Medicinal Products

AVANDIA 4 mg

Generic drug of the therapeutic class: Metabolism and nutrition
Active ingredients: Rosiglitazone
laboratory: Smithkline Beecham Plc

Coated tablet
Box of 84
All forms

Indication

Rosiglitazone is indicated for the treatment of type 2 diabetes:
- as monotherapy :
in patients (particularly overweight patients) who are inadequately controlled by diet and exercise and for whom metformin is not appropriate due to contraindications or intolerance.
- Oral dual therapy in combination with:
. metformin, in patients (particularly those overweight) inadequately balanced with metformin monotherapy at maximum tolerated dose.
. a sulphonylurea that is hypoglycaemic only in patients who are intolerant to metformin or for whom metformin is contraindicated and who are insufficiently controlled by a sulphonylurea.
- in oral triple therapy in combination with:
metformin and a sulphonylurea in patients (particularly those who are overweight) who are insufficiently controlled by oral dual therapy (see section cautionary statements and precautions for use).

Dosage AVANDIA 4 mg Film-coated tablet Box of 84

- The clinical trial experience with rosiglitazone is currently limited to three years. The long-term benefits of rosiglitazone treatment have not been demonstrated (see section 5.1).
- Treatment with rosiglitazone may be initiated at a dose of 4 mg per day. This dose may be increased to 8 mg daily after 8 weeks, if better glycemic control is needed. An increase in rosiglitazone dosage to 8 mg / day should be made with caution after a careful clinical evaluation of the patient's risk of developing an adverse effect with fluid retention (see sections cautionary and precautions for use and adverse effects). ).
- Rosiglitazone can be given once or twice daily.
- Rosiglitazone can be taken occasionally or outside of meals.
- Elderly (see section on warnings and precautions for use Fluid retention and heart failure):
No dose adjustment is necessary in the elderly.
- Patients with renal impairment (see section on warnings and precautions for use Fluid retention and heart failure):
No dose adjustment is required in patients with moderate to moderate renal impairment. Data in patients with severe renal impairment (creatinine clearance <30 ml / min) are limited. Therefore rosiglitazone should be administered with caution in these patients.
- Hepatic insufficiency:
Rosiglitazone should not be used in patients with hepatic impairment.
- Child and teenagers:
There is no data on the use of rosiglitazone in patients younger than 10 years of age. Data on rosiglitazone monotherapy in children aged 10 to 17 years are limited (see sections on pharmacodynamic properties and pharmacokinetics). Available data do not demonstrate efficacy in the pediatric population; therefore, the use of rosiglitazone in pediatrics is not recommended.

Against indications

CONTRAINDICATED:
- Administration of rosiglitazone is contraindicated in patients with:
. known hypersensitivity to rosiglitazone or any of the excipients;
. heart failure or a history of heart failure (class I to IV);
. acute coronary syndrome (unstable angina, myocardial infarction with or without ST elevation) (see section on warnings and precautions for use);
. hepatic insufficiency;
. diabetic ketoacidosis or diabetic precoma.
- AVANDIA tablets contain lactose . Therefore, they should not be administered in patients with congenital galactosemia, Lapp lactase deficiency, or glucose-galactose malabsorption.
- Pregnancy: Rosiglitazone has been observed to cross the placental barrier in women and has been detected in fetal tissues.There is no sufficiently relevant information regarding the administration of rosiglitazone in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk in clinic is not known. Rosiglitazone should not be used during pregnancy.
- Breast-feeding: In animals, rosiglitazone has been detected in milk. It is not known if breastfeeding exposes the child to the product. Rosiglitazone should not be used in women who are breastfeeding.
- Patients should be informed of the risk of pregnancy and when a patient wishes to become pregnant or becomes pregnant treatment should be stopped (see section on pregnancy and breastfeeding).
NOT RECOMMENDED :
Children and adolescents: There are no data on the use of rosiglitazone in patients younger than 10 years of age. Data on rosiglitazone monotherapy in children aged 10 to 17 years are limited. Available data do not demonstrate efficacy in the pediatric population; therefore, the use of rosiglitazone in pediatrics is not recommended.

