Coversam (Perindopril and Amlodipine) - Dosage, Side effects

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

Drugs that directly impact the renin-angiotensin systems have the potential to harm or even kill a developing foetus. [US Boxed Warn]
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;
Idiopathic or hereditary angioedema may be treated with ACE inhibitor treatment.
Diabetes patients who also use aliskiren should not switch to or stop using a neprilysin inhibitor (such as sacubitril) within 36 hours of doing so.

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;
Renal artery constriction on both sides or renal artery narrowing in one kidney that is still functional.
The use of medications containing aliskiren is also permitted for the treatment of patients with severe or mild renal impairment.
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
- One study found that patients with severe obstructive or coronary artery disease (SOCAD) had a higher 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 may be at increased risk.
- Concurrent usage of mTOR inhibitor (such as everolimus) or neprilysin inhibitor (such as sacubitril) therapy may also enhance the risk.
- In cases where the tongue, glottis, or larynx are implicated, prolonged observation may be required because these structures have the potential to clog 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:
- Within the first few months following treatment, a dry, hacking, nonproductive cough typically appears. It ought to go away in one to four weeks.
- Prior to stopping treatment, it's necessary to take alternative cough reasons into account (eg, pulmonary congestion in heart failure patients).
Hematologic effects
- Captopril, another ACE inhibitor, has also been linked to anaemia, thrombocytopenia, and neutropenia with myeloid hypoplasia and agranulocytosis.
- The chance of developing neutropenia is increased in patients with severe renal impairment.
- Neutropenia is more likely to occur in patients with collagen vascular disease and renal impairment (such as systemic lupus erythematosus).
- In such patients, routinely do a differential CBC.
Hyperkalemia:
- When ACE inhibitors, potassium-sparing diuretics, sodium supplements, and/or potassium salts are used, this may happen.
- These agents should be used with caution and potassium should be monitored closely.
Hypersensitivity reactions
- With ACE inhibitors, anaphylactic/anaphylactoid responses can happen.
- Hemodialysis (CVVHD, high-flux dialysis membranes, AN69, etc.) and low density lipoprotein (LDL) apheresis utilising dextran sulfatecellulose may both cause severe anaphylactoid reactions.
- 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.
- The rate of blood pressure reduction must be suitable for the patient's medical condition.
- Even though it could be required to lower doses, hypotension is not a reason to stop using ACE inhibitors in the future.
- This is especially true for heart disease patients, for whom a reduction in systolic pressure is preferred.
Renal function deterioration:
- Perindopril can worsen renal function and raise blood creatinine and/or BUN levels, especially in individuals with limited renal flow (such as those with heart failure or kidney artery stenosis) and whose GFR depends on the efferent arterial vasoconstriction of angiotensin 2. Oliguria and abrupt renal failure may result from this.
- Patients with substantial and ongoing renal dysfunction may first see slight increases in serum creatinine.
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:
- Perindopril use should be monitored in patients with collagen vascular disease, especially in those who also have concurrent kidney impairment. They might be more likely to experience 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 should exercise caution if they have mild or severe renal impairment (CrCl >=30mL/minute).
- Patients with severe renal impairment (CrCl 30mL/minute) should not use it.

