Glucovance Adverse Reactions

GLUCOVANCE in Clinical Trials: In double-blind clinical trials involving GLUCOVANCE, a total of 642 patients received GLUCOVANCE, 312 received metformin therapy, 324 received glibenclamide therapy, and 161 received placebo. The percent of patients reporting events and types of adverse events reported in clinical trials of GLUCOVANCE (all strengths) as initial therapy and second-line therapy are listed in Table 1. (See Table 1.)

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Disulfiram-like reactions have very rarely been reported in patients treated with glibenclamide tablets.
Hypoglycemia: In controlled clinical trials of GLUCOVANCE (Metformin HCl and Glibenclamide Tablets) there were no hypoglycemic episodes requiring medical intervention and/or pharmacologic therapy: all events were managed by the patients. The incidence of reported symptoms of hypoglycemia (such as dizziness, shakiness, sweating, and hunger), in the initial therapy trial of GLUCOVANCE are summarized in Table 2. The frequency of hypoglycemic symptoms in patients treated with GLUCOVANCE 250 mg/1.25 mg was highest in patients with a baseline HbA_1c <7%, lower in those with a baseline HbA_1c of between 7 and 8%, and was comparable to placebo and metformin in those with a baseline HbA_1c >8%. For patients with a baseline HbA_1c between 8% and 11 % treated with GLUCOVANCE 500mg/2.5 mg as initial therapy, the frequency of hypoglycemic symptoms was 30-35%. As second-line therapy in patients inadequately controlled on sulfonylurea alone, approximately 6.8% of all patients treated with GLUCOVANCE experienced hypoglycemic symptoms. (See PRECAUTIONS.)
Gastrointestinal Reactions: The incidence of GI side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in Table 2. Across all GLUCOVANCE trials, GI symptoms were the most common adverse events with GLUCOVANCE and were more frequent at higher dose levels. In controlled trials, <2% of patients discontinued GLUCOVANCE therapy due to GI adverse events. (See Table 2.)

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Post Marketing Surveillance: The following undesirable effects may occur under treatment with GLUCOVANCE. Frequencies are defined as follows: very common: ≥1/10; common ≥1/100, <1/10; uncommon: ≥1/1,000, <1/100; rare ≥1/10,000, <1/1,000; very rare <1/10,000 not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Investigations: Uncommon: Average to moderate elevations in serum urea and creatinine concentrations.
Very rare: Hyponatremia.
Blood and lymphatic system disorders: These are reversible upon treatment discontinuation.
Rare: Leukopenia, thrombocytopenia.
Very rare: Agranulocytosis, haemolytic anaemia, bone marrow aplasia and pancytopenia.
Nervous system disorders: Common: Taste disturbance.
Eye disorders: Transient visual disturbances may occur at the start of treatment due to a decrease in glycaemia levels.
Gastrointestinal disorders: Very common: Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. These undesirable effects occur more frequently during treatment initiation and resolve spontaneously in most cases. To prevent them, it is recommended that GLUCOVANCE be taken in 2 or 3 daily doses. A slow increase of the dose may also improve gastrointestinal tolerability.
Skin and subcutaneous tissue disorders: Rare: Skin reactions such as pruritus, urticaria, maculopapular rash.
Very rare: Cutaneous or visceral allergic angiitis, erythema multiforme, exfoliative dermatitis, photosensitization, urticaria evolving to shock.
A cross reactivity to sulphonamide(s) and their derivatives may occur.
Metabolism and nutrition disorders: Hypoglycaemia (see PRECAUTIONS).
Common: Vitamin B12 deficiency, consideration of such aetiology is recommended if a patient presents with megaloblastic anaemia (see PRECAUTIONS). Therefore, serum B₁₂ levels should be appropriately monitored or periodic parenteral B₁₂ supplementation considered.
Uncommon: Crises of hepatic porphyria and porphyria cutanea.
Very rare: Lactic acidosis (see WARNINGS).
Disulfiram-like reaction with alcohol intake.
Hepatobiliary disorders: Very rare: Liver function test abnormalities or hepatitis requiring treatment discontinuation.