The following serious adverse reactions are discussed in more detail below and elsewhere in the labeling:
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, 580 patients from 31 to 87 years of age received GLUCOTROL XL in doses from 5 mg to 60 mg in both controlled and open trials. The dosages above 20 mg are not recommended dosages. In these trials, approximately 180 patients were treated with GLUCOTROL XL for at least 6 months.
Table 1 summarizes the incidence of adverse reactions, other than hypoglycemia, that were reported in pooled double-blind, placebo-controlled trials in ≥3% of GLUCOTROL XL-treated patients and more commonly than in patients who received placebo.
Table 1: Incidence (%) of Adverse Reactions Reported in ≥3% of Patients Treated in Placebo-Controlled Clinical Trials and More Commonly in Patients Treated with GLUCOTROL XL (Excluding Hypoglycemia) | GLUCOTROL XL (%)
(N=278) | Placebo (%)
(N=69) |
|---|
| Adverse Effect | | |
|---|
Dizziness | 6.8 | 5.8 |
Diarrhea | 5.4 | 0.0 |
Nervousness | 3.6 | 2.9 |
Tremor | 3.6 | 0.0 |
Flatulence | 3.2 | 1.4 |
Hypoglycemia
Of the 580 patients that received GLUCOTROL XL in clinical trials, 3.4% had hypoglycemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia and 2.6% of patients discontinued for this reason. Hypoglycemia was not reported for any placebo patients.
Gastrointestinal Reactions
In clinical trials, the incidence of gastrointestinal (GI) side effects (nausea, vomiting, constipation, dyspepsia), occurred in less than 3% of GLUCOTROL XL-treated patients and were more common in GLUCOTROL XL-treated patients than those receiving placebo.
Dermatologic Reactions
In clinical trials, allergic skin reactions, i.e., urticaria occurred in less than 1.5% of treated patients and were more common in GLUCOTROL XL treated patients than those receiving placebo. These may be transient and may disappear despite continued use of glipizide XL; if skin reactions persist, the drug should be discontinued.
Laboratory Tests
Mild to moderate elevations of ALT, LDH, alkaline phosphatase, BUN and creatinine have been noted. The relationship of these abnormalities to glipizide is uncertain.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of GLUCOTROL XL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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- Abdominal pain
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- Cholestatic and hepatocellular forms of liver injury accompanied by jaundice
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- Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia [see Warnings and Precautions (5.2)], aplastic anemia, pancytopenia
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- Hepatic porphyria and disulfiram-like reactions
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- Hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion
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- Rash
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- There have been reports of gastrointestinal irritation and gastrointestinal bleeding with use of another drug with this non-dissolvable extended release formulation.