HYDRALAZINE, HYDROCHLOROTHIAZIDE W/ RESERPINE
Clinical safety rating: safe
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
Hydralazine: direct vasodilation of arterioles, decreasing peripheral resistance. Hydrochlorothiazide: thiazide diuretic inhibiting NaCl reabsorption in distal convoluted tubule. Reserpine: depletes catecholamines from postganglionic sympathetic nerve endings.
| Metabolism | Hydralazine: N-acetylation (NAT2), CYP450 (minor). Hydrochlorothiazide: not metabolized. Reserpine: extensive hepatic metabolism. |
| Excretion | Hydralazine: 86% renal (48% unchanged, 38% metabolites); Hydrochlorothiazide: >95% renal (unchanged); Reserpine: 30% renal (metabolites), 60% fecal. |
| Half-life | Hydralazine: 2-4 hours (fast acetylators), 4-8 hours (slow acetylators); Hydrochlorothiazide: 6-15 hours; Reserpine: 50-100 hours (biphasic, terminal). Clinical context: hydralazine dosing adjusted by acetylator status; hydrochlorothiazide once daily covers 24h; reserpine accumulates with repeated dosing. |
| Protein binding | Hydralazine: 85-90% (albumin); Hydrochlorothiazide: 40-68% (albumin); Reserpine: 96% (albumin and lipoproteins). |
| Volume of Distribution | Hydralazine: 1.5-1.8 L/kg (extensive tissue distribution); Hydrochlorothiazide: 3-15 L (approx 0.2 L/kg, limited to extracellular fluid); Reserpine: 20-35 L/kg (large, extensive tissue binding, especially brain). |
| Bioavailability | Hydralazine: oral 26-55% (first-pass metabolism, variable for acetylator status); Hydrochlorothiazide: oral 65-75% (food increases); Reserpine: oral 30-50% (first-pass). |
| Onset of Action | Oral: Hydralazine 20-30 min, Hydrochlorothiazide 2 hours, Reserpine 3-6 days (delayed due to catecholamine depletion). IV: Hydralazine 5-20 min; other components not available IV. |
| Duration of Action | Hydralazine: 2-6 hours (dose-dependent); Hydrochlorothiazide: 12-16 hours; Reserpine: 2-6 weeks (prolonged effect on norepinephrine stores). Note: combination may require QD to BID dosing. |
1 tablet (Hydralazine 25 mg / Hydrochlorothiazide 25 mg / Reserpine 0.1 mg) orally 2 to 4 times daily. Max dose: Hydralazine 200 mg/day, Hydrochlorothiazide 50 mg/day, Reserpine 0.25 mg/day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in anuria. For CrCl <30 mL/min: avoid hydrochlorothiazide; adjust hydralazine dose based on response. For CrCl 30-60 mL/min: use with caution, consider reducing dose or extending interval. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce hydralazine dose by 50% (start 12.5 mg component) and monitor. Child-Pugh Class C: contraindicated due to risk of hepatic coma from reserpine and impaired hydralazine metabolism. |
| Pediatric use | Not recommended for children. No established safety and efficacy. If used: hydralazine 0.75-3 mg/kg/day in 3-4 divided doses; hydrochlorothiazide 1-2 mg/kg/day; reserpine 0.005-0.02 mg/kg/day (max 0.25 mg/day). |
| Geriatric use | Initiate at low dose (e.g., half tablet) due to increased sensitivity to hypotension and electrolyte disturbances. Monitor renal function, avoid in CrCl <30 mL/min. Use cautiously with high risk of depression and bradycardia from reserpine. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
| FDA category | Animal |
| Breastfeeding | Hydralazine and reserpine are excreted in breast milk; hydrochlorothiazide is present in low amounts. M/P ratio: unknown. Reserpine may cause galactorrhea and respiratory depression in infants. Hydrochlorothiazide may decrease milk production. Caution is advised; avoid if possible. |
| Teratogenic Risk | First trimester: Reserpine may cause respiratory depression, nasal congestion, and hypothermia in neonates; limited human data for hydralazine and hydrochlorothiazide, but animal studies suggest low teratogenic risk. Second and third trimesters: Hydralazine is associated with maternal hypotension, potentially reducing uteroplacental perfusion; hydrochlorothiazide may cause electrolyte imbalance, jaundice, thrombocytopenia; reserpine may increase risk of neonatal respiratory depression. Avoid in pregnancy unless essential. |
■ FDA Black Box Warning
None
| Common Effects | Depression |
| Serious Effects |
["Hypersensitivity to any component","Aortic dissection or severe mitral stenosis (hydralazine)","Recent MI or coronary artery disease (hydralazine)","Sulfonamide allergy (hydrochlorothiazide)","Anuria (hydrochlorothiazide)","History of depression, active peptic ulcer, or ulcerative colitis (reserpine)","Pheochromocytoma (reserpine)","Concurrent MAOI therapy (reserpine)"]
| Precautions | ["Lupus-like syndrome (hydralazine)","Orthostatic hypotension (reserpine)","Electrolyte imbalance (hydrochlorothiazide)","Depression (reserpine)","Sulfonamide allergy cross-reactivity (hydrochlorothiazide)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, electrolytes, and renal function. Fetal monitoring: assess growth and amniotic fluid volume, especially with hydrochlorothiazide. Neonatal: observe for respiratory depression, nasal congestion, electrolyte disturbances. |
| Fertility Effects | Hydralazine may cause systemic lupus erythematosus-like syndrome affecting fertility. Hydrochlorothiazide may cause electrolyte imbalances impacting reproductive function. Reserpine can lead to hyperprolactinemia, amenorrhea, and impaired fertility. Overall, potential for negative impact on fertility. |