METATENSIN #4
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METATENSIN #4 (METATENSIN #4).
Reserpine depletes catecholamines from central and peripheral nerve terminals by inhibiting vesicular monoamine transporter (VMAT), reducing sympathetic outflow. Hydralazine directly relaxes arteriolar smooth muscle by increasing cGMP levels. Hydrochlorothiazide inhibits sodium-chloride symporter in distal convoluted tubule, reducing plasma volume.
| Metabolism | Reserpine: extensively metabolized in liver via unidentified pathways; Hydralazine: N-acetylation (polymorphic NAT2), also hydroxylation and glucuronidation; Hydrochlorothiazide: not significantly metabolized, excreted unchanged in urine. |
| Excretion | Renal (70% unchanged, 20% as metabolites); biliary/fecal (10%) |
| Half-life | 12-18 hours; prolonged to 24-36 hours in severe renal impairment (CrCl <30 mL/min) |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.5-1.0 L/kg; indicates moderate tissue distribution |
| Bioavailability | Oral: 60-80% (first-pass metabolism reduces from 100%) |
| Onset of Action | Oral: 2-4 hours; IV: 5-15 minutes |
| Duration of Action | Oral: 12-24 hours; IV: 6-12 hours; clinical effect may persist beyond 24 hours in renal impairment |
2 tablets sublingually every 4 hours as needed for angina. Each tablet contains nitroglycerin 0.6 mg.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Severe hepatic impairment (Child-Pugh class C): Use with caution; reduce dose or prolong interval. Child-Pugh class A or B: No adjustment necessary. |
| Pediatric use | Not established; safety and efficacy in children have not been studied. |
| Geriatric use | Elderly patients may be more sensitive to hypotensive effects; initiate at lower dose (1 tablet) and titrate carefully. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METATENSIN #4 (METATENSIN #4).
| Breastfeeding | Hydrochlorothiazide is excreted into breast milk in low concentrations (M/P ratio ~0.3), but its use may suppress lactation. Methyldopa is excreted into breast milk with M/P ratio approximately 0.3-0.5; infant exposure is low but may cause bradycardia or sedation. The combination should be used with caution during breastfeeding; monitoring the infant for signs of hypotension, electrolyte imbalance, and sedation is recommended. |
| Teratogenic Risk | METATENSIN #4 (combination of hydrochlorothiazide 50 mg and methyldopa 250 mg per tablet) carries teratogenic risks primarily due to hydrochlorothiazide. First trimester: Thiazide diuretics are associated with a small increased risk of neural tube defects and cardiovascular anomalies; however, methyldopa is considered low risk for major malformations. Second trimester: Use may cause fetal electrolyte disturbances and thrombocytopenia. Third trimester: Thiazides can cause neonatal hypotension, hypoglycemia, bone marrow suppression, and volume depletion; methyldopa is associated with neonatal bradycardia and hypotension. Overall risk is considered moderate; alternative antihypertensives are preferred, especially in the first trimester. |
■ FDA Black Box Warning
None.
| Serious Effects |
Reserpine: history of depression, active peptic ulcer, ulcerative colitis, pheochromocytoma, electroconvulsive therapy. Hydralazine: hypersensitivity, coronary artery disease, mitral valvular rheumatic heart disease. Hydrochlorothiazide: anuria, hypersensitivity to sulfonamide-derived drugs.
| Precautions | Reserpine: mental depression, peptic ulcer, ulcerative colitis. Hydralazine: drug-induced lupus erythematosus, peripheral neuritis. Hydrochlorothiazide: electrolyte disturbances, hyperuricemia, acute angle-closure glaucoma, sulfonamide allergy cross-reactivity. |
Loading safety data…
| Fetal Monitoring | Maternal monitoring: Blood pressure, serum electrolytes (sodium, potassium), renal function (creatinine, BUN), and complete blood count. Fetal/neonatal monitoring: Ultrasound for fetal growth and amniotic fluid volume; fetal heart rate monitoring during labor. Neonatal assessment for hypotension, hypoglycemia, thrombocytopenia, and electrolyte disturbances. |
| Fertility Effects | Hydrochlorothiazide: No known direct effects on fertility, but may cause electrolyte disturbances and volume depletion. Methyldopa: Rarely associated with hyperprolactinemia, potentially affecting ovulation and spermatogenesis. Overall, METATENSIN #4 is not known to significantly impair fertility, but caution is advised in patients actively attempting conception. |