Radizid XR30 mg

Type 2 Diabetes Mellitus

Radizid XR is an established, guideline-supported oral antidiabetic medicine indicated for the treatment of type 2 diabetes mellitus in adults, used as an adjunct to diet and exercise when these measures alone do not adequately control blood glucose. Radizid XR is approved and marketed in numerous countries, including Bangladesh, as monotherapy, and Radizid XR is also commonly used in combination with other oral antidiabetic agents (such as metformin, alpha-glucosidase inhibitors, or DPP-4 inhibitors) or with insulin, when glycemic control is not achieved with a single agent.

Combination Therapy

When type 2 diabetes is not adequately controlled on metformin or another single agent alone, Radizid XR may be added as a second-line agent, consistent with international treatment guidelines; combination use of Radizid XR with other antidiabetic drugs requires the addition of that second agent, and this goal is not achieved by Radizid XR alone.

Each tablet contains Gliclazide 80 mg (conventional/immediate-release form), or Gliclazide 30 mg / 60 mg as a modified-release (MR) tablet, depending on the marketed brand and formulation.

Radizid XR is an oral antidiabetic medicine belonging to the second-generation sulfonylurea class, used to help control blood glucose levels in adults with type 2 diabetes mellitus. Radizid XR works mainly by stimulating the pancreas to release more insulin, and Radizid XR also has additional effects on blood vessel and platelet function. Radizid XR is used as an adjunct to diet, exercise, and weight management, either alone or together with other antidiabetic medicines. Radizid XR does not treat type 1 diabetes and is not a substitute for insulin in patients who require it. Radizid XR should be taken exactly as prescribed by a qualified healthcare professional, with regular monitoring of blood glucose.

Antidiabetic agent (Second-generation Sulfonylurea)

Gliclazide lowers blood glucose primarily by stimulating insulin secretion from pancreatic beta cells. Gliclazide binds to specific receptors on the beta-cell membrane, closing ATP-sensitive potassium channels; this depolarizes the cell membrane, opens voltage-dependent calcium channels, and increases intracellular calcium influx, which triggers insulin release by exocytosis. Gliclazide also restores the early phase of insulin secretion that is characteristically blunted in type 2 diabetes, and Gliclazide is reported to have additional hemobiological effects, including reducing platelet adhesiveness and aggregation and enhancing fibrinolytic activity, which may help lower the risk of small-vessel complications, although these effects are secondary to the primary glucose-lowering action of Gliclazide. Gliclazide is well absorbed after oral administration; the modified-release formulation of Gliclazide is designed to release the drug gradually over 24 hours to support once-daily dosing. Gliclazide is extensively metabolized in the liver to inactive metabolites and is excreted mainly in urine, with a plasma half-life of approximately 10-12 hours for conventional Gliclazide.

• Take Radizid XR with or shortly before a meal (typically breakfast), never on an empty stomach, to reduce the risk of hypoglycemia.
• Swallow modified-release (MR) tablets of Radizid XR whole with a glass of water; do not chew, crush, or split MR tablets of Radizid XR.
• Take Radizid XR at approximately the same time each day.
• If a dose of Radizid XR is missed, do not take a double dose to make up for it; take the next dose of Radizid XR at the usual time.
• Do not skip meals while taking Radizid XR, as this increases the risk of hypoglycemia.
• Continue Radizid XR exactly as prescribed and do not stop or change the dose without consulting a physician, even if blood glucose appears well controlled.

