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Isoniazid / pyrazinamide / rifampin Disease Interactions

There are 17 disease interactions with isoniazid / pyrazinamide / rifampin:

Major

Antibiotics (applies to isoniazid/pyrazinamide/rifampin) colitis

Major Potential Hazard, Low plausibility. Applicable conditions: Colitis/Enteritis (Noninfectious)

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

References

  1. Moriarty HJ, Scobie BA "Pseudomembranous colitis in a patient on rifampicin and ethambutol." N Z Med J 04/23/80 (1980): 294-5
  2. Thomas E, Mehta JB "Pseudomembranous colitis due to oxacillin therapy." South Med J 77 (1984): 532-3
  3. Bauwens JE, McFarland LV, Melcher SA "Recurrent clostridium difficile disease following ciprofloxacin use." Ann Pharmacother 31 (1997): 1090
  4. Davies J, Beck E "Recurrent colitis following antibiotic-associated pseudomembranous colitis." Postgrad Med J 57 (1981): 599-601
  5. Dan M, Samra Z "Clostridium difficile colitis associated with ofloxacin therapy." Am J Med 87 (1989): 479
  6. Harmon T, Burkhart G, Applebaum H "Perforated pseudomembranous colitis in the breast-fed infant." J Pediatr Surg 27 (1992): 744-6
  7. Milstone EB, McDonald AJ, Scholhamer CF Jr "Pseudomembranous colitis after topical application of clindamycin." Arch Dermatol 117 (1981): 154-5
  8. Cone JB, Wetzel W "Toxic megacolon secondary to pseudomembranous colitis." Dis Colon Rectum 25 (1982): 478-82
  9. Burt RA "A review of the drug events reported by 12,917 patients treated with cephalexin." Postgrad Med J 59 (1983): 47-50,51-3
  10. Cannon SR, Dyson PH, Sanderson PJ "Pseudomembranous colitis associated with antibiotic prophylaxis in orthopaedic surgery." J Bone Joint Surg Br 70-B (1988): 600-2
  11. Miller DL, Sedlack JD, Holt RW "Perforation complicating rifampin-associated pseudomembranous enteritis." Arch Surg 124 (1989): 1082
  12. Wang C, Calandra GB, Aziz MA, Brown KR "Efficacy and safety of imipenem/cilastatin: a review of worldwide clinical experience." Rev Infect Dis 7 (1985): s528-36
  13. Miller SN, Ringler RP "Vancomycin-induced pseudomembranous colitis." J Clin Gastroenterol 9 (1987): 114-5
  14. Bernstein L "Adverse reaction to trimethoprim-sulfamethoxazole, with particular reference to long-term therapy." Can Med Assoc J 112 (1975): s96-8
  15. Calandra GB, Brown KR, Grad LC, et al "Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin." Am J Med 78 (1985): 73-8
  16. Pokorney BH, Nichols TW, Jr "Pseudomembranous colitis. A complication of sulfasalazine therapy in a patient with Crohn's colitis." Am J Gastroenterol 76 (1981): 374-6
  17. Sankarankutty M, McGeorge D, Galasko CS "Pseudomembranous colitis following cephradine prophylaxis." Postgrad Med J 58 (1982): 726-8
  18. Van Ness MM, Cattau EL Jr "Fulminant colitis complicating antibiotic-associated pseudomembranous colitis: case report and review of the clinical manifestations and treatment." Am J Gastroenterol 82 (1987): 374-7
  19. Hutcheon DF, Milligan FD, Yardley JH, Hendrix TR "Cephalosporin-associated pseudomembranous colitis." Am J Dig Dis 23 (1978): 321-6
  20. Gordin F, Gibert C, Schmidt ME "Clostridium difficile colitis associated with trimethoprim-sulfamethoxazole given as prophylaxis for pneumocystis carinii pneumonia." Am J Med 96 (1994): 94-5
  21. Bingley PJ, Harding GM "Clostridium difficile colitis following treatment with metronidazole and vancomycin." Postgrad Med J 63 (1987): 993-4
  22. Hinton NA "The effect of oral tetracycline HCl and doxycycline on the intestinal flora." Curr Ther Res Clin Exp 12 (1970): 341-52
