Perindopril/ Amlodipine

Registered South African indications:

• Hypertension
  - In patients already stabilised with perindopril and amlodipine at equivalent dosages
  - In patients uncontrolled on either perindopril or amlodipine monotherapy

Linked to perindopril: Should a woman become pregnant while receiving perindopril/ amlodipine, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine

Registered South African contraindications

Linked to perindopril

• Hypersensitivity to perindopril (ACE inhibitor) or any other ACE-inhibitor 
• History of angioedema (Quincke’s oedema) associated with previous ACE inhibitor therapy: These patients must never again be given these medicines
• Hereditary/idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Pregnancy
• Lactation
• Severe renal function impairment (Creatinine clearance <30ml/min)
• Concomitant use with aliskiren-containing products
• Concomitant use with sacubitril/valsartan. Treatment with sacubitril/valsartan and perindopril must be separated by at least 36 hours. Neither should be initiated within 36 hours of the last dose of the other
• Extracorporeal treatments leading to contact of blood with negatively charged surfaces
• Aortic stenosis
• Concomitant therapy with potassium-sparing diuretics such as spironolactone, triamterene, amiloride
• Porphyria
• Lithium therapy: Concomitant administration with perindopril/ amlodipine may lead to toxic blood concentrations of lithium
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Concomitant use of fluoroquinolones with ACE-inhibitors/ renin angiotensin receptor blockers is contraindicated in patients with moderate to severe renal failure and in elderly patients 
  - Creatinine clearance ≤30ml/min (5/5 (mg), 10/5 (mg), 5/10 (mg), 10/10 (mg))
  - Creatinine clearance ≤50ml/min (4/5 (mg), 4/10 (mg), 8/5 (mg), 8/10 (mg))

Linked to amlodipine

• Hypersensitivity to amlodipine or to any other dihydropyridine derivatives
• Severe hypotension
• Shock, including cardiogenic shock
• Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
• Haemodynamically unstable heart failure after acute myocardial infarction

Linked to perindopril/ amlodipine

• Hypersensitivity to any of the excipients
• All contraindications related to each mono-component, as listed above, should also apply to the fixed combination of perindopril and amlodipine

Contraindications registered in other jurisdictions

Linked to perindopril

• Hypersensitivity to perindopril or to any other ACE inhibitor
• History of angioedema associated with previous ACE inhibitor therapy
• Hereditary or idiopathic angioedema
• Second and third trimesters of pregnancy
• Concomitant use with sacubitril/valsartan therapy. Perindopril/ amlodipine must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan
• Extracorporeal treatments leading to contact of blood with negatively charged surfaces
• Significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney

Linked to amlodipine

• Hypersensitivity to amlodipine or to any other dihydropyridines
• Severe hypotension
• Shock, including cardiogenic shock
• Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
• Haemodynamically unstable heart failure after acute myocardial infarction

Linked to perindopril/ amlodipine

• Hypersensitivity to any of the excipients
• All contraindications related to each monocomponent, as listed above, should apply also to the fixed combination of perindopril/ amlodipine
• Concomitant use of perindopril/ amlodipine with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73m²)

Recommendations in South Africa & other jurisdictions

Caution in the following patient groups

• First trimester of pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment (CrCl<60ml/min)
• Hepatic impairment
• Elderly

Linked to perindopril

Hypersensitivity/ angioedema

• Angioedema of the face, extremities, lips, mucous membranes, tongue, glottis, and/or larynx has been reported in patients treated with ACE-inhibitors, including perindopril. This can occur at any time during therapy
• Perindopril/ amlodipine should be promptly discontinued and appropriate monitoring should be initiated and continued until complete resolution of symptoms has occurred. Swelling confined to the face and lips generally resolves without treatment, although antihistamines can be useful in relieving symptoms
• Angioedema associated with laryngeal oedema may be fatal. If the tongue, glottis, or larynx is involved, likely causing airway obstruction, emergency therapy should be administered promptly, potentially including the administration of epinephrine (adrenaline) and/or maintenance of the patient’s airway
• Patients should be under close medical supervision until complete and sustained resolution of symptoms has occurred