• Miconazole (systemic, including oral gel): concurrent use with Radizid XR can precipitate severe hypoglycemia, including coma; concurrent use is contraindicated (see Contraindications).
• Other azole antifungals (e.g. fluconazole) and CYP2C9 inhibitors: may increase blood levels of Radizid XR and increase the risk of hypoglycemia; dose adjustment and closer monitoring may be needed.
• Alcohol: can potentiate the blood-glucose-lowering effect of Radizid XR and increase the risk of severe hypoglycemia; a disulfiram-like reaction has also been reported with sulfonylureas including Radizid XR; alcohol should be avoided or limited.
• Beta-blockers: may mask the warning symptoms of hypoglycemia (such as tremor and palpitations) caused by Radizid XR and can potentiate its glucose-lowering effect; use with caution.
• NSAIDs, ACE inhibitors, and other antidiabetic agents/insulin: may enhance the hypoglycemic effect of Radizid XR; closer blood glucose monitoring is advised when these are combined with Radizid XR.
• Danazol: has an inherent hyperglycemic effect that can antagonize the effect of Radizid XR; concurrent use is generally avoided unless glucose monitoring is intensified.
• Corticosteroids and thiazide diuretics: can raise blood glucose and reduce the effectiveness of Radizid XR; dose adjustment of Radizid XR may be needed if these are started or stopped.
• Warfarin and other coumarin anticoagulants: sulfonylureas including Radizid XR may potentiate anticoagulant effect; monitoring of anticoagulation is advised.

Common Side Effects

• Hypoglycemia (low blood sugar) - the most frequent and clinically important side effect of Radizid XR; see Precautions and Warnings.
• Gastrointestinal disturbances such as nausea, vomiting, abdominal pain, diarrhea, or constipation.
• Mild, transient visual disturbances related to changes in blood glucose levels, especially at the start of treatment with Radizid XR.

Less Common / Serious Side Effects (Seek Medical Attention)

• Skin reactions such as rash, itching, or hives caused by Radizid XR; rarely, severe reactions such as Stevens-Johnson syndrome or angioedema.
• Blood disorders (rare) associated with Radizid XR, including low white blood cell count, low platelet count, anemia, or pancytopenia, which may present as unusual bruising, bleeding, infections, or fatigue.
• Liver problems (rare) associated with Radizid XR, including raised liver enzymes, cholestatic jaundice, or hepatitis, which may present as yellowing of the skin/eyes, dark urine, or unusual tiredness.
• Weight gain associated with Radizid XR.

Pregnancy

Radizid XR is generally not recommended for use in pregnancy. Sulfonylureas such as Radizid XR can cross the placenta, and poorly controlled maternal blood glucose itself carries risk to the fetus; insulin is generally the preferred agent for achieving glycemic control during pregnancy because of its long safety record in this setting. If a woman taking Radizid XR becomes pregnant, or is planning pregnancy, she should be switched to insulin under medical supervision. Radizid XR should be used in pregnancy only if clearly needed and no suitable alternative is available, with the potential benefit weighed against potential risk to the fetus, and only under the direct guidance of a physician.

Breastfeeding

Radizid XR is not recommended during breastfeeding, because of the risk of hypoglycemia in the nursing infant and a lack of adequate safety data on Radizid XR in this setting. Women who need treatment for type 2 diabetes while breastfeeding should discuss alternative options, such as insulin, with their physician instead of using Radizid XR.

• Hypoglycemia: Radizid XR can cause hypoglycemia, particularly if meals are missed or delayed, after unusual physical exertion, with alcohol intake, or in elderly, malnourished, or renally/hepatically impaired patients. Patients taking Radizid XR should be counseled to recognize symptoms of hypoglycemia (sweating, tremor, hunger, confusion, palpitations) and how to manage them (e.g., taking fast-acting glucose), and to seek urgent medical attention for severe or persistent hypoglycemia.
• Renal and hepatic impairment: Radizid XR is metabolized by the liver and excreted by the kidneys; impaired function of either organ can prolong the action of Radizid XR and increase the risk of hypoglycemia. Use a lower starting dose of Radizid XR and monitor closely in mild-to-moderate impairment; severe impairment is a contraindication to Radizid XR (see Contraindications).
• Loss of glycemic control: during periods of stress such as fever, trauma, infection, or surgery, blood glucose control with Radizid XR may deteriorate, and temporary insulin therapy may be required in place of Radizid XR.
• Cardiovascular considerations: some older sulfonylureas have historically been associated with a possible increase in cardiovascular mortality compared with diet alone or newer agents; this is a class-wide consideration for sulfonylureas including Radizid XR, and patients with cardiovascular disease should discuss the balance of benefits and risks of Radizid XR with their physician.
• Weight gain: Radizid XR, like other sulfonylureas, may be associated with weight gain; this should be considered as part of overall diabetes management alongside Radizid XR.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: sulfonylureas including Radizid XR may rarely cause hemolytic anemia in patients with G6PD deficiency; use Radizid XR with caution in this population, and consider a non-sulfonylurea alternative where possible.
• Driving and operating machinery: hypoglycemia or hyperglycemia caused by Radizid XR can impair concentration and reaction ability; patients should be cautious, especially when starting Radizid XR or changing its dose.

