Tolazamide (Desumide) is a first-generation sulfonylurea that is now rarely used to treat patients with diabetes mellitus type 2.

Tolazamide Uses:

• Used in conjunction with diet as a management tool for stable, mild-to-moderate-severe type 2 diabetes.

• Guidelines' suggested actions Tolazamide and other first-generation sulfonylureas are not advised for the treatment of  type II diabetes; instead, glipizide and other later-generation sulfonylureas with fewer hypoglycemia risks are chosen.

Tolazamide (Desumide) Dose in Adults

Tolazamide (Desumide) Dose in the treatment of Diabetes mellitus, Type 2: Oral:

• Initial:
  • 100 to 250 mg once a day with breakfast or the first main meal of the day
  • Fasting blood sugar <200 mg/dL: 100 mg once a day
  • Fasting blood sugar >200 mg/dL: 250 mg once a day
  • Patient is not eating adequately, is underweight, or is malnourished: once daily 100 mg

• Adjustment/titration:

  • Depending on the response, the dose should be increased by 100 to 250 mg/day per week; doses greater than 500 mg/day may be administered in two separate doses; 1 g is the maximum daily dose; higher amounts are less likely to help blood sugar  management.

  • Conversion from insulin to tolazamide:

    • <20 units day = 100 mg once a day
    • 21 to <40 units/day = 250 once a day
    • ≥40 units/day = 250 mg once a day and 50% of insulin dose

Use in Children:

Not indicated.

Pregnancy Risk Factor C

• Sulfonylurea-using moms have given birth to babies who have suffered from severe hypoglycemia for up to ten days.
• A mother's glycemic control may be to blame for other negative occurrences that have been reported.
• Manufacturers recommend discontinuing use of the drug at least two weeks prior to the delivery date. If used during pregnancy.
• Poor glycemic control in pregnancy can lead to adverse maternal and fetal outcomes, including dka and preeclampsia.
• Preventing adverse outcomes by keeping maternal blood glucose and HbA as close as possible to their target levels before conception and throughout pregnancy is key. Hypoglycemia should also be avoided.
• For treating diabetes mellitus in pregnancy, it is recommended that you use agents other than tolazamide.

Use while breastfeeding

• It is unknown if breast milk contains tolazamide.
• According to the manufacturer, there is a risk of hypoglycemia in breastfeeding infants.
• Determining whether to stop taking the medication or to continue breastfeeding is therefore crucial.

Dose in Kidney Disease:

• The manufacturer's labeling does not include any dosage adjustments. 
• It is recommended to use conservative doses for initial and maintenance (active metabolites can be eliminated by the kidneys).

Dose in Liver disease:

• The manufacturer's labeling does not include any dosage adjustments. 
• It is recommended to use conservative dosages for initial and maintenance, and to monitor blood glucose closely.

Side effects of Tolazamide (Desumide):

• Central Nervous System:

  • Disulfiram-Like Reaction
  • Vertigo
  • Headache
  • Dizziness
  • Fatigue
  • Malaise

• Dermatologic:

  • Maculopapular Rash
  • Morbilliform Rash
  • Pruritus
  • Skin Photosensitivity
  • Skin Rash
  • Urticaria

• Endocrine & Metabolic:

  • Hepatic Porphyria
  • SIADH (Syndrome Of Inappropriate Antidiuretic Hormone Secretion)
  • Hyponatremia
  • Hypoglycemia
  • Porphyria Cutanea Tarda

• Gastrointestinal:

  • Anorexia
  • Vomiting
  • Diarrhea
  • Constipation
  • Heartburn
  • Epigastric Fullness
  • Nausea

• Genitourinary:

  • Diuretic Effect

• Hematologic & Oncologic:

  • Agranulocytosis
  • Pancytopenia
  • Aplastic Anemia
  • Leukopenia
  • Hemolytic Anemia
  • Thrombocytopenia

• Hepatic:

  • Cholestatic Jaundice

• Neuromuscular & Skeletal:

  • Weakness

Contraindications to Tolazamide (Desumide):

• Hypersensitivity to tolazamide, the sulfonylureas or any other component of the formulation
• Type 1 Diabetes
• DKA

Warnings and precautions

• Cardiovascular mortality

  • When compared to treatment with food and insulin, the product states that oral hypoglycemic medicines may increase  cardiovascular mortality.
  • This association is not supported by sufficient data. Numerous studies, including one large prospective study (UKPDS), do not support it.
  • Patients with an existing atherosclerotic heart disease may prefer to use other agents.

