Tolbutamide

Name: Tolbutamide

Before taking tolbutamide

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start taking tolbutamide it is important that your doctor knows:

  • If you are pregnant or breast-feeding.
  • If you have any problems with the way your liver works, or if you have any problems with the way your kidneys work.
  • If you have been told you have either porphyria or glucose-6-phosphate dehydrogenase (G6PD) deficiency. These are both rare inherited disorders.
  • If you are taking any other medicines. This includes any medicines which are available to buy without a prescription, as well as herbal and complementary medicines.
  • If you have ever had an allergic reaction to a medicine.

Getting the most from your treatment

  • It is important that you keep your regular doctor's and clinic appointments. This is so your progress can be monitored. You are likely to need regular check-ups with an eye clinic and a foot clinic as well as with your doctor and diabetes clinic.
  • Your doctor may recommend that you test for sugar (glucose) in your blood regularly to check that your diabetes is being controlled. Your doctor or diabetes nurse will show you how to do this.
  • If you have been given advice by your doctor about changes to your diet, stopping smoking or taking regular exercise, it is important for you to follow the advice you have been given.
  • Make sure you know what it feels like if your blood sugar is too low. This is known as hypoglycaemia, or a 'hypo'. The first signs of hypoglycaemia are feeling shaky or anxious, sweating, looking pale, feeling hungry, having a feeling that your heart is pounding (palpitations), and feeling dizzy. If this happens, eat something containing sugar, such as dextrose tablets, or sugary sweets or drinks (non-diet), and then follow this up with a snack such as a sandwich or a banana.
  • Hypoglycaemia can occur in particular if you miss a meal, if you exercise more than usual, if you are ill, or if you drink a lot of alcohol.
  • If you are a driver you should take special care, as your ability to concentrate may be affected if your diabetes is not well controlled. You may be advised to check your blood sugar levels before you travel and to have a snack with you on long journeys.
  • Drivers in the UK may need to inform the Driver and Vehicle Licensing Agency (DVLA) if they experience an episode of severe hypoglycaemia or experience a 'hypo' whilst driving. Ask your doctor for advice. Drivers in other countries should contact the relevant vehicle licensing agency.
  • Check with your doctor before taking up any new physical exercise, as this will have an effect on your blood sugar levels and you may need to check your blood levels more regularly.
  • Drinking alcohol is not advisable with tolbutamide. If you do have a drink, keep well within the recommended alcohol limits, as alcohol will affect the control of your blood sugar.
  • If you get unusually thirsty, pass urine more frequently, and feel very tired then let your doctor know. Your dose of tolbutamide may need adjusting.
  • If you are due to have an operation or dental treatment, you should tell the person carrying out the treatment that you have diabetes and that you are taking tolbutamide.
  • If you buy any medicines, check with a pharmacist that they are suitable for you to take. This is because some medicines may interfere with tolbutamide.
  • Treatment for diabetes is lifelong. Continue to take the tablets unless you are advised otherwise by your doctor.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat, and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Brand names

  • Orinase®

Pregnancy & Lactation

Pregnancy Category: C

Lactation: Controversial, avoid

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of tolbutamide can cause severe hypoglycemia.

Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

What other drugs will affect tolbutamide?

You may be more likely to have hypoglycemia (low blood sugar) if you take tolbutamide with other drugs that can lower blood sugar, such as:

  • exenatide (Byetta);

  • probenecid (Benemid);

  • aspirin or other salicylates (including Pepto Bismol);

  • a blood thinner (warfarin, Coumadin, Jantoven);

  • sulfa drugs (Bactrim, SMZ-TMP, and others);

  • a monoamine oxidase inhibitor (MAOI); or

  • insulin or other oral diabetes medications.

This list is not complete, and many other medicines can increase or decrease the effects of tolbutamide on lowering your blood sugar. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with tolbutamide. Not all possible interactions are listed in this medication guide.

