Adult Dosing
Adjunct therapy in adults with type 2 diabetes mellitus
Patients requiring saxagliptin 5 mg and who are currently not treated with metformin
- Starting dose: 500 mg/5 mg (metformin/saxagliptin) tab PO qd; gradually escalate dose to reduce the GI adverse effects of metformin
Patients requiring saxagliptin 2.5 mg in combination with metformin extended-release
- Administer 1000 mg/2.5 mg (metformin/saxagliptin) tab PO qd
- Use individual components in patients requiring saxagliptin 2.5 mg who are either metformin naive or who require a dose of metformin >1000 mg
Patients on metformin
- Select dose of metformin/saxagliptin ER to provide metformin at the current dose being taken or the nearest therapeutically appropriate dose
- Closely monitor glycemic control and make dose adjustments accordingly, following a switch from metformin immediate-release to metformin extended-release
Concomitant administration of strong CYP3A4/5 inhibitors
- Maximum dose: 1000 mg/2.5 mg (metformin/saxagliptin) PO qd
Notes:- Administer once daily with the evening meal
- Individualize dosage based on the patient’s current regimen, effectiveness, and tolerability
- Perform dose escalation gradually to reduce the GI side effects associated with metformin use
- Maximum daily dose: 2000 mg/5 mg (metformin/saxagliptin)
- Swallow whole; do not crush, cut, or chew
- When co-administered with an insulin secretagogue such as a sulfonylurea, a lower dosage of insulin secretagogue may be considered to reduce the risk of hypoglycemia
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
See Supplemental Patient Information
- Accumulation of metformin may cause a rare, but fatal, complication called lactic acidosis. Patients with sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF are at a greater risk for developing lactic acidosis [US Black Box Warning]
- Lactic acidosis may also occur in association with certain pathophysiologic conditions, including diabetes mellitus, and in presence of significant tissue hypoperfusion and hypoxemia
- Lab abnormalities include elevated blood lactate levels (>5 mmol/L), low blood pH, electrolyte disturbances with an increased anion gap, and an elevated lactate/pyruvate ratio [US Black Box Warning]
- Diabetic patients with significant renal impairment, including intrinsic renal disorder and renal hypoperfusion, often in the setting of multiple concurrent medical/surgical problems and multiple concurrent medications are more prone to lactic acidosis
- The risk of lactic acidosis increases with the patient's age and degree of renal impairment. Periodically monitor renal function in patients receiving this combination drug, particularly in geriatric patients. Avoid therapy unless measurement of creatinine clearance demonstrates that renal function is not reduced. Withdraw therapy in the presence of any condition associated with hypoxemia, dehydration, or sepsis
- Avoid therapy in patients with clinical or laboratory evidence of hepatic impairment
- Lactic acidosis onset is often subtle and is manifested by nonspecific symptoms including malaise, myalgias, respiratory distress, increasing somnolence, and abdominal distress [US Black Box Warning]
- Severe acidosis may be associated with hypothermia, hypotension, and resistant bradyarrhythmias. Educate patients to recognize and promptly report these symptoms. Discontinue therapy until lactic acidosis is ruled out, if such symptoms occur
- GI symptoms, common during initiation of therapy with metformin, are unlikely to be drug related. Later occurring GI symptoms could be due to lactic acidosis or other serious disease
- Fasting venous plasma lactate levels above the upper limit of normal but <5 mmol/L in patients receiving therapy do not necessarily signify impending lactic acidosis, and may occur as a result of poorly controlled diabetes /obesity, vigorous physical activity, or technical issues in sample handling
- Suspect lactic acidosis in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis including ketonuria and ketonemia [US Black Box Warning]
- Treat lactic acidosis in a hospital setting; discontinue therapy immediately if lactic acidosis occurs and promptly institute supportive measures in such patients [US Black Box Warning]
- Prompt hemodialysis is recommended to correct the acidosis, as metformin hydrochloride is dialyzable
- Post-marketing reports of acute pancreatitis have been reported in patients receiving saxagliptin; monitor carefully for signs and symptoms of pancreatitis after therapy initiation. Discontinue therapy and initiate appropriate management if pancreatitis is suspected
- Renal impairment increases the risk of metformin accumulation, thereby increasing the risk of lactic acidosis. Therapy is therefore contraindicated in patients with renal impairment
- Assess renal function and confirm it to be normal before therapy initiation and regularly thereafter. In patients with anticipated renal impairment (e.g. elderly), assess renal function more frequently and discontinue therapy if there is an evidence of renal impairment