Avandia side effects

CLINICAL STUDY DATA :
- Adverse effects for each treatment are presented below, by organ system and absolute frequency. For dose-related adverse events, the indicated frequency category corresponds to that of the highest dose of rosiglitazone. The different frequency categories do not take into account other factors such as different study durations, patient history and their characteristics at entry into clinical studies. Frequency categories are those observed in clinical studies and may not reflect the frequency of adverse events occurring in daily clinical practice. The frequencies are defined as follows:
very common> = 1/10; frequent> = 1/100, = 1/1000, <1/100.
Table 1 presents the adverse effects identified in the clinical trial population that includes more than 5000 patients treated with rosiglitazone. For each organ system, the adverse effects are presented in the table in order of decreasing frequency for rosiglitazone monotherapy. For each frequency category, adverse effects are presented in order of decreasing severity.
TABLE 1. Frequency of adverse events identified in clinical studies .
ROSIGLITAZONE IN MONOTHERAPY:
- Hematological and lymphatic system disorders:
Frequent : anemia.
- Metabolism and nutrition disorders:
Frequent : hypercholesterolemia (1), hypertriglyceridaemia, hyperlipemia, weight gain, increased appetite.
- Cardiac disorders:
Common : cardiac ischemia (3) *.
- Gastrointestinal disorders:
Common : constipation
- Musculoskeletal and systemic disorders:
Frequent : bone fractures (4).
- General disorders and anomalies at the site of administration:
Frequent : edema.
ROSIGLITAZONE ASSOCIATED WITH METFORMIN:
- Hematological and lymphatic system disorders:
Frequent : anemia.
- Metabolism and nutrition disorders:
Frequent : hypercholesterolemia (1), hyperlipemia, weight gain, hypoglycemia.
- disorders of the nervous system:
Frequent : dizzying sensations *.
- Cardiac disorders:
Common : cardiac ischemia (3) *.
- Gastrointestinal disorders:
Common : constipation
- General disorders and anomalies at the site of administration:
Frequent : edema.
ROSIGLITAZONE ASSOCIATED WITH HYPOGLYCEMIC SULFAMIDE:
- Hematological and lymphatic system disorders:
Frequent : anemia, leukopenia, thrombocytopenia.
- Metabolism and nutrition disorders:
. Frequent : hypercholesterolemia (1), hypertriglyceridaemia, hyperlipemia, weight gain.
. Uncommon : increased appetite.
. Very common : hypoglycaemia.
- disorders of the nervous system:
Frequent : dizzying sensations *.
- Cardiac disorders:
Common : heart failure (2), cardiac ischemia (3) *.
- Gastrointestinal disorders:
Common : constipation
- General disorders and anomalies at the site of administration:
Very common : edema.
ROSIGLITAZONE ASSOCIATED WITH METFORMIN AND A HYPOGLYCEMIC SULFAMIDE:
- Hematological and lymphatic system disorders:
Common : anemia, granulocytopenia.
- Metabolism and nutrition disorders:
. Frequent : hypercholesterolemia (1), hyperlipemia, weight gain.
. Very common : hypoglycaemia.
- disorders of the nervous system:
Frequent : headache *.
- Cardiac disorders:
Common : heart failure (2), cardiac ischemia (3) *.
- Gastrointestinal disorders:
Common : constipation
- Musculoskeletal and systemic disorders:
Frequent : myalgia *.
- General disorders and anomalies at the site of administration:
Very common : edema.
* These side effects were noted as "common" in the placebo group of clinical studies.
(1) Hypercholesterolemia has been reported up to 5.3% of patients treated with rosiglitazone (as monotherapy, dual therapy or oral triple therapy). The increase in total cholesterol involved an increase in the LDLc and HDLc fractions, but the total cholesterol / HDLc ratio remained stable or improved in the long-term studies. Overall, these effects were generally mild to moderate and usually did not necessitate discontinuation of treatment.
