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Drug Interactions between Sumycin 250 and Xultophy

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

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Interactions between your drugs

Moderate

tetracycline insulin degludec

Applies to: Sumycin 250 (tetracycline) and Xultophy (insulin degludec / liraglutide)

MONITOR: Tetracyclines may enhance the hypoglycemic effect of insulin. 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 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 last past 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 based on the half-life of the antibiotic involved. The insulin dosage may require an adjustment if an interaction is suspected. Patients should be counseled on the signs and symptoms of hypoglycemia (e.g., fast heartbeat, shaking, sweating, anxiety, irritability, confusion, dizziness, and/or hunger), how to treat it, and to contact their physician if it occurs unexpectedly.

References

  1. Dalpe-Scott M, Heick HM, Begin-Heick N "Insulin secretion in the obese (ob/ob) mouse: the effect of oxytetracycline on insulin release." Diabetes 32 (1983): 932-7
  2. Dalpe-Scott M, Begin-Heick N "Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat." Diabetes 31 (1982): 53-9
  3. Begin-Heick N, Heick HM, Norman MG "Regranulation of Islets of Langerhans and normalization of in vivo insulin secretion in ob/ob mice treated with oxytetracycline." Diabetes 28 (1979): 65-70
  4. Phillips PJ, Easterbrook G "Phenformin, tetracycline and lactic acidosis." Ann Intern Med 86 (1977): 111
  5. Miller JB "Hypoglycaemic effect of oxytetracycline." BMJ 2 (1966): 1007
  6. Hiatt N, Bonorris G "Insulin response in pancreatectomized dogs treated with oxytetracycline." Diabetes 19 (1970): 307-11
  7. Amiri B, Hosseini NS, Taktaz F, et al. "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 (2019): 1-16
  8. Kennedy KE, Teng C, Patek TM, Frei CR "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 (2020): 363-9
  9. Ashraf S, Saberinia H, Desimone M "Doxycycline induced hypoglycemia in an adult without diabetes." J Basic Clin Pharma 9 (2018): 115-7
  10. Douglas Y, grant mb, Moshiree B "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" (2023):
  11. Ijete E, Hosni M, Dadey E, Nikookam K, Rehmani H, Mlawa G "Uncommon side effect of a common drug: doxycyline induced hypoglycemia." Endocrine Abstracts 81 (2022): P347
View all 11 references

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Moderate

liraglutide insulin degludec

Applies to: Xultophy (insulin degludec / liraglutide) and Xultophy (insulin degludec / liraglutide)

ADJUST DOSE: Coadministration of a glucagon-like peptide-1 (GLP-1) receptor agonist or dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist with insulin may potentiate the risk of hypoglycemia. GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists lower blood glucose by stimulating insulin secretion and lowering glucagon secretion. An increased incidence of hypoglycemia has been observed in patients treated with a combination of basal insulin and GLP-1 or dual GLP-1 and GIP receptor agonists. Additionally, patients with diabetic retinopathy who received treatment with basal insulin and subcutaneous semaglutide in one clinical trial had an increased risk of developing diabetic retinopathy complications. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. The safety and efficacy of GLP-1 or dual GLP-1 and GIP receptor agonists in combination with non-basal insulin have not been established.

MANAGEMENT: When a GLP-1 receptor agonist or dual GLP-1 and GIP receptor agonist is used as add-on therapy to basal insulin, a lower dosage of insulin may be required. Some clinical trials have reduced the basal insulin dose by 20% in patients with a baseline hemoglobin A1c <= 8% when a GLP-1 or dual GLP-1 and GIP receptor agonist was initiated. Because diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin, a stepwise approach to insulin dose reduction is recommended and blood glucose levels should be closely monitored. Patients should receive guidance on the recognition and management of hypoglycemia as well as precautions to take to avoid hypoglycemia, particularly while driving or operating hazardous machinery. Those with diabetic retinopathy should also be monitored for progression of the condition or complications. A rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy.