- Therapy not recommended in patients with hepatic impairment, as metformin use in patients with hepatic impairment has been associated with lactic acidosis
- Metformin may cause reductions in vitamin B12 levels, which is very rarely associated with anemia; this may be reversed by discontinuation of therapy or vitamin B12 supplementation. Monitor hematologic parameters and vitamin B12 levels regularly during therapy. Appropriately investigate and manage any apparent abnormalities
- Temporarily discontinue treatment prior to any intravascular radiocontrast study and for any surgical procedure that necessitates restricted intake of food or fluids. Withhold therapy for 48 hours subsequent to the procedure and reinstitute only after renal function is confirmed to be normal
- Alcohol may augment the effect of metformin on lactate metabolism. Caution patients against excessive intake of alcohol during therapy
- Promptly evaluate for evidence of ketoacidosis or lactic acidosis in patients with type 2 diabetes who was previously well controlled with therapy and who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness). Evaluate serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels. Discontinue therapy immediately on occurrence of acidosis of either form and initiate appropriate corrective measures
- When co-administered with an insulin secretagogue such as a sulfonylurea, a lower dosage of insulin secretagogue may be considered to reduce the risk of hypoglycemia
- Hypoglycemia may occur with metformin therapy when used concomitantly with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol or in conditions when caloric intake is deficient
- Elderly, alcoholic, debilitated or malnourished patients and those with adrenal or pituitary insufficiency are at a greater risk of hypoglycemia
- Exercise caution when using metformin/saxagliptin concomitantly with drugs that may affect renal function or result in marked hemodynamic change or may interfere with metformin disposition
- Cardiovascular collapse resulting from acute CHF, acute MI, and other conditions characterized by hypoxemia has been associated with lactic acidosis and may cause prerenal azotemia. Discontinue therapy if such symptoms occur
- Lack of conclusive evidence exists for macrovascular risk reduction associated with metformin/saxagliptin or any other antidiabetic drug
- Postmarketing reports of serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin conditions, have been reported in patients receiving saxagliptin. Promptly discontinue therapy and institute alternative treatment for diabetes if such reaction occurs
- Use cautiously in patients with a history of angioedema to another DPP4 inhibitor as it is unknown whether such patients will be predisposed to angioedema with metformin/saxagliptin therapy
Cautions: Use cautiously in
- CHF
- Risk of hypoglycemia
- Alcohol intoxication
- Concomitant use of cationic drugs
- Concomitant use with beta-adrenergic blockers
- Elderly patients
Supplemental Patient Information
- Caution patients against excessive alcohol intake, either acute or chronic, while receiving metformin/saxagliptin therapy
- Educate patients about the importance of adherence to dietary instructions, regular exercise program, regular monitoring of blood glucose, HbA1c, renal function and hematologic parameters
- Advise patients to remain alert to signs and symptoms of lactic acidosis and promptly notify any unexplained symptoms to their physician
Pregnancy Category:B
Breastfeeding: Low levels of metformin are detectable in the serum of breastfed infants. Metformin levels in milk are relatively constant during maternal metformin use and infants receive <0.5% of the maternal weight-adjusted dosage. Use cautiously when nursing newborn/premature infants and those with renal impairment. Because no information is available regarding saxagliptin use during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 22 August 2011). As per manufacturer's data, both metformin and saxagliptin are secreted in the milk of lactating rats when given individually. It is unknown whether metformin or saxagliptin are secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when administering this combination drug to nursing women.
US Trade Name(s)
US Availability
Kombiglyze XR (metformin/saxagliptin)
- ETABS:
- 500 mg/5 mg
- 1000 mg/2.5 mg
- 1000 mg/5 mg
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
Pricing data from www.DrugStore.com in U.S.A.
- Kombiglyze XR 5-500 MG TB24 [Bottle] (B-M SQUIBB U.S. (PRIMARY CARE))
30 mg = $240
90 mg = $699.98 - Kombiglyze XR 2.5-1000 MG TB24 [Bottle] (B-M SQUIBB U.S. (PRIMARY CARE))
30 mg = $119.99
90 mg = $344.98 - Kombiglyze XR 5-1000 MG TB24 [Bottle] (B-M SQUIBB U.S. (PRIMARY CARE))
30 mg = $236.98
90 mg = $679
Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.