Tolbutamide Side Effects

Medically reviewed by Drugs.com. Last updated on Mar 22, 2025.

Applies to tolbutamide: oral tablet.

Precautions

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

It is very important to follow carefully any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep your recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.
• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes and a list of all of your medicines.

Check with your doctor right away if you start having chest pain or discomfort; nausea; pain or discomfort in arms, jaw, back, or neck; shortness of breath; sweating; or vomiting while you are using this medicine. These may be symptoms of a serious heart problem, including a heart attack.

Tolbutamide can cause low blood sugar. However, this can also occur if you delay or miss a meal or snack, drink alcohol, exercise more than usual, cannot eat because of nausea or vomiting, take certain medicines, or take tolbutamide with another type of diabetes medicine. The symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so you can treat it quickly.

Symptoms of low blood sugar include anxiety; behavior change similar to being drunk; blurred vision; cold sweats; confusion; cool, pale skin; difficulty in thinking; drowsiness; excessive hunger; fast heartbeat; headache (continuing); nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; or unusual tiredness or weakness.

If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes; or drink fruit juice, non-diet soft drink, or sugar dissolved in water. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe or needle, and know how to use it. Members of your household also should know how to use it.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Common side effects of tolbutamide

Some side effects of tolbutamide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Serious side effects of tolbutamide

Along with its needed effects, tolbutamide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tolbutamide:

Get emergency help immediately if any of the following symptoms of overdose occur while taking tolbutamide:

Symptoms of overdose

• anxiety
• blurred vision
• cold sweats
• cool, pale skin
• increased hunger
• nervousness
• nightmares
• shakiness
• slurred speech

For healthcare professionals

Applies to tolbutamide: intravenous powder for injection, oral tablet.

General adverse events

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

Cardiovascular

• Frequency not reported: Increased cardiovascular mortality^[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]

Gastrointestinal

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

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

Metabolic

• Frequency not reported: Hypoglycemia, increased appetite, weight gain

Sulfonylureas:

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

Hypersensitivity

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

Dermatologic

• Frequency not reported: Photosensitivity

Sulfonylureas:

• Frequency not reported: Porphyria cutanea tarda^[Ref]

Other

• Frequency not reported: Tinnitus, alcohol intolerance^[Ref]

Nervous system

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

Hematologic

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

Hepatic

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

Endocrine

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

See also:

Further information

Tolbutamide side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer