Rg Zone G

Rg Zone G Uses, Dosage, Side Effects, Food Interaction and all others data.

Gliclazide stimulates the release of insulin from pancreatic beta-cells by facilitating Ca++ transport across the beta-cell membranes. It lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects also may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Two extrapancreatic effects shown to be important in the action of Gliclazide are an increase in insulin sensitivity and a decrease in hepatic glucose production. The anti-oxidant, platelet inhibiting and fibrinolytic actions of Gliclazide involve processes which have been implicated in the pathogenesis of vascular complications of type 2 diabetes.

Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.

Rosiglitazone, a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor gamma (PPAR-γ). In humans, PPAR receptors are found in key target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-γ nuclear receptors regulates the transcription of insulinresponsive genes involved in the control of glucose production, transport, and utilization. In addition, PPAR-γ-responsive genes also participate in the regulation of fatty acid metabolism. Pharmacological studies in animal models indicate that Rosiglitazone improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Rosiglitazone maleate is not chemically or functionally related to the sulfonylureas, the biguanides, or the alpha glucosidase inhibitors.

When rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time.

Rg Zone G
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Rg Zone G
Generic	Gliclazide + Rosiglitazone
Type	Tablet
Therapeutic Class
Manufacturer	Zee Laboratories Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Gliclazide is used for control of blood glucose in patients with non-insulin dependent diabetes mellitus (Type-II, maturity onset diabetes mellitus) whose hyperglycemia cannot be controlled by diet alone.

Rosiglitazone is used

As monotherapy for glycemic control.
For use in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and a single agent do not result in adequate glycemic control.
Also for use in combination with a sulfonylurea plus metformin when diet, exercise, and both agents do not result in adequate glycemic control.

Rg Zone G is also used to associated treatment for these conditions: Type 2 Diabetes MellitusType 2 Diabetes Mellitus

How Rg Zone G works

Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.

Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin.

Dosage

Rg Zone G dosage

Adult: The usual initial dose of Gliclazideis 40 to 80 mg daily, gradually increased, if necessary up to 320 mg daily until adequate control is achieved. A single dose should not exceed 160 mg. When higher doses are required it should be taken twice daily, according to the main meals of the day. For extended release tablet the initial recommended dose is 30 mg daily, even in elderly patients (>65 years); the daily dose may vary from 30 to 120 mg taken orally, once daily.

Gliclazide extend release tablet should be taken with food because there is increased risk of hypoglycemia if a meal is taken late. It is recommended that the medication be taken at breakfast time. If a dose is forgotten, the dose taken on the next day should not be increased. Dose titration should be carried out in steps of 30 mg, according to the fasting blood glucose response. Each step should last for at least two weeks. Gliclazide extend release tabletshould be neither broken nor chewed. Gliclazide extend release tablet30 mg, can replace Gliclazide 80 mg tabletsfor doses of 1 to 4 tablets per day.

Elderly: Plasma clearance of Gliclazide is not altered in the elderly and steady state plasma levels are similar to those in adults under 65 years. Clinical experience in the elderly shows that it is effective and well tolerated.

Children: Gliclazide as with other sulfonylureas is not indicated for the treatment of juvenile onset diabetes mellitus.

The management of antidiabetic therapy should be individualized. Rosiglitazone may be administered either at a starting dose of 4 mg as a single daily dose or divided and administered in the morning and evening. For patients who respond inadequately following 8 to 12 weeks of treatment, as determined by reduction in FPG, the dose may be increased to 8 mg daily as monotherapy or in combination with metformin, sulfonylurea, or sulfonylurea plus metformin. Rosiglitazone may be taken with or without food.

Monotherapy: The usual starting dose of Rosiglitazone is 4 mg administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4 mg twice daily regimen resulted in the greatest reduction in FPG and HbA1c.

Combination therapy: When Rosiglitazone is added to existing therapy, the current dose(s) of the agent(s) can be continued upon initiation of Rosiglitazone therapy.

Sulfonylurea: When used in combination with sulfonylurea, the usual starting dose of Rosiglitazone is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin: The usual starting dose of Rosiglitazone in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with Rosiglitazone.

Insulin: For patients stabilized on insulin, the insulin dose should be continued upon initiation of therapy with Rosiglitazone. Rosiglitazone should be dosed at 4 mg daily. Doses of Rosiglitazone greater than 4 mg daily in combination with insulin are not currently indicated. It is recommended that the insulin dose be decreased by 10% to 25% if the patient reports hypoglycemia or if FPG concentrations decrease to less than 100 mg/dL. Further adjustments should be individualized based on glucose-lowering response.

Sulfonylurea plus metformin: The usual starting dose of Rosiglitazone in combination with a sulfonylurea plus metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Maximum Recommended Dose: The dose of Rosiglitazone should not exceed 8 mg daily, as a single dose or divided twice daily. The 8 mg daily dose has been shown to be safe and effective in clinical studies as monotherapy and in combination with metformin, sulfonylurea, or sulfonylurea plus metformin. Doses of Rosiglitazone greater than 4 mg daily in combination with insulin are not currently indicated. No dosage adjustments are required for the elderly. No dosage adjustment is necessary when Rosiglitazone is used as monotherapy in patients with renal impairment.

