Chlorpropamide Side Effects

Some side effects of chlorpropamide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to chlorpropamide: oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking chlorpropamide: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Hypoglycemia, or low blood sugar, is the most common side effect of chlorpropamide. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, trouble concentrating, rapid breathing, fast heartbeat, fainting, or seizure (severe hypoglycemia can be fatal). Carry hard candy or glucose tablets with you in case you have low blood sugar.

Stop taking chlorpropamide and call your doctor at once if you have a serious side effect such as:

• easy bruising or bleeding, unusual weakness;

• pale skin, fever, confusion;

• trouble concentrating, memory problems, feeling unsteady, hallucinations;

• feeling light-headed, fainting;

• nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• throbbing headache, sweating, severe nausea, trouble breathing, fast or pounding heartbeats, blurred vision, spinning sensation; or

• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects of chlorpropamide may include:

• mild nausea, vomiting, diarrhea;

• mild hunger; or

• mild skin rash, redness, or itching.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to chlorpropamide: oral tablet

Metabolic

Metabolic side effects have included hypoglycemia, an extension of chlorpropamide's pharmacologic effects. Hypoglycemia may be severe and protracted. In addition, hyponatremia, hepatic porphyria, and disulfiram-like reactions are reported.

Hypoglycemia, an extension of chlorpropamide's pharmacologic effects, may be severe, protracted, refractory to glucose infusion, and, in some cases, may require diazoxide. Hypoglycemia may present as coma or disturbed consciousness. Other signs of hypoglycemia include tachycardia, tremor, and increased sweating.

Patients with renal dysfunction, liver disease, adrenal or pituitary insufficiency, or congestive heart failure may be at increased risk for hypoglycemia, as are those who are elderly, debilitated, or malnourished. In addition, acute illness, lack of adherence to diet, ethanol ingestion, or strenuous exercise may precipitate hypoglycemia.

A syndrome similar to the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), with hyponatremia, low serum osmolality, and high urine osmolality, is reported with chlorpropamide (1% to 4%). This syndrome appears to be more common in the elderly, in women, in patients with an underlying edematous disorder, and in patients receiving 500 mg or more of chlorpropamide per day.

Patients with renal dysfunction may be at increased risk for hypoglycemia as chlorpropamide elimination, as well as gluconeogenesis and glycogenolysis, may be impaired.

Elderly patients with renal dysfunction and liver disease may be at increased risk for hypoglycemia as such patients are particularly sensitive to the hypoglycemic effects of the oral sulfonylureas and chlorpropamide metabolism and elimination, as well as hepatic gluconeogenesis and glycogenolysis, may be impaired .

Dermatologic

Dermatologic side effects have included pruritus (3%), photosensitivity, porphyria cutanea tarda, and rare cases of Stevens-Johnson syndrome. Skin eruptions rarely progressing to erythema multiforme and exfoliative dermatitis have also been reported.

Facial skin flushing has been reported in 10% to 15% of patients, and may have been dose-related. Alcohol appeared to potentiate this effect.

Hypersensitivity

Hypersensitivity side effects have included rash and eosinophilia which may have been associated with hepatitis, glomerulonephritis, interstitial nephritis, and hemolytic anemia. In addition, there are rare case reports suggestive of a chlorpropamide-induced eosinophilic pneumonia.

Hypersensitivity reactions usually respond to steroid therapy and drug withdrawal.

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, diarrhea, and anorexia.

Hepatic

In patients with liver disease, frequent monitoring of liver function tests is recommended during chlorpropamide administration.

Hepatic side effects have included hepatitis which presented as cholestatic jaundice (0.5%), fever, and pruritus, and was thought to be due to hypersensitivity to chlorpropamide. This typically presents within 2 to 5 weeks after initiating chlorpropamide therapy.

Renal

Renal side effects have been rare, and have included case reports of proteinuria, mild renal insufficiency, hypersensitivity glomerulonephritis, and interstitial nephritis.

The case reports of glomerulonephritis and interstitial nephritis are associated with other stigmata of hypersensitivity to chlorpropamide, such as rash, eosinophilia, and fever.

In patients with renal insufficiency, frequent monitoring of the kidney function is recommended during chlorpropamide administration.

Hematologic

Hematological side effects have included leukopenia, thrombocytopenia, and anemia. Pure white cell and pure red cell aplasias, hemolytic anemia, and isolated thrombocytopenia have also been reported and were thought to be due to an immune complex-mediated process. Chlorpropamide has induced a photohemolysis in vitro, through a photodynamic mechanism mediated with oxygen.

Ocular

Ocular side effects have been rare and have included a case report in which optic neuropathy and loss of vision were definitely associated with chlorpropamide administration.

Although extremely rare, optic neuropathy should be considered in diabetic patients on chlorpropamide therapy who complain of vision disturbances.

Cardiovascular

Cardiovascular side effects have included elevations in systolic blood pressure.

A retrospective analysis of 22 type II diabetic patients switched from insulin to chlorpropamide revealed a significant increase in systolic blood pressures after initiation of chlorpropamide therapy. Diastolic pressures were not significantly affected. Chlorpropamide-induced hypertension occurred more frequently in black patients, although the study population was too small to adequately evaluate this effect.

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