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Drug Interactions between Lantus SoloStar and metformin / rosiglitazone

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

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Interactions between your drugs

Moderate

metFORMIN insulin glargine

Applies to: metformin / rosiglitazone and Lantus SoloStar (insulin glargine)

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

  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

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Moderate

rosiglitazone insulin glargine

Applies to: metformin / rosiglitazone and Lantus SoloStar (insulin glargine)

ADJUST DOSE: Coadministration of a thiazolidinedione in combination with insulin may increase the risk of edema compared to insulin alone. The mechanism is unknown but may involve enhancement of the antinatriuretic and/or peripheral vasodilatory effects of insulin. In a retrospective study of 79 patients who were initially on a thiazolidinedione or insulin separately but were subsequently given both in combination, 20 patients (25.3%) developed edema during the combination, compared to 7 of 71 patients (9.9%) during insulin alone and 1 of 8 patients (12.5%) during thiazolidinedione alone. In a study of 319 type 2 diabetic patients inadequately controlled on twice-daily insulin monotherapy, edema occurred in 13.1% and 16.2% of the patients coadministered rosiglitazone 4 mg/day and 8 mg/day, respectively, compared to 4.7% of those coadministered a matching placebo. The specific combination of rosiglitazone and insulin has also been associated with an increased incidence of heart failure and other cardiovascular adverse events compared to insulin and placebo. Data are derived from three 26-week trials involving 876 patients with type 2 diabetes, including those with longstanding diabetes and a high prevalence of preexisting medical conditions (peripheral neuropathy, retinopathy, ischemic heart disease, vascular disease, and congestive heart failure). An increased incidence of edema, heart failure, and other adverse effects occurred in the patients receiving the combination compared to patients receiving insulin alone. In the studies, patients who experienced heart failure with the combination were on average older, had a longer duration of diabetes, and were mostly on the higher 8 mg daily dosage of rosiglitazone. However, 3 of 10 had no known prior evidence of any underlying cardiac condition. A subsequent study involving 220 type 2 diabetes patients with chronic renal failure found no difference in cardiovascular adverse events among patients receiving the combination and controls receiving insulin with placebo.

MANAGEMENT: When used with insulin, the manufacturer recommends that rosiglitazone dosage not exceed 4 mg/day and that patients be monitored for cardiovascular adverse effects. The combination should be discontinued if there is a lack of response (defined as a reduction in HbA1c or insulin dose after 4 to 5 months) or significant adverse effects occur. Patients should be advised to notify their physician immediately if they experience signs and symptoms of heart failure such as fluid retention, edema, rapid weight gain, or shortness of breath. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations.

References

  1. (2001) "Product Information. Avandia (rosiglitazone)." SmithKline Beecham
  2. Raskin P, Rendell M, Riddle MC, Dole JF, Freed MI, Rosenstock J (2001) "A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes." Diabetes Care, 24, p. 1226-32
  3. King KA, Levi VE (2004) "Prevalence of edema in patients receiving combination therapy with insulin and thiazolidinedione." Am J Health Syst Pharm, 61, p. 390-3

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Drug and food interactions

Major

metFORMIN food

Applies to: metformin / rosiglitazone

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

  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

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Moderate

rosiglitazone food

Applies to: metformin / rosiglitazone

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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Moderate

insulin glargine food

Applies to: Lantus SoloStar (insulin glargine)

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

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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.