  23. Ring FA, Hershfield NB, Machin GA, Scott RB "Sulfasalazine-induced colitis complicating idiopathic ulcerative colitis." Can Med Assoc J 131 (1984): 43-5
  24. Saginur R, Hawley CR, Bartlett JG "Colitis associated with metronidazole therapy." J Infect Dis 141 (1980): 772-4
  25. Friedman RJ, Mayer IE, Galambos JT, Hersh T "Oxacillin-induced pseudomembranous colitis." Am J Gastroenterol 73 (1980): 445-7
  26. "Multum Information Services, Inc. Expert Review Panel"
  27. Midtvedt T, Carlstedt-Duke B, Hoverstad T, et al "Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects." Eur J Clin Invest 16 (1986): 11-7
  28. Leigh DA, Simmons K, Williams S "Gastrointestinal side effects following clindamycin and lincomycin treatment: a follow up study." J Antimicrob Chemother 6 (1980): 639-45
  29. Altamirano A, Bondani A "Adverse reactions to furazolidone and other drugs. A comparative review." Scand J Gastroenterol Suppl 169 (1989): 70-80
  30. Hecht JR, Olinger EJ "Clostridium difficile colitis secondary to intravenous vancomycin." Dig Dis Sci 34 (1989): 148-9
  31. Brause BD, Romankiewicz JA, Gotz V, Franklin JE Jr, Roberts RB "Comparative study of diarrhea associated with clindamycin and ampicillin therapy." Am J Gastroenterol 73 (1980): 244-8
  32. Boriello SP, Jones RH, Phillips I "Rifampicin-associated pseudomembranous colitis." Br Med J 281 (1980): 1180-1
  33. Klinger D, Radford P, Collin J "Pneumoperitoneum without faecal peritonitis in a patient with pseudomembranous colitis." Br Med J 288 (1984): 1271-2
  34. Saadah HA "Carbenicillin and pseudomembranous enterocolitis." Ann Intern Med 93 (1980): 645
  35. Lyon JA "Imipenem/cilastatin: the first carbapenem antibiotic." Drug Intell Clin Pharm 19 (1985): 894-8
  36. Daly JJ, Chowdary KV "Pseudomembranous colitis secondary to metronidazole." Dig Dis Sci 28 (1983): 573-4
  37. Trexler MF, Fraser TG, Jones MP "Fulminant pseudomembranous colitis caused by clindamycin phosphate vaginal cream." Am J Gastroenterol 92 (1997): 2112-3
  38. Edlund C, Brismar B, Nord CE "Effect of lomefloxacin on the normal oral and intestinal microflora." Eur J Clin Microbiol Infect Dis 1 (1990): 35-9
  39. O'Meara TF, Simmons RA "Carbenicillin and pseudomembranous enterocolitis." Ann Intern Med 92 (1980): 440-1
  40. Meadowcroft AM, Diaz PR, Latham GS "Clostridium difficile toxin-induced colitis after use of clindmycin phosphate vaginal cream." Ann Pharmacother 32 (1998): 309-11
  41. Ehrenpreis ED, Lievens MW, Craig RM "Clostridium difficile-associated diarrhea after norfloxacin." J Clin Gastroenterol 12 (1990): 188-9
  42. Osler T, Lott D, Bordley J, et al "Cefazolin-induced pseudomembranous colitis resulting in perforation of the sigmoid colon." Dis Colon Rectum 29 (1986): 140-3
  43. Parry MF, Rha CK "Pseudomembranous colitis caused by topical clindamycin phosphate." Arch Dermatol 122 (1986): 583-4
  44. Clissold SP, Todd PA, Campoli-Richards DM "Imipenem/cilastatin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy." Drugs 33 (1987): 185-241
  45. Sugarman B "Trimethoprim-sulfamethoxazole, pseudomembranous colitis, and spinal cord injury." South Med J 78 (1985): 711-3
  46. Golledge CL, Riley TV "Clostridium difficile-associated diarrhoea after doxycycline malaria prophylaxis." Lancet 345 (1995): 1377-8
  47. Edlund C, Lidbeck A, Kager L, Nord CE "Effect of enoxacin on colonic microflora of healthy volunteers." Eur J Clin Microbiol 6 (1987): 298-300
View all 47 references
Major

