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Drug Interactions between eravacycline and glyburide / metformin

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

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Interactions between your drugs

Moderate

glyBURIDE metFORMIN

Applies to: glyburide / metformin and glyburide / metformin

MONITOR: Coadministration of metformin with an insulin secretagogue (e.g., sulfonylurea, meglitinide) or insulin may potentiate the risk of hypoglycemia. Although metformin alone generally does not cause hypoglycemia under normal circumstances of use, the added therapeutic effect when combined with other antidiabetic agents may result in hypoglycemia. The risk is further increased when caloric intake is deficient or when strenuous exercise is not compensated by caloric supplementation.

MANAGEMENT: A lower dosage of the insulin secretagogue or insulin may be required when used with metformin. Blood glucose should be closely monitored, and patients should be educated on the potential signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, tachycardia) and appropriate remedial actions to take if it occurs. Patients should also be advised to take precautions to avoid hypoglycemia while driving or operating hazardous machinery.

References (2)
  1. Wiernsperger N, Rapin JR (1995) "Metformin-insulin interactions: from organ to cell." Diabetes Metab Rev, 11 Suppl, s3-12
  2. Okada S, Ishii K, Hamada H, Tanokuchi S, Ichiki K, Ota Z (1995) "Can alpha-glucosidase inhibitors reduce the insulin dosage administered to patients with non-insulin-dependent diabetes mellitus?" J Int Med Res, 23, p. 487-91
Moderate

glyBURIDE eravacycline

Applies to: glyburide / metformin and eravacycline

MONITOR: Tetracyclines may enhance the hypoglycemic effects of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). The exact mechanism is unknown; however, proposed mechanisms include increasing the sensitivity of insulin, increasing the half-life of insulin via inhibition of insulin degradation in the liver, interference with epinephrine-induced hyperglycemia via inhibition of glycogenolysis, and tetracycline-induced hepatotoxicity. The authors of one study suggest that tetracycline may also be able to inhibit alpha-amylase and/or alpha-glucosidase, as substrates for these enzymes have similar functional groups to those found in tetracycline. There are case reports available documenting hypoglycemia for patients on doxycycline and one case report demonstrating improved insulin sensitivity in a patient on minocycline. It is possible that other tetracyclines may possess similar abilities to lower glucose levels.

MANAGEMENT: Blood glucose should be monitored more closely during therapy with a tetracycline antibiotic. As the effects of the antibiotic may persist beyond the last dose, it is possible that patients may need to be monitored more closely until the antibiotic is fully eliminated from their body, which will differ depending on the half-life of the antibiotic involved. Insulin and insulin secretagogues may require dosage adjustments if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their doctor if it occurs unexpectedly. Conversely, patients should be observed for loss of glycemic control following completion of tetracycline therapy.

References (12)
  1. Dalpe-Scott M, Heick HM, Begin-Heick N (1983) "Insulin secretion in the obese (ob/ob) mouse: the effect of oxytetracycline on insulin release." Diabetes, 32, p. 932-7
  2. Dalpe-Scott M, Begin-Heick N (1982) "Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat." Diabetes, 31, p. 53-9
  3. Begin-Heick N, Heick HM, Norman MG (1979) "Regranulation of Islets of Langerhans and normalization of in vivo insulin secretion in ob/ob mice treated with oxytetracycline." Diabetes, 28, p. 65-70
  4. Phillips PJ, Easterbrook G (1977) "Phenformin, tetracycline and lactic acidosis." Ann Intern Med, 86, p. 111
  5. Miller JB (1966) "Hypoglycaemic effect of oxytetracycline." BMJ, 2, p. 1007
  6. Hiatt N, Bonorris G (1970) "Insulin response in pancreatectomized dogs treated with oxytetracycline." Diabetes, 19, p. 307-11
  7. Amiri B, Hosseini NS, Taktaz F, et al. (2019) "Inhibitory effects of selected antibiotics on the activities of alpha-amylase and alpha-glucosidase: In-vitro, in-vivo and theoretical studies" Eur J Pharm Sci, 138, p. 1-16
  8. Kennedy KE, Teng C, Patek TM, Frei CR (2020) "Hypoglycemia associated with antibiotics alone and in combination with sulfonylureas and meglitinides: an epidemiologic surveillance study of the FDA adverse event reporting system (FAERS)." Drug Saf, 43, p. 363-9
  9. Ashraf S, Saberinia H, Desimone M (2018) "Doxycycline induced hypoglycemia in an adult without diabetes." J Basic Clin Pharma, 9, p. 115-7
  10. Douglas Y, grant mb, Moshiree B (2023) Case report open access minocycline attenuates severe hyperglycemia in patient with lipodystrophy. https://www.omicsonline.org/open-access/minocycline-attenuates-severe-hyperglycemia-in-patient-with-lipodystrophy-ijm-1000136.php?aid=76310
  11. Ijete E, Hosni M, Dadey E, Nikookam K, Rehmani H, Mlawa G (2022) "Uncommon side effect of a common drug: doxycyline induced hypoglycemia." Endocrine Abstracts, 81, P347
  12. (2020) "Product Information. Tetracycline (tetracycline)." Sigma Pharmaceuticals Australia Pty Ltd

Drug and food interactions

Major

metFORMIN food

Applies to: glyburide / metformin

GENERALLY AVOID: Alcohol can potentiate the effect of metformin on lactate metabolism and increase the risk of lactic acidosis. In addition, alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Although hypoglycemia rarely occurs during treatment with metformin alone, the risk may increase with 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.

Food may have varying effects on the absorption of metformin from immediate-release versus extended-release formulations. When a single 850 mg dose of immediate-release metformin was administered with food, mean peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 25%, respectively, and time to peak plasma concentration (Tmax) increased by 35 minutes compared to administration under fasting conditions. By contrast, administration of extended-release metformin with food increased AUC by 50% without affecting Cmax or Tmax, and both high- and low-fat meals had the same effect. These data may not be applicable to formulations that contain metformin with other oral antidiabetic agents.

MANAGEMENT: Metformin should be taken with meals, and excessive alcohol intake should be avoided during treatment. Diabetes patients in general should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Alcohol should not be consumed on an empty stomach or following exercise, as it may increase the risk of hypoglycemia. Patients should contact their physician immediately if they experience potential signs and symptoms of lactic acidosis such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific abdominal distress (especially after stabilization of metformin therapy, when gastrointestinal symptoms are uncommon). With more marked acidosis, there may also be associated hypothermia, hypotension, and resistant bradyarrhythmias. Metformin should be withdrawn promptly if lactic acidosis is suspected. Serum electrolytes, ketones, blood glucose, blood pH, lactate levels, and blood metformin levels may be useful in establishing a diagnosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

References (2)
  1. (2001) "Product Information. Glucophage (metformin)." Bristol-Myers Squibb
  2. (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
Moderate

glyBURIDE food

Applies to: glyburide / metformin

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 (10)
  1. Jerntorp P, Almer LO (1981) "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand, 656, p. 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. (1983) "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol, 24, p. 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. (1983) "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia, 24, p. 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A (1987) "Interaction of ethanol and glipizide in humans." Diabetes Care, 10, p. 683-6
  5. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  6. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM (1981) "The pharmacology of sulfonylureas." Am J Med, 70, p. 361-72
  9. (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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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.

Further information

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

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