Chlorpropamide

Diabinese is an oral antidiabetic drug (sulfonylurea) useful in the tratment of NIDDM (Non-Insulin Dependent Diabetes Mellitus) (also called adult - maturity onset diabetes mellitus); and is used in conjunction with a diet low in fat and carbohydrates to control blood glucose levels.
Diabinese is also used in the treatment of mild forms of diabetes insipidus, where it decreases urine production by increasing water reabsorption in the kidneys.
Diabinese stimulates the synthesis and release of endogenous insulin from the beta-cells of pancreatic islet tissue and by promoting the uptake of glucose into body cells. Extra pancreatic effects may also play a part in the action of oral sulfonylureas.

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Chlorpropamide is rapidly absorbed from the gastrointestinal tract, and is extensively bound to plasma proteins (about 90%). It is readily detectable in the blood within one hour, reaching a maximum within two to four hours.
It is metabolised in the liver and excreted in the urine as the unchanged drug, or as hydroxylated or hydrolysed metabolites.
Chlorpropamide has a biological half-life that averages about 36 hours, and within 96 hours, 80 - 90% of a single oral dose will have been excreted. In long-term use, absorption and excretion rates become stabilised, usually in about 5 to 7 days, so preventing accumulation of the drug in the blood.

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Information for Users:

Special Precautions:
You should tell your doctor if:
   You have long-term liver or kidney problems.
   You are allergic to sulfonamide drugs.
   You have thyroid problems.
   You are taking other medications.

Diabinese should should be stored at room temperature, away from heat and light.
As with all drugs, you should follow the instructions provided by your doctor. Diabinese should be taken with breakfast or first main meal unless otherwise directed. A missed dose should should be taken as soon as possible, unless it is almost time for the next dose. Do not take two doses at once.
You should not stop taking Diabinese without first consulting with your doctor.
As Diabinese is prescribed in conjunction with a low fat and carbohydrate diet, users should follow the advice &/or dietary plan provided by the doctor.
Diabinese may cause hypoglycemia (low blood sugar). Signs of hypoglycemia include an increased heart rate, headache, sweating, tremor, increased hunger, changes in vision, nervousness or tiredness. If any of these syptoms are experienced, they should be discussed with a doctor immediately.
Alcohol should be avoided as it may upset diabetic control and react adversely with the drug.
Chlorpropamide may interact with other drugs, enhancing its effects, leading to low blood sugar; and some drugs may increase blood sugar levels, leading to loss of control by Chlorpropamide.

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Chlorpropamide and:
   Pregnancy:
Chlorpropamide is not usually prescribed for pregnant women as it may decrease blood glucose in the fetus and cause birth defects. Insulin is generally used in pregnancy as it gives better control.
   Breast feeding:
Chlorpropamide passes into breast milk, and it is not recommended that a woman breast feed while taking the drug, as it may cause low blood sugar in the baby.
   Infants and Children:
Sulfonylureas are useless in the treatment of IDDM (Insulin Dependent Diabetes Mellitus), although it may be used for diabetes insipidus, where a reduced dose would be prescribed.
   The Elderly:
Elderly diabetics tend to be more sensitive to Chlorpropamide, so increasing the risk of hypoglycemia. Either a reduced dose is used or an alternative antidiabetic drug is prescribed.
   Driving and Hazardous Work:
There is usually no problem with driving or operating machinery, although they must be avoided if any of the symptoms associated with hypoglycemia are experienced.

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Usual Dose:

Chlorpropamide is the longest acting of the oral antidiabetics, and as such need only be taken once a day.
The dosage varies between 100mg per day to 500mg per day as a single morning dose. Most moderately severe, middle-aged stable diabetics are controlled on 250mg daily. Milder diabetics may do well on lower doses; more severe diabetics will need higher doses.

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Drug Interactions:

Numerous drugs may prolong or potentiate the effects of sulfonylureas, increasing the risk of hypoglycemia.
These include drugs that are highly protein-bound, such as non-steroidal anti-inflammatory agents, salicylates, sulphonamides, chloramphenicol, probenecid, coumarins, monomaine oxidase inhibitors and beta-adrenergic blocking agents.
Alcohol may produce a disulfiram-like reaction.
Various drugs can produce hyperglycemia (high blood sugar), leading to loss of control by chlorpropamide.
These include diuretics and thiazides, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and isoniazid.
For a more detailed list of drugs that interact with Chlorpropamide click here.

