chemother 31 (1987): 1328-31
  2. Freundt KJ, Kitson TM "Inactivation of aldehyde dehydrogenase by a putative metabolite of cefamandole." Infection 14 (1986): 44-7
  3. Freundt KJ, Schreiner E, Christmann-Kleiss U "Cefamandole: a competitive inhibitor of aldehyde dehydrogenase." Infection 13 (1985): 91
  4. McMahon FG "Disulfiram-like reaction to a cephalosporin." JAMA 243 (1980): 2397
  5. Reeves DS, Davies AJ "Antabuse effect with cephalosporins." Lancet 2 (1980): 540
  6. Brown KR, Guglielmo BJ, Pons VG, Jacobs RA "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med 97 (1982): 621-2
  7. Umeda S, Arai T "Disulfiram-like reaction to moxalactam after celiac plexus alcohol block." Anesth Analg 64 (1985): 377
  8. Foster TS, Raehl CL, Wilson HD "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm 37 (1980): 858-9
  9. McMahon FG, Ryan JR, Jain AK, LaCorte W, Ginzler F "Absence of disulfiram-type reactions to single and multiple doses of cefonicid: a placebo-controlled study." J Antimicrob Chemother 20 (1987): 913-8
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.

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