Coversam is an orally available medicine for the treatment of hypertension. It is a combination of perindopril (an Angiotensin-converting enzyme inhibitor) and amlodipine.
Coversam (Perindopril and amlodipine) Uses:
-
Hypertension:
- Management of hypertension.
Coversam (Perindopril and amlodipine) Dose in Adults
Coversam Dose in the treatment of Hypertension:
- Oral: Initial: Perindopril 3.5 mg/amlodipine 2.5 mg once a day;
- adjust dose to achieve response in 7- to 14-day intervals;
- maximum dose: perindopril 14 mg/amlodipine 10 mg per 24 hours.
Coversam (Perindopril and amlodipine) Dose in Childrens
Not recommended for use in children.
Pregnancy Risk Factor D
- [US Boxed Warn] Drugs that directly affect the renin-angiotensin systems can cause injury or death for the baby in development.
- Once pregnancy is confirmed, discontinue use of the drug as soon as you can.
- Talk to individual agents.
Use of amlodipine and perindopril while breastfeeding
- Breast milk contains amlodipine (Naito 2015); however, it is unknown if breast milk contains perindopril.
- The drug manufacturer's labeling suggests that you stop breastfeeding or discontinue therapy due to the possibility of serious adverse reactions in breastfeeding infants.
- See individual agents.
Coversam Dose in Kidney Disease:
-
CrCl 30 to 80 mL/minute:
- Maximum dose: Perindopril 7 mg/amlodipine 5 mg per day.
-
CrCl <30 mL/minute:
- Use is not recommended.
-
Hemodialysis:
- Perindopril and perindoprilat are dialyzable. Amlodipine is not dialyzable.
Coversam Dose in Liver Disease:
- There are dosage adjustments provided in the drug manufacturer’s labeling.
- Perindoprilat bioavailability is increased and amlodipine clearance is decreased with hepatic impairment.
Side Effects of Perindopril and amlodipine Include:
-
Cardiovascular:
- Peripheral Edema
- Exacerbation Of Angina Pectoris
- Hypotension
- Myocardial Infarction
-
Central Nervous System:
- Dizziness
- Headache
-
Dermatologic:
- Skin Rash
-
Endocrine & Metabolic:
- Hyperkalemia
-
Gastrointestinal:
- Diarrhea
- Nausea
-
Renal:
- Renal Insufficiency
-
Respiratory:
- Cough
Contraindications to Coversam (Perindopril and amlodipine):
- Hypersensitivity/Allergy to perindopril, other ACE inhibitors, amlodipine, or any component of the formulation;
- ACE inhibitor therapy may be used to treat angioedema that is inherited or idiopathic.
- concomitant use with aliskiren in patients with diabetes;
- concomitant use or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
Canadian labeling:Additional contraindications not listed in the US labeling:
- Hypersensitivity to dihydropyridine derivatives
- Pregnant women may have renal impairment (CrCl 60 mg/minute).
- Women planning to get pregnant or with childbearing potential are not using a sufficient contraceptive.
- Breastfeeding
- Mitral valve stenosis or left ventricular obstruction (eg, hypertrophic cardiomyopathy, aortic stasis)
- heart failure;
- Bilateral renal artery narrowing or renal artery narrowing in one functioning kidney.
- Patients with severe or moderately impaired renal function may also be treated with aliskiren-containing drugs.
- Extracorporeal treatment that involves blood contact with negatively charged surfaces
- Galactose intolerance, glucose galactose malabsorption or Lapp lactase deficiencies are hereditary issues.
Warnings and precautions
-
Angina and MI
- Patients with severe obstructive or coronary artery disease (SOCAD) have experienced an increase in their risk of MI and/or angina.
-
Angioedema
- Angioedema can occur at any time, especially after the first dose of ACE inhibitors. It may be a rare occurrence.
- Patients with ACE inhibitor therapy and patients who are black or have a history of angioedema, such as idiopathic angioedema or hereditary angioedema, may be at increased risk.
- The risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) or neprilysin inhibitor (eg, sacubitril) therapy.
- Extended monitoring may be necessary, especially if the tongue, glottis or larynx is involved, as they can cause obstruction of the airways.
- Patients who have had previous airway surgery may be at greater risk for obstruction.
- It is crucial to be aggressive early and appropriately managed.
- Patients with angioedema, whether with or without prior ACE inhibitor treatment, are not advised to use this medication.
-
Cholestatic jaundice
- Cholestatic jaundice is a rare toxicity that can be caused by ACE inhibitors. This may lead to fulminant hepatic neoplasms.
