PRESTALIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRESTALIA (PRESTALIA).
PRESTALIA is a fixed-dose combination of perindopril, an angiotensin-converting enzyme inhibitor, and amlodipine, a dihydropyridine calcium channel blocker. Perindopril inhibits ACE, reducing angiotensin II formation, leading to vasodilation and decreased aldosterone secretion. Amlodipine inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, causing vasodilation and reduced peripheral resistance.
| Metabolism | Perindopril is hydrolyzed to its active metabolite perindoprilat mainly by esterases. Amlodipine is extensively metabolized in the liver via CYP3A4. |
| Excretion | Perindopril: 75% renal (as perindoprilat), 25% biliary/fecal. Indapamide: 70% renal, 20% biliary/fecal. |
| Half-life | Perindoprilat: 30–120 hours (terminal, prolonged in renal impairment; effective half-life for accumulation ~24h). Indapamide: 14–24 hours (terminal). |
| Protein binding | Perindoprilat: 10–20% (mainly to ACE). Indapamide: 71–79% (to plasma proteins). |
| Volume of Distribution | Perindoprilat: 0.2–0.3 L/kg (distributes to tissues, low Vd). Indapamide: 0.5–1.0 L/kg (moderate distribution). |
| Bioavailability | Perindopril: 75–95% (oral, active metabolite perindoprilat ~25%). Indapamide: 93% (oral). |
| Onset of Action | Perindopril: 1–2 hours (oral antihypertensive effect). Indapamide: 1–2 hours (oral diuretic effect). |
| Duration of Action | Perindopril: 24 hours (once-daily dosing for BP control). Indapamide: ≥24 hours (antihypertensive and diuretic effects). |
One tablet orally once daily, preferably in the morning. PRESTALIA is a fixed-dose combination of perindopril arginine (2.5 mg, 5 mg, or 10 mg) and amlodipine (5 mg or 10 mg). Initial dose: 3.5 mg perindopril arginine/2.5 mg amlodipine or 5 mg perindopril arginine/5 mg amlodipine. Titrate based on blood pressure response. Maximum dose: 10 mg perindopril arginine/10 mg amlodipine.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR < 30 mL/min/1.73 m². For GFR 30-60 mL/min/1.73 m²: maximum perindopril dose 5 mg per day. Use lowest effective dose. Monitor renal function and serum potassium. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). For moderate impairment (Child-Pugh B): start with lowest perindopril dose (2.5 mg) and amlodipine dose (2.5 mg) if available; amlodipine dose should be titrated slowly. For mild impairment (Child-Pugh A): no dose adjustment necessary, but use caution. |
| Pediatric use | Not recommended for use in patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | Start at the lowest available dose (perindopril arginine 2.5 mg/amlodipine 2.5 mg in some regions, or 3.5 mg/2.5 mg). Monitor renal function and blood pressure carefully. Titrate slowly. Avoid in patients with severe renal impairment (CrCl <30 mL/min). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRESTALIA (PRESTALIA).
| Breastfeeding | Perindopril is excreted in breast milk in low amounts (M/P ratio unknown). Amlodipine is excreted in breast milk; M/P ratio approximately 1.1. Effects on breastfed infants are unknown but likely minimal due to low concentrations. Caution is advised; consider alternative antihypertensives with established safety in lactation. |
| Teratogenic Risk | First trimester: Drugs acting directly on the renin-angiotensin system (RAS) can cause fetal renal dysplasia, oligohydramnios, and skull ossification defects. Perindopril and amlodipine are not recommended in first trimester. Second and third trimesters: Exposure to RAS antagonists can cause oligohydramnios, fetal renal impairment, skull hypoplasia, pulmonary hypoplasia, and neonatal anuria. Amlodipine may cause fetal cardiovascular effects. Both drugs are contraindicated in second and third trimesters. |
■ FDA Black Box Warning
WARNING: FETAL TOXICITY - When pregnancy is detected, discontinue PRESTALIA as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
| Serious Effects |
["History of angioedema related to previous ACE inhibitor therapy","Hereditary or idiopathic angioedema","Concomitant use with aliskiren in patients with diabetes or renal impairment (GFR <60 mL/min)","Hypersensitivity to perindopril, amlodipine, or any component of the formulation"]
| Precautions | ["Fetal toxicity","Angioedema","Hypotension","Hepatic impairment","Renal impairment","Hyperkalemia","Cough","Risk of myocardial infarction or increased angina with calcium channel blockers"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and electrolytes. Fetal monitoring includes ultrasound for amniotic fluid volume and fetal renal function if exposed after first trimester. Neonatal monitoring for hypotension, oliguria, and hyperkalemia if exposed near delivery. |
| Fertility Effects | No specific studies on fertility effects of perindopril/amlodipine combination. RAS antagonists may impair fertility in women by affecting ovarian function. Calcium channel blockers have been associated with reversible male infertility (sperm motility impairment). |