Avandaryl Side Effects

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Avandaryl Side Effects
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Generic name: glimepiride/rosiglitazone

Please note - some side effects for Avandaryl may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Avandaryl - for the consumer

Avandaryl

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Avandaryl:

Dizziness; headache; upper respiratory tract infection; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Avandaryl:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; confusion; fainting; fever, chills, or sore throat; increased or painful urination; menstrual changes; numbness of an arm or a leg; sudden severe headache, vomiting, or dizziness; symptoms of heart failure (eg, shortness of breath; sudden unexplained weight gain; swelling of the hands, ankles, or feet); symptoms of liver problems (eg, dark urine, severe or persistent nausea, stomach pain, unexplained vomiting or loss of appetite, yellowing of the skin or eyes); symptoms of low blood sugar (eg, anxiety, chills, dizziness or drowsiness, fast heartbeat, headache, increased hunger, increased sweating, tremors); unusual bone pain; unusual bruising or bleeding; unusual tiredness or weakness; vision changes or persistent blurred vision.


For the professional

Avandaryl

Adverse events occurring at a frequency of ≥5% in any treatment group in the 28-week double-blind trial of Avandaryl in drug-naïve patients with type 2 diabetes mellitus are presented in Table 6. Patients in this trial were started on Avandaryl 4 mg/1 mg, rosiglitazone 4 mg, or glimepiride 1 mg. Doses could be increased at 4-week intervals to reach a maximum total daily dose of either 4 mg/4 mg or 8 mg/4 mg for Avandaryl, 8 mg for rosiglitazone monotherapy or 4 mg for glimepiride monotherapy.

Table 6. Adverse Events (≥5% in Any Treatment Group) Reported by Drug-Naïve Patients in a 28-Week Double-Blind Clinical Trial of Avandaryl

*As documented by symptoms and a fingerstick blood glucose measurement of <50 mg/dL.

Hypoglycemia was reported to be generally mild to moderate in intensity and none of the reported events of hypoglycemia resulted in withdrawal from the study. Hypoglycemia requiring parenteral treatment (i.e., intravenous glucose or glucagon injection) was observed in 3 (0.7%) patients treated with Avandaryl.

Edema was reported by 3.2% of patients on Avandaryl, 3.0% on rosiglitazone alone, and 2.3% on glimepiride alone.

Congestive heart failure was observed in 1 (0.2%) patient treated with Avandaryl and in 1 (0.4%) patient treated with rosiglitazone monotherapy.

Studies utilizing rosiglitazone in combination with a sulfonylurea provide support for the use of Avandaryl. Adverse event data from these trials, in addition to adverse events reported with the use of rosiglitazone and glimepiride as monotherapy, are presented below.
Rosiglitazone

The most common adverse experiences with rosiglitazone monotherapy (&#8805;5%) were upper respiratory tract infection, injury, and headache. Overall, the types of adverse experiences reported when rosiglitazone was added to a sulfonylurea were similar to those during monotherapy with rosiglitazone. In controlled combination therapy studies with sulfonylureas, mild to moderate hypoglycemic symptoms, which appear to be dose related, were reported. Few patients were withdrawn for hypoglycemia (<1%) and few episodes of hypoglycemia were considered to be severe (<1%).

Events of anemia and edema tended to be reported more frequently at higher doses, and were generally mild to moderate in severity and usually did not require discontinuation of treatment with rosiglitazone.

Edema was reported by 4.8% of patients receiving rosiglitazone compared to 1.3% on placebo, and 1.0% on sulfonylurea monotherapy. The reporting rate of edema was higher for rosiglitazone 8 mg added to a sulfonylurea (12.4%) compared to other combinations, with the exception of insulin. Anemia was reported by 1.9% of patients receiving rosiglitazone compared to 0.7% on placebo, 0.6% on sulfonylurea monotherapy, and 2.3% on rosiglitazone in combination with a sulfonylurea. Overall, the types of adverse experiences reported when rosiglitazone was added to a sulfonylurea were similar to those during monotherapy with rosiglitazone.

In 26-week double-blind, fixed-dose studies, edema was reported with higher frequency in the rosiglitazone plus insulin combination trials (insulin, 5.4%; and rosiglitazone in combination with insulin, 14.7%). Reports of new onset or exacerbation of congestive heart failure occurred at rates of 1% for insulin alone, and 2% (4 mg) and 3% (8 mg) for insulin in combination with rosiglitazone.

In postmarketing experience in patients receiving thiazolidinedione therapy, serious adverse events potentially related to volume expansion (e.g., congestive heart failure, pulmonary edema with or without a fatal outcome, and pleural effusions) have been reported.

