METATENSIN #2
Clinical safety rating
cautionComprehensive clinical and safety monograph for METATENSIN #2 (METATENSIN #2).
METATENSIN #2 contains reserpine and methyclothiazide. Reserpine inhibits vesicular monoamine transporter (VMAT), depleting catecholamines from peripheral neurons. Methyclothiazide inhibits sodium-chloride symporter in distal convoluted tubule, reducing fluid volume.
| Metabolism | Reserpine: primarily metabolized by CYP3A4; methyclothiazide: not extensively metabolized, excreted unchanged in urine. |
| Excretion | Renal (80% unchanged, 15% as glucuronide metabolite); biliary/fecal (5%) |
| Half-life | 12 hours (terminal); clinical context: twice-daily dosing maintains stable plasma levels |
| Protein binding | 85% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 2.5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 60% (first-pass metabolism reduces bioavailability) |
| Onset of Action | Oral: 1–2 hours; IV: 5–10 minutes |
| Duration of Action | 24 hours (oral); 12 hours (IV); clinical note: antihypertensive effect may persist beyond plasma half-life due to tissue binding |
| Molecular Weight | 448.5 Da |
1-2 tablets orally every 12 hours; each tablet contains reserpine 0.1 mg, hydralazine 25 mg, hydrochlorothiazide 15 mg.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min. For CrCl 30-60 mL/min, reduce dose by 50%; avoid if possible. Monitor potassium and creatinine. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class A or B, use with caution; reduce dose by 50% and monitor liver function. |
| Pediatric use | Not recommended for children; safety and efficacy not established. Use alternative antihypertensives. |
| Geriatric use | Start at half the standard dose (0.5-1 tablet every 12 hours). Monitor for hypotension, electrolyte imbalance, and CNS effects (depression, sedation). Avoid in frail elderly. |
| 1st trimester | Contraindicated: risk of fetal renal impairment and oligohydramnios. |
| 2nd trimester | Contraindicated: associated with fetal hypotension, anuria, and renal failure. |
| 3rd trimester | Contraindicated: can cause fetal and neonatal hypotension, oligohydramnios, and renal dysfunction. |
Clinical note
Comprehensive clinical and safety monograph for METATENSIN #2 (METATENSIN #2).
| Placental transfer | Crosses placenta by passive diffusion; fetal exposure comparable to maternal. |
| Breastfeeding | Present in breast milk in low concentrations; use with caution, especially in preterm infants due to risk of hypotension and renal effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of cardiovascular and neural tube defects due to inhibition of folate-dependent enzymes. Second and third trimesters: Fetal bradycardia, oligohydramnios, intrauterine growth restriction, and neonatal hypotension. Avoid throughout pregnancy unless maternal benefit outweighs risks. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, and serum electrolyte levels. Fetal: Ultrasound for growth parameters, amniotic fluid index, and fetal heart rate monitoring. Neonatal: Assess for bradycardia, hypotension, and hypoglycemia after delivery. |
| Fertility Effects | Not known to impair fertility in males or females. May cause hormonal alterations in men leading to decreased libido or erectile dysfunction. No evidence of adverse effects on spermatogenesis or ovulation. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to methyldopa or any componentActive hepatic disease (e.g., hepatitis, cirrhosis)Monoamine oxidase inhibitor (MAOI) therapy
| Precautions | Mental depression, Electrolyte imbalance (hypokalemia, hyponatremia), Orthostatic hypotension, Increased gastric acid secretion, Pancreatitis, Exacerbation of systemic lupus erythematosus |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, leafy greens) as hydrochlorothiazide can cause hypokalemia; monitor potassium levels. Use salt substitutes cautiously due to potassium content. Avoid excessive sodium intake which may counteract antihypertensive effects. Grapefruit juice may reduce methyldopa absorption; separate by 2 hours. |
| Clinical Pearls | METATENSIN #2 is a fixed-dose combination of methyldopa and hydrochlorothiazide. Monitor for hypotension, especially during initial dosing. LFTs and CBC at baseline and periodically due to methyldopa's risk of hepatotoxicity and hemolytic anemia. Use with caution in renal impairment (CrCl <30 mL/min). Discontinue if jaundice occurs. Adjust dose in hepatic disease. |
| Patient Advice | Take exactly as prescribed at the same time each day. · May cause dizziness or drowsiness; avoid driving until effects are known. · Rise slowly from sitting or lying to prevent lightheadedness. · Report jaundice, fever, unexplained bruising/bleeding, or severe fatigue. · Use sun protection; hydrochlorothiazide increases photosensitivity. · Avoid alcohol, as it may worsen hypotension. · Do not stop abruptly; withdrawal can cause severe hypertension. |
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