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Drug Interactions between Prevymis and rosiglitazone

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

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Interactions between your drugs

Moderate

rosiglitazone letermovir

Applies to: rosiglitazone and Prevymis (letermovir)

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of rosiglitazone, 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 4 mg dose of rosiglitazone on day 3, mean rosiglitazone systemic exposure (AUC) increased by 127% and elimination half-life from 3.6 to 7.6 hours, while the plasma concentration measured 24 hours after dosing increased by 9.8-fold. In 10 healthy volunteers given the less potent CYP450 2C8 inhibitor trimethoprim (160 mg orally twice a day) for 4 days prior to coadministration with a single 4 mg dose of rosiglitazone, mean AUC of rosiglitazone increased by 37% and half-life from 3.8 to 4.8 hours. Nearly identical results were reported in eight healthy volunteers in another study administered trimethoprim and rosiglitazone.

MANAGEMENT: Given the potential for dose-related adverse events with rosiglitazone, caution is advised during coadministration with CYP450 2C8 inhibitors, particularly in patients already receiving a higher dosage of rosiglitazone (e.g., 8 mg/day). 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; angina; 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 rosiglitazone 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 rosiglitazone dosage adjusted as necessary.

References

  1. (2001) "Product Information. Avandia (rosiglitazone)." SmithKline Beecham
  2. Baldwin SJ, Clarke SE, Chenery RJ (1999) "Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone." Br J Clin Pharmacol, 48, p. 424-32
  3. Wen X, Wang JS, Backman JT, Laitila J, Neuvonen PJ (2002) "Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively." Drug Metab Dispos, 30, p. 631-635
  4. Niemi M, Backman JT, Neuvonen PJ (2004) "Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone." Clin Pharmacol Ther, 76, p. 239-49
  5. Hruska MW, Amico JA, Langaee TY, Ferrell RE, Fitzgerald SM, Frye RF (2005) "The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects." Br J Clin Pharmacol, 59, p. 70-9
  6. Scheen AJ (2007) "Pharmacokinetic interactions with thiazolidinediones." Clin Pharmacokinet, 46, p. 1-12
  7. Niemi M, Backman JT, Granfors M, Laitila J, Neuvonen M, Neuvonen PJ (2003) "Gemfibrozil considerably increases the plasma concentrations of rosiglitazone." Diabetologia, 46, p. 1319-23
View all 7 references

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Drug and food interactions

Moderate

rosiglitazone food

Applies to: 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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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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