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Drug Interactions between Actos and Sulfatrim Pediatric

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

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Interactions between your drugs

Moderate

trimethoprim pioglitazone

Applies to: Sulfatrim Pediatric (sulfamethoxazole / trimethoprim) and Actos (pioglitazone)

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of pioglitazone, which is primarily metabolized by the isoenzyme. In 10 healthy volunteers given the potent CYP450 2C8 inhibitor gemfibrozil (600 mg twice daily) for two days prior to coadministration with a single 30 mg dose of pioglitazone on day 3, mean pioglitazone systemic exposure (AUC) increased by 3.4-fold and elimination half-life (T 1/2) increased from 6.5 to 15.1 hours. In two other studies of 12 and 30 healthy volunteers, gemfibrozil administered similarly increased the mean AUC of a single 15 mg dose of pioglitazone by 3.2- and 4.3-fold, respectively, and nearly tripled the mean T 1/2. When 160 mg twice daily of trimethoprim, a relatively weak CYP450 2C8 inhibitor, was given similarly in a study of 16 healthy volunteers, the mean AUC of a 15 mg dose of pioglitazone increased by 42% and T 1/2 increased from 3.9 to 5.1 hours. Likewise, administration of pioglitazone with a single 1000 mg dose of abiraterone acetate, another CYP450 2C8 inhibitor, resulted in a 46% increase in pioglitazone AUC. The interaction is subject to a high degree of interpatient variability, which may be at least partially attributable to CYP450 2C8 polymorphism.

MANAGEMENT: Given the potential for dose-related adverse events with pioglitazone, caution is advised during coadministration with CYP450 2C8 inhibitors. Close monitoring for the development of hypoglycemia and other adverse effects is recommended, such as fluid retention; weight gain; new or worsening heart failure; pulmonary, peripheral, and macular edema; bone fractures; anemia; and liver enzyme elevations. Patients should regularly monitor their blood sugar and learn how to recognize and treat hypoglycemia, which may include symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitation. The dosage of pioglitazone may require adjustment if an interaction is suspected. Likewise, patients should be observed for potential loss of glycemic control following discontinuation of the CYP450 2C8 inhibitor, and the pioglitazone dosage adjusted as necessary.

References

  1. "Product Information. Actos (pioglitazone)." Takeda Pharmaceuticals America PROD (2001):
  2. Wen X, Wang JS, Backman JT, Laitila J, Neuvonen PJ "Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively." Drug Metab Dispos 30 (2002): 631-635
  3. Jaakkola T, Backman JT, Neuvonen M, Neuvonen PJ "Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone." Clin Pharmacol Ther 77 (2005): 404-14
  4. Deng LJ, Wang F, Li HD "Effect of gemfibrozil on the pharmacokinetics of pioglitazone." Eur J Clin Pharmacol 61 (2005): 831-6
  5. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT "Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors." Basic Clin Pharmacol Toxicol 99 (2006): 44-51
  6. Scheen AJ "Pharmacokinetic interactions with thiazolidinediones." Clin Pharmacokinet 46 (2007): 1-12
  7. Totah RA, Rettie AE "Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance." Clin Pharmacol Ther 77 (2005): 341-52
  8. Daily EB, Aquilante CL "Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies." Pharmacogenomics 10 (2009): 1489-510
  9. Aquilante CL, Kosmiski LA, Bourne DW, et al. "Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone." Br J Clin Pharmacol 75 (2013): 217-26
View all 9 references

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Drug and food interactions

Moderate

pioglitazone food

Applies to: Actos (pioglitazone)

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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Moderate

sulfamethoxazole food

Applies to: Sulfatrim Pediatric (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother 64 (2020): e02167-19

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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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