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Tolbutamide (United States and Canada: Not available): Drug information

Tolbutamide (United States and Canada: Not available): Drug information
(For additional information see "Tolbutamide (United States and Canada: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Antidiabetic Agent, Sulfonylurea
Dosing: Adult

Note: Tolbutamide has been discontinued in the United States for >1 year.

Diabetes mellitus, type 2

Diabetes mellitus, type 2: Oral: Initial: 1-2 g/day as a single dose in the morning or in divided doses throughout the day. Maintenance dose: 0.25-3 g/day; however, a maintenance dose >2 g/day is seldom required. Note: Divided doses may improve gastrointestinal tolerance

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, conservative initial and maintenance doses are recommended.

Hemodialysis: Not dialyzable (0% to 5%)

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, conservative initial and maintenance doses and careful monitoring of blood glucose are recommended.

Dosing: Older Adult

Initial: 250 mg 1-3 times/day; usual: 500-2000 mg; maximum: 3 g/day

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Generic: 500 mg [DSC]

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 500 mg

Product Availability

Tolbutamide has been discontinued in the United States for >1 year.

Administration: Adult

Oral: Entire dose can be administered in AM, divided doses may improve GI tolerance.

Use: Labeled Indications

Diabetes mellitus, type 2: Adjunct to diet for the management of type 2 diabetes mellitus

Guideline recommendations: First-generation sulfonylureas (eg, tolbutamide) are not recommended treatment options for type 2 diabetes; later-generation sulfonylureas with lower hypoglycemic risks (eg, glipizide) are preferred (ADA 2020).

Medication Safety Issues
Sound-alike/look-alike issues:

TOLBUTamide may be confused with terbutaline, TOLAZamide, tolcapone

Orinase may be confused with Orabase, Ornex, Tolinase

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Central nervous system: Disulfiram-like reaction, headache

Dermatologic: Erythema, maculopapular rash, morbilliform rash, pruritus, skin photosensitivity, urticaria

Endocrine & metabolic: Hepatic porphyria, hypoglycemia, hyponatremia, porphyria cutanea tarda, SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Gastrointestinal: Dysgeusia, epigastric fullness, heartburn, nausea

Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia

Hepatic: Cholestatic jaundice

Hypersensitivity: Hypersensitivity reaction

Contraindications

Hypersensitivity to tolbutamide, sulfonylureas, or any component of the formulation; treatment of type 1 diabetes; diabetic ketoacidosis

Warnings/Precautions

Concerns related to adverse reactions:

• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS), have not supported an association. In patients with established atherosclerotic cardiovascular disease (ASCVD), other agents are preferred (ADA 2020).

• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal or hepatic function; use with caution.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Bariatric surgery:

– Altered absorption: Use IR formulations after surgery to minimize the potential effects of bypassing stomach and proximal small bowel with gastric bypass or more rapid gastric emptying and proximal small bowel transit with sleeve gastrectomy (Apovian 2015). ER formulations may have altered release and absorption patterns after gastric bypass or sleeve gastrectomy (but not gastric band). Compared to control, Tmax in a gastric bypass cohort administered tolbutamide was significantly shorter (1.4 ± 1.8 vs 5.1 ± 1.7 hours; P < 0.001), while Cmax and AUC0- were not altered (Tandra 2013).

– Hypoglycemia: Use an antidiabetic agent without the potential for hypoglycemia if possible; hypoglycemia may occur after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). First-phase insulin secretion and hepatic insulin sensitivity have been shown to be significantly improved in the immediate days after gastric bypass and sleeve gastrectomy. The restorative effects of these procedures on peripheral insulin sensitivity may occur later in the 3- to 12-month period postsurgery (Mingrone 2016).

– Weight gain: Evaluate risk vs benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.

• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Other warnings/precautions:

• Secondary failure: Loss of efficacy may be observed following prolonged use as a result of the progression of type 2 diabetes mellitus which results in continued beta cell destruction. In patients who were previously responding to sulfonylurea therapy, consider additional factors which may be contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet and exercise regimen). If no contributing factors can be identified, consider discontinuing use of the sulfonylurea due to secondary failure of treatment.