References

  1. "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc (2005):
  2. "Product Information. Victoza (liraglutide)." Novo Nordisk Pharmaceuticals Inc (2010):
  3. "Product Information. Tanzeum (albiglutide)." GlaxoSmithKline (2014):
  4. "Product Information. Trulicity (dulaglutide)." Eli Lilly and Company (2014):
  5. "Product Information. Adlyxin (lixisenatide)." sanofi-aventis (2016):
  6. "Product Information. Ozempic (1 mg dose) (semaglutide)." Novo Nordisk Pharmaceuticals Inc (2022):
  7. "Product Information. Mounjaro (tirzepatide)." Lilly, Eli and Company ORIG-1 (2022):
  8. "Product Information. Wegovy (2.4 mg dose) (semaglutide)." Novo Nordisk Pharmaceuticals Inc SUPPL-3 (2022):
  9. "Product Information. Bydureon BCise (exenatide)." AstraZeneca UK Ltd (2023):
  10. "Product Information. Byetta Prefilled Pen (exenatide)." Astra-Zeneca Pharmaceuticals (2022):
  11. "Product Information. Eperzan (albiglutide)." GlaxoSmithKline UK Ltd (2014):
  12. "Product Information. Trulicity (dulaglutide)." Eli Lilly and Company Ltd (2023):
  13. "Product Information. Saxenda (liraglutide)." Novo Nordisk Ltd (2022):
  14. "Product Information. Victoza (liraglutide)." Novo Nordisk Ltd (2022):
  15. "Product Information. Lyxumia (lixisenatide)." Sanofi (2022):
  16. "Product Information. Ozempic (semaglutide)." Novo Nordisk Ltd (2023):
View all 16 references

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Drug and food interactions

Moderate

tetracycline food

Applies to: Sumycin 250 (tetracycline)

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

References

  1. "Product Information. Achromycin (tetracycline)." Lederle Laboratories PROD (2001):
  2. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):

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Moderate

liraglutide food

Applies to: Xultophy (insulin degludec / liraglutide)

MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can delay gastric emptying, which may impact the absorption of concomitantly administered oral medications. Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others. According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel. Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin). The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be dose- and time-dependent, with the greatest effect observed after a single 5 mg dose but diminished after subsequent doses. When acetaminophen was administered following a single 5 mg dose of tirzepatide, acetaminophen peak plasma concentration (Cmax) was decreased by 50% and its median time to peak plasma concentration (Tmax) delayed by 1 hour. However, no significant impact on acetaminophen Cmax and Tmax was observed after 4 consecutive weekly doses of tirzepatide (5 mg/5 mg/8 mg/10 mg), and the overall exposure (AUC) of acetaminophen was unaffected. Tirzepatide at lower doses of 0.5 mg and 1.5 mg also had minimal effects on acetaminophen exposure.

MANAGEMENT: Although no specific dosage adjustment of concomitant medications is generally recommended based on available data, potential clinical impact on some oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics). Pharmacologic response to concomitantly administered oral medications should be monitored more closely following initiation, dose adjustment, or discontinuation of a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.

References

  1. "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc (2005):
  2. "Product Information. Victoza (liraglutide)." Novo Nordisk Pharmaceuticals Inc (2010):
  3. "Product Information. Tanzeum (albiglutide)." GlaxoSmithKline (2014):
  4. "Product Information. Trulicity (dulaglutide)." Eli Lilly and Company (2014):
  5. "Product Information. Adlyxin (lixisenatide)." sanofi-aventis (2016):
  6. "Product Information. Ozempic (1 mg dose) (semaglutide)." Novo Nordisk Pharmaceuticals Inc (2022):
  7. "Product Information. Mounjaro (tirzepatide)." Eli Lilly and Company Ltd (2023):
  8. "Product Information. Mounjaro (tirzepatide)." Lilly, Eli and Company (2023):
  9. Eli Lilly Canada Inc. "Product monograph including patient medication information MOUNJARO tirzepatide injection. https://pdf.hres.ca/dpd_pm/00068421.PDF" (2023):
View all 9 references

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Moderate

insulin degludec food

Applies to: Xultophy (insulin degludec / liraglutide)

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
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "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) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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Moderate

tetracycline food

Applies to: Sumycin 250 (tetracycline)

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  3. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  4. "Product Information. Minocin (minocycline)." Lederle Laboratories PROD (2002):
  5. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  6. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  8. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  9. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  10. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  11. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 11 references

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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.


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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.