Glyza2.5 mg

Glyza is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated for the following use:

Established / FDA-approved use

• Type 2 diabetes mellitus (adults): Glyza is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used as monotherapy or in combination with other antidiabetic agents such as metformin, sulfonylureas, thiazolidinediones, or insulin, when these agents alone do not provide adequate glycemic control.

Not indicated for

• Type 1 diabetes mellitus.
• Treatment of diabetic ketoacidosis (should not be used for this purpose).

Glyza is not a substitute for insulin in patients who require insulin therapy and should not be used to treat type 1 diabetes.

Each film-coated tablet contains Saxagliptin as the active ingredient, commonly available in strengths of 2.5 mg and 5 mg for oral administration. Saxagliptin is also available in fixed-dose combination products with metformin hydrochloride extended-release for patients who require dual therapy. Tablets contain standard pharmaceutical excipients such as microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and a film coating.

Glyza is an orally administered dipeptidyl peptidase-4 (DPP-4) inhibitor used in the management of type 2 diabetes mellitus. By inhibiting the DPP-4 enzyme, Glyza slows the breakdown of incretin hormones (GLP-1 and GIP), leading to increased glucose-dependent insulin release from pancreatic beta cells and reduced glucagon secretion from alpha cells, which together lower blood glucose levels.

Glyza is typically taken once daily, with or without food, and is often used alone or combined with other oral antidiabetic medicines or insulin when diet, exercise, and a single agent do not achieve adequate glycemic control.

Glyza belongs to the therapeutic class of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, a group of oral antidiabetic (antihyperglycemic) agents also known as "gliptins".

Saxagliptin is a competitive, reversible inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 is responsible for the rapid degradation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are released by the intestine in response to meals.

By inhibiting DPP-4, Saxagliptin increases circulating concentrations of active incretin hormones. This leads to:

• Increased glucose-dependent insulin synthesis and release from pancreatic beta cells.
• Decreased glucagon secretion from pancreatic alpha cells.

These effects occur in a glucose-dependent manner, which is why Saxagliptin carries a low intrinsic risk of causing hypoglycemia when used alone. Saxagliptin is absorbed after oral administration, metabolized partly via the CYP3A4/5 enzyme system to an active metabolite, and eliminated via both renal and hepatic pathways.

Glyza tablets should be swallowed whole with a glass of water, with or without food, once daily at a consistent time. Do not split, crush, or chew the tablet unless specifically directed. If a dose is missed, it should be taken as soon as remembered unless it is close to the time of the next dose, in which case the missed dose should be skipped — do not double the dose. Glyza should be taken exactly as prescribed by a physician, alongside continued diet and exercise measures.

Glyza has clinically significant interactions with the following:

• Strong CYP3A4/5 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin, atazanavir): these significantly increase plasma concentrations of Glyza by reducing its metabolism; the dose of Glyza should be limited to 2.5 mg once daily when co-administered with these agents.
• Insulin and insulin secretagogues (sulfonylureas): combining Glyza with insulin or a sulfonylurea increases the risk of hypoglycemia compared with either agent alone; a lower dose of the insulin or sulfonylurea may be needed.
• Other antidiabetic agents: when Glyza is combined with other glucose-lowering medicines, blood glucose should be monitored closely to detect hypoglycemia or inadequate control.

Glyza itself is not a significant inhibitor or inducer of major cytochrome P450 enzymes or P-glycoprotein, so it has a comparatively low potential to affect the levels of other drugs. Always inform your physician or pharmacist of all medicines, supplements, and herbal products being taken before starting Glyza.

Common side effects

• Upper respiratory tract infection, nasopharyngitis
• Headache
• Urinary tract infection
• Gastroenteritis, sinusitis

Less common but serious side effects

• Heart failure: increased risk of hospitalization for heart failure has been observed with Glyza in cardiovascular outcomes studies. Seek medical attention for symptoms such as unusual shortness of breath, rapid weight gain, or swelling of the legs/ankles (see Precautions and Warnings).
• Acute pancreatitis: persistent, severe abdominal pain, sometimes radiating to the back, with or without vomiting.
• Hypersensitivity reactions: including anaphylaxis, angioedema, and exfoliative skin conditions (see Contraindications).
• Bullous pemphigoid: a blistering skin condition, reported with DPP-4 inhibitors including Glyza.
• Severe and disabling joint pain (arthralgia).
• Hypoglycemia (mainly when combined with insulin or sulfonylureas).
• Lymphopenia (mild reduction in lymphocyte count).

Report any severe, persistent, or worsening symptoms to a physician promptly.

