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Drug Interactions between Combigan and insulin degludec

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

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Interactions between your drugs

Moderate

timolol ophthalmic brimonidine ophthalmic

Applies to: Combigan (brimonidine / timolol ophthalmic) and Combigan (brimonidine / timolol ophthalmic)

MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects such as hypotension and bradycardia. The possibility for an additive or potentiating effect on blood pressure and heart rate should be considered when used with other medications that affect these parameters, such as ophthalmic and systemic beta blockers, vasodilators, cardiac glycosides, and antihypertensive agents.

MANAGEMENT: Blood pressure and pulse rate should be monitored regularly when topical alpha-2 adrenergic receptor agonists are prescribed in combination with cardiovascular drugs. Patients should be advised to notify their physician if they experience slow pulse, irregular heartbeat, dizziness, lightheadedness, or syncope.

References

  1. King MH, Richards DW "Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy." Am J Ophthalmol 110 (1990): 308-9
  2. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc PROD
  3. Nordlund JR, Pasquale LR, Robin AL, Rudikoff MT, Ordman J, Chen KS, Walt J "The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine." Arch Ophthalmol 113 (1995): 77-83
  4. "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc PROD (2001):
  5. Walters TR "Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies." Surv Ophthalmol 41 ( Suppl (1996): s19-26
  6. Pekdemir M, Yanturali S, Karakus G "More than just an ocular solution." Emerg Med J 22 (2005): 753-4
  7. "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc (2013):
View all 7 references

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Moderate

timolol ophthalmic insulin degludec

Applies to: Combigan (brimonidine / timolol ophthalmic) and insulin degludec

MONITOR: Beta-blockers may inhibit some of the normal physiologic response to hypoglycemia. Symptoms of hypoglycemia such as tremor and tachycardia may be absent, making it more difficult for patients to recognize an oncoming episode. In addition, multiple effects on glucose metabolism have been reported, usually with the noncardioselective beta-blockers (e.g., propranolol, pindolol, timolol) but occasionally also with relatively beta-1 selective agents (e.g., atenolol, metoprolol, nebivolol). Specifically, inhibition of catecholamine-mediated glycogenolysis and glucose mobilization in association with beta-blockade can potentiate insulin-induced hypoglycemia in diabetics and delay the recovery of normal blood glucose levels. Prolonged and severe hypoglycemia may occur, although these events have rarely been reported. Significant increases in blood pressure and bradycardia can also occur during hypoglycemia in diabetics treated with insulin and beta-blockers due to antagonism of epinephrine's effect on beta-2 adrenergic receptors, which leads to unopposed alpha-adrenergic effects including vasoconstriction. Other effects reported with various beta-blockers include decreased glucose tolerance and decreased glucose-induced insulin secretion.

MANAGEMENT: In general, cardioselective beta-blockers are considered safer than noncardioselective agents in the treatment of diabetic patients. Nevertheless, caution is advised if they are prescribed to patients treated with insulin or oral antidiabetic agents that can cause hypoglycemia (e.g., insulin secretagogues), as cardioselectivity is not absolute and larger doses of beta-1 selective agents may pose some of the same risks as nonselective agents. Patients should be advised of the need for regular blood glucose monitoring and be aware that certain symptoms of hypoglycemia such as tremor and tachycardia may be masked. However, other symptoms such as headache, dizziness, drowsiness, confusion, nausea, hunger, weakness, and perspiration may be unaffected. The same precautions are applicable in diabetic patients treated with ophthalmic beta-blockers.

References

  1. Shepherd AM, Lin M-S, Keeton TK "Hypoglycemia-induced hypertension in a diabetic patient on metoprolol." Ann Intern Med 94 (1981): 357-8
  2. Micossi P, Pollavini G, Raggi U, et al. "Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus." Horm Metab Res 16 (1984): 59-63
  3. Popp DA, Tse TF, Shah SD, et al. "Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus." Diabetes Care 7 (1984): 243-7
  4. Mann SJ, Krakoff LR "Hypertensive crisis caused by hypoglycemia and propranolol." Arch Intern Med 144 (1984): 2427-8
  5. Groop L, Totterman KJ, Harno K, Gordin A "Influence of beta-blocking drugs on glucose metabolism in patients with non-insulin dependent diabetes mellitus." Acta Med Scand 211 (1982): 7-12
  6. Viberti GC, Keen H, Bloom SR "Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in insulin-dependent diabetics." Metabolism 29 (1980): 873-9
  7. Viberti GC, Keen H, Bloom SR "Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in normal subjects." Metabolism 29 (1980): 866-72
  8. Newman RJ "Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia." Br Med J 2 (1976): 447-9
  9. Smith U "Beta blockade in diabetes." N Engl J Med 299 (1978): 1467
  10. Zaman R, Kendall MJ, Biggs PI "The effect of acebutolol and propranolol on the hypoglycaemic action of glibenclamide." Br J Clin Pharmacol 13 (1982): 507-12
  11. Munroe WP, Rindone JP, Kershner RM "Systemic side effects associated with the ophthalmic administratiion of timolol." Drug Intell Clin Pharm 19 (1985): 85-9
  12. Ostman J "B-adrenergic blockade and diabetes mellitus." Acta Med Scand 672 (1983): 69-77
  13. Deacon SP, Karunanayake A, Barnett D "Acebutolol, atenolol, and propranolol and metabolic responses to acute hypoglycaemia in diabetes." Br Med J 12 (1977): 1255-7
  14. Pollare T, Lithell H, Selinus I, Berne C "Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients." BMJ 298 (1989): 1152-7
  15. Sinclair AJ, Davies IB, Warrington SJ "Betaxolol and glucose-insulin relationships: studies in normal subjects taking glibenclamide or metformin." Br J Clin Pharmacol 30 (1990): 699-702
  16. "New Zealand Committee on Adverse Drug Reactions. Ninth Annual Report." N Z Dent J 71 (1975): 28-32
View all 16 references

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Drug and food interactions

Moderate

insulin degludec food

Applies to: insulin degludec

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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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

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