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Side-Effects

Some side-effects that may go away during treatment include nausea, heartburn, vomiting, a feeling of fullness, itching and rash. If these persist you should consult a doctor.
The most common and most worrying side-effect however is excessive blood-sugar reducion - hypoglycemia.
Other side-effects are not common.

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Hypoglycemia, Hyperglycemia and Adverse Reactions:

   Hypoglycemia:
Severe hypoglycemia may occur with all sulfonylureas, so proper patient selection, dosage and instructions are important.
Renal or hepatic insufficiency can cause elevated levels of the drug, and hepatic insufficiency may also diminish gluconeogenic capacity, both increasing the risk of serious hypoglycemic reaction.
Elderly, malnourished or debilitated patients, and those with adrenal or pituitary insufficiency are particularly susceptible to the effects of glucose-lowering drugs.
Hypoglycemia can be difficult to recognise in the elderly and in those taking beta-blockers.
Hypoglycemia is most likely to occur when caloric intake is deficient, after heavy exercise, after consumption of alcohol, or when more than one glucose-lowering drug is taken.
Because of the long t_½ of Chlorpropamide, patients who become hypoglycemic require careful supervision of the dose and frequent meals for at least 3 to 5 days. Hospitalisation and intavenous glucose drip may be required.
   Hyperglycemia:
When exposed to stress, such as fever, trauma, infection or surgery; or drugs that promote blood glucose, blood glucose levels may be raised, causing a loss of drug control. In such cases, Chlorpropamide may be discontinued and insulin administered.
   Adverse Reactions:Serious adverse reactions with Chlorpropamide are very rare.
      Gastrointestinal Reactions:
Cholestatic jaundice may occur rarely. In such cases, Chlorpropamide should be discontinued.
      Dermatological Reactions
Pruritus has been reported. Other allergic skin reactions, e.g., urticaria and maculopapular eruptions have also been reported.
Skin eruptions, progressing to erythema multiforme and exfoliative dermatitis may rarely be caused.
If skin reactions persist, Chlorpropamide should be discontinued.
      Haematological Reactions:
Leucopenia, agranulocytosis, thrombocytopenia, haemolytic anaemia, aplastic anaemia and pancytopenia.
      Metabolic Reactions:
Hepatic porphyria and disulfiram-like reactions occur rarely.
      Endocrine Reactions:
A reaction identicle to the syndrome of inappropriate ADH (AntiDiuretic Hormone) secretion occurs rarely.
      Other Effects:
Chlorpropamide has been known to affect the eyes, causing drug-induced neuropathy.
Nephrotic syndrome and immune complex glomerulonephrit is associated with Chlorpropamide therapy.
Drug-induced acute liver disease may be associated with Chlorpropamide therapy.

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Overdose:

Medical advice must be sought immediately in all cases. If symptoms of hypoglycemia occur, eat or drink something sugary. Emergency action must be taken if fits or loss of conciousness occur.

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Other Details Concerning Chlorpropamide:

Emergency Procedures:

   Skin Contact with Pure Chemical:
Immediately flood the affected area with water and remove and isolate all affected clothing.
Gently wash all affected skin areas thouroughly with soap and water. If syptoms such as redness or rash develop, see a doctor.
   Inhalation of Chlorpropamide:
Immediately leave the contaminated area and take deep breaths of fresh air.
If symptoms such as wheezing, coughing, shortness of breath, or burning in the mouth, nose or chest develop, see a doctor.
   Eye Contact:
Remove contact lenses if present. Wash eyes with water or saline solution for 20-30 minutes, and see a doctor.
   Ingestion:
Do not induce vomiting.
If victim is concious and not convulsing, give them 1 or 2 glasses of water to dilute the chemical and call a hospital.
If victim is unconcious, ensure airway is open, and transport to hospital immediately.

Spills and Leakage:

Remove all sources of ignition, and then dampen solid spill with 60-70% ethanol. Then transport dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to clear up any remaining material, and wash all affected surfaces with 60-70% ethanol.

Shipping Name (IATA:

CAS N^o. 94-20-2
Hazard class: Susidiary risk
Packing group: Labels required
Special provisions: None

Use in Sport:

The use of Chlorpropamide (Diabinese) is permitted in sports.

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