ADVERSE REACTIONS
In U.S. controlled studies the frequency of serious adverse experiences reported was very low and causal relationship has not been established.
The 580 patients from 31 to 87 years of age who received GLUCOTROL XL Extended Release Tablets in doses from 5 mg to 60 mg in both controlled and open trials were included in the evaluation of adverse experiences. All adverse experiences reported were tabulated independently of their possible causal relation to medication.
Hypoglycemia
See
PRECAUTIONS
and
OVERDOSAGE
sections.
Only 3.4% of patients receiving GLUCOTROL XL Extended Release Tablets had hypoglycemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia. In a comparative efficacy study of GLUCOTROL XL and Glucotrol, hypoglycemia occurred rarely with an incidence of less than 1% with both drugs.
In double-blind, placebo-controlled studies the adverse experiences reported with an incidence of 3% or more in GLUCOTROL XL-treated patients include:
|
GLUCOTROL XL (%) |
Placebo (%) |
|
(N=278) |
(N=69) |
| Adverse Effect |
|
|
| Asthenia |
10.1 |
13.0 |
| Headache |
8.6 |
8.7 |
| Dizziness |
6.8 |
5.8 |
| Nervousness |
3.6 |
2.9 |
| Tremor |
3.6 |
0.0 |
| Diarrhea |
5.4 |
0.0 |
| Flatulence |
3.2 |
1.4 |
The following adverse experiences occurred with an incidence of less than 3% in GLUCOTROL XL-treated patients:
-
Body as a whole–pain
-
Nervous system–insomnia, paresthesia, anxiety, depression and hypesthesia
-
Gastrointestinal–nausea, dyspepsia, constipation and vomiting
-
Metabolic–hypoglycemia
-
Musculoskeletal–arthralgia, leg cramps and myalgia
-
Cardiovascular–syncope
-
Skin–sweating and pruritus
-
Respiratory–rhinitis
-
Special senses–blurred vision
-
Urogenital–polyuria
Other adverse experiences occurred with an incidence of less than 1% in GLUCOTROL XL-treated patients:
-
Body as a whole–chills
-
Nervous system–hypertonia, confusion, vertigo, somnolence, gait abnormality and decreased libido
-
Gastrointestinal–anorexia and trace blood in stool
-
Metabolic–thirst and edema
-
Cardiovascular–arrhythmia, migraine, flushing and hypertension
-
Skin–rash and urticaria
-
Respiratory–pharyngitis and dyspnea
-
Special senses–pain in the eye, conjunctivitis and retinal hemorrhage
-
Urogenital–dysuria
Although these adverse experiences occurred in patients treated with GLUCOTROL XL, a causal relationship to the medication has not been established in all cases.
There have been rare reports of gastrointestinal irritation and gastrointestinal bleeding with use of another drug in this non-deformable sustained release formulation, although causal relationship to the drug is uncertain.
Post-Marketing Experience
The following adverse events have been reported in post-marketing surveillance:
Gastrointestinal
abdominal pain
Hepatobiliary
Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; GLUCOTROL XL should be discontinued if this occurs.
The following are adverse experiences reported with immediate release glipizide and other sulfonylureas, but have not been observed with GLUCOTROL XL:
Hematologic
Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see
PRECAUTIONS), aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic
Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas. In the mouse, glipizide pretreatment did not cause an accumulation of acetaldehyde after ethanol administration. Clinical experience to date has shown that glipizide has an extremely low incidence of disulfiram-like alcohol reactions.
Endocrine Reactions
Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with glipizide and other sulfonylureas.
Laboratory Tests
The pattern of laboratory test abnormalities observed with glipizide was similar to that for other sulfonylureas. Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN and creatinine were noted. One case of jaundice was reported. The relationship of these abnormalities to glipizide is uncertain, and they have rarely been associated with clinical symptoms.
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