Perindopril and amlodipine: Drug Interaction

Risk Factor C (Monitor therapy)
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 elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Aprotinin	May lessen the effectiveness of angiotensin-converting enzyme inhibitors in treating hypertension.
ARIPiprazole	ARIPiprazole's serum levels may rise in response to CYP3A4 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.
Atosiban	Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk.
AzaTHIOprine	AzaTHIOprine's myelosuppressive effects may be enhanced by angiotensin-converting enzyme inhibitors.
Barbiturates	Calcium Channel Blockers' metabolic rate might be increased. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The Canadian labelling for nimodipine specifically warns against using it alongside phenobarbital.
Barbiturates	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Benperidol	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Bosentan	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Brigatinib	May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib.
Brimonidine (Topical	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Calcium Channel Blockers (Nondihydropyridine)	Dihydropyridine, a calcium channel blocker, may increase the hypotensive effects of calcium channel blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may cause an increase in serum calcium channel blocker concentration (Dihydropyridine).
Calcium Salts	May reduce calcium channel blockers' therapeutic efficacy.
Clofazimine	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Clopidogrel	Calcium channel blockers may reduce Clopidogrel's therapeutic efficacy.
CycloSPORINE (Systemic)	The serum concentration of CycloSPORINE may rise when Calcium Channel Blockers (Dihydropyridine) are taken (Systemic). Calcium Channel Blockers' serum levels may rise when CycloSPORINE (Systemic) is used (Dihydropyridine).
CYP3A4 Inducers (Moderate)	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	AmLODIPine serum concentration can rise.
CYP3A4 Inhibitors (Strong)	AmLODIPine serum concentration can rise.
Dapoxetine	May increase the angiotensin-converting enzyme inhibitors' orthostatic hypotensive effects.
Dapoxetine	May intensify calcium channel blockers' orthostatic hypotensive effects.
Deferasirox	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dexmethylphenidate	Can lessen an antihypertensive drug's therapeutic impact.
Diazoxide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Dipeptidyl Peptidase-IV Inhibitors	May worsen angiotensin-converting enzyme inhibitors' toxic or severe effects. Particularly, there may be a higher incidence of angioedema.
Dofetilide	Dofetilide's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak).
Drospirenone	Drospirenone's hyperkalemic impact may be enhanced by angiotensin-converting enzyme inhibitors.
DULoxetine	The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.
Duvelisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Efavirenz	Calcium Channel Blockers' serum concentration can drop.
Eplerenone	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Erdafitinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Erdafitinib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Everolimus	May intensify angiotensin-converting enzyme inhibitors' harmful or hazardous effects. Particularly, there may be a higher incidence of angioedema.
Ferric Gluconate	Angiotensin-Converting Enzyme Inhibitors might make ferric gluconate more harmful or poisonous.
Ferric Hydroxide Polymaltose Complex	Ferric Hydroxide Polymaltose Complex may have a more negative or toxic effect when taken with angiotensin-converting enzyme inhibitors. In particular, there may be an elevated risk for angioedema or allergic responses.
Flibanserin	The serum levels of Flibanserin may rise in response to CYP3A4 Inhibitors (Weak).
Fluconazole	Calcium Channel Blockers' serum levels can rise.
Fosaprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fosnetupitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Gelatin (Succinylated)	Gelatin's harmful or toxic effects may be increased by angiotensin-converting enzyme inhibitors (Succinylated). Particularly, there may be a higher chance of a paradoxical hypotensive reaction.
Gold Sodium Thiomalate	Gold Sodium Thiomalate may have a more negative or toxic effect when used with angiotensin-converting enzyme inhibitors. Nitritoid responses are more likely now, it has been noted.
Heparin	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Heparins (Low Molecular Weight)	Angiotensin-Converting Enzyme Inhibitors may have an enhanced hyperkalemic impact.
Herbs (Hypertensive Properties)	May lessen the effectiveness of antihypertensive agents.
Herbs (Hypotensive Properties)	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Hypotension-Associated Agents	The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications.
Icatibant	May lessen the effectiveness of angiotensin-converting enzyme inhibitors in treating hypertension.
Ivosidenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Larotrectinib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Loop Diuretics	May strengthen angiotensin-converting enzyme inhibitors' hypotensive effects. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be increased by loop diuretics.
Lormetazepam	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Lovastatin	AmLODIPine may make lovastatin more concentrated in the blood.
Magnesium Salts	Calcium channel blockers might make magnesium salts more harmful or poisonous. Calcium Channel Blockers' hypotensive effects may be strengthened by magnesium salts.
Melatonin	May reduce the effectiveness of calcium channel blockers as an antihypertensive (Dihydropyridine).
Methylphenidate	May lessen the effectiveness of antihypertensive agents.
Molsidomine	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Naftopidil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Netupitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Neuromuscular-Blocking Agents (Nondepolarizing)	The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing).
Nicergoline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nicorandil	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Nicorandil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
NiMODipine	NiMODipine's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak).
Nitroprusside	Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.
Nonsteroidal Anti-Inflammatory Agents	Nonsteroidal Anti-Inflammatory Agents' negative/toxic effects may be increased by angiotensin-converting enzyme inhibitors. In particular, the combination may cause a marked decline in renal function. Angiotensin-Converting Enzyme Inhibitors' antihypertensive effects may be lessened by nonsteroidal anti-inflammatory drugs.
Palbociclib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Pentoxifylline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Pholcodine	Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.
Phosphodiesterase 5 Inhibitors	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Potassium Salts	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Potassium-Sparing Diuretics	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Pregabalin	Angiotensin-Converting Enzyme Inhibitors may intensify Pregabalin's negative/toxic effects. Particularly, there may be a higher incidence of angioedema.
Prostacyclin Analogues	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Quinagolide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
QuiNIDine	The serum concentration of QuiNIDine may be lowered by calcium channel blockers (Dihydropyridine). The serum concentration of QuiNIDine may rise in response to calcium channel blockers (Dihydropyridine). Calcium Channel Blockers' serum levels may rise in response to quinine (Dihydropyridine).
Racecadotril	May intensify angiotensin-converting enzyme inhibitors' harmful or hazardous effects. In particular, this combination may make angioedema more likely.
Ranolazine	May intensify angiotensin-converting enzyme inhibitors' harmful or hazardous effects.
Salicylates	May intensify angiotensin-converting enzyme inhibitors' nephrotoxic effects. The therapeutic benefit of angiotensin-converting enzyme inhibitors may be reduced by salicylates.
Sarilumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Siltuximab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Simeprevir	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Sirolimus	May intensify angiotensin-converting enzyme inhibitors' harmful or hazardous effects.
Tacrolimus (Systemic)	Tacrolimus serum levels may rise when Calcium Channel Blockers (Dihydropyridine) are used (Systemic).
Tacrolimus (Systemic)	Tacrolimus's effect of making you more hyperkalemic may be enhanced by angiotensin-converting enzyme inhibitors (Systemic).
Temsirolimus	May intensify angiotensin-converting enzyme inhibitors' harmful or hazardous effects.
Thiazide and Thiazide-Like Diuretics	May increase the angiotensin-converting enzyme inhibitors' hypotensive effects. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be increased by thiazide and thiazide-like diuretics.
TiZANidine	May strengthen angiotensin-converting enzyme inhibitors' hypotensive effects.
Tocilizumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Tolvaptan	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Trimethoprim	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects.
Yohimbine	May lessen the effectiveness of antihypertensive agents.
Risk Factor D (Consider therapy modification)
Aliskiren	Angiotensin-Converting Enzyme Inhibitors may intensify their hyperkalemic effects. Angiotensin-Converting Enzyme Inhibitors' hypotensive effects may be strengthened by aliskiren. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be made worse by aliskiren. Treatment: It is not advised for diabetic patients to take aliskiren along with ACEIs or ARBs. Combination therapy should be avoided in other patients, especially when CrCl is less than 60 mL/min. If combined, keep a close eye on your blood pressure, potassium, and creatinine levels.
Allopurinol	Angiotensin-Converting Enzyme Inhibitors might make Allopurinol more likely to cause allergic or hypersensitive reactions.
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 worsen angiotensin-converting enzyme inhibitors' toxic or severe effects. Angiotensin-Converting Enzyme Inhibitors' serum levels may rise in response to angiotensin II receptor blockers. Management: According to US labelling, it is not advisable to take telmisartan and ramipril. It is unclear whether another ACE inhibitor and ARB combo would be any safer. When possible, take into account alternatives to the mix.
Antifungal Agents (Azole Derivatives, Systemic	Calcium Channel Blockers' harmful or toxic effects could be exacerbated. In particular, itraconazole may make verapamil or diltiazem's unfavourable inotropic effects worse. Calcium Channel Blockers' metabolism may be slowed down by antifungal agents (systemic azole derivatives). Fluconazole and isavuconazonium, which are covered in different monographs, probably have less powerful effects than those of other azoles.
Antihepaciviral Combination Products	AmLODIPine serum concentration can rise. Management: If an antihepaciviral combo treatment is started, reduce the dose of amlodipine by at least 50% and watch for any increased amlodipine side effects (such as hypotension).
CarBAMazepine	Calcium Channel Blockers' metabolism could be accelerated (Dihydropyridine). In individuals receiving concurrent carbamazepine, consider adjusting the dosage of calcium channel blockers (CCBs) or switching to an alternative form of treatment. The Canadian labelling for nimodipine expressly forbids taking it alongside carbamazepine.
CYP3A4 Inducers (Strong)	May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Enzalutamide	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.
Fosphenytoin	Calcium channel blockers may raise the level of fosphenytoin in the blood. Monitoring for phenytoin toxicity while using a calcium channel blocker (CCB) at the same time or reduced phenytoin effects while stopping the CCB are the two management options. Check for diminished therapeutic effects of CCB.
Grass Pollen Allergen Extract (5 Grass Extract)	Grass pollen allergen extract may have a more negative or toxic effect if angiotensin-converting enzyme inhibitors are used (5 Grass Extract). With regard to grass pollen allergen extract, ACE inhibitors may specifically enhance the likelihood of a severe allergic reaction (5 Grass Extract).
Iron Dextran Complex	Angiotensin-Converting Enzyme Inhibitors might make Iron Dextran Complex more harmful or poisonous. Patients taking an ACE inhibitor may be more susceptible to events of the anaphylactic variety. Management: Adhere strictly to the instructions for iron dextran administration, including the use of a test dose before the initial therapeutic dose and the availability of resuscitation tools and qualified people.
Lanthanum	May lower angiotensin-converting enzyme inhibitors' serum concentration. Angiotensin-converting enzyme inhibitors should be given at least two hours before or after lanthanum.
Lithium	The serum concentration of lithium may rise in response to angiotensin-converting enzyme inhibitors. Management: After adding an ACE inhibitor, lithium dosage decreases will probably be required. Following the addition or discontinuation of concurrent ACE inhibitor therapy, carefully monitor the patient's response to lithium.
Lomitapide	The blood levels of lomitapide may rise in the presence of CYP3A4 Inhibitors (Weak). Treatment: Patients taking 5 mg/day of lomitapide may continue doing so. Patients taking 10 mg or more of lomitapide per day should cut their dosage in half. A maximum adult dose of 30 mg/day may then be reached by titrating the lomitapide dose.
Lorlatinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Avoid using lorlatinib concurrently with any CYP3A4 substrates when even a slight drop in serum levels of the substrate could have harmful effects.
Macrolide Antibiotics	Calcium Channel Blockers' metabolic rate might be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Exceptions: Fidaxomicin, Roxithromycin, Spiramycin, and systemic azithromycin.
MiFEPRIStone	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided.
Mitotane	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.
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	The serum levels of phenytoin may rise when calcium channel blockers are used. Calcium Channel Blockers' serum levels may be reduced by phenytoin. Avoid combining nimodipine or nifedipine with phenytoin for management. With any concurrent use, keep an eye out for phenytoin toxicity and/or diminished calcium channel blocker effects.
Rifamycin Derivatives	Calcium Channel Blockers' serum concentration can drop. This predominantly affects calcium channel blockers used orally. Management: Using rifampin with certain calcium channel blockers is not advised according to the labelling in the US and Canada. Look up the relevant labelling.
Simvastatin	Simvastatin's serum levels may rise in response to AmLODIPine. Management: When at all feasible, refrain from taking simvastatin and amlodipine together. If combined, stay away from simvastatin doses higher than 20 mg per day (for adults).
Sincalide	The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility.
Sodium Phosphates	The nephrotoxic impact of sodium phosphates may be enhanced by angiotensin-converting enzyme inhibitors. In particular, there may be an increased risk of acute phosphate nephropathy. Treatment: You might want to temporarily stop taking ACEIs or look into alternatives to the oral sodium phosphate bowel preparation in order to prevent this combo. Maintaining appropriate hydration and properly monitoring renal function should be done if the combination cannot be avoided.
St John's Wort	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
Stiripentol	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.
Urapidil	Angiotensin-Converting Enzyme Inhibitors may interact with them through an unidentified method. Avoid taking urapidil and ACE inhibitors simultaneously as a management strategy.
Risk Factor X (Avoid combination)
Bromperidol	The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol.
Conivaptan	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fusidic Acid (Systemic)	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Pimozide	Pimozide's serum levels may rise in response to CYP3A4 Inhibitors (Weak).
Sacubitril	The negative or hazardous effects of sacubitril may be increased by angiotensin-converting enzyme inhibitors. In particular, this combination may raise the risk of angioedema.

