METRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METRA (METRA).
Metformin primarily decreases hepatic glucose production and improves insulin sensitivity by activating AMP-activated protein kinase (AMPK), leading to reduced gluconeogenesis and increased peripheral glucose uptake.
| Metabolism | Metformin is excreted unchanged in urine; does not undergo hepatic metabolism or cytochrome P450 metabolism. |
| Excretion | Primarily renal: 70-80% unchanged drug via glomerular filtration and active tubular secretion; 15-20% biliary/fecal as metabolites. |
| Half-life | Terminal elimination half-life: 3-7 hours (mean 4.5 hours). Increased to 8-15 hours in moderate-to-severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 80-85% bound to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 1.5-2.5 L/kg (mean 2.0 L/kg). Extensive tissue distribution; crosses blood-brain barrier and placenta. |
| Bioavailability | Oral: 60-75% (due to first-pass metabolism); intramuscular: 90-100%; topical: 10-20% (formulation-dependent). |
| Onset of Action | Intravenous: 5-10 minutes; oral: 30-60 minutes; topical: 1-2 hours. |
| Duration of Action | 4-6 hours; prolonged to 8-12 hours with sustained-release oral formulations. Clinical effect correlates with drug levels above minimum effective concentration. |
| Molecular Weight | 336.43 |
Adults: 20 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥30 mL/min: no adjustment; eGFR <30 mL/min: 10 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 10 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Weight ≥30 kg: 20 mg once daily; weight <30 kg: 10 mg once daily. |
| Geriatric use | ≥65 years: initial dose 10 mg once daily, titrate as tolerated. |
| 1st trimester | Avoid. Limited human data; animal studies show embryotoxicity at high doses. Potential for teratogenicity, especially during organogenesis. |
| 2nd trimester | Avoid. Use only if maternal benefit outweighs fetal risk. May cause fetal growth restriction and oligohydramnios. |
| 3rd trimester | Avoid. Risk of premature closure of ductus arteriosus, fetal nephrotoxicity, and persistent pulmonary hypertension in neonate. |
Clinical note
Comprehensive clinical and safety monograph for METRA (METRA).
| Placental transfer | Crosses placenta readily; fetal concentrations approximate maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations. Use with caution in nursing mothers, especially in preterm infants or those with renal impairment. Monitor infant for adverse effects. |
■ FDA Black Box Warning
Lactic acidosis: Metformin use has been associated with lactic acidosis, a rare but serious metabolic complication. Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years, and hepatic disease.
| Serious Effects |
Hypersensitivity to metra or any componentHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsPerioperative pain in setting of coronary artery bypass graft (CABG) surgeryActive gastrointestinal bleedingSevere renal impairment (CrCl <30 mL/min)Advanced hepatic failure
| Precautions | Lactic acidosis risk, impaired renal function (monitor eGFR), vitamin B12 deficiency, acute metabolic acidosis, perioperative use, and concurrent iodinated contrast agents. |
| Food/Dietary | Avoid high-sodium foods as they may counteract the antihypertensive effect. Consumption of potassium-rich foods (e.g., bananas, oranges) is not restricted unless hypokalemia develops, but monitor potassium levels. Grapefruit juice may increase metolazone absorption; avoid concurrent use. Limit alcohol intake as it may enhance hypotensive effects. |
Loading safety data…
| Lactation Rating |
| L3 - Moderately Safe |
| Teratogenic Risk | METRA is contraindicated in pregnancy due to documented teratogenicity, including neural tube defects, cardiovascular malformations, and craniofacial abnormalities in first trimester. Second and third trimester exposure may cause low birth weight and transient neonatal metabolic disturbances. Use effective contraception during treatment. |
| Fetal Monitoring | Monitor renal function, liver enzymes, and CBC monthly. Assess fetal growth by ultrasound in second and third trimesters. Evaluate for signs of premature labor. In newborns, monitor for hypoglycemia, electrolyte imbalances, and hematologic abnormalities for first 48 hours. |
| Fertility Effects | METRA impairs spermatogenesis and oogenesis by interfering with DNA synthesis, leading to reduced fertility in both males and females. Ovarian suppression may cause amenorrhea and anovulation. Effects are generally reversible following discontinuation of therapy but may persist for months. |
| Clinical Pearls | METRA is a brand name for metolazone, a thiazide-like diuretic. Use with caution in severe renal impairment (eGFR <20 mL/min) as effectiveness diminishes. Monitor for hypokalemia, especially when used with loop diuretics. Do not use in hepatic coma or pre-coma. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · May cause dizziness or lightheadedness due to blood pressure changes; rise slowly from sitting or lying positions. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · Report signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, or extreme thirst. · Do not consume alcohol or take other blood pressure medications without consulting your doctor. |