INH (applies to isoniazid/pyrazinamide/rifampin) hepatotoxicity

Major Potential Hazard, High plausibility. Applicable conditions: Liver Disease, Alcoholism

The use of isoniazid is contraindicated in patients with acute liver disease or a history of hepatic injury due to isoniazid. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. Isoniazid has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of nearly 14,000 isoniazid patients, the incidence of hepatitis was 1.25%, of which 4.6% was fatal. However, more recent studies have reported considerably lower rates when CDC guidelines for selection and monitoring of patients were followed. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.

References

  1. U.S. Departmnet of Health and Human Services / Public Health Service "Severe isoniazid-associated hepatitis--New York, 1991-1993." MMWR Morb Mortal Wkly Rep 42 (1993): 545-7
  2. Moulding TS, Redeker AG, Kanel GC "Twenty isoniazid-associated deaths in one state." Am Rev Respir Dis 140 (1989): 700-5
  3. Yamamoto T, Suou T, Hirayama C "Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype." Hepatology 6 (1986): 295-8
  4. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  5. Mitchell JR, Zimmerman HJ, Ishak KG, et al "Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis." Ann Intern Med 84 (1976): 181-92
  6. Maddrey WC, Boitnott JK "Isoniazid hepatitis." Ann Intern Med 79 (1973): 1-12
  7. Franks AL, Binkin NJ, Snider DE, et al "Isoniazid hepatitis among pregnant and postpartum Hispanic patients." Public Health Rep 104 (1989): 151-5
  8. Bartelink AK, Lenders JW, van Herwaarden CL, et al "Fatal hepatitis after treatment with isoniazid and rifampicin in a patient on anticonvulsant therapy." Tubercle 64 (1983): 125-8
  9. Dutt AK, Moers D, Stead WW "Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis." Am Rev Respir Dis 128 (1983): 419-24
  10. Israel HL, Gottlieb JE, Maddrey WC "Perspective: preventive isoniazid therapy and the liver." Chest 101 (1992): 1298-301
  11. Maddrey WC "Drug-related acute and chronic hepatitis." Clin Gastroenterol 9 (1980): 213-24
  12. Snider DE, Caras GJ "Isoniazid-associated hepatitis deaths: a review of available information." Am Rev Respir Dis 145 (1992): 494-7
  13. Yoshikawa TT, Nagami PH "Adverse drug reactions in TB therapy: risks and recommendations." Geriatrics 37 (1982): 61-8
  14. "Product Information. Nydrazid (isoniazid)" Apothecon Inc, Princeton, NJ.
  15. Maddrey WC "Isoniazid-induced liver disease." Semin Liver Dis 1 (1981): 129-33
View all 15 references
Major

INH (applies to isoniazid/pyrazinamide/rifampin) liver disease

Major Potential Hazard, High plausibility.

Isoniazid is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from isoniazid due to decreased drug clearance. Dosage reductions are recommended in these patients.

References

  1. Acocella G, Bonollo L, Garimoldi M, et al "Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease." Gut 13 (1972): 47-53
  2. "Product Information. Nydrazid (isoniazid)" Apothecon Inc, Princeton, NJ.
  3. Weber WW, Hein DW "Clinical pharmacokinetics of isoniazid." Clin Pharmacokinet 4 (1979): 401-22
  4. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  5. Reed MD, Blumer JL "Clinical pharmacology of antitubercular drugs." Pediatr Clin North Am 30 (1983): 177-93
  6. Ellard GA, Gammon PT "Pharmacokinetics of isoniazid metabolism in man." J Pharmacokinet Biopharm 4 (1976): 83-113
View all 6 references
Major

INH (applies to isoniazid/pyrazinamide/rifampin) peripheral neuropathy

Major Potential Hazard, High plausibility. Applicable conditions: Malnourished, Diabetes Mellitus, Alcoholism

