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Drug Interactions between cefazolin and rifampin

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

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Interactions between your drugs

Major

ceFAZolin rifAMPin

Applies to: cefazolin and rifampin

GENERALLY AVOID: Coadministration of rifampin with other antibiotics which cause vitamin K dependent coagulopathy, such as cephalosporins with the N-methyl-thiotetrazole (NMTT) side chain, may increase the risk of severe coagulation disorders, which may result in fatal outcomes (particularly with high doses). The mechanism for this interaction has not been clearly delineated; however, proposed mechanisms include inhibited growth of vitamin K-producing intestinal bacteria, inhibited production of vitamin K-dependent clotting factors, interference with the biosynthesis of prothrombin, and/or inhibited platelet activity. Decreased prothrombin activity has been reported during treatment with rifampin and various cephalosporins. Risk factors may include the elderly, renal or hepatic impairment, poor nutritional state, protracted antimicrobial therapy, and chronic anticoagulation therapy.

MANAGEMENT: The concomitant use of rifampin with other antibiotics which cause vitamin K dependent coagulopathy, such as cephalosporins, should be avoided. If coadministration is unavoidable, monitoring of prothrombin time and INR should be considered and the patient should be observed for signs of bleeding. Patients should be advised to notify their physicians if they experience any signs or symptoms that may indicate excessive anticoagulation, such as unusual or prolonged bleeding, bruising, coffee ground emesis, change in stool or urine color, headache, dizziness, or weakness.

References (19)
  1. Lerner PI, Lubin A (1974) "Coagulopathy with cefazolin in uremia." N Engl J Med, 290, p. 1324
  2. Sieradzan RR, Bottner WA, Fasco MJ, Bertino JS Jr (1988) "Comparative effects of cefoxitin and cefotetan on vitamin K metabolism." Antimicrob Agents Chemother, 32, p. 1446-9
  3. Cristiano P (1984) "Hypoprothrombinemia associated with cefoperazone treatment." Drug Intell Clin Pharm, 18, p. 314-6
  4. Meisel S (1984) "Hypoprothrombinemia due to cefoperazone." Drug Intell Clin Pharm, 18, p. 316
  5. Parker SW, Baxter J, Beam TR (1984) "Cefoperazone-induced coagulopathy." Lancet, 1, p. 1016
  6. Reddy J, Bailey RR (1980) "Vitamin K deficiency developing in patients with renal failure treated with cephalosporin antibiotics." N Z Med J, 92, p. 378-80
  7. Natelson EA, Brown CH, 3d Bradshaw MW, Alfrey CP, Jr Williams TW, Jr (1976) "Influence of cephalosporin antibiotics on blood coagulation and platelet function." Antimicrob Agents Chemother, 9, p. 91-3
  8. Khaleeli M, Giorgio AJ (1976) "Defective platelet function after cephalosporin administration." Blood, 48, p. 791-2
  9. Haubenstock A, Schmidt P, Zazgornik J, et al. (1983) "Hypoprothrombinaemic bleeding associated with ceftriaxone." Lancet, 1, p. 1215-6
  10. Lipsky JJ (1983) "N-methyl-thio-tetrazole inhibition of the gamma carboxylation of glutamic acid: possible mechanism for antibiotic-associated hypoprothrombinaemia." Lancet, 2, p. 192-3
  11. Osborne JC (1985) "Hypoprothrombinemia and bleeding due to cefoperazone." Ann Intern Med, 102, p. 721-2
  12. Shearer MJ, Bechtold H, Andrassy K, Koderisch J, McCarthy PT, Trenk D, Jahnchen E, Ritz E (1988) "Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status." J Clin Pharmacol, 28, p. 88-95
  13. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  14. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  15. Cerner Multum, Inc. "Australian Product Information."
  16. Wood T, Johnson K, Naylor S, Weinshilboum R (2002) "Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia." Drug Metab Dispos, 30, p. 1123-1128
  17. Mackie IJ, Walshe K, et al. (1986) "Effects of N-methyl-thiotetrazole cephalosporin on haemostasis in patients with reduced serum vitamin K1 concentrations." J Clin Pathol, 39, p. 1245-1249
  18. Agnelli G, Del Favero A, et al. (1986) "Cephalosporin-Induced Hypoprothrombinemia: Is the N-Methylthiotetrazole Side Chain the Culprit?" Antimicrob Agents Chemother, 29, p. 1108-1109
  19. Chen LJ, Hsiao FY, et al. (2016) "Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study." PLoS One, 11, p. 1-11

Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References (6)
  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.

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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