(2) An increase in the incidence of heart failure was observed when rosiglitazone was associated with treatment with a sulphonylurea (whether dual therapy or triple therapy); this increase is higher with a dose of 8 mg rosiglitazone than with a dose of 4 mg rosiglitazone (total daily dose). The incidence of heart failure in triple oral therapy was 1.4% in the main double-blind study compared to 0.4% for the combination metformin and sulphonylurea. The incidence of heart failure in combination with insulin (rosiglitazone being added to insulin treatment already in progress) was 2.4%, compared with insulin alone, 1.1%.
In addition, in patients with congestive heart failure class I-II a 1-year placebo-controlled study showed worsening or possible worsening of heart failure in 6.4% of patients treated with rosiglitazone compared to 3.5% with placebo.
(3) A retrospective analysis of data from 42 short-term pooled clinical studies found that the overall incidence of events specifically associated with cardiac ischemia was higher in therapeutic strategies including rosiglitazone, which was 1.99% versus 1%., 51% [Hazard ratio 1.31 (95% confidence interval 1.01-1.70)] with active comparators and placebo. This risk was increased when rosiglitazone was combined with insulin therapy and in patients receiving nitrate derivatives for known ischemic heart disease.
- A wide observational study where the patient population was well distributed at entry to the study showed that the incidence of composite myocardial infarction and coronary revascularization was 17.46 events per 1000 person-years for treatment. medications including rosiglitazone and 17.57 events per 1000 person-years for other antidiabetic agents [Hazard ratio 0.93 (95% confidence interval 0.8 - 1.10)]. Three large, prospective, randomized controlled long-term (average duration of 41 months; 14067 patients) clinical trials comparing rosiglitazone with other oral antidiabetic drugs or placebo did not confirm or rule out this risk. Overall, the available data on the risk of myocardial ischemia are inconclusive.
(4) In a long-term (4 to 6 years) randomized monotherapy study in patients with newly diagnosed type 2 diabetes, an increase in the incidence of bone fractures was observed after the first year of treatment in female patients receiving rosiglitazone (9.3%, 2.7 patients per 100 patients-year) vs metformin (5.1%, 1.5 patients per 100 patients-year) or glyburide / glibenclamide (3.5 %, 1.3 patients per 100 patient-years). This increased risk of fracture was found throughout the study. The majority of fractures in women treated with rosiglitazone were seen in the foot, hand and arm.
- In double-blind clinical trials with rosiglitazone, the incidence of elevation of ALT 3-fold higher than the high value of normal was similar to placebo (0.2%) and lower than that observed with comparators ( 0.5% metformin / sulfonylurea). The incidence of all adverse events related to hepatic or biliary systems was less than 1.5% in the treatment groups and comparable to placebo.
POST-MARKETING DATA :
In addition to the adverse effects identified in the clinical studies, the adverse reactions presented in Table 2 were identified after the marketing of rosiglitazone. The frequencies are defined as follows: rare> = 1/10000, <1/1000; and very rare <1/10000 including isolated notifications.
TABLE 2: Frequency of adverse effects identified after marketing of rosiglitazone .
- Metabolism and nutrition disorders:
Very rare : rapid and excessive weight gain.
- Immune system disorders (see skin and subcutaneous tissue disorders):
Very rare : anaphylactic reaction.
- Eye disorders:
Rare : Macular edema.
- Cardiac disorders:
Rare : congestive heart failure / pulmonary edema.
- Hepatobiliary disorders:
Rare : impaired liver function, mainly evidenced by elevated liver enzymes (5).
- Skin and subcutaneous tissue disorders (see Immune system disorders):
Very rare : angioedema, skin reactions (eg urticaria, pruritus, rash).
(5) Rare cases of elevated liver enzymes and hepatocellular dysfunction have been reported. In very rare cases, a fatal evolution has been reported.

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