Tolbutamide

Tolbutamide increases binding of dantrolene to plasma proteins, potentially decreasing free drug concentration.

Tolbutamide increases dantrolene binding to plasma proteins, potentially affecting dantrolene distribution and levels.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

May decrease thyroid hormone secretion, which may result in hypothyroidism when used with levothyroxine.

Nitisinone is a moderate CYP2C9 inhibitor that increases exposure of tolbutamide. Dosage reduction by half is recommended with additional adjustments as needed.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

CYP2C19 substrate/inhibitor that may increase blood levels and/or toxicity of propranolol.

Salicylate competes with tolbutamide for serum albumin binding, potentiating hypoglycemia.

Salicylate competition for serum albumin binding potentiates hypoglycemia.

Tolcapone has affinity to CYP 2C9 in vitro and may interfere with tolbutamide clearance, though in vivo study showed no pharmacokinetic changes.

Zafirlukast may interact with tolbutamide as it is metabolized by CYP2C9. Care should be exercised when coadministered.

Prazosin has been administered without adverse drug interaction with tolbutamide in limited clinical experience.

Administered without adverse drug interaction in limited clinical experience.

No significant interactions with digoxin, hydrochlorothiazide, hydralazine, sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been observed.

Tolbutamide's conversion to inactive metabolites has been shown to be catalyzed by xanthine oxidase from rat liver.

DRUG-DRUG INTERACTIONS Patients who are applying bexarotene gel should not concurrently use products that contain DEET ( N,N -diethyl- m -toluamide), a common component of insect repellent products.

Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see CLINICAL PHARMACOLOGY ).

Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see CLINICAL PHARMACOLOGY ).

No depressant effect on blood levels in humans was noted when colestipol hydrochloride was administered with any of the following drugs: aspirin, clindamycin, clofibrate, methyldopa, nicotinic acid (niacin), tolbutamide, phenytoin or warfarin.

Since desogestrel is mainly metabolized by the cytochrome P450 2C9 enzyme (CYP 2C9) to form etonogestrel, the active progestin, there is a possibility of interaction with CYP 2C9 substrates or inhibitors (such as: ibuprofen, piroxicam, naproxen, phenytoin, fluconazole, diclofenac, tolbutamide, glipizide, celecoxib, sulfamethoxazole, isoniazid, torsemide, irbesartan, losartan, and valsartan).

Tolbutamide In diabetic patients receiving diflunisal and tolbutamide, no significant effects were seen on tolbutamide plasma levels or fasting blood glucose.

Tolbutamide From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

Tolbutamide: From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

Tolbutamide From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

(See CONTRAINDICATIONS and PRECAUTIONS .) Oral hypoglycemics: The effects of fluconazole on the pharmacokinetics of the sulfonylurea oral hypoglycemic agents tolbutamide, glipizide, and glyburide were evaluated in three placebo-controlled studies in normal volunteers. (See PRECAUTIONS .) Tolbutamide: In 13 normal male volunteers, there was significant increase in tolbutamide (500 mg single dose) AUC and C max following the administration of fluconazole. There was a mean ± SD increase in tolbutamide AUC of 26% ± 9% (range: 12 to 39%).

7.5 Drugs with No Observed Clinically Significant Interactions with MAVYRET No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/ cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.

In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol.

In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol.

In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites with the known cytochrome CYP 2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine.

Therapeutic concentrations of digoxin , warfarin , ibuprofen , naproxen , piroxicam , acetaminophen , phenytoin and tolbutamide did not alter ketorolac tromethamine protein binding.

Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when sertraline hydrochloride is administered concomitantly [ See Clinical Pharmacology ( 12.3 ) ].

Hypoglycemic Drugs –In a placebo-controlled trial in normal volunteers, administration of sertraline hydrochloride for 22 days (including 200 mg/day for the final 13 days) caused a statistically significant 16% decrease from baseline in the clearance of tolbutamide following an intravenous 1000 mg dose. Sertraline hydrochloride administration did not noticeably change either the plasma protein binding or the apparent volume of distribution of tolbutamide, suggesting that the decreased clearance was due to a change in the metabolism of the drug. The clinical significance of this decrease in tolbutamide clearance is unknown.

In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin.

In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin.

In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin.

Glimepiride Glipizide Glyburide Pioglitazone Repaglinide Tolbutamide ↔ Glimepiride (CYP2C9) ↔ Glipizide (CYP2C9) ↔ Glyburide (CYP2C9) ↕ Pioglitazone (CYP2C8 and CYP3A4) ↕ Repaglinide (CYP2C8 and CYP3A4) ↔ Tolbutamide (CYP2C9) The effect of TPV/ritonavir on CYP2C8 substrate is not known.

7.6 Effect of Toremifene on CYP2C9 Substrates In a study of 20 healthy subjects, 500 mg tolbutamide once daily (days 7 and 19) coadministered with toremifene as a 480 mg loading dose followed by 80 mg once daily for 16 days. Following coadministration on days 7 and 19 plasma tolbutamide Cmax and AUC were increased by less than 30%. A reduction of similar magnitude was observed for hydroxytolbutamide and carboxytolbutamide Cmax and AUC.

Tolbutamide From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

Tolbutamide From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

In vivo , venlafaxine 75 mg by mouth every 12 hours did not alter the pharmacokinetics of a single 500 mg dose of tolbutamide or the CYP2C9 mediated formation of 4-hydroxy-tolbutamide.

In vivo , venlafaxine 75 mg by mouth every 12 hours did not alter the pharmacokinetics of a single 500 mg dose of tolbutamide or the CYP2C9 mediated formation of 4-hydroxy-tolbutamide.

In vivo , venlafaxine 75 mg by mouth every 12 hours did not alter the pharmacokinetics of a single 500 mg dose of tolbutamide or the CYP2C9 mediated formation of 4-hydroxy-tolbutamide.