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paresthesias of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with preexisting peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

References

  1. Dippenaar J, Jameson C, Dowse R "Side-effects of isoniazid." S Afr Med J 72 (1987): 89
  2. Siskind MS, Thienemann D, Kirlin L "Isoniazid-induced neurotoxicity in chronic dialysis patients: report of three cases and a review of the literature." Nephron 64 (1993): 303-6
  3. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  4. Gonzalez-Gay MA, Sanchez-Andrade A, Aguero JJ, Alonso MD, Rodriguez E, Criado JR "Optic neuritis following treatment with isoniazid in a hemodialyzed patient." Nephron 63 (1993): 360
  5. Jimenez-Lucho VE, del Busto R, Odel J "Isoniazid and ethambutol as a cause of optic neuropathy." Eur J Respir Dis 71 (1987): 42-5
  6. "Product Information. Nydrazid (isoniazid)" Apothecon Inc, Princeton, NJ.
  7. Mandell GL, Bennett JE, Dolin R, eds.. "Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed." New York, NY: Churchill Livingston 1 (1995):
View all 7 references
Major

PZA (applies to isoniazid/pyrazinamide/rifampin) gout

Major Potential Hazard, High plausibility.

The use of pyrazinamide is contraindicated in patients with acute gout. Pyrazinamide inhibits the renal excretion of uric acid, which may frequently result in precipitation or exacerbation of gout. Therapy with pyrazinamide should be administered cautiously in patients with hyperuricemia or a history of gout. Serum uric acid levels should be monitored regularly, and appropriate measures (e.g., administration of uricosuric agents) taken to prevent the development of gout. If gouty arthritis occurs, pyrazinamide should be discontinued.

References

  1. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
  2. Amodio MI, Bengualid V, Lowy FD "Development of acute gout secondary to pyrazinamide in a patient without a prior history of gout." DICP 24 (1990): 1115-6
Major

PZA (applies to isoniazid/pyrazinamide/rifampin) hepatotoxicity

Major Potential Hazard, High plausibility. Applicable conditions: Alcoholism, Liver Disease

The use of pyrazinamide is contraindicated in patients with severe liver damage. Pyrazinamide may cause hepatocellular injury, particularly in patients with underlying liver disease and during coadministration with other hepatotoxic agents including other antituberculous drugs such as isoniazid and rifampin. Therapy with pyrazinamide should be administered cautiously and under strict medical supervision in patients with liver disease or a history of alcoholism. Serum transaminases (ALT, AST) and bilirubin should be measured at baseline and monitored closely during therapy. Patients should be instructed to discontinue the drug promptly and seek medical attention if signs and symptoms of hepatic injury develop, including fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. To lessen the risk of hepatotoxicity, the maximum dosage should not exceed 2 g/day when treatment is administered daily or 3 g/day when administered twice weekly.

References

  1. Mandell GL, Bennett JE, Dolin R, eds.. "Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed." New York, NY: Churchill Livingston 1 (1995):
  2. Cohen CD, Sayed AR, Kirsch RE "Hepatic complications of antituberculosis therapy revisited." S Afr Med J 63 (1983): 960-3
  3. CDC. Centers for Disease Control. "Update: fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001." Morb Mortal Wkly Rep 50 (2001): 733-5
  4. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
  5. Danan G, Pessayre D, Larrey D, Benhamou JP "Pyrazinamide fulminant hepatitis: an old hepatotoxin strikes again." Lancet 2 (1981): 1056-7
View all 5 references
Major

PZA (applies to isoniazid/pyrazinamide/rifampin) liver disease

Major Potential Hazard, High plausibility.

Pyrazinamide is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from pyrazinamide due to decreased drug clearance. Dosage reductions are recommended in these patients if the drug is used.

References

  1. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
  2. Ellard GA "Absorption, metabolism and excretion of pyrazinamide in man." Tubercle 50 (1969): 144-58
  3. Lacroix C, Tranvouez JL, Hoang T, Duwoos H, LaFont O "Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency." Arzneimittelforschung 40 (1990): 76-9
Major

PZA (applies to isoniazid/pyrazinamide/rifampin) renal dysfunction

Major Potential Hazard, Moderate plausibility.

