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. |
| Molecular Weight | 358.46 |
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 | Avoid due to risk of fetal anomalies; alternative therapy recommended. |
| 2nd trimester | Use only if potential benefit justifies potential risk to the fetus; monitor fetal growth. |
| 3rd trimester | Avoid near term due to risk of adverse neonatal effects (e.g., hypoglycemia, respiratory distress). |
Clinical note
Comprehensive clinical and safety monograph for QTERNMET XR (QTERNMET XR).
| Placental transfer | Crosses placenta readily; documented in animal studies and clinical evidence. |
| Breastfeeding | Excreted into breast milk; avoid breastfeeding due to potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ 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 |
Known hypersensitivity to active substance or excipientsSevere hepatic impairmentPregnancy (first trimester unless clearly necessary)BreastfeedingConcomitant use with MAOIs
| 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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| L5 (Contraindicated) |
| 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 | 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. |
| Food/Dietary | Avoid excessive alcohol consumption (≥3 drinks/day) while taking metformin due to increased risk of lactic acidosis. Alcohol can also affect blood glucose control. No specific food restrictions with dapagliflozin; however, ensure consistent carbohydrate intake to manage blood glucose. Grapefruit juice has no known interaction. Taking with food or after meals reduces metformin-related gastrointestinal side effects. Avoid high-fat meals if they cause gastrointestinal discomfort. |
| Clinical Pearls | Qternmet XR is a fixed-dose combination of dapagliflozin (SGLT2 inhibitor) and metformin extended-release. Avoid in severe renal impairment (eGFR <30 mL/min/1.73 m²). Hold temporarily prior to iodinated contrast imaging procedures (≥48 hours) and restart after ≥48 hours if renal function stable. Monitor for lactic acidosis, especially in patients with hepatic impairment, acute kidney injury, or sepsis. Assess volume status and renal function before initiation. May cause hypotension in patients with low systolic BP, diuretics, or elderly. Do not use in type 1 diabetes or diabetic ketoacidosis (DKA). DKA has been reported even with near-normal glucose levels; check for ketones if patient presents with metabolic acidosis. Concomitant use with insulin or insulin secretagogues increases hypoglycemia risk; consider dose reduction. Beneficial effects on heart failure hospitalization and renal outcomes in type 2 diabetes with established cardiovascular disease or multiple risk factors. |
| Patient Advice | Take once daily with food in the morning to reduce gastrointestinal upset. · Swallow tablets whole; do not crush, chew, or split. · Stay well hydrated to prevent dehydration and hypotension; inform your doctor if you experience excessive thirst, dizziness, or lightheadedness. · Monitor for signs of genital yeast infections and urinary tract infections; report burning, itching, discharge, or foul-smelling urine. · Seek immediate medical attention if you experience symptoms of lactic acidosis: unusual muscle pain, trouble breathing, severe drowsiness, slow/irregular heartbeat, or feeling cold. · Discontinue Qternmet XR temporarily before any surgery or imaging procedure involving intravenous contrast dye; follow your doctor's instructions for restarting. · Do not use if you are breastfeeding or have severe kidney disease, metabolic acidosis, or history of diabetic ketoacidosis. · Check blood sugar as directed and be aware of signs of low blood sugar (shakiness, sweating, confusion, rapid heartbeat) when used with insulin or sulfonylureas. · Report symptoms of ketoacidosis even if blood sugar is not high: nausea, vomiting, abdominal pain, tiredness, trouble breathing. |