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Rifamycins and Anti-Diabetic Agents: Drug-Drug Interactions
General Tuberculosis (TB) Therapy Information
Developed by Kelly Bujnoch, PharmD Candidate 2011 with the assistance of Regina Tabor, RPh, DPh, Robert Petrossian and Barbara Seaworth, MD Many diabetic medications are metabolized via the Cytochrome P450 (CYP450) enzymatic system in the liver. Rifampin is a potent inducer of the Cytochrome P450 and accounts for many of the drug interactions Rifabutin is a weaker inducer of the Cytochrome P450 system, pot entially interacting with some of the same medications as Rifampin. Enzyme induction effects can last 2-4 weeks after discontinuation of rifampin. Glucose levels should be monitored and diabetic medications should be readjusted at the end of treatment.
BIGUANIDE (METFORMIN) BASED
CLINICAL EFFECT
RIFAMPIN (RIF) DRUG-DRUG INTERACTIONS
RECOMMENDATIONS
Glucophage® Metformin
Absorption of glucose by intestines Insulin sensitivity Glucovance® Glyburide+
Glyburide levels 39% Consider glipizide as first choice sulfonylurea to minimize interactions Metformin
Secretion of insulin from the pancreas Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Metaglip® Glipizide+ Glipizide:
Metformin
Secretion of insulin from the pancreas Metformin: Janumet® Sitagliptin+
Metformin
Secretion of insulin from the pancreas  Increase monitoring; interaction may be minimal and require no adjustments Production of glucose by the liver Absorption of glucose by intestines Insulin sensitivity SULFONYLUREA BASED
Micronase® Glyburide
Secretion of insulin from the pancreas Glyburide levels 39% Consider glipizide as first choice sulfonylurea to minimize interactions Amaryl® Glimepiride
Secretion of insulin from the pancreas Glimepiride levels 30% Glucotrol® Glipizide
Secretion of insulin from the pancreas Glipizide levels 22% Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Glucovance® Glyburide
+ Glyburide:
Metformin
Secretion of insulin from the pancreas Consider glipizide as first choice sulfonylurea to minimize interactions Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Metaglip® Glipizide+ Secretion of insulin from the pancreas Glipizide levels 22% No contraindications
Metformin
Avandaryl® Pioglitazone Pioglitazone:
Pioglitazone levels 54% Pioglitazone: + Glimepiride Insulin sensitivity (body and liver cells) Glimepiride levels 30%
Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Secretion of insulin from the pancreas Consider glipizide as first choice sulfonylurea to minimize interaction Metformin: No contraindications Duetact® Rosiglitazone
Rosiglitazone levels 54-65% Rosiglitazone: + Glimepiride Insulin sensitivity (body and liver cells) Glimiprde levels 30%
Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Consider glipizide as first choice sulfonylurea to minimize interaction Secretion of insulin from the pancreas █COMBO DRUGS
APRIL 16, 2012
Rifamycins and Anti-Diabetic Agents: Drug-Drug Interactions continued
MEGLITINIDE ANALOGUE
CLINICAL EFFECT
RIFAMPIN (RIF) DRUG-DRUG INTERACTIONS
RECOMMENDATIONS
Prandin® Repaglinide
Secretion of insulin from the pancreas Increase monitoring Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Starlix® Nateglinide
Secretion of insulin from the pancreas Increase monitoring
Consider dose adjustment of antidiabetic agents or alternative glucose control therapy.
THIAZOLIDINEDIONE (PPAR Y-AGONIST)
Avandia® Rosiglitazone
Insulin sensitivity (body and liver cells) Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Actos® Pioglitazone
Insulin sensitivity (body and liver cells) Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Duetact® Rosiglitazone
Rosiglitazone levels 54-65% Increase monitoring +Glimepiride
Insulin sensitivity (body and liver cells) Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Consider glipizide as first choice sulfonylurea to minimize interaction Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Secretion of insulin from the pancreas Avandaryl® Pioglitazone Pioglitazone:
 Pioglitazone levels 54% Increase monitoring +Glimepiride
Insulin sensitivity (body and liver cells) Glimepiride levels 30% Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Consider glipizide as first choice sulfonylurea to minimize interaction Increase monitoring Consider dose adjustment of antidiabetic agents or alternative glucose control therapy. Α-GLUCOSIDASE INHIBITOR
Precose® Acarbose Digestion and absorption of glucose by
Glyset® Miglitol Digestion and absorption of glucose by
INCRETIN MIMETIC (GLP-1 RECEPTOR AGONIST)
Byetta® Exenatide
Secretion of insulin from the pancreas  delays gastric emptying Appetite Glucagon release after meals DIPEPTIDYL PEPTIDASE IV INHIBITOR
Januvia® Sitagliptin Secretion of insulin from the pancreas
Increase monitoring; interaction may be minimal and require no adjustments  delays gastric emptying Appetite Glucagon release after meals Onglyza® Saxagliptin
Secretion of insulin from the pancreas Increase monitoring; interaction may be minimal and require no adjustments Appetite Glucagon release after meals Janumet®
Sitagliptin +
Metformin
Secretion of insulin from the pancreas Increase monitoring; interaction may be minimal and require no adjustments Absorption of glucose by intestines Insulin sensitivity AMYLINOMIMETIC
Symlin® Pramlintide
Appetite Glucagon release after meals REFERENCES
Hatorp V, Hansen KT, and Thomsen MS (2003), Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol 43:649 – 660. Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. April 1, 2011 <http://www.thomsonhc.com>. Niemi M., Backman JT, Neuvonen M., Neuvonen PJ, Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects. British Journal of Clinical Pharmacology 56, 427-432 (2003). Niemi M., Backman JT, et al. Pharmacokinetic Interactions with Rifampicin. Clin Pharmacokinet. 2003; 42(9):819-850. Niemi M., Backman JT, Neuvonen PJ. Effects of Trimethoprim and Rifampin on the Pharmacokinetics of the Cytochrome P450 2C8 Substrate Rosiglitazone. Clin Pharmacol Ther. September 2004: 239-49. Niemi M., Backman JT, Neuvonen M., Neuvonen PJ, Kivisto KT. Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide. Clinical Pharmacology & Therapeutics (2001) 69, 400–406; doi: 10.1067/mcp.2001.115822 Park JY, Kim KA, et al. Effect of Rifampin on the Pharmacokinetics of Rosiglitazone in Healthy Subjects. Clin Pharm Ther. March Sahi J., Black CB, Hamilton GA, Zheng X., Jolley S., Rose KA, Gilbert D., LeCluyse EL., Sinz MW (2003), Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos 31, 439–46. Jaakkola T., Backman JT, Neuvonen M., Laitila J., and Neuvonen PJ. Effect of rifampicin on the pharmacokinetics of pioglitazone. Br J Clin Pharmacol, 61 (2006), pp. 70–78. Upreti, VV, Boulton, DW, Li, L., Ching, A., Su, H., LaCreta, FP and Patel, CG.(2011). Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. British Journal of Clinical Pharmacology, 72: 92–102. doi: 10.1111/j.1365-2125.2011.03937x.

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