Intestinal angioedema

• Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain, with or without nausea or vomiting
• In some cases, there was no prior facial angioedema and C-1 esterase levels were normal. Diagnosis was made through procedures including abdominal CT scan, ultrasound, or surgery
• Symptoms resolved after stopping the ACE inhibitor.  Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain

Concomitant use of NEP inhibitors and ACE inhibitors

• Concomitant use of other NEP inhibitors (e.g., racecadotril) with an ACE inhibitor may increase the risk of angioedema
• A careful assessment of the benefit-to-risk ratio is necessary before initiating treatment with NEP inhibitors (e.g., racecadotril) in patients receiving perindopril

Concomitant use of ACE inhibitors with mTOR inhibitors or vildagliptin

• Concomitant use of ACE inhibitors with mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus) or vildagliptin may increase the risk of angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment
• Caution should be used when starting mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus) or vildagliptin in a patient already taking an ACE inhibitor

Anaphylactoid reactions during LDL apheresis

• Life-threatening anaphylactoid reactions have been experienced by patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulphate. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis

Anaphylactoid reactions during desensitisation

• Patients receiving ACE inhibitors during desensitisation treatment (e.g., hymenoptera venom) have experienced anaphylactoid reactions. These reactions were avoided when ACE inhibitors were temporarily withheld but reappeared upon inadvertent resumption of treatment

Neutropenia/agranulocytosis/thrombocytopenia/anaemia

• These conditions have been reported in patients receiving ACE inhibitors. Neutropenia occurs rarely in patients with normal renal function and no other complicating factors
• Perindopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these factors, especially if there is pre-existing impaired renal function
• Serious infections that do not respond to intensive antibiotic therapy have occurred in some patients. Periodical monitoring of white blood cell counts is advised, and patients should report any signs of infection (e.g., sore throat, fever)

Renovascular hypertension

• There is an increased risk of hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors. Treatment with diuretics may contribute to this risk
• Loss of renal function may occur with only minor changes in serum creatinine, even in patients with unilateral renal artery stenosis

Primary hyperaldosteronism

• Patients with primary hyperaldosteronism typically do not respond to antihypertensive medicines that inhibit the renin-angiotensin system
• As a result, the use of this medicine is not recommended for these patients

Hypotension

• ACE inhibitors may cause a fall in blood pressure. Symptomatic hypotension is rare in uncomplicated hypertensive patients but more likely in those who are volume-depleted (e.g., by diuretic therapy, dietary salt restriction, dialysis, diarrhoea, or vomiting) or have severe renin-dependent hypertension
• In high-risk patients, monitor blood pressure, renal function, and serum potassium closely during treatment with perindopril and amlodipine
• Similar considerations apply to patients with ischaemic heart or cerebrovascular disease, where an excessive fall in blood pressure could lead to myocardial infarction or cerebrovascular accident
• If hypotension occurs, place the patient in the supine position and, if necessary, administer an intravenous infusion of isotonic sodium chloride
• Transient hypotension is not a contraindication to further doses, which can usually be given without difficulty once blood pressure has increased after volume expansion

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy

• As with other ACE inhibitors, perindopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy

Race

• ACE inhibitors cause a higher rate of angioedema in black patients compared to non-black patients
• Perindopril may be less effective in lowering blood pressure in black patients, possibly due to a higher prevalence of low-renin states in the black hypertensive population

Cough

• A dry, non-productive, and persistent cough has been reported with the use of ACE inhibitors
• The cough typically resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough

Surgery/ anaesthesia

• In patients undergoing major surgery or during anaesthesia with hypotension-inducing agents, perindopril/ amlodipine may block angiotensin II formation due to compensatory renin release
• Treatment should be discontinued one day prior to surgery. Hypotension due to this mechanism can be corrected by volume expansion

