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

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

For abbreviations, symbols, and age group definitions 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: Liver 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

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 2023).

• 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.

Product Availability

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

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

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.

Dosage Forms: Canada

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

Tablet, Oral:

Generic: 500 mg [DSC]

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 2023).

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 drug classes (sulfonylurea hypoglycemics, oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

Alcohol (Ethyl): Sulfonylureas may increase adverse/toxic effects of Alcohol (Ethyl). A flushing reaction may occur. Alcohol (Ethyl) may increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Alpha-Glucosidase Inhibitors: May increase hypoglycemic effects 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 increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid

Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor

Amiodarone: May increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Antidiabetic Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor

Beta-Blockers (Nonselective): May increase hypoglycemic effects of Sulfonylureas. Beta-Blockers (Nonselective) may decrease therapeutic effects of Sulfonylureas. Risk C: Monitor

Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

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

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

Clarithromycin: May increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

Colesevelam: May decrease serum concentration of Sulfonylureas. Management: Administer sulfonylureas 4 hours prior to colesevelam. Risk D: Consider Therapy Modification

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

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

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

Dexketoprofen: May increase adverse/toxic effects of Sulfonamides. Risk C: Monitor

Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Dipeptidyl Peptidase-IV Inhibitors: May increase hypoglycemic effects 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 increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Fibric Acid Derivatives: May increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

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

Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Glucagon-Like Peptide-1 Agonists: May increase hypoglycemic effects of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider Therapy Modification

Guanethidine: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Herbal Products with Glucose Lowering Effects: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Hyperglycemia-Associated Agents: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Hypoglycemia-Associated Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Leflunomide: May increase 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 serum concentration of Leflunomide. Specifically, tolbutamide may increase the proportion of non-protein-bound (i.e., free fraction) teriflunomide. Risk C: Monitor

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

Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Mecamylamine: Sulfonamides may increase adverse/toxic effects of Mecamylamine. Risk X: Avoid

Methotrexate: Sulfonylureas may increase serum concentration of Methotrexate. Management: Avoid coadministration of methotrexate with sulfonylureas if possible. If coadministration cannot be avoided, monitor closely for methotrexate adverse effects. Risk D: Consider Therapy Modification

Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor

Metreleptin: May increase hypoglycemic effects 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

MetroNIDAZOLE (Systemic): May increase serum concentration of Sulfonylureas. Risk C: Monitor

Miconazole (Oral): May increase hypoglycemic effects of Sulfonylureas. Miconazole (Oral) may increase serum concentration of Sulfonylureas. Risk C: Monitor

Mitiglinide: May increase adverse/toxic effects of Sulfonylureas. Risk X: Avoid

Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

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

Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid

Probenecid: May increase serum concentration of Sulfonylureas. Risk C: Monitor

Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects 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

Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

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

Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

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

Sulfonamide Antibiotics: May increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Tetracyclines: May increase hypoglycemic effects of Sulfonylureas. Risk C: Monitor

Thiazide and Thiazide-Like Diuretics: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Thiazolidinediones: May increase hypoglycemic effects of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider Therapy Modification

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

Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Risk C: Monitor

Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor

Vitamin K Antagonists: May increase hypoglycemic effects of Sulfonylureas. Sulfonylureas may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

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

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 2023; 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 2023; Blumer 2013).

Agents other than tolbutamide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2023).

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 2023; KDIGO 2020).

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults with diabetes (AACE [Samson 2023], ADA 2023):

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 (SI: 4.4 to 7.2 mmol/L) (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 (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2023):

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% (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 (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).

Classification of hypoglycemia (ADA 2023):

Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL (SI: <3 mmol/L); 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 (Adult Data Unless Noted)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AU) Australia: Rastinon;
  • (CH) Switzerland: Rastinon;
  • (CL) Chile: Tolbutamida;
  • (CZ) Czech Republic: Dirastan;
  • (DE) Germany: Artosin | Guabeta n | Orabet | Tolbutamid;
  • (EE) Estonia: Butamid;
  • (FI) Finland: Rastinon;
  • (FR) France: Dolipol;
  • (GB) United Kingdom: Glyconon | Pramidex | Tolbutamide almus | Tolbutamide aps | Tolbutamide cox | Tolbutamide kent;
  • (HK) Hong Kong: Diatol;
  • (IL) Israel: Orsinon;
  • (IN) India: Rastinon;
  • (JP) Japan: Artosin | Ast | Butamide | Daikell 860 | Diaben | Diabetose | Diabex t | Mellitos d | Rastinon | Takazide | Tolbutamide nissin | Tolbutamide organon | Tolbutamide sato | Tolbutamide takeshima | Tolbutamide towa | Tolsiran | Tolumide;
  • (LT) Lithuania: Butamid | Dirastan;
  • (LV) Latvia: Butamid | Dirastan | Oranyl;
  • (MX) Mexico: Dabetil | Flusan | Rastinon | Tolbutamida | Tolbutamida gi sil;
  • (MY) Malaysia: Tobumide;
  • (NL) Netherlands: Tolbutamide accord | Tolbutamide Sandoz;
  • (NZ) New Zealand: Diatol;
  • (PL) Poland: Diabetol | Dirastan;
  • (RO) Romania: Tolbutamid;
  • (RU) Russian Federation: Butamid | Oranyl;
  • (SG) Singapore: Apo tolbutamide | Tobumide | Tolmide | Unitamide;
  • (SI) Slovenia: Tolbusal;
  • (SK) Slovakia: Dirastan;
  • (SR) Suriname: Apo tolbutamide | Tolbutamide accord | Tolbutamide apotex | Tolbutamide aurobindo | Tolbutamide cf;
  • (UA) Ukraine: Butamid | Dirastan;
  • (UY) Uruguay: Neobezeta | Rastinon
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