QTERNMET XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QTERNMET XR (QTERNMET XR).
Qternmet XR is a combination of saxagliptin (a DPP-4 inhibitor) and metformin (a biguanide). Saxagliptin increases incretin levels (GLP-1, GIP) by inhibiting DPP-4, enhancing glucose-dependent insulin secretion and suppressing glucagon release. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
| Metabolism | Saxagliptin is metabolized via CYP3A4/5 to active metabolite. Metformin is excreted unchanged in urine; not metabolized. |
| Excretion | Renal: 90% unchanged via glomerular filtration and tubular secretion; fecal: 10%. |
| Half-life | Terminal half-life: 4–6 hours; clinically relevant for dosing interval (every 6–8 hours) and steady-state achievement within 24 hours. |
| Protein binding | Reversible binding to albumin: 30–40%. |
| Volume of Distribution | 0.3–0.5 L/kg; indicates distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 90% (well absorbed with minimal first-pass metabolism). |
| Onset of Action | Oral: 1–2 hours (peak effect 4–6 hours). |
| Duration of Action | 8–12 hours; clinical effect lasts through dosing interval in patients with normal renal function. |
Adults: 500 mg orally once daily with the evening meal, increase by 500 mg every 1-2 weeks up to a maximum of 2000 mg once daily. For extended-release (XR) formulation, titrate from 500 mg to 2000 mg once daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-45 mL/min: Maximum 1000 mg once daily. eGFR 15-29 mL/min: Maximum 500 mg once daily. eGFR <15 mL/min: Use immediate-release metformin only, maximum 500 mg once daily. Not recommended for use in patients with eGFR <30 mL/min due to increased risk of lactic acidosis. |
| Liver impairment | Avoid use in patients with hepatic impairment (Child-Pugh Class B or C) due to risk of lactic acidosis. For Child-Pugh Class A, no dose adjustment specified; use caution. |
| Pediatric use | Not approved for use in pediatric patients <18 years of age. Safety and efficacy not established. |
| Geriatric use | Start at low dose (500 mg once daily) and titrate slowly. Monitor renal function closely as elderly are more prone to renal impairment. Maximum dose: 2000 mg daily if eGFR ≥45 mL/min. Avoid use if eGFR <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for QTERNMET XR (QTERNMET XR).
| Breastfeeding | Excreted in breast milk. M/P ratio is approximately 0.8. Discontinue nursing due to potential for serious adverse reactions in the nursing infant, including CNS depression and withdrawal symptoms. |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of Ebstein anomaly and other congenital heart defects; second and third trimesters: increased risk of preterm delivery, low birth weight, and neonatal withdrawal syndrome. |
| Fetal Monitoring |
■ FDA Black Box Warning
Lactic acidosis: Metformin-associated lactic acidosis is rare but can be fatal. Risk increases with renal impairment, sepsis, dehydration, alcohol intake, hepatic impairment, and acute heart failure. Discontinue if acidosis suspected; monitor renal function.
| Common Effects | Upper respiratory tract infection Urinary tract infection Hypercholesterolemia high cholesterol |
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m2)","Acute or chronic metabolic acidosis (including diabetic ketoacidosis)","History of hypersensitivity to saxagliptin, metformin, or any component","Concomitant use with insulin or sulfonylureas is not contraindicated but may increase hypoglycemia risk"]
| Precautions | ["Lactic acidosis risk (see boxed warning)","Pancreatitis: Discontinue if suspected","Renal impairment: Contraindicated if eGFR <30 mL/min/1.73 m2; not recommended if eGFR 30-45","Heart failure: May increase risk; monitor","Hypoglycemia: Risk when combined with sulfonylureas or insulin","Vitamin B12 deficiency: Long-term metformin use may decrease B12 levels","Hypersensitivity reactions: Postmarketing reports of angioedema, Stevens-Johnson syndrome"] |
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| Maternal: Serum valproate levels, liver function tests, complete blood count, and coagulation parameters. Fetal: Targeted ultrasound for congenital anomalies, especially cardiac, and neonatal monitoring for withdrawal and hepatotoxicity. |
| Fertility Effects | May cause menstrual irregularities, anovulation, and polycystic ovary syndrome (PCOS)-like hormonal changes, reducing fertility. Reversible upon discontinuation. |