The half-life of pyrazinamide may be prolonged in patients with renal impairment. In addition, the drug's metabolites, at least one of which is pharmacologically active, may accumulate. Therapy with pyrazinamide should be administered cautiously in patients with renal dysfunction. Dosage adjustments may be necessary.

References

  1. Stamatakis G, Montes C, Trouvin JH, et al "Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure." Clin Nephrol 30 (1988): 230-4
  2. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
  3. Ellard GA "Absorption, metabolism and excretion of pyrazinamide in man." Tubercle 50 (1969): 144-58
  4. Mandell GL, Bennett JE, Dolin R, eds.. "Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed." New York, NY: Churchill Livingston 1 (1995):
View all 4 references
Major

Rifampin (applies to isoniazid/pyrazinamide/rifampin) hematopoietic disturbances

Major Potential Hazard, Low plausibility. Applicable conditions: Bone Marrow Depression/Low Blood Counts

Rifampin may infrequently cause hematopoietic abnormalities such as thrombocytopenia, leukopenia, decreased hemoglobin, and acute hemolytic anemia. Hemolysis has been described as part of an immune-mediated reaction which generally occurs after gaps in therapy. Thrombocytopenia is observed most frequently in patients receiving high-dose intermittent therapy or after a lapse in therapy, but very rarely during daily administration. It is reversible if rifampin is discontinued as soon as purpura appears. Patients with preexisting bone marrow depression or blood dyscrasias should be monitored closely during rifampin therapy for further decreases in blood counts. Although rifampin-related hematologic effects are often transient, cerebral hemorrhage and fatalities have been reported with the continued administration of rifampin after the appearance of purpura.

References

  1. "Product Information. Rifadin (rifampin)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  2. Lee M, Berger HW "Eosinophilia caused by rifampin." Chest 77 (1980): 579
  3. Dutt AK, Moers D, Stead WW "Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis." Am Rev Respir Dis 128 (1983): 419-24
  4. Ferguson GC "Rifampicin and thrombocytopenia." Br Med J 3 (1971): 638
  5. Brook G, Pain A "Major adverse reactions to a short course of daily rifampicin." Scand J Infect Dis 19 (1987): 271-2
  6. Levine M, Collin K, Kassen BO "Acute hemolysis and renal failure following discontinuous use of rifampin." DICP 25 (1991): 743-4
  7. Hall AP, Thorpe JW, Seaton D "New hazard of meningococcal chemoprophylaxis." J Antimicrob Chemother 31 (1993): 451
  8. Tahan SR, Diamond JR, Blank JM, Horan RF "Acute hemolysis and renal failure with rifampicin-dependent antibodies after discontinuous administration." Transfusion 25 (1985): 124-7
  9. Allen RJ, Almond SN, Caiolsa SM, et al "Rifampin." Drug Intell Clin Pharm 5 (1971): 364-5
  10. Nolan RL, Cleary JD, Chapman SW "Fever associated with daily rifampin therapy." Clin Pharm 9 (1990): 57-8
  11. Mariette X, Mitjavila MT, Moulinie JP, et al "Rifampicin-induced pure red cell aplasia." Am J Med 87 (1989): 459-60
  12. Hadfield JW "Rifampicin-induced thrombocytopenia." Postgrad Med J 56 (1980): 59-60
  13. Kindelan JM, Serrano I, Jurado R, Villanueva JL, Garcialazaro M, Garciaherola A, Cisneros JT "Rifampin-induced severe thrombocytopenia in a patient with pulmonary tuberculosis." Ann Pharmacother 28 (1994): 1304-5
  14. Lee CH, Lee CJ "Thrombocytopenia: a rare but potentially serious side effect of initial daily and interrupted use of rifampicin." Chest 96 (1989): 202-3
  15. van Assendelft AH "Renal failure and haemolysis caused by rifampicin." Tubercle 67 (1986): 234-5
View all 15 references
Major

