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Drug Interaction Report

5 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

betamethasone topical liraglutide

Applies to: Betatrex (betamethasone topical), insulin degludec / liraglutide

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by topical corticosteroids in situations where they are absorbed systemically. Corticosteroids can raise blood glucose levels by antagonizing the action and suppressing the secretion of insulin, which results in inhibition of peripheral glucose uptake and increased gluconeogenesis. Factors that can affect the likelihood of systemic absorption include the steroid's potency and formulation, duration of exposure, application surface area, use on occluded areas of skin, and thickness and/or integrity of skin in the applied areas. Infants and small children also have an increased risk of systemic absorption due to their larger skin surface to body mass ratios. The interaction was suspected in a case report of a 71-year-old patient with type 1 diabetes mellitus that had been well controlled on an insulin pump. The patient developed acute hyperglycemia after using fluocinonide 0.1% cream for 2 days due to a psoriasis flare. He was applying the cream twice daily to a large area of his body (including his abdomen) and using occlusive techniques to increase its effectiveness. His insulin requirements increased from 73 units per day to 326 units in a 24-hour period. The patient's hyperglycemia resolved with discontinuation of the fluocinonide cream, allowing him to resume his previous insulin dosage.

MANAGEMENT: Close clinical monitoring of glycemic control is recommended when systemic absorption of topical corticosteroids is considered probable or likely (e.g., more potent agents, larger areas of application, longer duration of treatment, application on thinner skin like the face, occlusion of the application area, use on infants or young children), with adjustment of the patient's antidiabetic regimen as needed. The package labeling of the corticosteroid involved should be consulted to assess the risk.

References

  1. Seale JP, Compton MR (1986) "Side-effects of corticosteroid agents." Med J Aust, 144, p. 139-42
  2. Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R (1993) "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia, 36, p. 84-7
  3. Carruthers JA, Staughton RC, August PJ (1977) "Penetration of topical steroid preparations." Arch Dermatol, 113, p. 522
  4. Pace WE (1973) "Topical corticosteroids." Can Med Assoc J, 108, 11 passim
  5. (2022) "Product Information. Ultravate (halobetasol topical)." Apothecon Inc
  6. (2001) "Product Information. Diprolene (betamethasone topical)." Schering Corporation
  7. "Product Information. Temovate (clobetasol topical)." Glaxo Wellcome
  8. (2001) "Product Information. Psorcon (diflorasone topical)." Rhone Poulenc Rorer
  9. Sue LY, milanesi a (2023) Acute hyperglycemia due to topical corticosteroid administration. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334317/
  10. (2022) "Product Information. Dermovate (clobetasol topical)." GlaxoSmithKline UK Ltd
View all 10 references

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Moderate

betamethasone topical insulin degludec

Applies to: Betatrex (betamethasone topical), insulin degludec / liraglutide

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by topical corticosteroids in situations where they are absorbed systemically. Corticosteroids can raise blood glucose levels by antagonizing the action and suppressing the secretion of insulin, which results in inhibition of peripheral glucose uptake and increased gluconeogenesis. Factors that can affect the likelihood of systemic absorption include the steroid's potency and formulation, duration of exposure, application surface area, use on occluded areas of skin, and thickness and/or integrity of skin in the applied areas. Infants and small children also have an increased risk of systemic absorption due to their larger skin surface to body mass ratios. The interaction was suspected in a case report of a 71-year-old patient with type 1 diabetes mellitus that had been well controlled on an insulin pump. The patient developed acute hyperglycemia after using fluocinonide 0.1% cream for 2 days due to a psoriasis flare. He was applying the cream twice daily to a large area of his body (including his abdomen) and using occlusive techniques to increase its effectiveness. His insulin requirements increased from 73 units per day to 326 units in a 24-hour period. The patient's hyperglycemia resolved with discontinuation of the fluocinonide cream, allowing him to resume his previous insulin dosage.

MANAGEMENT: Close clinical monitoring of glycemic control is recommended when systemic absorption of topical corticosteroids is considered probable or likely (e.g., more potent agents, larger areas of application, longer duration of treatment, application on thinner skin like the face, occlusion of the application area, use on infants or young children), with adjustment of the patient's antidiabetic regimen as needed. The package labeling of the corticosteroid involved should be consulted to assess the risk.

References

  1. Seale JP, Compton MR (1986) "Side-effects of corticosteroid agents." Med J Aust, 144, p. 139-42
  2. Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R (1993) "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia, 36, p. 84-7
  3. Carruthers JA, Staughton RC, August PJ (1977) "Penetration of topical steroid preparations." Arch Dermatol, 113, p. 522
  4. Pace WE (1973) "Topical corticosteroids." Can Med Assoc J, 108, 11 passim
  5. (2022) "Product Information. Ultravate (halobetasol topical)." Apothecon Inc
  6. (2001) "Product Information. Diprolene (betamethasone topical)." Schering Corporation
  7. "Product Information. Temovate (clobetasol topical)." Glaxo Wellcome
  8. (2001) "Product Information. Psorcon (diflorasone topical)." Rhone Poulenc Rorer
  9. Sue LY, milanesi a (2023) Acute hyperglycemia due to topical corticosteroid administration. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334317/
  10. (2022) "Product Information. Dermovate (clobetasol topical)." GlaxoSmithKline UK Ltd
View all 10 references

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Moderate

liraglutide insulin degludec

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

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Drug and food interactions

Moderate

liraglutide food

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

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Moderate

insulin degludec food

Applies to: 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 (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."
View all 10 references

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Therapeutic duplication warnings

No duplication 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.

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Further information

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