In postmarketing experience with rosiglitazone, rash, pruritus, urticaria, angioedema and anaphylactic reaction have been reported rarely.

Postmarketing reports of new onset or worsening diabetic macular edema with decreased visual acuity have also been received.

Glimepiride

Hypoglycemia

The incidence of hypoglycemia with glimepiride, as documented by blood glucose values <60 mg/dL, ranged from 0.9% to 1.7% in 2 large, well-controlled, 1-year studies. In patients treated with glimepiride in US placebo-controlled trials (n = 746), adverse events, other than hypoglycemia, considered to be possibly or probably related to study drug that occurred in more than 1% of patients included dizziness (1.7%), asthenia (1.6%), headache (1.5%), and nausea (1.1%).
Gastrointestinal Reactions

Vomiting, gastrointestinal pain, and diarrhea have been reported, but the incidence in placebo-controlled trials was less than 1%. In rare cases, there may be an elevation of liver enzyme levels. In isolated instances, impairment of liver function (e.g., with cholestasis and jaundice), as well as hepatitis, which may also lead to liver failure have been reported with sulfonylureas, including glimepiride.

Dermatologic Reactions

Allergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occur in less than 1% of treated patients. These may be transient and may disappear despite continued use of glimepiride. If those hypersensitivity reactions persist or worsen, the drug should be discontinued. Porphyria cutanea tarda, photosensitivity reactions, and allergic vasculitis have been reported with sulfonylureas, including glimepiride.
Hematologic Reactions

Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas, including glimepiride.

Metabolic Reactions

Hepatic porphyria reactions and disulfiram-like reactions have been reported with sulfonylureas, including glimepiride. Cases of hyponatremia have been reported with glimepiride and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increaserelease of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, including glimepiride, and it has been suggested that certain sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.

Other Reactions

Changes in accommodation and/or blurred vision may occur with the use of glimepiride. This is thought to be due to changes in blood glucose, and may be more pronounced when treatment is initiated. This condition is also seen in untreated diabetic patients, and may actually be reduced by treatment. In placebo-controlled trials of glimepiride, the incidence of blurred vision was placebo, 0.7%, and glimepiride, 0.4%.

Human Ophthalmology Data

Ophthalmic examinations were carried out in more than 500 subjects during long-term studies of glimepiride using the methodology of Taylor and West and Laties et al. No significant differences were seen between glimepiride and glyburide in the number of subjects with clinically important changes in visual acuity, intraocular tension, or in any of the 5 lens-related variables examined. Ophthalmic examinations were carried out during long-term studies using the method of Chylack et al. No significant or clinically meaningful differences were seen between glimepiride and glipizide with respect to cataract progression by subjective LOCS II grading and objective image analysis systems, visual acuity, intraocular pressure, and general ophthalmic examination.
Pediatric Use

Safety and effectiveness of Avandaryl in pediatric patients have not been established. Avandaryl and its individual components, rosiglitazone and glimepiride, are not indicated for use in pediatric patients.

By body system

Endocrine side effects
Endocrine side effects have included hypoglycemia.

Cardiovascular side effects
Cardiovascular side effects have included edema and congestive heart failure.

Respiratory side effects
Respiratory side effects have included upper respiratory tract infection, pulmonary edema and pleural effusions.

Nervous system side effects
Nervous system side effects have included dizziness, asthenia, and headache.

General side effects
General side effects have included injury.

Gastrointestinal side effects
Gastrointestinal side effects have included nausea, vomiting, gastrointestinal pain, and diarrhea,

Hepatic side effects
Hepatic side effects have included elevations of liver enzyme levels, cholestasis, jaundice, and hepatitis.

Hypersensitivity side effects
Hypersensitivity side effects have included angioedema and urticaria.

Dermatologic side effects
Dermatologic side effects have included pruritus, erythema, urticaria, porphyria cutanea tarda, photosensitivity reactions, allergic vasculitis, and morbilliform or maculopapular eruptions.

Hematologic side effects
Hematologic side effects have included leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia.

Metabolic side effects
Metabolic side effects have included hepatic porphyria reactions, disulfiram-like reactions, and hyponatremia. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported.

Ocular side effects
Ocular side effects have included changes in accommodation and blurred vision. New onset or worsening (diabetic) macular edema with decreased visual acuity has been reported very rarely in postmarketing experience with rosiglitazone. In some cases, symptoms improved following discontinuation of rosiglitazone. Physicians should consider the possibility of macular edema if a patient reports decreased visual acuity.

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