Rifampin (applies to isoniazid/pyrazinamide/rifampin) hepatotoxicity

Major Potential Hazard, High plausibility. Applicable conditions: Liver Disease, Alcoholism

The use of rifampin has been associated with hepatocellular injury and liver dysfunction. Hepatitis and jaundice resulting in death have occurred, mostly in patients with underlying liver disease and during coadministration with other hepatotoxic agents including other antituberculous drugs such as isoniazid and pyrazinamide. Therapy with rifampin should be administered cautiously and under strict medical supervision in patients with liver disease or a history of alcoholism. Serum transaminases (ALT, AST) and bilirubin should be measured at baseline and every 2 to 4 weeks during therapy, but keeping in mind that elevated levels may occur transiently in 10% to 15% of patients, usually during the early days of treatment. Patients should be instructed to discontinue the drug promptly and seek medical attention if signs and symptoms of hepatic injury develop, including fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.

References

  1. Dutt AK, Moers D, Stead WW "Short-course chemotherapy for tuberculosis with mainly twice-weekly isoniazid and rifampin: community physicians' seven-year experience with mainly outpatients." Am J Med 77 (1984): 233-42
  2. Maddrey WC "Drug-related acute and chronic hepatitis." Clin Gastroenterol 9 (1980): 213-24
  3. Dutt AK, Moers D, Stead WW "Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis." Am Rev Respir Dis 128 (1983): 419-24
  4. CDC. Centers for Disease Control. "Update: fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001." Morb Mortal Wkly Rep 50 (2001): 733-5
  5. Yoshikawa TT, Nagami PH "Adverse drug reactions in TB therapy: risks and recommendations." Geriatrics 37 (1982): 61-8
  6. Bartelink AK, Lenders JW, van Herwaarden CL, et al "Fatal hepatitis after treatment with isoniazid and rifampicin in a patient on anticonvulsant therapy." Tubercle 64 (1983): 125-8
  7. "Product Information. Rifadin (rifampin)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Allen RJ, Almond SN, Caiolsa SM, et al "Rifampin." Drug Intell Clin Pharm 5 (1971): 364-5
  9. Gabriel R "Rifampin jaundice." Br Med J 3 (1971): 182
  10. O'Brien RJ, Long MW, Cross FS, et al "Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis." Pediatrics 72 (1983): 491-9
View all 10 references
Major

Rifampin (applies to isoniazid/pyrazinamide/rifampin) liver disease

Major Potential Hazard, High plausibility.

Rifampin is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from rifampin due to decreased drug clearance. In addition, the accumulation of rifampin may result in hyperbilirubinemia because rifampin competes with bilirubin for uptake by hepatocytes. Dosage adjustments are recommended in patients with liver disease. Withdrawal of rifampin therapy may be required if serum bilirubin is persistently high.

References

  1. "Product Information. Rifadin (rifampin)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  2. Loos U, Musch E, Jensen JC, et al "Pharmacokinetics of oral and intravenous rifampicin during chronic administration." Klin Wochenschr 63 (1985): 1205-11
  3. Nitti V, Virgilio R, Patricolo MR, Iuliano A "Pharmacokinetic study of intravenous rifampicin." Chemotherapy 23 (1977): 1-6
  4. Acocella G "Clinical pharmacokinetics of rifampicin." Clin Pharmacokinet 3 (1978): 108-27
View all 4 references
Major

Rifampin (applies to isoniazid/pyrazinamide/rifampin) porphyria

Major Potential Hazard, Moderate plausibility.

Rifampin may induce the activity of delta amino levulinic acid synthetase, an enzyme involved in the biosynthesis of porphyrins. The use of rifampin has been associated with isolated cases of porphyria exacerbation. Therapy with rifampin should be administered cautiously in patients with a history of porphyria.

References

  1. "Product Information. Rifadin (rifampin)." Hoechst Marion-Roussel Inc, Kansas City, MO.
Moderate

INH (applies to isoniazid/pyrazinamide/rifampin) hemodialysis

Moderate Potential Hazard, High plausibility.

