SER-AP-ES
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SER-AP-ES (SER-AP-ES).
SER-AP-ES is a combination product containing reserpine (depletes catecholamines from adrenergic nerve endings), hydralazine (direct vasodilation via smooth muscle relaxation), and hydrochlorothiazide (thiazide diuretic that inhibits sodium reabsorption in distal tubules).
| Metabolism | Reserpine: extensively metabolized in liver; Hydralazine: hepatic acetylation (N-acetyltransferase); Hydrochlorothiazide: not metabolized, excreted unchanged. |
| Excretion | Renal: 30-40% unchanged reserpine; 60-70% as metabolites (hydralazine: 50% renal, 15% fecal; hydrochlorothiazide: 95% renal unchanged). |
| Half-life | Reserpine: 50-100h (terminal); hydralazine: 2-8h (slow acetylators 4-8h, fast 2-4h); hydrochlorothiazide: 6-15h. Context: reserpine's long t½ accounts for prolonged effects; hydralazine requires dose adjustment for acetylator status. |
| Protein binding | Reserpine: 40% bound (albumin); hydralazine: 87% bound; hydrochlorothiazide: 40-68% bound (albumin). |
| Volume of Distribution | Reserpine: 6 L/kg; hydralazine: 1.6 L/kg; hydrochlorothiazide: 0.8 L/kg. Clinical meaning: reserpine extensive tissue distribution (fat, brain); hydralazine moderate; thiazide limited to extracellular fluid. |
| Bioavailability | Reserpine: 50% oral; hydralazine: 30-50% oral; hydrochlorothiazide: 65-75% oral. |
| Onset of Action | Oral: reserpine 3-6 days; hydralazine 20-30 min; hydrochlorothiazide 2h. |
| Duration of Action | Reserpine: 1-6 weeks (cumulative); hydralazine: 6-12h; hydrochlorothiazide: 12-16h. Note: reserpine's duration extends due to irreversible monoamine depletion. |
SER-AP-ES is a combination antihypertensive tablet containing reserpine 0.1 mg, hydralazine hydrochloride 25 mg, and hydrochlorothiazide 15 mg. Usual adult dose: one tablet orally twice daily. Increase as needed to a maximum of two tablets twice daily.
| Dosage form | TABLET |
| Renal impairment | Hydrochlorothiazide: Contraindicated if CrCl < 30 mL/min. For CrCl 30-50 mL/min: reduce dose of hydrochlorothiazide to 12.5 mg daily; consider using individual components. Reserpine and hydralazine: no specific GFR-based adjustment, but use with caution if severe renal impairment. |
| Liver impairment | Reserpine and hydralazine are contraindicated in severe hepatic impairment. For Child-Pugh A or B: no specific dose adjustment but monitor closely. For Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for pediatric use due to lack of safety and efficacy data. Use individual components with appropriate weight-based dosing if needed. |
| Geriatric use | Initiate with one tablet orally once daily. Titrate slowly due to increased risk of hypotension, electrolyte disturbances, and central nervous system effects. Monitor renal function and electrolytes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SER-AP-ES (SER-AP-ES).
| Breastfeeding | Reserpine: excreted into breast milk; M/P ratio ~0.5; may cause galactorrhea, breast engorgement, or adverse effects in infant (drowsiness, nasal congestion). Hydralazine: present in breast milk in low amounts (M/P ratio ~1); considered compatible but monitor infant for hypotension. Hydrochlorothiazide: excreted in breast milk in low concentrations (M/P ratio ~0.5); may suppress lactation and cause electrolyte imbalance in infant. Use caution; avoid if possible or monitor infant. |
| Teratogenic Risk | SER-AP-ES is a combination product containing reserpine, hydralazine, and hydrochlorothiazide. Reserpine: crosses placenta, animal studies show fetal abnormalities (skeletal and CNS) in high doses; first trimester risk uncertain, second/third trimester associated with neonatal respiratory depression, bradycardia, hypothermia. Hydralazine: animal studies show cleft palate, skeletal malformations; human data limited; risk not excluded. Hydrochlorothiazide: associated with neonatal thrombocytopenia, electrolyte disturbances, and possibly fetal or neonatal jaundice; second/third trimester use may cause fetal hypoxia and placental insufficiency. Overall, avoid in pregnancy unless benefit outweighs risk; first trimester highest risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to any component","History of depression (reserpine)","Severe renal impairment (hydralazine, hydrochlorothiazide)","Anuria (hydrochlorothiazide)"]
| Precautions | ["Reserpine: May cause depression, peptic ulcer activation.","Hydralazine: Drug-induced lupus, peripheral neuritis (pyridoxine deficiency), tachycardia.","Hydrochlorothiazide: Electrolyte imbalance, hyperuricemia, photosensitivity."] |
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| Fetal Monitoring | Maternal: blood pressure, heart rate, electrolytes (especially potassium, sodium), renal function, signs of lupus-like syndrome or hepatotoxicity (hydralazine), depression (reserpine). Fetal/neonatal: growth ultrasound, fetal heart rate monitoring, assessment for thrombocytopenia and electrolyte disturbances (hydrochlorothiazide), and respiratory depression (reserpine). |
| Fertility Effects | Reserpine may impair fertility by altering hypothalamic-pituitary-gonadal axis, causing amenorrhea or gynecomastia. Hydralazine and hydrochlorothiazide have not been associated with significant fertility impairment. Overall, potential reversible decrease in fertility with reserpine component. |