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6 Interactions found for:

metformin and Topamax
Interactions Summary
  • 4 Major
  • 0 Moderate
  • 2 Minor
  • metformin
  • Topamax

Drug Interactions

Major
Metformin + Topamax

The following applies to the ingredients: Metformin and Topiramate (found in Topamax)

MONITOR CLOSELY: Coadministration with carbonic anhydrase inhibitors may potentiate the risk of lactic acidosis associated with the use of metformin. Carbonic anhydrase inhibitors can decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use of topiramate, a carbonic anhydrase inhibitor, in epilepsy and migraine prophylaxis has frequently caused dose-dependent metabolic acidosis in both adult and pediatric patients in controlled trials. Theoretically, metformin-induced lactic acidosis may be more likely in this setting, albeit still rare. In a clinical study of obese patients with type 2 diabetes receiving metformin with topiramate, there were no reported cases of lactic acidosis in over 200 patients who received the combination for 24 weeks. Similarly, acidosis was not observed in a smaller study where 54 patients received the combination for up to 16 weeks.

Pharmacokinetically, topiramate may increase the plasma concentrations of metformin. In study subjects receiving topiramate 100 mg and metformin 500 mg every 12 hours, the average steady-state metformin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 25%, respectively, while plasma clearance decreased by 20%. The clinical significance of these changes is unknown. Topiramate pharmacokinetics were not affected.

MANAGEMENT: Caution is advised if metformin is used concomitantly with carbonic anhydrase inhibitors including topiramate. Close monitoring for the development of lactic acidosis is recommended, particularly in the elderly and patients with other risk factors such as unstable or acute congestive heart failure or other conditions that can lead to hypoperfusion and hypoxemia. 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. Topamax (topiramate)." Ortho McNeil Pharmaceutical PROD (2001):
  2. Rosenstock J, Hollander P, Gadde KM, Sun X, Strauss R, Leung A "A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of topiramate controlled-release in the treatment of obese, type 2 diabetic patients." Diabetes Care 30 (2007): 1480-6
  3. "Product Information. Janumet XR (metformin-sitagliptin)." Merck & Co., Inc (2012):
  4. Toplak H, Hamann A, Moore T, et al. "Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study." Int J Obes (Lond) 31 (2007): 138-46

Drug and Food Interactions

Major
Metformin + Food

The following applies to the ingredients: 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

Drug and Pregnancy Interactions

The following applies to the ingredients: Topiramate (found in Topamax)

Use only if clearly needed and benefit outweighs potential risk

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned

Risk Summary: This drug can cause fetal harm when administered to pregnant women. Data from a pregnancy registry and several epidemiologic studies have shown that infants exposed in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age; in multiple animal species, this drug has demonstrated developmental toxicity, including increased incidences of fetal malformations at clinically relevant doses.

Comments:
-If a patient becomes pregnant during therapy, she should be informed of the potential hazard to her fetus; women of childbearing potential should be counseled on the use effective contraception.
-Women of childbearing potential on antiepileptic drug therapy should receive pregnancy counseling regarding the risk of fetal abnormalities. Generally, antiepileptic therapy should be continued during pregnancy, with monotherapy at the lowest effective dose whenever possible. Folic acid supplementation (5 mg) should be commenced four weeks prior to and continued for 12 weeks after conception. Women should be followed by a specialist and offered detailed mid-trimester ultrasound.
-Pregnancy Registry: The North American Antiepileptic Drug (NAAED) Pregnancy Registry collects information about the safety of antiepileptic drugs during pregnancy; enrollment information: toll-free 1-888-233-2334 or http://www.aedpregnancyregistry.org/

Animal studies in multiple species of animals have revealed evidence of developmental toxicity. Topiramate has shown teratogenicity in mice, rats, and rabbits. In humans, clinical data from a pregnancy registry and several epidemiologic studies have shown infants exposed during the first trimester have an increased incidence of major congenital malformations compared with a reference group not taking antiepileptic drugs (AED). Infants exposed in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age (SGA). SGA has been observed at all doses and appears to be dose-dependent. The prevalence of SGA is greater in infants of women who received higher doses of topiramate during pregnancy. In addition, the prevalence of SGA in infants of women who continued topiramate use until later in pregnancy is higher compared to the prevalence in infants of women who stopped before the third trimester. This drug can cause metabolic acidosis. The effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the ability of the fetus to tolerate labor. There are no controlled data in human pregnancy.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Qudexy XR Sprinkle (topiramate)." Upsher-Smith Laboratories Inc (2017):
  4. "Product Information. Trokendi XR (topiramate)." Supernus Pharmaceuticals Inc (2017):
  5. "Product Information. Topiramate (topiramate)." Cipla USA Inc. (2017):

The following applies to the ingredients: Metformin

Benefit should outweigh risk

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Risk Summary: Data are not sufficient to inform a drug-associated risk for major birth defects or miscarriage; published studies have not reported an increased risk. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.