- If you notice a marked increase in hepatic transaminases and jaundice, discontinue use.
-
Cough:
- A dry, hacking, nonproductive ACE inhibitor cough usually develops within the first few months after treatment. It should resolve in approximately 1 to 4 weeks.
- Before discontinuing treatment, it is important to consider other causes of cough (eg, pulmonary congestion in heart failure patients).
-
Hematologic effects
- Another ACE inhibitor, captopril, has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred.
- Patients with severe renal impairment are at higher risk of developing neutropenia.
- Patients who have both collagen vascular disease and renal impairment (eg systemic lupus-erythematosus), are more at risk for developing neutropenia.
- Monitor CBC regularly with a differential in such patients.
-
Hyperkalemia:
- This may occur when ACE inhibitors are used together with potassium-sparing diuretics, sodium supplements and/or potassium salts.
- These agents should be used with caution and potassium should be monitored closely.
-
Hypersensitivity reactions
- Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors.
- Anaphylactoid reactions can be severe during hemodialysis (eg CVVHD) and high-flux dialysis membranes, (eg AN69), or, rarely, during low density lipoprotein (low-density lipoprotein) apheresis using dextran sulfatecellulose.
- Patients who have received ACE inhibitors and are subject to sensitization with Hymenoptera (bee or wasp) venom have had rare cases of anaphylactoid reactions.
-
Hypotension/syncope
- ACE inhibitors can cause symptoms of hypotension, with or without syncope (usually after the first few doses).
- Patients with low volume are more likely to experience these effects.
- correct volume depletion prior to initiation;
- Particularly with the initial dose and subsequent increases in dosing, close supervision of patients is essential.
- Blood pressure must be reduced at a pace that is appropriate for the patient's medical condition.
- Hypotension, even though it may be necessary to reduce doses, is not a reason to stop future ACE inhibitor usage.
- This is especially true for patients with heart disease where a decrease in systolic pressure is desirable.
-
Renal function deterioration:
- Perindopril can cause deterioration in renal function, as well as increases in serum creatinine and/or BUN, especially in patients with low renal flow (eg, kidney artery stenosis or heart failure) and whose GFR is dependent upon efferent arterial vasoconstriction of angiotensin 2. This may lead to oliguria and acute renal failure.
- Patients with significant and progressive deterioration of renal function may experience small increases in serum creatinine after initiation.
-
Aortic stenosis
- Patients with severe aortic blockage should be cautious.
- It can lead to decreased coronary perfusion, which could result in ischemia.
-
Cardiovascular disease
- Patients with ischemic heart disease and cerebrovascular diseases should be closely monitored when initiating therapy.
- This is because of the possible consequences of falling blood pressure (eg stroke, MI).
- If necessary, fluid replacement may be required to optimize blood pressure. Therapy may then be restarted.
- Patients with hypotension recur should be stopped from receiving therapy.
-
Collagen vascular disease:
- Patients with collagen vascular disease, especially those with concomitant kidney impairment, should be cautious about using perindopril. They may be at greater risk of developing hematologic toxicities.
-
Hepatic impairment
- Patients with hepatic impairment should be cautious.
-
Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)
- Patients with HCM or outflow tract obstruction should be cautious as a reduction in afterload could worsen the symptoms.
-
Renal artery stenosis
- Patients with stented bilateral or unilateral renal artery stenosis should not be given perindopril.
- If unstented bilateral renal arterial stenosis exists, it is best to avoid its use.
-
Renal impairment
- Patients with mild or moderate renal impairment (CrCl >=30mL/minute) should be cautious.
- Patients with severe renal impairment (CrCl 30mL/minute) should not use it.