Pregnancy: Data on the use of Glyza in pregnant women are limited. Animal reproduction studies have not shown definite harm to the fetus at clinically relevant exposures, but adequate, well-controlled studies in pregnant women are lacking. Uncontrolled hyperglycemia during pregnancy carries risks for the mother and fetus; Glyza should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus. Consult a physician promptly if pregnancy occurs or is planned while taking Glyza, as insulin is generally preferred to manage diabetes during pregnancy.

Lactation: It is not known whether Glyza passes into human breast milk. Because many drugs are excreted in breast milk and the effects on a nursing infant are unknown, Glyza should be used during breastfeeding only after consulting a physician, who can weigh the benefits of treatment against any potential risk to the infant.

Heart failure

An important safety warning applies to Glyza: cardiovascular outcomes data have shown an increased risk of hospitalization for heart failure in patients taking Glyza, particularly those with pre-existing heart or kidney disease. Patients should be monitored for signs and symptoms of heart failure (e.g., unusual shortness of breath, rapid weight gain, or swelling of the legs/ankles) during treatment, and discontinuation of Glyza should be considered if heart failure develops.

Pancreatitis

Cases of acute pancreatitis, including fatal cases, have been reported with DPP-4 inhibitors such as Glyza. If pancreatitis is suspected, Glyza should be discontinued promptly and the patient evaluated.

Hypoglycemia

Glyza alone does not typically cause significant hypoglycemia, as its action is glucose-dependent. However, the risk of hypoglycemia is increased when Glyza is used together with insulin or sulfonylureas; a lower dose of these agents may be required.

Renal impairment

Dose adjustment of Glyza is required in patients with moderate-to-severe renal impairment or end-stage renal disease (see Dosage and Administration). Renal function should be assessed before starting Glyza and periodically thereafter.

Hypersensitivity and skin reactions

Serious hypersensitivity reactions, including anaphylaxis, angioedema, and bullous pemphigoid, have been reported, sometimes after the first dose. If a serious hypersensitivity reaction is suspected, Glyza should be discontinued, other potential causes assessed, and alternative diabetes therapy instituted.

Joint pain

Severe and disabling joint pain has been reported with DPP-4 inhibitor use; onset can occur from one day to years after starting treatment. Consider this diagnosis in patients who develop new severe joint pain.

Limited data are available on overdose with Glyza. In the event of a suspected overdose, general supportive measures should be initiated based on the patient's clinical signs and symptoms, and blood glucose should be closely monitored for signs of hypoglycemia. Glyza and its major metabolite can be removed by hemodialysis (a modest fraction is removed over a 4-hour session). Anyone who has taken more than the prescribed dose of Glyza should seek immediate medical attention or contact a poison control center / emergency services rather than attempting to manage the situation at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Dose reduction of Glyza to 2.5 mg once daily is required in patients with moderate-to-severe renal impairment or end-stage renal disease, including those on hemodialysis (see Dosage and Administration).

Hepatic impairment

No dose adjustment is generally needed in mild-to-moderate hepatic impairment. Data in severe hepatic impairment are limited, so Glyza should be used with caution in this group.

Elderly patients

No overall dose adjustment is required based on age alone, but elderly patients are more likely to have reduced renal function, so renal status should be assessed and the dose of Glyza adjusted accordingly. Elderly patients may also be more susceptible to hypoglycemia when Glyza is combined with insulin or a sulfonylurea.

Pediatric patients

Safety and effectiveness of Glyza in patients under 18 years of age have not been established; it is not recommended for use in this age group.

Glyza is generally used as a long-term, ongoing treatment for type 2 diabetes mellitus as part of chronic disease management, alongside diet and exercise. There is no fixed treatment duration; a physician will periodically review blood glucose control (e.g., via HbA1c) and overall response to determine whether to continue, adjust, or change therapy. Glyza should not be stopped or the dose changed without medical advice.

Dipeptidyl peptidase-4 (DPP-4) inhibitors; Oral antidiabetic (antihyperglycemic) agents

Saxagliptin works by selectively and reversibly inhibiting the DPP-4 enzyme, which normally breaks down the incretin hormones GLP-1 and GIP within minutes of their release. By blocking this breakdown, Saxagliptin prolongs the activity of these incretins, resulting in increased, glucose-dependent insulin secretion from pancreatic beta cells and decreased glucagon secretion from alpha cells. The net effect is a reduction in fasting and postprandial blood glucose levels without a high intrinsic risk of hypoglycemia.

B

The safety and effectiveness of Glyza have not been established in pediatric patients (under 18 years of age). Glyza is therefore not recommended for use in children and adolescents, and should only be used in adults with type 2 diabetes mellitus as prescribed by a physician.