tolbutamide (Rx)

Brand and Other Names:Orinase
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 500mg

Type 2 Diabetes

250 mg-2 g PO qDay or q8-12hr; not to exceed 3 g/day; maintenance dose >2 g/day seldom required

Divided doses may minimize gastrointestinal side effects

Renal Impairment

Dose adjustment not necessary

Hepatic Impairment

May require a lower dose (monitor)

Safety and efficacy not established

250 mg PO qDay or q8-12hr; not to exceed 3 g/day; maintenance dose >2 g/day seldom required

Divided doses may minimize gastrointestinal side effects

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Interactions

Interaction Checker

and tolbutamide

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              Serious - Use Alternative (8)

              • aminolevulinic acid oral

                aminolevulinic acid oral, tolbutamide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

              • aminolevulinic acid topical

                tolbutamide increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

              • erdafitinib

                tolbutamide will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

              • ethanol

                ethanol, tolbutamide. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.

              • ivosidenib

                ivosidenib will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

              • methyl aminolevulinate

                tolbutamide, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

              • siponimod

                tolbutamide will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              Monitor Closely (164)

              • aceclofenac

                aceclofenac increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • acemetacin

                acemetacin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • albiglutide

                albiglutide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • alogliptin

                alogliptin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

              • alpelisib

                alpelisib will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

              • aluminum hydroxide

                aluminum hydroxide will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • apalutamide

                apalutamide will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

              • aripiprazole

                aripiprazole, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • asenapine

                asenapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • aspirin

                aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • aspirin rectal

                aspirin rectal increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • atazanavir

                atazanavir decreases effects of tolbutamide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • benazepril

                benazepril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • bexarotene

                bexarotene increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

              • bitter melon

                bitter melon increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

              • calcium carbonate

                calcium carbonate will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • canagliflozin

                tolbutamide, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.

              • cannabidiol

                cannabidiol will increase the level or effect of tolbutamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

              • captopril

                captopril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • celecoxib

                celecoxib increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • choline magnesium trisalicylate

                choline magnesium trisalicylate increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • cimetidine

                cimetidine will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • cinnamon

                cinnamon increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

              • ciprofibrate

                ciprofibrate increases effects of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              • ciprofloxacin

                ciprofloxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

              • clarithromycin

                clarithromycin increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Risk of hypoglycemia.

              • clotrimazole

                clotrimazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • clozapine

                clozapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • cyclosporine

                tolbutamide increases levels of cyclosporine by unknown mechanism. Use Caution/Monitor. Coadministration of tolbutamide and cyclosporine may increase cyclosporine levels and reduce therapeutic effects of tolbutamide.

              • dapagliflozin

                tolbutamide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.

              • darunavir

                darunavir, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Darunavir may increase or decrease levels of tolbutamide. Use alternatives if available. Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • diclofenac

                diclofenac increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

                tolbutamide will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • diflunisal

                diflunisal increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • disopyramide

                disopyramide increases effects of tolbutamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • dronabinol

                tolbutamide will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

              • dulaglutide

                dulaglutide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • efavirenz

                efavirenz will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • eluxadoline

                tolbutamide increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

              • empagliflozin

                empagliflozin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

              • enalapril

                enalapril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • ertugliflozin

                ertugliflozin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

              • esomeprazole

                esomeprazole will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • etodolac

                etodolac increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • exenatide injectable solution

                exenatide injectable solution, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia. .

              • exenatide injectable suspension

                exenatide injectable suspension, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia.

              • famotidine

                famotidine will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • fenofibrate

                fenofibrate increases effects of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              • fenofibrate micronized

                fenofibrate micronized increases effects of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              • fenofibric acid

                fenofibric acid increases effects of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              • fenoprofen

                fenoprofen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • fleroxacin

                fleroxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • fluconazole

                fluconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • fluoxetine

                fluoxetine will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

                fluoxetine increases effects of tolbutamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • flurbiprofen

                flurbiprofen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • fluvoxamine

                fluvoxamine will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • fosamprenavir

                fosamprenavir, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Fosamprenavir may increase or decrease levels of tolbutamide. Use alternatives if available. Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • fosinopril

                fosinopril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • gemfibrozil

                gemfibrozil increases effects of tolbutamide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              • gemifloxacin

                gemifloxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • glyburide

                tolbutamide increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

              • ibuprofen

                ibuprofen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • ibuprofen IV

                ibuprofen IV increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • ibuprofen/famotidine

                ibuprofen/famotidine will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • iloperidone

                iloperidone, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • imatinib

                imatinib will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • imidapril

                imidapril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • indomethacin

                indomethacin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • insulin aspart

                tolbutamide, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin aspart protamine/insulin aspart

                tolbutamide, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin degludec

                tolbutamide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin degludec/insulin aspart

                tolbutamide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin detemir

                tolbutamide, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin glargine

                tolbutamide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin glulisine

                tolbutamide, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin inhaled

                tolbutamide, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin isophane human/insulin regular human

                tolbutamide, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin lispro

                tolbutamide, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin lispro protamine/insulin lispro

                tolbutamide, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin NPH

                tolbutamide, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • insulin regular human

                tolbutamide, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • isocarboxazid

                isocarboxazid increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.

              • ketoconazole

                ketoconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • ketoprofen

                ketoprofen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • ketorolac

                ketorolac increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • ketorolac intranasal

                ketorolac intranasal increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • ketotifen, ophthalmic

                ketotifen, ophthalmic, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

              • lacosamide

                tolbutamide increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP2C9 inhibitors.

              • lansoprazole

                lansoprazole will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • lesinurad

                tolbutamide will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

              • levofloxacin

                levofloxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • linagliptin

                tolbutamide, linagliptin. Other (see comment). Use Caution/Monitor. Comment: When linagliptin is used in combination with sulfonylureas, a lower dose of the sulfonylurea may be required to reduce risk of hypoglycemia.

              • linezolid

                linezolid increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.

              • liraglutide

                liraglutide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

              • lisinopril

                lisinopril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • lixisenatide

                lixisenatide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with sulfonylureas. Sulfonylurea dosage reduction may be required.

              • lopinavir

                lopinavir, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Lopinavir may increase or decrease levels of tolbutamide. Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • lornoxicam

                lornoxicam increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • lurasidone

                lurasidone, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • marijuana

                marijuana decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor.

              • mecasermin

                mecasermin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

              • meclofenamate

                meclofenamate increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • mefenamic acid

                mefenamic acid increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • meloxicam

                meloxicam increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • metreleptin

                tolbutamide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

              • miconazole vaginal

                miconazole vaginal increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • moexipril

                moexipril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • moxifloxacin

                moxifloxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • nabumetone

                nabumetone increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • nadolol

                nadolol decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

              • naproxen

                naproxen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • nitisinone

                nitisinone will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • ofloxacin

                ofloxacin increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • olanzapine

                olanzapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • opuntia ficus indica

                opuntia ficus indica increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • ospemifene

                tolbutamide increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

                tolbutamide, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

              • oxaprozin

                oxaprozin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • paliperidone

                paliperidone, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • parecoxib

                parecoxib increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • peginterferon alfa 2b

                peginterferon alfa 2b decreases levels of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .

              • perindopril

                perindopril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • phenelzine

                phenelzine increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.

              • pindolol

                pindolol decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

              • piroxicam

                piroxicam increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • posaconazole

                posaconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • probenecid

                probenecid increases levels of tolbutamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • propranolol

                propranolol decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

              • quetiapine

                quetiapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • quinapril

                quinapril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • ramipril

                ramipril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • rifabutin

                rifabutin decreases levels of tolbutamide by increasing metabolism. Use Caution/Monitor.

              • rifampin

                rifampin decreases levels of tolbutamide by increasing metabolism. Use Caution/Monitor.

              • rifapentine

                rifapentine decreases levels of tolbutamide by increasing metabolism. Use Caution/Monitor.

              • risperidone

                risperidone, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • ritonavir

                ritonavir, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Ritonavir may increase or decrease levels of tolbutamide. Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

              • rucaparib

                rucaparib will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

              • salicylates (non-asa)

                salicylates (non-asa) increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • salsalate

                salsalate increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • selegiline

                selegiline increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic medications. Hypoglycemic effects may be increased.

              • selegiline transdermal

                selegiline transdermal increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.