Isoniazid is substantially removed by hemodialysis and should be administered after dialysis.

References

  1. Gold CH, Buchanan N, Tringham V, et al "Isoniazid pharmacokinetics in patients with chronic renal failure." Clin Nephrol 6 (1976): 365-9
  2. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  3. "Product Information. Nydrazid (isoniazid)" Apothecon Inc, Princeton, NJ.
Moderate

INH (applies to isoniazid/pyrazinamide/rifampin) renal dysfunction

Moderate Potential Hazard, Moderate plausibility.

Isoniazid is metabolized primarily by acetylation and dehydrazination in the liver. It is not significantly excreted by the kidney. Dosage adjustments in renal impairment are generally not necessary except in slow acetylators with a creatinine clearance below 10 mL/min. The rate of acetylation is genetically determined. Approximately 50% of blacks and caucasians are slow acetylators, and the majority of Eskimos and Asians are rapid acetylators.

References

  1. "Product Information. Nydrazid (isoniazid)" Apothecon Inc, Princeton, NJ.
  2. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  3. Andrew OT, Schoenfeld PY, Hopewell PC, Humphreys MH "Tuberculosis in patients with end-stage renal disease." Am J Med 68 (1980): 59-65
  4. Bowerson DW, Winterbauer RH, Stewart GL, et al "Isoniazid dosage in patients with renal failure." N Engl J Med 289 (1973): 84-7
  5. Kim YG, Shin JG, Shin SG, Jang IJ, Kim SG, Lee JS, Han JS, Cha YN "Decreased acetylation of isoniazid in chronic renal failure." Clin Pharmacol Ther 54 (1993): 612-20
  6. Reidenberg MM, Shear L, Cohen RV "Elimination of isoniazid in patients with impaired renal function." Am Rev Respir Dis 108 (1973): 1426-8
  7. Gold CH, Buchanan N, Tringham V, et al "Isoniazid pharmacokinetics in patients with chronic renal failure." Clin Nephrol 6 (1976): 365-9
  8. Boxenbaum HG, Bekersky I, Mattaliano V, Kaplan SA "Plasma and salivary concentrations of isoniazid in man: preliminary findings in two slow acetylator subjects." J Pharmacokinet Biopharm 3 (1975): 443-56
  9. Mitchison DA, Ellard GA "Tuberculosis in patients having dialysis." Br Med J 280 (1980): 1533
View all 9 references
Moderate

PZA (applies to isoniazid/pyrazinamide/rifampin) diabetes mellitus

Moderate Potential Hazard, Moderate plausibility.

The use of pyrazinamide may be associated with poor diabetic control. Patients with diabetes mellitus should be monitored more closely during therapy with pyrazinamide, and their antidiabetic regimen adjusted accordingly.

References

  1. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
Moderate

PZA (applies to isoniazid/pyrazinamide/rifampin) hemodialysis

Moderate Potential Hazard, High plausibility.

Pyrazinamide is removed by hemodialysis and should be administered after dialysis.

References

  1. "Product Information. Pyrazinamide (pyrazinamide)." VersaPharm Inc, Marietta, GA.
  2. Woo J, Leung A, Chan K, Lai KN, Teoh R "Pyrazinamide and rifampicin regimens for patients on maintenance dialysis." Int J Artif Organs 11 (1988): 181-5
Moderate

Rifampin (applies to isoniazid/pyrazinamide/rifampin) enzyme induction

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Hyperthyroidism, Hyperadrenocorticism, Hypoparathyroidism, Hypothyroidism, Panhypopituitarism, Hyperparathyroidism, Adrenal Insufficiency

Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.

References

  1. "Product Information. Rifadin (rifampin)." Hoechst Marion-Roussel Inc, Kansas City, MO.

Isoniazid / pyrazinamide / rifampin drug interactions

There are 623 drug interactions with isoniazid / pyrazinamide / rifampin

Isoniazid / pyrazinamide / rifampin alcohol/food interactions

There are 2 alcohol/food interactions with isoniazid / pyrazinamide / rifampin

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.