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Adagrasib: May increase the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of adagrasib and these narrow therapeutic/sensitive substrates of CYP2C9 when possible. If combined, monitor for increased toxicities of these substrates. Risk D: Consider therapy modification

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Risk C: Monitor therapy

Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amiodarone: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy

Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy

Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Carbocisteine: Sulfonylureas may enhance the adverse/toxic effect of Carbocisteine. Specifically, sulfonylureas may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Risk C: Monitor therapy

Chloramphenicol (Systemic): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

Clarithromycin: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

CYP2C9 Inducers (Moderate): May decrease the serum concentration of Sulfonylureas. Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

CYP2C9 Inhibitors (Weak): May increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: TOLBUTamide may decrease the protein binding of Fosphenytoin-Phenytoin. Specifically concentrations of free phenytoin may be increased. Risk C: Monitor therapy

Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Leflunomide: May increase the serum concentration of TOLBUTamide. Specifically, the active metabolite of leflunomide (teriflunomide) may both increase total tolbutamide concentrations and increase the free fraction (i.e., non-protein bound) of tolbutamide. TOLBUTamide may increase the serum concentration of Leflunomide. Specifically, tolbutamide may increase the proportion of non-protein-bound (i.e., free fraction) teriflunomide. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs or symptoms of hypoglycemia. Risk D: Consider therapy modification

Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Sulfonamide Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Tetracyclines: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Thiazolidinediones: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider therapy modification

Toremifene: May increase the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Food Interactions

Possible disulfiram-like reaction with concurrent ethanol use. Management: Monitor patients.

Reproductive Considerations

Sulfonylureas are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)

Pregnancy Considerations

Tolbutamide crosses the placenta and can be measured in the serum of newborn infants following maternal use during pregnancy (Miller 1962).

Severe hypoglycemia lasting 4 to 10 days has been noted in infants born to mothers taking a sulfonylurea at the time of delivery. Additional adverse events have been reported and may be influenced by maternal glycemic control (Larsson 1960; Saili 1991; Schiff 1970). The manufacturer recommends if tolbutamide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date.

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).

Agents other than tolbutamide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).

Breastfeeding Considerations

Tolbutamide is present in breast milk (Moiel 1967).

According to the manufacturer, due to the potential for hypoglycemia in the breastfeeding infant, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring Parameters

Blood glucose; signs and symptoms of hypoglycemia.

HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults with diabetes (ADA 2021):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.

Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2021):

Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (LeRoith 2019).

HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.

Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).

Classification of hypoglycemia (ADA 2021):

Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.

Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites, suppression of glucagon may also contribute

Pharmacokinetics

Onset of action: 1 hour

Duration: Oral: 6-24 hours

Absorption: Oral: Rapid

Distribution: Vd: 0.15 L/kg

Protein binding: ~95% (concentration dependent)

Metabolism: Hepatic via CYP2C9 to hydroxymethyltolbutamide (mildly active) and carboxytolbutamide (inactive); metabolism does not appear to be affected by age

Half-life elimination: 4.5-6.5 hours (range: 4-25 hours)

Time to peak, serum: 3-4 hours

Excretion: Urine (75% to 85% primarily as metabolites); feces

Pricing: US

Tablets (TOLBUTamide Oral)

500 mg (per each): $1.18

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aglycid (IT);
  • Artosin (CR, DE, DO, GT, HN, JP, MX, NI, PA, SV);
  • Asto (JP);
  • Butamide (JP);
  • Diaben (JP);
  • Diabeton Metilato (IT);
  • Diabetose (JP);
  • Diatol (NZ);
  • Dirastan (CZ);
  • Dolipol (FR);
  • Flusan (MX);
  • Mellitos D (JP);
  • Neobezeta (UY);
  • Orabet (DE);
  • Rastinon (AE, AT, AU, BE, BH, CH, CY, EG, GR, IE, IN, IQ, IR, IT, JO, KW, LB, LU, LY, MX, OM, SA, SY, YE);
  • Tobumide (SG);
  • Tolbutamid R.A.N. (DE);
  • Tolmide (SG);
  • Tolsiran (JP);
  • Tolumide (JP);
  • Tydadex (ZA)


