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Drug Interactions between metformin and Triumeq

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

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Interactions between your drugs

Major

metFORMIN dolutegravir

Applies to: metformin and Triumeq (abacavir / dolutegravir / lamivudine)

MONITOR CLOSELY: Coadministration with dolutegravir may decrease the renal elimination of metformin resulting in increased metformin plasma concentrations and an increased risk of lactic acidosis. The proposed mechanism is dolutegravir-mediated inhibition of the renal organic cation transporter 2 (OCT2) of which metformin is a substrate. In a pharmacokinetic study in 30 healthy subjects receiving metformin 500 mg every 12 hours, half the subjects were coadministered dolutegravir 50 mg once a day while half were coadministered dolutegravir 50 mg every 12 hours. Coadministration of dolutegravir 50 mg once a day increased AUC and Cmax by 79% and 66%, respectively; coadministration of dolutegravir 50 mg every 12 hours increased AUC and Cmax by 145% and 111%, respectively. While metformin has a wide therapeutic index and is not associated with hypoglycemia at recommended doses, elevated levels of metformin are associated with lactic acidosis. Lactic acidosis tends to occur in patients with risk factors that also result in increased metformin levels such as renal insufficiency and hepatic impairment.

MANAGEMENT: Caution is advised if dolutegravir must be used concurrently with metformin. The dose of metformin may require adjustment whenever dolutegravir is added to or withdrawn from therapy, especially in patients with risk factors for increased metformin levels. One manufacturer recommends the total daily dose of metformin be limited to 1000 mg if these drugs must be used together. Clinical and laboratory monitoring, including renal function and blood glucose monitoring should be performed when these drugs are used concomitantly.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):
  4. "Product Information. Triumeq (abacavir/dolutegravir/lamivudine)." ViiV Healthcare (2014):
  5. "Product Information. Juluca (dolutegravir-rilpivirine)." ViiV Healthcare (2017):
  6. Soong IH, Zong J, Borland J, et al. "The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects." J Acquir Immune Defic Syndr 72 (2016): 400-7
  7. Masich A, Badowski ME, Liedtke MD, Fulco PP "Evaluation of the concurrent use of dolutegravir and metformin in human immunodeficiency virus-infected patients." Int J STD AIDS 28 (2017): 1229-33
View all 7 references

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Drug and food interactions

Major

metFORMIN food

Applies to: 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

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. "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

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Minor

dolutegravir food

Applies to: Triumeq (abacavir / dolutegravir / lamivudine)

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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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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