              • semaglutide

                semaglutide, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

              • shark cartilage

                shark cartilage increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

              • sodium bicarbonate

                sodium bicarbonate will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • sodium citrate/citric acid

                sodium citrate/citric acid will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              • sodium zirconium cyclosilicate

                sodium zirconium cyclosilicate will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.

              • somapacitan

                somapacitan decreases effects of tolbutamide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

              • sulfadiazine

                sulfadiazine increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor.

              • sulfamethoxazole

                sulfamethoxazole increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor.

              • sulfamethoxypyridazine

                sulfamethoxypyridazine increases effects of tolbutamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • sulfasalazine

                sulfasalazine increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • sulfisoxazole

                sulfisoxazole increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor.

              • sulindac

                sulindac increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • terbinafine

                tolbutamide will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • timolol

                timolol decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

              • tipranavir

                tipranavir, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.

              • tolfenamic acid

                tolfenamic acid increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • tolmetin

                tolmetin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              • trandolapril

                trandolapril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

              • tranylcypromine

                tranylcypromine increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of tolbutamide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

              • voriconazole

                voriconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

              • xipamide

                xipamide decreases levels of tolbutamide by increasing renal clearance. Use Caution/Monitor.

              • ziprasidone

                ziprasidone, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              Minor (120)

              • agrimony

                agrimony increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • American ginseng

                American ginseng increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • amiodarone

                amiodarone will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • amitriptyline

                amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • amobarbital

                amobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • amoxapine

                amoxapine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • anamu

                anamu increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

              • aspirin

                aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • aspirin rectal

                aspirin rectal increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • balsalazide

                balsalazide increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • bendroflumethiazide

                bendroflumethiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • bosentan

                bosentan will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • budesonide

                budesonide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • butabarbital

                butabarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • butalbital

                butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • carbamazepine

                carbamazepine will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • chloramphenicol

                chloramphenicol increases levels of tolbutamide by decreasing metabolism. Minor/Significance Unknown.

              • chlorothiazide

                chlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • chlorthalidone

                chlorthalidone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • choline magnesium trisalicylate

                choline magnesium trisalicylate increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • chromium

                chromium increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • cimetidine

                cimetidine will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • clomipramine

                clomipramine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • clonidine

                clonidine decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, tolbutamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • clopidogrel

                clopidogrel increases levels of tolbutamide by decreasing metabolism. Minor/Significance Unknown.

              • cornsilk

                cornsilk increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

              • cortisone

                cortisone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • cyclopenthiazide

                cyclopenthiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • damiana

                damiana decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

              • danazol

                danazol increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • deflazacort

                deflazacort decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • desipramine

                desipramine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • devil's claw

                devil's claw increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • dexamethasone

                dexamethasone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • diflunisal

                diflunisal increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • disulfiram

                disulfiram will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • doxepin

                doxepin increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • elderberry

                elderberry increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

              • ethotoin

                tolbutamide increases levels of ethotoin by plasma protein binding competition. Minor/Significance Unknown.

                ethotoin decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • etravirine

                etravirine will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • eucalyptus

                eucalyptus increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

              • felbamate

                felbamate will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • fluconazole

                fluconazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • fludrocortisone

                fludrocortisone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • fluoxymesterone

                fluoxymesterone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • fo-ti

                fo-ti increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • forskolin

                forskolin increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

              • fosphenytoin

                tolbutamide increases levels of fosphenytoin by plasma protein binding competition. Minor/Significance Unknown.

                fosphenytoin decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • gotu kola

                gotu kola increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

              • guanfacine

                guanfacine decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                guanfacine, tolbutamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • gymnema

                gymnema increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • halofenate

                halofenate increases effects of tolbutamide by unknown mechanism. Minor/Significance Unknown.

              • horse chestnut seed

                horse chestnut seed increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • hydrochlorothiazide

                hydrochlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • hydrocortisone

                hydrocortisone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • imipramine

                imipramine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • indapamide

                indapamide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • isoniazid

                isoniazid decreases effects of tolbutamide by unspecified interaction mechanism. Minor/Significance Unknown.

