Interaksi Gemfibrozil dan Repaglinid

Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ).

Combination therapy of gemfibrozil with simvastatin or with repaglinide, which are OATP1B1 substrates, is contraindicated (see CONTRAINDICATIONS ).

Co-administration of gemfibrozil and repaglinide increases the risk of severe hypoglycemia and is contraindicated (see CONTRAINDICATIONS ).

Repaglinide In healthy volunteers, co-administration with gemfibrozil (600 mg twice daily for 3 days) resulted in an 8.1-fold (range 5.5- to 15.0- fold) higher repaglinide AUC and a 28.6-fold (range 18.5- to 80.1-fold) higher repaglinide plasma concentration 7 hours after the dose.

In the same study, gemfibrozil (600 mg twice daily for 3 days) + itraconazole (200 mg in the morning and 100 mg in the evening at Day 1, then 100 mg twice daily at Day 2–3) resulted in a 19.4- (range 12.9- to 24.7-fold) higher repaglinide AUC and a 70.4-fold (range 42.9- to 119.2-fold) higher repaglinide plasma concentration 7 hours after the dose.

Repaglinide tablets are contraindicated in patients with: Concomitant use of gemfibrozil [see Drug Interactions (7.1) ] .

Concomitant use with gemfibrozil ( 4 )

Intervention: Do not administer repaglinide tablets to patients receiving gemfibrozil [see Contraindications (4) ] .

Table 3: Clinically Important Drug Interactions with Repaglinide Tablets Gemfibrozil Clinical Impact: Gemfibrozil significantly increased repaglinide tablets exposures by 8.1 fold [see Clinical Pharmacology (12.3) ].

Drugs that are known to inhibit CYP2C8 include trimethoprim, gemfibrozil, montelukast, deferasirox, and clopidiogrel.