Perindopril/amlodipine

Dosage Forms & 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

• CrCl <30 mL/min: Not recommended
• CrCl 30-80 mL/min (mild or moderate renal impairment): Do not exceed 7/5 mg

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

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

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

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 of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

Coadministration with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)

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 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

Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema

Persistent cough reported with all ACE inhibitors, presumably because of the inhibition of the degradation of endogenous bradykinin; generally resolves after discontinuing

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death; patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up

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
• Perindoprilat elimination is decreased in renally impaired patients, with a marked increase in accumulation when creatinine clearance < 30 mL/min
• Drugs that affect renin-angiotensin system can cause reductions in renal function, including acute renal failure; patients whose renal function may depend in part on activity of renin-angiotensin system—(e.g., patients with renal artery stenosis, severe heart failure, post-myocardial infarction or volume depletion) or who are on non-steroidal anti-inflammatory agents (NSAIDS) or angiotensin receptor blockers, 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])

Perindopril/amlodipine is a prescription medication used to treat high blood pressure.

It is a single product containing 2 medications: perindopril and amlodipine. Perindopril belongs to a group of drugs called angiotensin converting enzyme (ACE) inhibitors, which relax blood vessels to lower blood pressure and make the heart more efficient. Amlodipine belongs to a group of drugs called calcium channel blockers, which help relax blood vessels. This makes it easier for the heart to pump blood.

This medication comes in tablet form and is usually taken once daily.

Common side effects of perindopril/amlodipine include swelling of the hands, legs, and feet, cough, and headache.

Perindopril/amlodipine can also cause dizziness. Do not drive or operate heavy machinery until you know how perindopril/amlodipine affects you.

Serious side effects have been reported with perindopril/amlodipine. See the “Perindopril & Amlodipine Precautions” section.

Common side effects of perindopril/amlodipine include:

• swelling of the hands, legs, and feet
• cough
• headache
• dizziness

This is not a complete list of perindopril/amlodipine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• potassium supplements
• potassium-sparing diuretics such as spironolactone (Aldactone), triamterene (Dyrenium), amiloride (Midamor)
• lithium (Eskalith, Lithobid)
• injectable gold
• other medications for high blood pressure such as furosemide (Lasix), hydrochlorothiazide, torsemide (Demadex)
• non-steroidal anti-inflammatory drugs such as celecoxib (Celebrex), diclofenac (Cambia,Cataflam, Flector, Voltaren, Zipsor and others), etodolac (Lodine), ibuprofen (Advil, Motrin, Nuprin), indomethacin (Indocin, Indocin SR), ketoprofen (Orudis, Actron, Oruvail), ketorolac (Toradol), meloxicam (Mobic), nabumetone (Relafen), naproxen (Naprosyn), naproxen sodium (Aleve, Anaprox, Naprelan), oxaprozin (Daypro),piroxicam (Feldene)

This is not a complete list of perindopril/amlodipine drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Perindopril/amlodipine falls into category D. It has been shown that use of perindopril/amlodipine in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.