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Paul Auwaerter, M.D. and Paul A. Pham, Pharm.D.
04-23-2010
- Certain antibiotics may produce undesired changes in glycemic control when used in persons with diabetes.
- No apparent interactions are described between antibiotics and insulins.
- Serum concentrations of hypoglycemic agents may change due to inhibition or induction of oxidative metabolism (i.e. cytochrome P450 system) including: meglitinides (repaglinide, nateglinide), sulfonylureas (glyburide, glipizide), and glitizones (pioglitazone, rosiglitazone).
- Specific cytochrome P450 substrates: repaglinide (2C8, 3A4); nateglinide (2C9>3A4); glyburide and glipizide (2C9); pioglitazone (3A4>2C8); rosiglitazone (2C8> 2C9).
- Limited number of potential drug-drug interactions observed with metformin.
- Both outpatients and inpatients are at risk. Elderly and more severely ill may be at higher risk of dysglycemic reactions.
- Patients with diabetes under treatment for tuberculosis may be at higher risk for treatment failure due to lowered serum concentrations of rifampin, especially if high BMI.
- Obese people with diabetes may be at higher risk for treatment failure if weight-based dosing is not followed for certain antimicrobials (e.g., vancomycin, daptomycin, fluconazole, caspofungin, penicillins, trimethoprim/sulfamethoxazole, cephalosporins, aminoglycosides, and rifamycins).
- Hypo- or hyperglycemia in severely ill patients may be a consequence of systemic complications (e.g. from sepsis, liver disorders) and therefore be difficult to separate from a potential drug interaction.
- Drug may slow movement of antibiotics through digestive tract.
- Recommended to take antibiotics at least one hour prior to exenatide injection.
- Both hypo- and hyperglycemia reported, but effect may be variable within the class and appears dose dependent. Often difficult to sort out between drug effect or underlying systemic disorder.
- Gatifloxacin was withdrawn from U.S. market (2006) due to occurrence of hypo- and hyperglycemia, especially in elderly diabetic patients on oral hypoglycemics. Seen with other fluoroquinolones, some have argued that it is a class effect.
- Hypo- and hyperglycemia effects: gatifloxacin > levofloxacin >> ciprofloxacin and azithromycin (as a comparator)(Aspinall). Although moxifloxacin reported less dysglycemia than gatifloxacin or levofloxacin, this may be due to usage issues.
- Mechanism may be due to fluoroquinolone effect in enhancing release of insulin by interference with ATP-sensitive K+ channels of pancreatic ß cells [Saraya].
- Consider using alternative to levofloxacin in unstable people with diabetes or severely ill. Ciprofloxacin appears to have usually minimal effects and can be safely used. Moxifloxacin likely also with less dysglycemic effect, but less well studied.
- Clarithromycin increased repaglinide area under the inhibitory curve (AUC) by 40%. Consider decreasing repaglinide dose to avoid hypoglycemia.
- Class may increase concentrations of pioglitazone, effect unclear.
- Class may increase sulfonylureas serum concentration. Consider decreasing sulfonylurea dose with co-administration to avoid hypoglycemia.
- Azithromycin, specifically, can be considered without regard to use of repaglinide and sulfonylureas co-administration.
- Repaglinide AUC increased 15% with ketoconazole co-administration. Nateglinide AUC increased 48% with fluconazole co-administration. Consider decreasing meglitinides dose with azole co-administration to avoid causing hypoglycemia.
- May increase level of sulfonylureas. Fluconazole increased glyburide AUC 44%. Consider dose adjustment with azoles co-administration.
- Rosiglitazone AUC increased 47% with ketoconazole co-administration. Consider decreasing rosiglitazone with azole co-administration.
- May increase levels of pioglitazone..
- Rifamycin class significantly induces cytochrome P450. Always review drug interactions when prescribing this class of drugs.
- May significantly decrease drug concentrations of nateglinide, pioglitazone, rosiglitazone, repaglinide and sulfonylureas.
- Rifampin decreased repaglinide and nateglinide AUC by 31% and 24%, respectively. Rifampin also decreased rosiglitazone and pioglitazone AUC by 66% and 54%, respectively.
- If used for tuberculosis, consider higher dose for continuation phase of treatment especially in patients with high BMI due to increased treatment failure risk ascribed to lower rifampin levels in this population (Nijland; Ruslami). No recommendations for dose, but consider adding 300-600mg to usual amount given.
- Cephalexin: increased metformin AUC 24%. Clinical significance unknown.
- Isoniazid: reports in both experimental animal studies and humans for altered insulin secretion and hypoglycemia; this remains controversial, especially given the infrequency of the observation.
- Pentamidine: systemic administration may cause hyper- or hypoglycemia due to toxic effect on B-cell function and inappropriate insulin secretion. This is seen more in patients with prolonged and high doses of the drug or in patients with reduced renal function leading to drug accumulation (Assan). Aerosolized drug not likely to cause this degree of effect.
- Trimethoprim: may increase metformin serum concentrations by inhibition of tubular secretion; increased repaglinide AUC 61%; increased rosiglitazone AUC 31%. Consider dose adjustment.
- Vancomycin: tissue penetration of antibiotic decreased in diabetic patients (Skhirtladze). Important to use Actual Body Weight (ABW) when dosing vancomycin. Recommended vancomycin dose, for normal renal function: 15 mg/kg IV of actual body weight q12h.
- People with diabetes and high BMI may need adjusted doses of antibiotics when treating serious infections. Consult references, pharmacists or infectious disease specialists for assistance when dosing drugs such as vancomycin, daptomycin, fluconazole, caspofungin, penicillins, cephalosporins, trimethoprim/sulfamethoxazole, aminoglycosides and rifamycins.
- Fluoroquinolones are frequently employed in the treatment of infections in diabetics, including UTIs and diabetic foot infections. Ciprofloxacin likely has minimal chances of significant alteration in glucose homeostasis; however, levofloxacin may and should be used with some caution. Uncertain whether moxifloxacin has significant dysglycemic effects, but no good data has yet been suggested.
- Worse outcomes in the treatment of tuberculosis has been seen in diabetic populations. Some good evidence suggests that this may be due to altered drug concentrations, especially rifampin. No formal recommendations yet exist for different dosing in diabetics; however, some argue that rifampin doses should be increased when switched from daily therapy.
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