Side Effects

Hypoglycemia may occur in concurrent conditions such as hepatic & renal diseases, alcohol intoxication and adrenal and pituitary insufficiency. Mild gastro-intestinal disturbances including nausea, dyspepsia, diarrhea, and constipation have been reported but these types of adverse reactions can be avoided if Gliclazide is taken during a meal. Allergic dermatological reactions including rash, prurits, erythema, bullous eruption have been reported during treatment with the drug but are not known to be directly attributable to it. More serious reactions like leucopenia, thrombocytopenia, agranulocytosis, pancytopenia, hemolytic anemia, cholestatic jaundice, GI hemorrhage have not been reported with Gliclazide.

The incidence and types of adverse events reported in clinical trials of Rosiglitazone as monotherapy are similar to that of placebo. Overall, the types of adverse experiences reported when Rosiglitazone was used in combination with a sulfonylurea or metformin were similar to those during monotherapy with Rosiglitazone. 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.

Toxicity

LD₅₀=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating.

Side effects include fluid retention, congestive heart failure (CHF), liver disease

Precaution

Gliclazide should be used carefully in patients with hepatic impairment. If there is definite hepatic disease then gliclazide should not be used. Consucon (Gliclazide) can be used safely in patients with renal insufficiency as it is extensively metabolized. Consucon has less sudden hypoglycaemic episode than other sulfonylurea group of drugs.

Due to its mechanism of action, Rosiglitazone is active only in the presence of endogenous insulin. Therefore, Rosiglitazone should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Rosiglitazone, like other thiazolidinediones, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure. Patients should be observed for signs and symptoms of heart failure. In combination with insulin, thiazolidinediones may also increase the risk of other cardiovascular adverse events. Rosiglitazone should be discontinued if any deterioration in cardiac status occurs. Rosiglitazone should be used with caution in patients with edema. Liver enzymes should be checked prior to the initiation of therapy with Rosiglitazone in all patients and periodically thereafter per the clinical judgement of the healthcare professional. Therapy with Rosiglitazone should not be initiated in patients with increased baseline liver enzyme levels (ALT >2.5X upper limit of normal).

Interaction

The hypoglycemic effect of Gliclazide may be potentiated by NSAID (in particular aspirin), phenylbutazone, sulfonamides, coumarin derivatives, MAOIs, beta-adrenergic blockers, tetracyclines, chloramphenicol, clofibrate, cimetidine and miconazole tablets. Ingestion of alcohol may also increase the hypoglycemic effect of Gliclazide. Some drugs may on the contrary, reduce its activity e.g. barbiturates, corticosteroides, thiazide diuretics, thyroid hormones, laxatives and oral contraceptives.

In vitro drug metabolism studies suggest that Rosiglitazone does not inhibit any of the major P450 enzymes at clinically relevant concentrations. A decrease in the dose of Rosiglitazone may be needed when gemfibrozil is introduced. Dosage adjustment is also required when administered with rifampin. Rosiglitazone was shown to have no clinically relevant effect on the pharmacokinetics of nifedipine and oral contraceptives.

Volume of Distribution

17.6 L [oral volume of distribution Vss/F]
13.5 L [population mean, pediatric patients]

Elimination Route

Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.

The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in C_max and a delay in T_max (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food. Maximum plasma concentration (Cmax) and the area under the curve (AUC) of rosiglitazone increase in a dose-proportional manner over the therapeutic dose range.

Half Life

10.4 hours. Duration of action is 10-24 hours.

3-4 hours (single oral dose, independent of dose)

Clearance

Oral clearance (CL) = 3.03 ± 0.87 L/hr [1 mg Fasting]
Oral CL = 2.89 ± 0.71 L/hr [2 mg Fasting]
Oral CL = 2.85 ± 0.69 L/hr [8 mg Fasting]
Oral CL = 2.97 ± 0.81 L/hr [8 mg Fed]
3.15 L/hr [Population mean, Pediatric patients]

Elimination Route

Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).

Following oral or intravenous administration of [14C]rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively.

Pregnancy & Breastfeeding use

Pregnant Women: Gliclazide should not be used in pregnant women although animal studies of Gliclazide have not shown any teratogenic effect.

Nursing Mothers: This drug is contraindicated when breast feeding.

There are no adequate and well-controlled studies in pregnant women. Rosiglitazone should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Drug-related material was detected in milk from lactating rats. It is not known whether Rosiglitazone is excreted in human milk. Because many drugs are excreted in human milk, Rosiglitazone should not be administered to a nursing woman.

Contraindication

Hypersensitivity to sulfonylurea, diabetes complicated by ketoacidosis with coma, as a sole therapy of insulin-dependent (Type-1) diabetes mellitus, diabetes when complicated by pregnancy & breast-feeding.

Rosiglitazone is contraindicated in patients with known hypersensitivity to this product or any of its components.

Special Warning

Children: Gliclazide as with other sulfonylureas is not indicated for the treatment of juvenile onset diabetes mellitus.

Use in Children: The safety and effectiveness of Rosiglitazone in pediatric patients have not been established.

Acute Overdose

Symptoms: Hypoglycaemia with or without coma, convulsions or other neurological disorders.

Management: Carbohydrate intake, dosage adjustment and/or change of diet may be helpful. Admin rapid IV inj of concentrated glucose soln for hypoglycaemic coma.