Advice to Patients

  • Importance of informing patients of potential risks and advantages of tolbutamide therapy and of alternative forms of treatment.a

  • Importance of regular testing of blood glucose concentrations and HbA1c.122 a

  • According to manufacturer, patients should test their urine for glucose and acetone ≥3 times daily during insulin withdrawal.a b Report abnormal results to clinician for appropriate adjustments in therapy.a b

  • Importance of hygiene and avoidance of infection.b

  • Advise patients about nature of diabetes mellitus, prevention and detection of complications, and importance of glycemic control.b

  • Risks of hypoglycemia.a Importance of patients and responsible family members understanding symptoms and treatment of hypoglycemic reactions and identifying conditions that predispose to development of such reactions.a

  • Importance of understanding primary and secondary failure to therapy.a

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

  • Importance of informing patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

TOLBUTamide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

500 mg*

TOLBUTamide Tablets (scored)

Mylan

Precautions While Using tolbutamide

It is very important that your doctor check your progress at regular visits to make sure that tolbutamide 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 tolbutamide. 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.

Tolbutamide - Clinical Pharmacology

Actions

Tolbutamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which Tolbutamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood-glucose-lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Some patients who are initially responsive to oral hypoglycemic drugs, including Tolbutamide, may become unresponsive or poorly responsive over time. Alternatively, Tolbutamide may be effective in some patients who have become unresponsive to one or more of the other sulfonylurea drugs.

Pharmacokinetics

When administered orally, Tolbutamide is readily absorbed from the gastrointestinal tract. Absorption is not impaired and glucose lowering and insulin releasing effects are not altered if the drug is taken with food. Detectable levels are present in the plasma within 20 minutes after oral ingestion of a 500 mg Tolbutamide tablet, with peak levels occurring at 3 to 4 hours and only small amounts detectable at 24 hours. The half-life of Tolbutamide is 4.5 to 6.5 hours. As Tolbutamide has no p-amino group, it cannot be acetylated, which is one of the common modes of metabolic degradation for the antibacterial sulfonamides. However, the presence of the p-methyl group renders Tolbutamide susceptible to oxidation, and this appears to be the principal manner of its metabolic degradation in man. The p-methyl group is oxidized to form a carboxyl group, converting Tolbutamide into the totally inactive metabolite 1-butyl-3-p-carboxy-phenylsulfonylurea, which can be recovered in the urine within 24 hours in amounts accounting for up to 75% of the administered dose.

The major Tolbutamide metabolite has been found to have no hypoglycemic or other action when administered orally and IV to both normal and diabetic subjects. This Tolbutamide metabolite is highly soluble over the critical acid range of urinary pH values, and its solubility increases with increase in pH. Because of the marked solubility of the Tolbutamide metabolite, crystalluria does not occur. A second metabolite, 1-butyl-3-(p-hydroxymethyl) phenyl sulfonylurea also occurs to a limited extent. It is an inactive metabolite.

The administration of 3 grams of Tolbutamide to either nondiabetic or Tolbutamide-responsive diabetic subjects will, in both instances, occasion a gradual lowering of blood glucose. Increasing the dose to 6 grams does not usually cause a response which is significantly different from that produced by the 3 gram dose. Following the administration of a 3 gram dose of Tolbutamide solution, non-diabetic fasting adults exhibit a 30% or greater reduction in blood glucose within one hour, following which the blood glucose gradually returns to the fasting level over 6 to 12 hours. Following the administration of a 3 gram dose of Tolbutamide solution, Tolbutamide responsive diabetic patients show a gradually progressive blood glucose lowering effect, the maximal response being reached between 5 to 8 hours after ingestion of a single 3 gram dose. The blood glucose then rises gradually and by the 24th hour has usually returned to pretest levels. The magnitude of the reduction, when expressed in terms of percent of the pretest blood glucose, tends to be similar to the response seen in the nondiabetic subject.

Pronunciation

(tole BYOO ta mide)

Dosage Forms

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

Tablet, Oral:

Generic: 500 mg

Onset of Action

1 hour

Time to Peak

Serum: 3-4 hours

Adverse Reactions

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

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