wwwsdhskcaRxFiles Hypoglycemic Drug Interactions 1 What drugs should not be used in combination with oral hypoglycemicsDespite numerous interactions affecting hypoglycemics few are of major sig ID: 961014
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The Rx FilesQ&A SummaryDRAFT - October 2001 www.sdh.sk.ca/RxFiles Hypoglycemic Drug Interactions 1. What drugs should not be used in combination with oral hypoglycemics?Despite numerous interactions affecting hypoglycemics, few are of major significance. These agents can be usedrelatively safely with almost all other medications with a couple notable exceptions: Phenylbutazonecan cause severe hypoglycemia when given together with oral sulfonylureas Alcoholcan cause a disulfiram-like reaction when taken in combination with oral sulfonylureasparticularly medications have on hypoglycemic efficacy?Although there are numerous interactions between hypoglycemics and some of the major classes of cardiac drugs,the majority are of moderate clinical significance. Most can be managed with more frequent blood sugarmonitoring and dose adjustments if use of alternate agents is not readily convenient. These include:Antihypertensives:Thiazide diuretics and furosemide tend to cause hyperglycemiaCalcium channel blockers TENORMIN, bisoprolol MONOCOR, or metoprolol LOPRESOR,BETALOC may be safer.Antihyperlipidemics:Fibrate antihyperlipidemics and some beta blockers can displace sulfonylureas and repaglinide GLUCONORMfrom plasma protein binding thereby potentiating their effects & possibly causing hypoglycemia Prepared by Sharon Downey BSP, in consultation with RxFiles advisors & reviewers. DISCLAIMER:The content of this newsletter represents the research, experience and opinions of the authors and not those of the Board or Administration o f Saskatoon District Health. Neither the authors nor Saskatoon District Health nor any other party who has been involved in the preparation or publication of thiswork warrants or represents that the information contained herein is accurate or complete, and they are not responsible for any f Saskatoon District Health, it employees, servants or agents. Readers are encouraged to confirm the information contained herein with other sources. See also chart, Page 2 The Rx FilesQ&A SummaryDRAFT - October 2001 www.sdh.sk.ca/RxFiles Hypoglycemic Agents: Drug Interactions 1,2,3 Effects Increased by: (Potential for Hypoglycemia) Effects Decreased by: (Potential for Hyperglycemia) Other Interactions: Chlorpropamide Gliclazide DIAMICRON Glyburide DIABETA highly PPB cytochrome P450substrate (CYP 3A3/4) Tolbutamide cytochrome P450substrate (CYP2C8/9/18) andinhibitor (CYP 2C19)Displacement from PlasmaProteinBindi
ng (PPB) PhenylbutazoneFibratesFluoroquinolones (with Glyburide)Oral anticoagulantsPhenytoinSalicylatesSulfonamides Renal clearance FibratesSalicylatesSulfonamides Metabolism Azole antifungals (Tolbutamide)Chloramphenicol (with chlorpropamide & tolbutamide)Cimetidine (with Glyburide, Gliclazide & Tolbutamide)Sulfonamides metabolism Alcohol-chronic useRifampinAlcohol: disulfiram-like rx flushing, warmth, dizziness, nausea, tachycardiachlorpropamide butalso reported with other SUsOral anticoagulants: may beaffected due to PPBdisplacement and alteredmetabolism initially = effect chronically = effectH2 Antagonists, ProtonPump inhibitors &Antacids: can absorption; also effect of glyburide & gliclazide MetforminGLUCOPHAGEnegligible PPB Renal clearance (Cationic drugs): AmilorideCimetidineDigoxinMorphineProcainamideTriamtereneQuinine & QuinidineTrimethoprimVancomycinAlcohol: may potentiatemetformins effect on lactatemetabolism AcarbosePRANDASE MiglitolGLYSETCholestyramine Absorption AmylaseCharcoalPancreatin absorption & effect of:DigoxinPropranololRanitidine PioglitazoneACTOS RosiglitazoneAVANDIAOral contraceptives:pioglitazone may theirmetabolism and efficacy RepaglinideCytochromeP450 substratehighly proteinDisplacement Beta Blockers, someChloramphenicolMAOIsPhenylbutazonePhenytoinSalicylatesSulfomamides Metabolism Azole antifungalsErythromycin Metabolism BarbituratesCarbamazepineRifampinDrugs causing hyperglycemia Beta BlockersCalcium Channel Blockers, someCorticosteroids, someEstrogens/ oral contraceptivesFurosemideIsoniazidPhenothiazinesPhenytoinNicotinic AcidSympathomimetics (e.g. decongestants)ThiazidesThyroid hormones Bolded drugs = major interactions. Avoid combination and use alternate agentsAll other drugs = moderate to mild interactions. More frequent blood glucose monitoring and dose adjustments may be required. Beta Blockers mask signs and symptoms of hypoglycemia (e.g. tachycardia, tremor, blurred vision, hunger & headache) except sweating;also impair insulin release and glycogenolysis; cardioselective agents maybe safer (acebutolol, atenolol, bisoprolol, metoprolo = drug interactions MAOIs = monoamine oxidase inhibitors PPB = plasma protein bindingSUs = sulfonylureas SU-1 = first generation SU SU-2 = 2 generation SU. D ru s potentiating hypoglycemia Alcohol*Beta BlockersMAOIsTricyclic antidepressants DRAFT Cytochrome P450 substrates so potentialfor some DIs as yet unknown