Dosing and uses of Prestalia (perindopril/amlodipine)
Adult dosage forms and strengths
perindopril arginine/amlodipine
tablet
- 3.5mg/2.5mg
- 7mg/5mg
- 14mg/10mg
Hypertension
Indicated for the treatment of hypertension in patients whose blood pressure is not adequately controlled on monotherapy or as initial therapy in patients likely to need multiple drugs to achieve blood pressure goals
Initial: 3.5 mg/2.5 mg PO qDay with or without food
Adjust dose according to blood pressure goals; wait 7-14 days between titration steps
Not to exceed 14 mg/10 mg qDay
Dosage modifications
Renal impairment (ie, CrCl <60 mL/min): There are no data to guide dosing recommendations
Hepatic impairment: There are no data to guide dosing recommendations
Heart failure: There are no data to guide dosing recommendations
Dosing Considerations
May be 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
Geriatric Dosage & Indications
Not recommended: There are no data to guide dosing recommendations in patients aged >65 years
Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40-60%
A similar increase in AUC was observed in patients with moderate -o-severe heart failure
Pediatric dosage forms and strengths
Safety and efficacy not established
Neonates with a history of in utero exposure: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function
Prestalia (perindopril/amlodipine) adverse (side) effects
1-10%
Peripheral edema (7.2%)
Cough (3.2%)
Headache (2.5%)
Dizziness (2.5%)
Frequency not defined
Dermatologic: Rash
Digestive: Nausea, diarrhea
Postmarketing Reports
PerindopriL
- Cardiac arrest
- Eosinophilic pneumonitis
- Acute renal failure, nephritis
- Falls
- Hepatic failure, jaundice (hepatocellular or cholestatic), acute pancreatitis
- Symptomatic bullous pemphigoid, pemphigus
- Exfoliative dermatitis, psoriasis, and a syndrome that may include arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations
- Positive antinuclear antibody (ANA), symptomatic hyponatremia, thrombocytopenia, neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), leukocytosis, eosinophilia, or an elevated erythrocyte sedimentation rate (ESR)
Amlodipine
- Palpitations
- Gynecomastia
- Jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), some requiring hospitalization
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; ACE inhibitors affect renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
History of hereditary or acquired angioedema associated with previous ACE inhibitor treatment
Coadministration with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Pregnancy (second and third trimesters): significant risk of fetal/neonatal morbidity and mortality
Cautions
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black box warnings and Pregnancy)
Worsening angina and acute MI can develop after starting or increasing the dose, particularly in patients with severe obstructive CAd
Hyperkalemia reported; monitor serum potassium levels
Persistent cough reported with all ACE inhibitors, presumably because of the inhibition of the degradation of endogenous bradykinin; generally resolves after discontinuing
Hypotension
- May cause symptomatic hypotension; most likely to occur in patients who have been volume-or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting
- Patients with severe aortic stenosis may be more likely to experience symptomatic hypotension
- Correct hypotension in patients undergoing major surgery or during anesthesia with agents that produce hypotension with volume expansion
- In patients at risk of excessive hypotension, monitor closely for the first 2 weeks of treatment and whenever the therapeutic 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 IV infusion of physiological saline; therapy can usually be continued following restoration of volume and blood pressure
Renal impairment
- Monitor renal function periodically
- Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the renin-angiotensin system Patients whose renal function may depend in part on the activity of the renin-angiotensin system (eg, renal artery stenosis, severe CHF, post-MI, volume depletion) may be at particular risk of developing acute renal failure
Anaphylactoid reactions
- ACE inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin; therefore, patients taking ACE inhibitors may be subject to a variety of bradykinin- or prostaglandin-mediated adverse reactions, some of them serious
- Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema
- Black patients receiving ACE inhibitors have a higher incidence of angioedema compared with nonblacks
- Intestinal angioedema
- Presents as abdominal pain (with or without nausea or vomiting)
- Diagnosed by imaging studies (eg, abdominal CT or ultrasound) or at surgery
- Angioedema of the face, extremities, lips, tongue, glottis, and larynx
- Discontinue perindopril treatment immediately and observe until the swelling disappears
- When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, administer appropriate therapy promptly (eg, SC epinephrine solution 1:1000 [0.3-0.5 mL])
Pregnancy and lactation
Pregnancy category: d
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death
Lactation: Unknown if distributed in human breast milk; because of the potential for adverse effects on the nursing infant, decide whether to discontinue nursing or discontinue the drug
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Prestalia (perindopril/amlodipine)
Mechanism of action
Perindopril: A prodrug that is hydrolyzed to perindoprilat; competitively inhibits angiotensin-converting enzyme (ACE) that initially results in decreased plasma angiotensin II concentrations, and, consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion
Amlodipine: A dihydropyridine calcium antagonist; it inhibits transmembrane influx of extracellular calcium ions across membranes of myocardial cells and vascular smooth muscle cells without changing serum calcium concentrations; this inhibits cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries
Absorption
Bioavailability (amlodipine): 64-90%
Peak plasma concentration
- Perindopril: 1 hr
- Perindoprilat: 4 hr
- Amlodipine: 6-12 hr
Distribution
Protein bound (amlodipine): 93%
Metabolism
Perindopril: Extensively metabolized to 6 metabolites resulting from hydrolysis, glucuronidation, and cyclization via dehydration, including the active moiety, perindoprilat
Amlodipine: Extensively (~90%) metabolized in the liver to inactive metabolites
Elimination
Excretion (amlodipine): Mostly in urine (60% as metabolites, 10% as unchanged drug)
Half-life
- Perindoprilat: ~100 hr
- Amlodipine: ~30-50 hr
Administration
Instructions
May take with or without food
