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Drug Interactions between Humalog and IsonaRif

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

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Major

rifAMPin isoniazid

Applies to: IsonaRif (isoniazid / rifampin) and IsonaRif (isoniazid / rifampin)

MONITOR CLOSELY: The risk of hepatotoxicity is greater when rifampin and isoniazid (INH) are given concomitantly, than when either drug is given alone. The proposed mechanism is rifampin's induction of isoniazid hydrolase, an enzyme involved in the conversion of INH to isonicotinic acid and hydrazine. Hydrazine is the proposed toxic metabolite of INH, which has been shown in animal studies to cause steatosis, hepatocyte vacuolation and glutathione depletion. Some studies have also shown that slow acetylators have a two-fold increased risk of developing antituberculosis drug-induced hepatotoxicity (ATDH) as compared with fast acetylators due to more available INH for direct hydrolysis to hydrazine. Theoretically, a similar reaction may occur with rifabutin and isoniazid. Additional risk factors for developing hepatotoxicity include patients with advanced age, malnutrition, existing hepatic impairment, daily alcohol consumption, female gender, HIV infection, extra-pulmonary tuberculosis and/or patients who are taking other potent CYP450-inducing agents.

MANAGEMENT: Caution and close monitoring should be considered if isoniazid (INH) is coadministered with rifampin or rifabutin. In cases where coadministration is required, careful monitoring of liver function, especially ALT and AST, should be done at baseline and then every 2 to 4 weeks during therapy, or in accordance with individual product labeling. Some manufacturers of INH recommend strongly considering its discontinuation if serum aminotransferase concentrations (AST or SGOT, ALT or SGPT) exceed 3 to 5 times the upper limit of normal. Product labeling for rifampin also recommends the immediate discontinuation of therapy if hepatic damage is suspected. INH product labeling suggests alternate drugs be used if hepatitis is attributed to INH in patients with tuberculosis. However, if INH must be used, it should only be resumed after the patient's symptoms and laboratory abnormalities have cleared. It should also be restarted in very small, gradually increasing doses and immediately withdrawn if there is any indication of recurrent liver involvement. Patients should be counseled to immediately report signs or symptoms consistent with liver damage and notified that prodromal symptoms usually consist of fatigue, weakness, malaise, anorexia, nausea, and/or vomiting.

References

  1. O'Brien RJ, Long MW, Cross FS, et al. "Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis." Pediatrics 72 (1983): 491-9
  2. Kumar A, Misra PK, Mehotra R, et al. "Hepatotoxicity of rifampin and isoniazid." Am Rev Respir Dis 143 (1991): 1350-2
  3. Abadie-Kemmerly S, Pankey GA, Dalvisio JR "Failure of ketoconazole treatment of blastomyces dermatidis due to interaction of isoniazid and rifampin." Ann Intern Med 109 (1988): 844-5
  4. 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
  5. Yamamoto T, Suou T, Hirayama C "Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype." Hepatology 6 (1986): 295-8
  6. Steele MA, Burk RF, Des Prez RM "Toxic hepatitis with isoniazid and rifampin." Chest 99 (1991): 465-71
  7. "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
  8. Sarma G, Immanuel C, Kailasam S, Narayana AS, Venkatesan P "Rifampin-induced release of hydrazine from isoniazid." Am Rev Respir Dis 133 (1986): 1072-5
  9. "Product Information. Mycobutin (rifabutin)." Pharmacia and Upjohn PROD (2001):
  10. "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel PROD (2001):
  11. Askgaard DS, Wilcke T, Dossing M "Hepatotoxicity caused by the combined action of isoniazid and rifampicin." Thorax 50 (1995): 213-4
  12. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  13. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  14. Cerner Multum, Inc. "Australian Product Information." O 0
  15. "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC. (2023):
  16. "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd (2023):
  17. "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB (2023):
  18. Sarma GR, Immanual C, Kailasam S, Narayana AS, Venkatesan P "Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin https://pubmed.ncbi.nlm.nih.gov/3717759/" (2024):
  19. Tostmann A, Boeree MJ, Aarnoutse RE, De Lange WCM, Van Der Ven AJAM, Dekhuijzen R "Antituberculosis drug-induced hepatotoxicity: concise up-to-date review https://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2007.05207.x" (2024):
  20. "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc. (2021):
  21. "Product Information. Rifampin (rifAMPin)." Akorn Inc (2022):
  22. "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc (2022):
  23. "Product Information. Rifadin (rifampicin)." Sanofi (2023):
  24. "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd (2024):
  25. "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc. (2019):
View all 25 references

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Moderate

isoniazid insulin lispro

Applies to: IsonaRif (isoniazid / rifampin) and Humalog (insulin lispro)