Overdose of Radizid XR can cause hypoglycemia, which may range from mild symptoms (sweating, tremor, hunger, palpitations, confusion) to severe hypoglycemia with seizures, loss of consciousness, or coma. If Radizid XR overdose is suspected and the patient is conscious, give sugar or a glucose-containing drink or food immediately. Seek emergency medical attention or contact a poison control center right away, as hypoglycemia caused by Radizid XR overdose, especially with modified-release formulations of Radizid XR, can be severe and prolonged, requiring hospitalization, intravenous glucose administration, and extended monitoring of blood glucose (often for 24 hours or more) even after apparent recovery. Do not attempt to manage a suspected overdose of Radizid XR at home without medical guidance.

Store Radizid XR at room temperature (below 30°C), away from light and moisture. Keep Radizid XR out of the reach and sight of children. Do not use Radizid XR beyond its expiry date.

Children

The safety and efficacy of Radizid XR have not been established in children and adolescents under 18 years of age. Radizid XR is not recommended for use in this age group.

Elderly

Elderly patients are more susceptible to the hypoglycemic effects of Radizid XR. Treatment with Radizid XR should be started at the lowest available dose, with careful, gradual titration and close monitoring of blood glucose.

Renal Impairment

Patients with mild-to-moderate renal impairment should start Radizid XR at a low dose with close monitoring, because reduced clearance can prolong the action of Radizid XR and increase the risk of hypoglycemia. Radizid XR is contraindicated in severe renal impairment.

Hepatic Impairment

Because Radizid XR is extensively metabolized in the liver, patients with mild-to-moderate hepatic impairment should start Radizid XR at a low dose with close monitoring. Radizid XR is contraindicated in severe hepatic impairment.

Pregnant and Breastfeeding Women

See the Pregnancy and Lactation section above for detailed guidance on the use of Radizid XR in this population.

Radizid XR is generally used long-term, as type 2 diabetes mellitus is a chronic condition requiring ongoing management. The duration of treatment with Radizid XR is determined by a physician based on periodic reassessment of blood glucose control (including HbA1c), tolerability, and the presence of any complications; Radizid XR is often continued indefinitely as part of a diabetes management plan, but the dose of Radizid XR may be adjusted, or Radizid XR may be combined with or switched to other antidiabetic therapy, over time. Patients should not stop taking Radizid XR without consulting their physician, even if they feel well, since discontinuation of Radizid XR can lead to loss of blood glucose control.

Sulfonylurea (second-generation oral antidiabetic agent)

Gliclazide lowers blood glucose by binding to sulfonylurea receptors on pancreatic beta-cell membranes and closing ATP-sensitive potassium channels. This causes membrane depolarization, opening of voltage-gated calcium channels, and an influx of calcium into the beta cell, which stimulates the release of stored insulin by exocytosis. By increasing circulating insulin, Gliclazide enhances glucose uptake by peripheral tissues and reduces hepatic glucose output, thereby lowering blood glucose levels. Gliclazide is also reported to reduce platelet aggregation and adhesiveness and to increase fibrinolytic activity, effects that are considered secondary to the primary glucose-lowering action of Gliclazide.

Radizid XR has not been established as safe and effective for use in children or adolescents under 18 years of age, and pediatric dosing of Radizid XR has not been defined. Type 2 diabetes in children and adolescents is generally managed with other agents (such as metformin or insulin) that have established pediatric safety and efficacy data, rather than with Radizid XR. Radizid XR should not be used in children unless specifically directed by a pediatric specialist in exceptional circumstances.