For country code abbreviations (show table)
  1. Alexopoulos AS, Blair R, Peters AL. Management of preexisting diabetes in pregnancy: a review. JAMA. 2019;321(18):1811-1819. doi:10.1001/jama.2019.4981 [PubMed 31087027]
  2. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 201: pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960. [PubMed 30461693]
  3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]
  4. American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care.diabetesjournals.org/content/44/Supplement_1. Accessed January 13, 2021.
  5. Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(5):2135-2136]. J Clin Endocrinol Metab. 2015;100(2):342-362. doi: 10.1210/jc.2014-3415 [PubMed 25590212]
  6. “A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-Onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53. [PubMed 992232]
  7. Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617]
  8. Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy. 2004;24(7):856-870. [PubMed 15303450]
  9. “Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65. [PubMed 9742977]
  10. Egan AM, Dow ML, Vella A. A review of the pathophysiology and management of diabetes in pregnancy. Mayo Clin Proc. 2020;95(12):2734-2746. doi:10.1016/j.mayocp.2020.02.019 [PubMed 32736942]
  11. Garratt KN, Brady PA, Hassinger NL, et al, “Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,” J Am Coll Cardiol, 1999, 33(1):119-24. [PubMed 9935017]
  12. Huupponen R, “Adverse Cardiovascular Effects of Sulphonylurea Drugs. Clinical Significance,” Med Toxicol, 1987, 2(3):190-209. [PubMed 3298923]
  13. “Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53. [PubMed 9742976]
  14. Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? [published correction appears in Ann Pharmacother. 2005;39(7-8):1373]. Ann Pharmacother. 2005;39(2):290-301. [PubMed 15644481]
  15. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(supp 4):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]
  16. Kirkman M, Briscoe VJ, Clark N, et al, "Diabetes in Older Adults: A Consensus Report," J Am Geriatr Soc, 2012; doi: 10.1111/jgs.12035. [PubMed 23106132]
  17. Klamann A, Sarfert P, Launhardt V, et al, “Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),” Eur Heart J, 2000, 21(3):220-9. [PubMed 10639304]
  18. Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi: 10.1038/ijo.2009.79 [PubMed 19417773]
  19. Larsson Y and Sterky G, "Possible Teratogenic Effect of Tolbutamide in a Pregnant Prediabetic," Lancet, 1960, 2:1424-5. [PubMed 13759229]
  20. Lazner J, “Fatal Hypoglycaemia From Tolbutamide in a Nondiabetic Patient,” Med J Aust, 1970, 1:327-8.
  21. LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi: 10.1210/jc.2019-00198. [PubMed 30903688]
  22. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]
  23. Meinert CL, Knatterud GL, Prout TE, et al, “A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,” Diabetes, 1970, 19:789-830. [PubMed 4926376]
  24. Miller AK, Adir J, and Vestal RE, “Effect of Age on the Pharmacokinetics of Tolbutamide in Man,” Pharmacologist, 1977, 19:128.
  25. Miller AK, Adir J, and Vestal RE, “Tolbutamide Binding to Plasma Proteins of Young and Old Human Subjects,” J Pharm Sci, 1978, 67(8):1192-3. [PubMed 671270]
  26. Miller DI, Wishinsky H, and Thompson G, "Transfer of Tolbutamide Across the Human Placenta," Diabetes, 1962, 11(Suppl):93-7.
  27. Mingrone G, Cummings DE. Changes of insulin sensitivity and secretion after bariatric/metabolic surgery. Surg Obes Relat Dis. 2016;12(6):1199-1205. doi: 10.1016/j.soard.2016.05.013. [PubMed 27568471]
  28. Moiel RH and Ryan JR, "Tolbutamide Orinase in Human Breast Milk," Clin Pediatr (Phila), 1967, 6(8):480. [PubMed 6029660]
  29. O'Keefe JH, Blackstone EH, Sergeant P, et al, “The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,” Eur Heart J, 1998, 19(11):1696-703. [PubMed 9857923]
  30. Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi: 10.1007/s11695-012-0622-3. [PubMed 22354457]
  31. Qaseem A, Humphrey LL, Sweet DE, et al,“Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline from the American College of Physicians,” Ann Intern Med, 2012, 156(3):218-31. [PubMed 22312141]
  32. Saili A and Sarna MS, "Tolbutamide: Teratogenic Effects," Indian Pediatr, 1991, 28(8):936-40. [PubMed 1808085]
  33. Schaefer-Graf UM, Hartmann R, Pawliczak J,et al. Association of breast-feeding and early childhood overweight in children from mothers with gestational diabetes mellitus. Diabetes Care. 2006;29(5):1105-1107. [PubMed 16644645]
  34. Schiff D, Aranda JV, and Stern L, "Neonatal Thrombocytopenia and Congenital Malformations Associated With Administration of Tolbutamide to the Mother," J Pediatr, 1970, 77(3):457-8. [PubMed 5502096]
  35. Seger D, “Toxic Emergencies of Endocrine and Metabolic Therapeutic Agents,” J Emerg Med, 1988, 6(6):527-37. [PubMed 3065405]
  36. Seltzer HS, “Drug-Induced Hypoglycemia: A Review Based on 473 Cases,” Diabetes, 1972, 21(9):955-66. [PubMed 4626706]
  37. Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin North Am. 2004;24(3):477-490. [PubMed 15242722]
  38. Tandra S, Chalasani N, Jones DR, Mattar S, Hall SD, Vuppalanchi R. Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Ann Surg. 2013;258(2):262-269. doi: 10.1097/SLA.0b013e31827a0e82 [PubMed 23222033]
  39. Tolbutamide [prescribing information]. Morgantown, WV: Mylan Laboratories; February 2009.
  40. Tornero P, De Barrio M, Baeza ML, Herrero T. Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing. Contact Dermatitis. 2004;51(2):57-62. [PubMed 15373844]
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