Metformin

Glumetza

1GM, 500MG tablet, extended releaseVereinigte StaatenNicht im HandelZugelassen am 3. Juni 2005

Inhalt auf Englisch

Anwendungsgebiete

Metformin Hydrochloride Extended-Release Tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Metformin Hydrochloride Extended-Release Tablets are a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 )

Gegenanzeigen

Metformin Hydrochloride Extended-Release Tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/minute/1.73 m 2 ) [see Warnings and Precautions ( 5.1 )] . Known hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment: (eGFR below 30 mL/minute/1.73 m 2 ) ( 4 , 5.1 ) Known hypersensitivity to metformin ( 4 ) Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma ( 4 )

Warnhinweise und Vorsichtsmaßnahmen

Lactic Acidosis : See boxed warning. ( 5.1 ) Vitamin B 12 Deficiency : Metformin may lower vitamin B 12 levels. Monitor hematological parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. ( 5.2 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues : Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required.

( 5.3 )

5.1Lactic Acidosis

There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels were generally >5 mcg/mL.

Anwendungsgebiete

Gegenanzeigen

Warnhinweise und Vorsichtsmaßnahmen

( 5.3 )

5.1Lactic Acidosis

Wechselwirkungen

Table 2 presents clinically significant drug interactions with Metformin Hydrochloride Extended-Release Tablets. Table 2: Clinically Significant Drug Interactions with Metformin Hydrochloride Extended-Release Tablets Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with Metformin Hydrochloride Extended-Release Tablets may increase the risk for lactic acidosis.

Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide. Drugs that Reduce Metformin Hydrochloride Extended-Release Tablets Clearance Clinical Impact: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology ( 12.3 )].

Intervention: Consider the benefits and risks of concomitant use with Metformin Hydrochloride Extended-Release Tablets. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving Metformin Hydrochloride Extended-Release Tablets. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of Metformin Hydrochloride Extended-Release Tablets with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia.

Intervention: Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin. Drugs Affecting Glycemic Control Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. Intervention: When such drugs are administered to a patient receiving Metformin Hydrochloride Extended-Release Tablets, observe the patient closely for loss of blood glucose control.

When such drugs are withdrawn from a patient receiving Metformin Hydrochloride Extended-Release Tablets, observe the patient closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. Carbonic anhydrase inhibitors may increase risk of lactic acidosis.

Consider more frequent monitoring. ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use. ( 7 ) Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake. ( 7 )

Schwangerschaft und Stillzeit

8.1Pregnancy Risk Summary

Limited data with Metformin Hydrochloride Extended-Release Tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations] .

No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 3 and 1 times, respectively, a 2,000 mg clinical dose, based on body surface area [see Data] . The estimated background risk of major birth defects is 6–10% in women with pregestational diabetes mellitus with an HbA1c >7 and has been reported to be as high as 20–25% in women with an HbA1c >10.

The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications.

Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups.

Animal Data Metformin HCl was not teratogenic or embyrolethal when administered to rats prior to pregnancy through the period of organogenesis at doses up to 900 mg/kg, or when administered to rabbits during the period of organogenesis at doses up to 90 mg/kg.

Nebenwirkungen

The following adverse reactions are discussed in more detail in other sections of the labeling: Lactic Acidosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] Vitamin B 12 Deficiency [see Warnings and Precautions ( 5.2 )] Hypoglycemia [see Warnings and Precautions ( 5.3 )] Adverse reactions occurring >5% in Metformin Hydrochloride Extended-Release Tablets clinical trials: hypoglycemia, diarrhea, and nausea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 conducted in the U.S., over 1,000 patients with type 2 diabetes mellitus have been treated with Metformin Hydrochloride Extended-Release Tablets 1,500 to 2,000 mg/day in active-controlled and placebo-controlled studies with the 500 mg dosage form.

In the add-on to sulfonylurea study, patients receiving background glyburide therapy were randomized to receive add-on treatment of either one of three different regimens of Metformin Hydrochloride Extended-Release Tablets or placebo. In total, 431 patients received Metformin Hydrochloride Extended-Release Tablets and glyburide and 144 patients received placebo and glyburide. Adverse reactions reported in greater than 5% of patients treated with Metformin Hydrochloride Extended-Release Tablets that were more common in the combined Metformin Hydrochloride Extended-Release Tablets and glyburide group than in the placebo and glyburide group are shown in Table 1.

In 0.7% of patients treated with Metformin Hydrochloride Extended-Release Tablets and glyburide, diarrhea was responsible for discontinuation of study medication compared to no patients in the placebo and glyburide group. Table 1: Adverse Reactions Reported by >5% Adverse reactions that were more common in the Metformin Hydrochloride Extended-Release Tablets-treated than in the placebo-treated patients. of Patients for the Combined Metformin Hydrochloride Extended-Release Tablets Groups Versus Placebo Group Adverse Reaction Metformin Hydrochloride Extended-Release Tablets + Glyburide (n=431) Placebo + Glyburide (n=144) Hypoglycemia 14% 5% Diarrhea 13% 6% Nausea 7% 4% Laboratory Tests Vitamin B 12 Concentrations In clinical trials of 29-week duration with metformin HCl tablets, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients.

6.2Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Metformin Hydrochloride Extended-Release Tablets. 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. Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.

Packung	Code	Status
METFORMIN HYDROCHLORIDE 1GM	NDA021748-002	Discontinued
METFORMIN HYDROCHLORIDE 500MG	NDA021748-001	Discontinued

Glumetza

Anwendungsgebiete

Gegenanzeigen

Warnhinweise und Vorsichtsmaßnahmen

5.1Lactic Acidosis

Zwei Arzneimittel in einer Frage?

Glumetza

Anwendungsgebiete

Gegenanzeigen

Warnhinweise und Vorsichtsmaßnahmen

5.1Lactic Acidosis

Zwei Arzneimittel in einer Frage?

5.2Vitamin B 12 Deficiency

5.3Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin

5.4Macrovascular Outcomes

Wechselwirkungen

Schwangerschaft und Stillzeit

8.1Pregnancy Risk Summary

Nebenwirkungen

6.1Clinical Trials Experience

6.2Postmarketing Experience

In anderen Ländern

Packungen

Dokumente

Quellen und Lizenzen

Auf einen Blick