Adult Dosing

Hypertension

• Initial dose: 3.5 mg/2.5 mg PO once daily, with or without food
• Maximum dose: 14 mg/10 mg once daily

Note:

• Adjust dose according to blood pressure goals; wait 7-14 days between titration steps
• Data on dosing recommendations for patients > 65 years is not available
• Used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals
• Consider use in patients unable to achieve adequate antihypertensive effect with amlodipine monotherapy because of dose-limiting peripheral edema caused by amlodipine

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of hypertension in patients whose blood pressure is not adequately controlled on monotherapy
• As initial therapy in patients likely to need multiple drugs to achieve blood pressure goals
• Treatment of patients unable to achieve adequate blood pressure control with amlodipine monotherapy because of dose-limiting peripheral edema caused by amlodipine

• Hypersensitivity to perindopril or any other ACE inhibitor, to amlodipine, or to any other ingredients of the product
• Hereditary or idiopathic angioedema, with or without previous ACE inhibitor treatment
• Coadministration of aliskiren with ACE inhibitors in patients with diabetes
• Pregnancy

• Discontinue therapy if pregnancy is detected
• Drugs that act directly on the renin-angiotensin system can reduce fetal renal function during the second and third trimesters of pregnancy and increase fetal and neonatal morbidity and death

Renal Dose Adjustment

• Moderate to severe renal impairment (CrCl < 60 mL/min): Not recommended

Hepatic Dose Adjustment

• Hepatic impairment: Not recommended

• Discontinue therapy if pregnancy is detected. Drugs that act directly on the renin-angiotensin system can reduce fetal renal function during the second and third trimesters of pregnancy and increase fetal and neonatal morbidity and death. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, and renal failure [US Black Box Warning]
• Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported (0.1% incidence). Involvement of the tongue, glottis or larynx may be fatal. Discontinue perindopril immediately and observe until the swelling disappears. In case of airway obstruction, administer subcutaneous epinephrine solution promptly. Concomitant mTOR inhibitor (e.g. temsirolimus) use may increase risk of angioedema. Intestinal angioedema has been reported in patients treated with ACE inhibitors
• Worsening of angina and acute myocardial infarction may develop after starting or increasing the dose, especially in patients with severe obstructive coronary artery disease
• Symptomatic hypotension can occur particularly in patients who have been volume- or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting and those with severe aortic stenosis. Monitor patients who are at risk of excessive hypotension closely for the first 2 weeks of treatment and whenever the dose is increased or a diuretic is added or its dose increased. If excessive hypotension occurs, immediately place patient in a supine position and, if necessary, treat patient with an intravenous infusion of physiological saline. Therapy may be continued following restoration of volume and blood pressure
• Hyperkalemia may occur; risk factors include renal insufficiency, diabetes mellitus, and concomitant use of agents such as potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes. Monitor serum potassium periodically
• Therapy may cause persistent non-productive cough. Consider ACE inhibitor induced cough in the differential diagnosis of cough
• If oligouria or hypotension occurs in neonates with a hx of in utero exposure to perindopril/amlodipine, direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required
• Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40-60%
• Therapy is not recommended in patients > 65 years of age.
• Therapy is not recommended in patients with heart failure

Cautions: Use cautiously in

• Hypotension
• Volume depletion
• Heart failure
• Coronary artery disease
• Diabetes mellitus
• Age > 65 years
• Renal insufficiency

Pregnancy Category:D

Breastfeeding: Safety unknown; however, because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or therapy, taking into account the importance of drug to the mother.

• CNS: Dizziness, headache
• RESP: Cough
• GI: Nausea, diarrhea, intestinal angioedema
• DERM: Rash, angioedema
• METABOLIC: Hyperkalemia
• MISC: Peripheral edema

Perindopril

• Angiotensin-converting enzyme (ACE) inhibitor; inhibits ACE (which catalyzes conversion of angiotensin I (inactive) to angiotensin II( vasoconstrictor)) resulting in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion, thus lowering the blood pressure
• Metabolism: Metabolized via hydrolysis by hepatic esterase to form perindoprilat, glucuronidation, and cyclization via dehydration
• Half-life: approximately 100 hrs

amlodipine

• Calcium channel blocker; inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle without affecting serum calcium concentrations. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure
• Absolute bioavailability: 64-90%
• Metabolism: Extensively metabolized in liver; CYP450: CYP3A4
• Excretion: Urine (60%)
• Half-life: 30-50 hrs

US Trade Name(s)

• Prestalia

US Availability

Prestalia (perindopril arginine/amlodipine)

• TABS: 3.5 mg/2.5 mg
• TABS: 7 mg/5 mg
• TABS: 14 mg/10 mg
• TABS: 10mg/14mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Antihypertensive Combinations