Comments:
-Maternal glucose levels should be well controlled prior to conception and throughout pregnancy to avoid maternal and fetal diabetes-associated risks.
-Premenopausal women should understand the potential for unintended pregnancy with use of this drug as ovulation may occur in some anovulatory women.

Animal studies do not indicate harmful effects with respect to pregnancy, embryo or fetal development, birth or postnatal development. Poorly-controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled maternal diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Published evidence suggests this drug has a good safety profile in women with no increased long-term effects in offspring up to 18 months; however, much of the evidence is from observational, small, and/or nonrandomized studies, and therefore data must be interpreted cautiously.

Many experts continue to recommend insulin as the drug of choice for type 1, type 2, and gestational diabetes when diet alone is unsuccessful in controlling blood sugars. The estimated background risk for major birth defects in women with pre-gestational diabetes mellitus with an HbA1C greater than 7 is 6% to 10% and for women with a HbA1C greater than 10, this risk has been reported to be as high as 20% to 25%. In the US, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated risk of miscarriage for pregnant women with diabetes is unknown. There are no adequate and well-controlled studies in pregnant women.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

References

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Fortamet (metformin)." Physicians Total Care (2014):
  5. "Product Information. Glumetza (metformin)." Biovail Pharmaceuticals Canada (2014):
  6. "Product Information. Riomet (metformin)." Ranbaxy Pharmaceuticals (2014):
  7. Lindsay RS, Loeken MR "Metformin use in pregnancy: promises and uncertainties" Diabetologia 60 (2017): 1612-9
  8. Kelley KW, Carroll DG, Meyer A "A review of current treatment strategies for gestational diabetes mellitus." Drugs Context 4 (2015): epub

Drug and Breastfeeding Interactions

The following applies to the ingredients: Topiramate (found in Topamax)

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects on the breastfed infant from this drug or from the underlying maternal condition.
-If this drug is used during breastfeeding, monitor breastfed infant for diarrhea, drowsiness, adequate weight gain, and developmental milestones, especially younger, exclusively breastfed infants.
-Some authorities recommend avoiding breastfeeding during therapy with this drug.

Limited data in women with epilepsy have shown drug levels in milk similar to those in maternal plasma. The excretion of topiramate has not been evaluated in controlled studies.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  4. "Product Information. Qudexy XR Sprinkle (topiramate)." Upsher-Smith Laboratories Inc (2017):
  5. "Product Information. Trokendi XR (topiramate)." Supernus Pharmaceuticals Inc (2017):
  6. "Product Information. Topiramate (topiramate)." Cipla USA Inc. (2017):

The following applies to the ingredients: Metformin

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Available data have not reported adverse effects in breastfed infants, however, this data is limited.
-Due to this limited data, product manufacturers recommend a decision should be made to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.
-Published data suggest this drug is compatible with breastfeeding; they recommend caution when nursing a newborn or premature infant, and those with renal impairment.

Drug levels are expected to be 0.5% (range 0.11% to 1%) of the mother's weight-adjusted dosage and milk/plasma ratio range between 0.13 and 1. Since milk levels are expected to be relatively constant, timing of breastfeeding with drug administration is expected to be of little benefit. One large prospective study found no adverse effects in breastfed infants. Low detectable serum levels were found in some breastfed infants.

References

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Feig DS, Briggs GG, Koren G "Oral antidiabetic agents in pregnancy and lactation: a paradigm shift?" Ann Pharmacother (2007): 1174-80
  4. Cerner Multum, Inc. "Australian Product Information." O 0
  5. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  6. "Product Information. Fortamet (metformin)." Physicians Total Care (2014):
  7. "Product Information. Glumetza (metformin)." Biovail Pharmaceuticals Canada (2014):
  8. "Product Information. Riomet (metformin)." Ranbaxy Pharmaceuticals (2014):
  9. Kelley KW, Carroll DG, Meyer A "A review of current treatment strategies for gestational diabetes mellitus." Drugs Context 4 (2015): epub

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.

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