Perindopril and amlodipine: Drug Interaction
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Alpha1-Blockers |
May enhance the hypotensive effect of Calcium Channel Blockers. |
|
Amphetamines |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Angiotensin II |
Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Aprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Aprotinin |
May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
ARIPiprazole |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. |
|
Atosiban |
Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. |
|
AzaTHIOprine |
Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. |
|
Barbiturates |
May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. |
|
Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Brigatinib |
May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. |
|
Brimonidine (Topical |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Calcium Channel Blockers (Nondihydropyridine) |
Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
Calcium Salts |
May diminish the therapeutic effect of Calcium Channel Blockers. |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Clopidogrel |
Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. |
|
CycloSPORINE (Systemic) |
Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Moderate) |
May increase the serum concentration of AmLODIPine. |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of AmLODIPine. |
|
Dapoxetine |
May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Dapoxetine |
May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dipeptidyl Peptidase-IV Inhibitors |
May enhance the adverse/toxic effect of AngiotensinConverting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. |
|
Dofetilide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. |
|
Drospirenone |
Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Drospirenone. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
Duvelisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Efavirenz |
May decrease the serum concentration of Calcium Channel Blockers. |
|
Eplerenone |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Everolimus |
May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. |
|
Ferric Gluconate |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. |
|
Ferric Hydroxide Polymaltose Complex |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. |
|
Flibanserin |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. |
|
Fluconazole |
May increase the serum concentration of Calcium Channel Blockers. |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Gelatin (Succinylated) |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. |
|
Gold Sodium Thiomalate |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. |
|
Heparin |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Heparins (Low Molecular Weight) |
May enhance the hyperkalemic effect of AngiotensinConverting Enzyme Inhibitors. |
|
Herbs (Hypertensive Properties) |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Icatibant |
May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Loop Diuretics |
May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Lovastatin |
AmLODIPine may increase the serum concentration of Lovastatin. |
|
Magnesium Salts |
Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. |
|
Melatonin |
May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
NiMODipine |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Nonsteroidal Anti-Inflammatory Agents |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Potassium Salts |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Potassium-Sparing Diuretics |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Pregabalin |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
QuiNIDine |
Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). |
|
Racecadotril |
May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. |
|
Ranolazine |
May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Salicylates |
May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Sirolimus |
May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Tacrolimus (Systemic) |
Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). |
|
Tacrolimus (Systemic) |
Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). |
|
Temsirolimus |
May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Thiazide and Thiazide-Like Diuretics |
May enhance the hypotensive effect of AngiotensinConverting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
TiZANidine |
May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Tolvaptan |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Trimethoprim |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Aliskiren |
May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. |
|
Allopurinol |
Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. |
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Angiotensin II Receptor Blockers |
May enhance the adverse/toxic effect of AngiotensinConverting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. |
|
Antifungal Agents (Azole Derivatives, Systemic |
May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. |
|
Antihepaciviral Combination Products |
May increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated. |
|
CarBAMazepine |
|
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Fosphenytoin |
Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. |
|
Grass Pollen Allergen Extract (5 Grass Extract) |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). |
|
Iron Dextran Complex |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. |
|
Lanthanum |
May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. |
|
Lithium |
Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. |
|
Lomitapide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Macrolide Antibiotics |
May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Phenytoin |
Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. |
|
Rifamycin Derivatives |
May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. |
|
Simvastatin |
AmLODIPine may increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). |
|
Sincalide |
Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. |
|
Sodium Phosphates |
Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Urapidil |
May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. |
|
Risk Factor X (Avoid combination) |
|
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Pimozide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. |
|
Sacubitril |
Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. |
Monitoring Parameters:
- Blood pressure;
- renal function and electrolytes;
- if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential.
- If doses > perindopril 7 mg/amlodipine 5 mg once daily are required in patients >65 years of age, monitor blood pressure up to 2 weeks following up-titration.
How to administer Coversam (Perindopril and amlodipine)?
- Administer with or without food.
Mechanism of action of Coversam (Perindopril and amlodipine):
- Amlodipine
- This inhibits calcium ion's entry into the "slow channel" or selected voltage-sensitive areas in vascular smooth muscles and myocardium during depolarization phase. It causes relaxation of coronary smooth muscle and coronary vasodilation.
- Amlodipine acts directly on the vascular smooth muscles to cause peripheral arterial vasodilation and reduce peripheral resistance.
- Perindopril
- This prevents angiotensin I from angiotensin 2, increases plasma renin activity and decreases aldosterone production.
See individual agents (Perindopril and amlodipine)
International Brands of Perindopril and amlodipine:
- Prestalia
- APO-Perindopril/Amlodipine
- Viacoram
- Acerycal
- Amlessa
- Amtas-PRP
- Beatil
- Calversum
- Co-Prestarium
- Coveram
- Covercard
- Covercor
- Coverlam
- Coversam
- Coversyl-AM
- Dalnessa
- Dalneva
- Mixanval
- Peramteva
- Prestalia
- Prestance
- Reaptan
- Viacoram
- Vidonorm
- Viiacoram Initio
Perindopril and amlodipine Brand Names in Pakistan:
Perindopril and amlodipine 4 mg Tablets |
|
| Amper | Nova Med Pharmaceuticals |
| Conext | Neutro Pharma (Pvt) Ltd. |
| Coversam 4/5 | Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd. |
| Coversam 4/10 | Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd. |
Perindopril and amlodipine 8 mg Tablets |
|
| Coversam 8/5 and 8/10 | Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd. |
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