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

References

  1. Greenstone MA, Shaw AB "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J 63 (1987): 761-4
  2. Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73
  3. Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
  4. Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
  5. Chaudhuri ML, Catania J "A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly." Br J Clin Pract 42 (1988): 427-9
  6. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol 105 (1969): 556-60
  7. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  8. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  9. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  10. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  11. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  12. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2
  13. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  14. Black DM, Filak AT "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract 28 (1989): 462-3
  15. Gunnarsson R, Lundgren G, Magnusson G, Ost L, Groth CG "Steroid diabetes--a sign of overtreatment with steroids in the renal graft recipient?" Scand J Urol Nephrol Suppl 54 (1980): 135-8
  16. Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet 2 (1982): 1293-5
  17. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  18. Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4
  19. Erle G, Basso M, Federspil G, Sicolo N, Scandellari C "Effect of chlorpromazine on blood glucose and plasma insulin in man." Eur J Clin Pharmacol 11 (1977): 15-8
  20. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham PROD (2002):
  21. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  22. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  23. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  24. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  25. "Product Information. Carafate (sucralfate)." Hoechst Marion Roussel PROD (2001):
  26. Stambaugh JE, Tucker DC "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes 23 (1974): 679-83
  27. Malherbe C, Burrill KC, Levin SR, Karam JH, Forsham PH "Effect of diphenylhydantoin on insulin secretion in man." N Engl J Med 286 (1972): 339-42
  28. Javier Z, Gershberg H, Hulse M "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism 17 (1968): 443-56
  29. Sotaniemi E, Kontturi M, Larmi T "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol 10 (1973): 438-41
  30. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  31. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  32. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  33. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
  34. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
  35. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S "Furosemide-induced hyperglycaemia - the implication of glycolytic kinases." Horm Metab Res 25 (1993): 557-9
  36. Goldman JA, Ovadia JL "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol 103 (1969): 172-8
  37. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  38. Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4
  39. Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia 36 (1993): 84-7
  40. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  41. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90
  42. Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H "Insulin action in insulin-dependent diabetics after short-term thiazide therapy." Diabetes Care 9 (1986): 631-6
  43. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther 253 (1981): 154-63
  44. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  45. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
  46. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  47. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  48. Harper R, Ennis CN, Heaney AP, Sheridan B, Gormley M, Atkinson AB, Johnston GD, Bell PM "A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM." Diabetologia 38 (1995): 853-9
  49. "Product Information. Precose (acarbose)." Bayer PROD (2001):
  50. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  51. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel PROD (2001):
  52. Charan VD, Desai N, Singh AP, Choudhry VP "Diabetes mellitus and pancreatitis as a complication of L- asparaginase therapy." Indian Pediatr 30 (1993): 809-10
  53. Seifer DB, Freedman LN, Cavender JR, Baker RA "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol 162 (1990): 474-5
  54. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  55. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4
  56. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  57. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  58. "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer PROD (2001):
  59. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc PROD (2001):
  60. "Product Information. Elspar (asparaginase)." Merck & Co., Inc PROD (2001):
  61. "Product Information. Hyperstat (diazoxide)." Apothecon Inc (2022):
  62. "Product Information. Megace (megestrol)." Bristol-Myers Squibb PROD (2001):
  63. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  64. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  65. Mauss S, Wolf E, Jaeger H "Impaired glucose tolerance in HIV-positive patients receiving and those not receiving protease inhibitors." Ann Intern Med 130 (1999): 162-3
  66. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  67. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn PROD (2001):
  68. "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn PROD (2001):
  69. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company PROD (2001):
  70. Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7
  71. Tsiodras S, Mantzoros C, Hammer S, Samore M "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med 160 (2000): 2050-6
  72. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  73. "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals PROD (2001):
  74. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  75. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
  76. "Product Information. NovoLOG Mix 70/30 (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc (2022):
  77. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  78. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  79. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  80. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
  81. "Product Information. Zolinza (vorinostat)." Merck & Co., Inc (2006):
  82. "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories (2007):
  83. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  84. "Product Information. Elzonris (tagraxofusp)." Stemline Therapeutics (2019):
  85. "Product Information. Piqray (alpelisib)." Novartis Pharmaceuticals (2019):
View all 85 references

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Drug and food interactions

Moderate

rifAMPin food

Applies to: IsonaRif (isoniazid / 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

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

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Moderate

isoniazid food

Applies to: IsonaRif (isoniazid / rifampin)

GENERALLY AVOID: Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.

GENERALLY AVOID: Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).

ADJUST DOSING INTERVAL: Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.

MANAGEMENT: The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 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 INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.

References

  1. Smith CK, Durack DT "Isoniazid and reaction to cheese." Ann Intern Med 88 (1978): 520-1
  2. Dimartini A "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol 10 (1995): 197-8
  3. Uragoda CG, Kottegoda SR "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle 58 (1977): 83-9
  4. Self TH, Chrisman CR, Baciewicz AM, Bronze MS "Isoniazid drug and food interactions." Am J Med Sci 317 (1999): 304-11
  5. "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India) 2 (2021):
  6. "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC. (2023):
  7. "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd (2023):
  8. "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB (2023):
  9. Saukkonen JJ, Cohn DL, Jasmer RM, et al. "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med 174 (2006): 935-52
  10. Bouazzi OE, Hammi S, Bourkadi JE, et al. "First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/" (2024):
  11. Wang P, Pradhan K, Zhong XB, Ma X "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B 6 (2016): 384-92
  12. Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother 71 (2016): 703-10
  13. Hahn JA, Ngabirano C, Fatch R, et al. "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS 37 (2023): 1535-43
  14. Huang YS, Chern HD, Su WJ, et al. "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology 37 (2003): 924-30
  15. Sousou JM, Griffith EM, Marsalisi C, Reddy P "Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/" (2024):
  16. Miki M, Ishikawa T, Okayama H "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med 44 (2005): 1133-6
  17. "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc. (2021):
View all 17 references

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Moderate

insulin lispro food

Applies to: Humalog (insulin lispro)

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
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  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
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  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
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Therapeutic duplication warnings

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

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