              • juniper

                juniper increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

              • ketoconazole

                ketoconazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • leflunomide

                leflunomide will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • lofepramine

                lofepramine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • lycopus

                lycopus increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

              • maitake

                maitake increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

              • maprotiline

                maprotiline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • mesalamine

                mesalamine increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • mesterolone

                mesterolone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • methyclothiazide

                methyclothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • methylprednisolone

                methylprednisolone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • methyltestosterone

                methyltestosterone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • metolazone

                metolazone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • metronidazole

                metronidazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • miconazole vaginal

                miconazole vaginal will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • nateglinide

                nateglinide will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • nettle

                nettle increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

              • nilotinib

                nilotinib will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • nitazoxanide

                nitazoxanide, tolbutamide. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

              • nizatidine

                nizatidine will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.

              • nortriptyline

                nortriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • ofloxacin

                ofloxacin, tolbutamide. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

              • omeprazole

                omeprazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • orlistat

                orlistat increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • oxandrolone

                oxandrolone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • oxymetholone

                oxymetholone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • pegvisomant

                pegvisomant increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • pentobarbital

                pentobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • phenobarbital

                phenobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • phenytoin

                tolbutamide increases levels of phenytoin by plasma protein binding competition. Minor/Significance Unknown.

                phenytoin decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • potassium acid phosphate

                potassium acid phosphate increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

              • potassium chloride

                potassium chloride increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

              • potassium citrate

                potassium citrate increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

              • prednisolone

                prednisolone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • prednisone

                prednisone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown.

              • primidone

                primidone will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • protriptyline

                protriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • rifampin

                rifampin will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • rifapentine

                rifapentine will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • sage

                sage increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • salicylates (non-asa)

                salicylates (non-asa) increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • salsalate

                salsalate increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • secobarbital

                secobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • sitagliptin

                sitagliptin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.

              • stevia

                stevia increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • sulfamethoxazole

                sulfamethoxazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • sulfasalazine

                sulfasalazine increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • tacrolimus

                tolbutamide increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

              • teniposide

                tolbutamide increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

              • testosterone

                testosterone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • testosterone buccal system

                testosterone buccal system increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • testosterone topical

                testosterone topical increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • ticlopidine

                ticlopidine will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • tongkat ali

                tongkat ali increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

              • trazodone

                trazodone increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • trimipramine

                trimipramine increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • valproic acid

                valproic acid will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • vanadium

                vanadium increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • voriconazole

                voriconazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • willow bark

                willow bark increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

              • zafirlukast

                zafirlukast will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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              Adverse Effects

              Frequency Not Defined

              Hypoglycemia

              Dermatologic recations

              Disulfiram-like reactions

              Agranulocytosis

              Hyponatremia

              Aplastic anemia

              Thrombocytopenia

              Heartburn

              Nausea/vomiting

              Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure

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              Warnings

              Contraindications

              Hypersensitivity, sulfa allergy

              Type I diabetes, diabetic ketoacidosis

              Cautions

              Patients with hypoglycemia, when caloric intake is decreased or there is increased stress due to infection, fever, trauma, or surgery (may need to discontinue treatment)

              Risk of cardiovascular mortality increases with oral hypoglycemic drug treatments compared to treatment with diet alone or diet plus insulin

              Risk of sulfonylurea-induced hemolytic anemia may increase in patients iwth glucose-6-phosphate dehydrogenase deficiency

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              Pregnancy & Lactation

              Pregnancy Category: C

              Lactation: Controversial, avoid

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Initial effect is to increase beta-cell insulin secretion

              May also decrease rate of hepatic glucose production, increases insulin receptor sensitivity, and increases number of insulin receptors

              Pharmacokinetics

              Half-Life: 4.5-6.5 hr

              Duration: 6-24 hr

              Onset: 1hr

              Max Effect: 5-8 hr

              Time to peak, serum: 3-4 hr

              Protein Bound: 80-99%

              Vd: 0.15 L/kg

              Metabolism: extensively, in liver to inactive metabolites by hepatic P450 enzyme CYP2C9

              Metabolites: carboxytolbutamide, hydroxymethyltolbutamide (inactive)

              Excretion: mainly in urine 70-80%

              Dialyzable

              • Hemodialysis: No
              • Peritoneal dialysis: No data
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              Images

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

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              Tier Description
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.