Monitoring Parameters:

Blood pressure;
renal function and electrolytes;
If the patient has collagen vascular disease or renal impairment, check their CBC with differential on a regular basis.
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 prevents calcium ions from entering the "slow channel" or particular voltage-sensitive regions of the heart and vascular smooth muscles during the depolarization phase. It results in coronary vasodilation and smooth muscle relaxation.
- Amlodipine causes peripheral arterial vasodilation and decreases peripheral resistance by acting directly on the vascular smooth muscles.
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.

Coversam (Perindopril and Amlodipine) - Dosage, Side effects

Coversam (Perindopril and amlodipine) Uses:

Hypertension:

Coversam (Perindopril and amlodipine) Dose in Adults

Coversam Dose in the treatment of Hypertension:

Coversam (Perindopril and amlodipine) Dose in Childrens

Pregnancy Risk Factor D

Use of amlodipine and perindopril while breastfeeding

Coversam Dose in Kidney Disease:

CrCl 30 to 80 mL/minute:

CrCl <30 mL/minute:

Hemodialysis:

Coversam Dose in Liver Disease:

Side Effects of Perindopril and amlodipine Include:

Cardiovascular:

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Renal:

Respiratory:

Contraindications to Coversam (Perindopril and amlodipine):

Canadian labeling:Additional contraindications not listed in the US labeling:

Warnings and precautions

Angina and MI

Angioedema

Cholestatic jaundice

Cough:

Hematologic effects

Hyperkalemia:

Hypersensitivity reactions

Hypotension/syncope

Renal function deterioration:

Aortic stenosis

Cardiovascular disease

Collagen vascular disease:

Hepatic impairment

Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

Renal artery stenosis

Renal impairment

Monitoring Parameters:

How to administer Coversam (Perindopril and amlodipine)?

Mechanism of action of Coversam (Perindopril and amlodipine):

International Brands of Perindopril and amlodipine:

Perindopril and amlodipine Brand Names in Pakistan:

Perindopril and amlodipine 4 mg Tablets

Perindopril and amlodipine 8 mg Tablets

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