Interaction between
Clopidogrel
and
Pioglitazone
Major
Metabolism
Basic Information
| ID | DDInter413 and DDInter1472 |
| Interaction | Coadministration with clopidogrel may significantly increase the plasma concentrations of pioglitazone. The proposed mechanism is inhibition of the CYP450 2C8-mediated metabolism of pioglitazone by clopidogrel's glucuronide metabolite, which has demonstrated strong inhibition of CYP450 2C8 in vitro. |
| Management | Given the potential for dose-related adverse events, reduction of pioglitazone dosage should be considered when used with clopidogrel. 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. Likewise, patients should be observed for potential loss of glycemic control following discontinuation of clopidogrel, and the pioglitazone dosage adjusted as necessary. |
| References | [1] "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb, Princeton, NJ. [2] Tornio A, Filppula A, Kailari O, et al. "Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as perpetrator of drug-drug interactions." Clin Pharmacol Ther 96 (2014): 498-507 [3] "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL. [4] Itkonen MK, Tornio A, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT "Clopidogrel Markedly Increases the Plasma Concentrations of the CYP2C8 Substrate Pioglitazone." Drug Metab Dispos (2016): [5] Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72 [6] "Product Information. Diabinese (chlorpropamide)." Pfizer US Pharmaceuticals, New York, NY. [7] 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 [8] "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY. [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] Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6 [11] "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO. [12] 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 [13] 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 [14] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [15] Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72 [16] "Product Information. Diabinese (chlorpropamide)." Pfizer US Pharmaceuticals, New York, NY. [17] 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 [18] "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY. [19] "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 [20] Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6 [21] "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO. [22] 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 [23] 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 [24] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 |
| Alternative for Clopidogrel |
B01A
|
| Alternative for Pioglitazone |
A10B
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.