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). |
| Molecular Weight | Perindopril erbumine: 441.6 Da; Amlodipine besylate: 567.1 Da |
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 | Avoid. ACE inhibitors and calcium channel blockers are associated with increased risk of congenital malformations, particularly cardiovascular and renal, when used in the first trimester. |
| 2nd trimester | Avoid. ACE inhibitors can cause fetal renal dysfunction, oligohydramnios, and skull ossification defects; calcium channel blockers may cause fetal hypoxia. |
| 3rd trimester | Avoid. ACE inhibitors risk fetal hypotension, anuria, and renal failure; calcium channel blockers may inhibit labor. |
Clinical note
Comprehensive clinical and safety monograph for PRESTALIA (PRESTALIA).
| Placental transfer | Both perindopril and amlodipine cross the placenta. ACE inhibitors are known to transfer and have fetal toxicity; calcium channel blockers also cross but with less evidence of harm. |
| Breastfeeding | Perindopril is excreted into breast milk in low amounts; amlodipine is excreted in low concentrations. Use with caution in breastfeeding women, especially in preterm or hypotensive infants. Monitor infant for hypotension, renal impairment, and electrolyte disturbances. |
■ 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 therapyHereditary or idiopathic angioedemaBilateral renal artery stenosis or artery stenosis of a solitary kidneyPregnancy (second and third trimesters especially)Hypersensitivity to perindopril, amlodipine, or other dihydropyridinesSevere hypotensionCardiogenic shockAortic or mitral valve stenosis (severe)Obstructive hypertrophic cardiomyopathyConcomitant use with aliskiren in patients with diabetes or renal impairment (GFR <60 mL/min/1.73m²)
| Precautions | Fetal toxicity, Angioedema, Hypotension, Hepatic impairment, Renal impairment, Hyperkalemia, Cough, Risk of myocardial infarction or increased angina with calcium channel blockers |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase amlodipine levels. Avoid high-potassium foods (e.g., bananas, oranges, spinach) in large amounts without consulting doctor due to perindopril's potassium-sparing effect. Limit salt substitutes containing potassium chloride. Avoid alcohol as it may potentiate hypotensive effects. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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). |
| Clinical Pearls | PRESTALIA is a fixed-dose combination of perindopril arginine and amlodipine besylate. Monitor serum potassium and renal function, especially in elderly and renally impaired patients. Avoid use in pregnancy due to risk of fetal renal dysfunction. Titrate from individual components for blood pressure control before switching to fixed-dose. Recheck blood pressure 2-4 weeks after initiation. Be cautious in patients with severe aortic stenosis or hypertrophic cardiomyopathy. |
| Patient Advice | Take PRESTALIA exactly as prescribed, usually once daily at the same time each day. · Do not use if pregnant or planning pregnancy; use effective contraception and notify your doctor immediately if you suspect pregnancy. · Avoid salt substitutes containing potassium unless advised by your doctor. · Report any symptoms of excessive low blood pressure: dizziness, lightheadedness, fainting. · Do not stop taking PRESTALIA suddenly as this may cause a rapid increase in blood pressure. · Avoid grapefruit and grapefruit juice as they may interact with amlodipine. · Limit alcohol intake as it may lower blood pressure further. |