Saxagliptin/metformin

— THERAPEUTIC CATEGORIES —
  • Diabetes

Saxagliptin/metformin Generic Name & Formulations

General Description

Saxagliptin, metformin HCl (ext-rel); 5mg/500mg, 5mg/1000mg, 2.5mg/1000mg; tabs.

Pharmacological Class

Dipeptidyl peptidase-4 (DPP-4) inhibitor + biguanide.

How Supplied

Contact supplier

Mechanism of Action

Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Metformin improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Saxagliptin/metformin Indications

Indications

Adjunct to diet and exercise to improve glycemic control in type 2 diabetes when treatment with both saxagliptin and metformin is appropriate.

Limitations of Use

Not for treatment of type 1 diabetes or diabetic ketoacidosis.

Saxagliptin/metformin Dosage and Administration

Adult

Individualize; titrate based on response. Swallow whole. Take once daily with evening meal. Not currently treated with metformin: initially 5mg/500mg daily. Previously on metformin alone: Saxagliptin/metformin ext-rel should provide current metformin dose. Max saxagliptin 5mg/day and metformin ext-rel 2000mg/day. Renal impairment (eGFR 30–45mL/min/1.73m2): not recommended; (eGFR <45mL/min/1.73m2): max saxagliptin 2.5mg/day. Concomitant strong CYP3A4/5 inhibitors: max 2.5mg/1000mg daily.

Children

<18yrs: not established.

Saxagliptin/metformin Contraindications

Contraindications

Severe renal impairment (eGFR <30mL/min/1.73m2). Metabolic acidosis, diabetic ketoacidosis.

Saxagliptin/metformin Boxed Warnings

Boxed Warning

Lactic acidosis.

Saxagliptin/metformin Warnings/Precautions

Warnings/Precautions

Increased risk of metformin-associated lactic acidosis in renal or hepatic impairment, concomitant use of certain drugs (eg, cationic drugs), ≥65yrs of age, undergoing radiological contrast study, surgery and other procedures, hypoxic states, and excessive alcohol intake; discontinue if lactic acidosis occurs. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR 30–60mL/min/1.73m2, history of hepatic impairment, alcoholism, heart failure, or will be given intra-arterial contrast; reevaluate eGFR 48hrs after procedure and restart therapy if renally stable. Suspend therapy if dehydration occurs or before surgery. Avoid if clinical or lab evidence of hepatic disease. Assess renal function prior to starting and periodically thereafter; more frequently in elderly or if eGFR <60mL/min/1.73m2. Consider risks/benefits in patients with known risk factors for heart failure; monitor for signs/symptoms and consider discontinuing if develops. Monitor for signs/symptoms of pancreatitis, serious hypersensitivity reactions, severe joint pain, or bullous pemphigoid; discontinue if suspected or occurs. History of angioedema to other DPP-4 inhibitors. Elderly, debilitated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Monitor hematology (esp. serum Vit. B12 in susceptible patients). Pregnancy. Nursing mothers.

Saxagliptin/metformin Pharmacokinetics

Absorption

Median time to maximum concentration: 2 hours (saxagliptin); 4–8 hours (metformin HCl).

Distribution

Volume of distribution of 654 ± 358 L (after metformin immediate-release).

Metabolism

Saxagliptin: Hepatic (CYP3A4/5).

Elimination

Saxagliptin: renal (75%), fecal (22%). Metformin HCl: renal. Half-life: 2.5 hours (saxagliptin); ~6.2 hours (metformin HCl).

Saxagliptin/metformin Interactions

Interactions

Increased risk of lactic acidosis with topiramate, other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide); monitor. Concomitant cationic drugs that interfere with renal tubular transport systems (eg, ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels; monitor. Potentiated by strong CYP3A4/5 inhibitors (eg, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Diuretics, steroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, sympathomimetics, calcium channel blockers, isoniazid, nicotinic acid, others may cause hyperglycemia. May need lower dose of concomitant sulfonylurea or insulin to reduce risk of hypoglycemia. β-blockers may mask hypoglycemia.

Saxagliptin/metformin Adverse Reactions

Adverse Reactions

Diarrhea, nausea, vomiting, URI, UTI, headache, nasopharyngitis; pancreatitis, heart failure, hypersensitivity reactions, severe and disabling arthralgia, bullous pemphigoid; rare: lactic acidosis (may be fatal).

Saxagliptin/metformin Clinical Trials

See Literature

Saxagliptin/metformin Note

Notes

Formerly known under the brand name Kombiglyze XR.

Saxagliptin/metformin Patient Counseling

See Literature