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Tolbutamide Side Effects

For the Consumer

Applies to tolbutamide: oral tablet

As well as its needed effects, tolbutamide may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking tolbutamide, check with your doctor immediately:

  • Abdominal or stomach pain
  • chills
  • clay-colored stools
  • dark urine
  • diarrhea
  • dizziness
  • fever
  • headache
  • itching
  • loss of appetite
  • nausea
  • rash
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vomiting of blood
Incidence not known:
  • Agitation
  • back or leg pains
  • bleeding gums
  • blood in urine or stools
  • bloody, black, or tarry stools
  • chest pain
  • coma
  • confusion
  • convulsions
  • cough or hoarseness
  • decreased urine output
  • depression
  • difficulty breathing
  • fast or irregular heartbeat
  • fatigue
  • fever with or without chills
  • fluid-filled skin blisters
  • general body swelling
  • general feeling of tiredness or weakness
  • high fever
  • hostility
  • increased thirst
  • irritability
  • lethargy
  • light-colored stools
  • lower back or side pain
  • muscle pain or cramps
  • muscle twitching
  • nosebleeds
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on skin
  • rapid weight gain
  • seizures
  • sensitivity to the sun
  • shortness of breath
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stupor
  • swelling of face, ankles, or hands
  • swollen or painful glands
  • tightness in the chest
  • unexplained bleeding or bruising
  • wheezing
  • yellow eyes or skin

If any of the following symptoms of overdose occur while taking tolbutamide, get emergency help immediately:

Symptoms of overdose:
  • Anxiety
  • blurred vision
  • cold sweats
  • cool, pale skin
  • increased hunger
  • nervousness
  • nightmares
  • shakiness
  • slurred speech

Minor Side Effects

Some tolbutamide side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:
  • Belching
  • indigestion
  • pain in the chest below the breastbone
  • passing of gas
  • stomach pain, fullness, or discomfort
Less common:
  • Flushing or redness of skin
  • unusually warm skin
Incidence not known:
  • Change in taste or bad, unusual, or unpleasant (after)taste
  • increased sensitivity of skin to sunlight
  • redness or other discoloration of skin
  • severe sunburn

For Healthcare Professionals

Applies to tolbutamide: intravenous powder for injection, oral tablet


The most commonly reported adverse reactions have included gastrointestinal disturbances such as nausea, epigastric fullness, and heartburn.[Ref]


In the University Group Diabetes Program (UGDP) study, cardiovascular mortality rate was approximately 2.5 times higher in patients treated for 5 to 8 years with diet plus tolbutamide 1.5 g per day compared with that of patients treated with diet alone. The UGDP study was a long-term prospective clinical trial designed to evaluate the effectiveness of glucose lowering drugs in preventing or delaying vascular complications in patients with type 2 diabetes mellitus (n=823). Tolbutamide was stopped based on the increase in cardiovascular mortality; a significant increase in total mortality was not observed, but stopping the drug may have limited the ability to measure that.[Ref]

Frequency not reported: Increased cardiovascular mortality[Ref]


Gastrointestinal disturbances such as nausea, epigastric fullness, and heartburn tend to be dose related and may disappear when dosage is reduced.[Ref]

Common (1% to 10%): Nausea, epigastric fullness, heartburn
Frequency not reported: Anorexia, diarrhea, vomiting, constipation[Ref]


Frequency not reported: Hypoglycemia, increased appetite, weight gain

Frequency not reported: Hepatic porphyria, disulfiram-like reactions[Ref]


Hypersensitivity reactions usually develop within 6 to 8 weeks of starting therapy. Allergic skin reactions may occur and progress rarely to erythema multiforme exfoliative dermatitis, and fever.[Ref]

Rare (less than 0.1%): Cholestatic jaundice
Frequency not reported: Hepatic function disturbances[Ref]


Frequency not reported: Photosensitivity

Frequency not reported: Porphyria cutanea tarda[Ref]


Frequency not reported: Tinnitus, alcohol intolerance[Ref]

Nervous system

Frequency not reported: Headache, taste disturbances, paraesthesia[Ref]


Rare (less than 0.1%): Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia[Ref]


Rare (less than 0.1%): Cholestatic jaundice
Frequency not reported: Hepatic function disturbances[Ref]


Frequency not reported: Hyponatremia, syndrome of inappropriate antidiuretic hormone (SIADH) secretion[Ref]


1. "Product Information. Tolbutamide (TOLBUTamide)." Mylan Pharmaceuticals Inc, Morgantown, WV.

It is possible that some side effects of tolbutamide may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

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