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Drug Interactions between metformin / repaglinide and porfimer

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

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Interactions between your drugs

Moderate

metFORMIN porfimer

Applies to: metformin / repaglinide and porfimer

GENERALLY AVOID: Patients exposed to photosensitizing agents at the same time as or in the 30 to 90 days following treatment with porfimer may be at an increased risk of a photosensitivity reaction (e.g., erythema, swelling, pruritus, burning sensations, feeling hot, and/or blisters). These agents have each been individually associated with photosensitivity reactions and may have additive effects if used together. Medicinal products with known phototoxic or photoallergic potential include, but are not limited to, hypericin-containing products (e.g., St. John's Wort), griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines. Photosensitivity with porfimer is due to residual drug being present in the skin. Porfimer is cleared from a variety of tissues over 40 to 72 hours after treatment, but organs of the reticuloendothelial system (e.g., liver, spleen), skin and the tumor itself retain the drug for a longer period. Patients treated with porfimer will be photosensitive for at least 30 days and possibly up to 90 days or more for patients with hepatic or severe renal dysfunction. In clinical studies of porfimer, photosensitivity reactions occurred in approximately 20% of cancer patients and 69% of high-grade dysplasia in Barrett's esophagus patients.

MANAGEMENT: Use of photosensitizing agents should be avoided for at least 30 days and maybe up to 90 days or longer after porfimer treatment depending on the patient's hepatic function, renal function, and/or ability to tolerate exposure to sunlight. Following treatment with porfimer, patients should follow measures outlined in the product labeling for light and sun exposure. It is important to counsel patients to expose their skin to ambient indoor light as it is not only safe but will help eliminate porfimer through the skin by a process called "photobleaching." Before exposing skin or eyes to direct sunlight or bright indoor light (e.g., examination lamps, dental lamps, operating room lamps, floodlights, halogen lamps, unshaded light bulbs at close proximity, etc.), patients should test for residual photosensitivity as described in porfimer's product labeling.

References (5)
  1. Hoffman GA, Gradl G, Schulz M, Haidinger G, Tanew A, Weber B (2020) "The frequency of photosensitizing drug dispensings in Austria and Germany: A correlation with their photosensitizing potential based on published literature." J Eur Acad Dermatol Venereol, 34, p. 589-600
  2. Blakely KM, Drucker AM, Rosen CF (2019) "Drug-induced photosensitivity—an update: Culprit drugs, prevention and management." Drug Saf, 42, p. 827-47
  3. (2023) "Product Information. Photofrin (porfimer)." Pinnacle Biologicals, Inc.
  4. Concordia Laboratories Inc. (2023) Photofrin sterile porfimer sodium for injection for intravenous use antineoplastic photosensitizing agent. https://pdf.hres.ca/dpd_pm/00028148.PDF
  5. Pinnacle Biologics B.V. (2023) Annex I summary of product characteristics https://www.ema.europa.eu/en/documents/product-information/photobarr-epar-product-information_en.pdf
Moderate

metFORMIN repaglinide

Applies to: metformin / repaglinide and metformin / repaglinide

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 (2)
  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

Drug and food interactions

Major

metFORMIN food

Applies to: metformin / repaglinide

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 (2)
  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
Moderate

repaglinide food

Applies to: metformin / repaglinide

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (32)
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  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
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  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
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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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