• Hypoglycemia

  • All sulphonylureas can cause severe hypoglycemia.
  • Hypoglycemia is more common after exercise or severe or prolonged activity, when ethanol intake is low, and when multiple glucose-lowering medications are used.
  • Old age, malnutrition, and people with compromised liver or renal function can also result in hypoglycemia. Take care.

• Allergy to sulfonamide ("sulfa")

  • Patients with history of allergic reactions to sulfuramides should consult their physician before using any medication containing sulfonamide chemical groups.
  • It is possible for members of a class to interact with one another (e.g, two antibiotics sulfonamides).
  • Crossreactivity concerns have been raised previously for all compounds with the sulfonamide structural (SO NH).
  • A deeper understanding of allergy mechanisms has shown that cross-reactivity between nonantibiotic and antibiotic sulfonamides is unlikely.
  • Non-antibiotic sulfonamides, in particular, are less likely than anaphylaxis to trigger mechanisms 
  • T-cell mediated (type I) reactions, such as a maculopapular skin rash, are less  well understood, although their possibility cannot be ruled out based on existing knowledge.
  • These classes are sometimes avoided by some clinicians if there has been a history or severe reaction (Stevens-Johnson syndrome/TEN).

• Bariatric surgery

  • Absorption altered:
    • IR formulations should always be bused to reduce the possibility of side effects such bypassing the stomach or  proximal bowel with gastric bypass, more fast gastric emptying, and proximal bowel transit with Sleeve gastrectomy.
    • The release and absorption of ER formulations may change after a gastric bypass or sleeve gastrectomy (but not the gastric band).
    • T was substantially shorter in the gastric bypass group that received tolbutamide (1.4 +-1.8 vs. 5.1 +-1.7 hours; P = 0.001) but C and AUC were unaffected.
  • Hypoglycemia
    • If possible, should be used as an anti-hypoglycemia agent. Hypoglycemia can occur following gastric bypass, gastric band, or sleeve gastricectomy.
    • The most effective operation is gastric bypass, which is closely followed by the sleeve. These surgeries can partially  or completely restore insulin secretion and sensitivity. 
    • In the days after gastric bypass and Sleeve gastrectomy, there was a considerable rise in hepatic insulin sensitivity as well as 1st-phase insulin secretion.
    • In the three to one year after surgery, these techniques might improve peripheral insulin sensitivity.
  • Weight loss
    • Gastric bypass evaluations should be performed to assess the risk and benefit of each treatment. This may help you avoid weight gain.
• Glucose-6phosphate dehydrogenase(G6PD) deficiency
  • Patients with G6PD deficits may be more susceptible to hemolytic anaemia brought on by sulfonylureas.
  • However, patients not diagnosed with G6PD deficiencies have had cases reported during postmarketing surveillance.
  • G6PD-deficient patients should be cautious and alternative therapy should be considered.
• Stress-related disorders:
  • If a patient is under stress, therapy might be stopped or insulin can be given (fever. Trauma. Infection. Surgery).

Tolazamide: Drug Interaction

Monitoring parameters:

• Hypoglycemia symptoms include fatigue, sweating, and numbness in the extremities.
• BSR
• Hemoglobin A (at minimum 6 months in patients who have stable glycemic control, are meeting their treatment goals, and 3 monthly for patients who are not meeting their treatment goals or need to change therapy.

How to administer Tolazamide (Desumide)?

P/O: Administer once day with breakfast or the first big meal; dosages over 500 mg/day should be divided into two doses.

Mechanism of action of Tolazamide (Desumide):

• It encourages pancreatic beta cells to secrete insulin.
• The liver's glucose output is decreased.
• This causes an increase in insulin sensitivity at the peripheral target sites.

The onset of hypoglycemic effect: 20 mins

Peak hypoglycemic effect: 4-6 hours

Duration: 10-24 hours

Absorption: Rapidly absorbed

Protein binding: Highly protein-bound (94%)

Metabolism: Extensively metabolized in liver to 5 metabolites (activity 0% to 70%)

Half-life elimination: 7 hours

Time to peak, serum: 3-4 hours

Excretion:

• 85 % in urine
• 7 % in feces

International Brand Names of Tolazamide:

• Desumide
• Diabewas
• Esulin
• Huacose
• Tolanase
• Tolinase

Tolazamide Brand Names in Pakistan:

No Brands Available in Pakistan.