Hyperkalaemia

• Elevations in serum potassium have been observed with ACE inhibitors like perindopril
• Risk factors include renal insufficiency, age over 70, diabetes mellitus, dehydration, acute cardiac decompensation, metabolic acidosis, and use of potassium-sparing diuretics, potassium supplements, or certain other medications
• Hyperkalaemia can cause serious, sometimes fatal dysrhythmias. Concomitant use of these medications should be done with caution and frequent serum potassium monitoring

Diabetic patients

• Glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor in diabetic patients treated with oral antidiabetic medicines or insulin

Linked to amlodipine

Use in patients with cardiac failure

• Patients with heart failure should be treated with caution
• A long-term, placebo-controlled study in patients with severe heart failure (NYHA class III and IV) reported a higher incidence of pulmonary oedema in the amlodipine-treated group than in the placebo group
• Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality

Hypertensive crisis

• The safety and efficacy of amlodipine in hypertensive crisis have not been established

Linked to perindopril/ amlodipine

Linked to the combination of perindopril and amlodipine

• All warnings related to each mono-component, as listed above, should apply also to the fixed combination of perindopril and amlodipine

Level of sodium

• Perindopril/ amlodipine contains less than 1mmol sodium (23mg) per tablet, i.e. essentially 'sodium-free'

Additional South African precautions

Linked to perindopril

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

• There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers (ARBs) or aliskiren may increase the risk of hypotension, hyperkalaemia and decreases renal function (including acute renal failure)
• Dual blockade of RAAS through the combined use of perindopril/ amlodipine and aliskiren is therefore contraindicated. Perindopril/ amlodipine should not be used concomitantly with aliskiren (see Contraindications)

Fluoroquinolones and ACE-inhibitors/ renin angiotensin receptor blockers

• Concomitant use of fluoroquinolones and ACE inhibitors or Renin angiotensin receptor blockers may precipitate acute kidney injury, especially in those with moderate to severe renal impairment and elderly patients
• Renal function should be assessed before and monitored during treatment with fluoroquinolones or ACE inhibitors/ renin angiotensin receptor blockers, whether used separately or together

Linked to perindopril/ amlodipine

Isomalt

• Patients with rare hereditary problems of fructose intolerance should not take this medicine (certain formulations - check product specific information)

Lactose

• Patients with rare hereditary problems of galactose intolerance e.g. galactasaemia, Lapp lactase deficiency, or glucose-galactose malabsorption or fructose intolerance should not take perindopril/ amlodipine (certain formulation check product specific information)

Ability to drive and use machines

• No studies on the effects of the combination of perindopril and amlodipine on the ability to drive and use machines have been performed
• Amlodipine can have minor or moderate influence on the ability to drive and use machines. If patients treated
  with amlodipine experience dizziness, headache, fatigue, weariness or nausea, the ability to react may be
  impaired. Caution is recommended especially at the start of treatment

Additional precautions in other jurisdictions

Link to perindopril

Dual blockade of the Renin-Angiotensin-Aldosterone System (RAAS)

• The concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalaemia, and decreased renal function, including acute renal failure
• Dual blockade of RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended
• If dual blockade therapy is deemed absolutely necessary, it should only occur under specialist supervision with frequent close monitoring of renal function, electrolytes, and blood pressure
• ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy

Linked to perindopril/ amlodipine

Interactions

• The concomitant use of perindopril/ amlodipine with lithium, potassium-sparing diuretics, or potassium supplements is not recommended

Effects on ability to drive and use machines

• No studies on the effects of perindopril/ amlodipine on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Hypertension
- In patients already stabilised with perindopril and amlodipine at equivalent dosages
- In patients uncontrolled on either perindopril or amlodipine monotherapy

Perindopril/ Amlodipine
4/5 (mg)
4/10 (mg)
8/5 (mg)
8/10 (mg)
5/5 (mg)
10/5 (mg)
5/10 (mg)
10/10 (mg)

• Oral (tab): 1 tab, daily preferably to be taken in the morning before breakfast

---

The fixed dose combination is not suitable for initiation therapy. If a change in dose is required, the dose of perindopril/ amlodipine should be modified

Not established for use in children and adolescents

Pregnancy

South African recommendations

• Contraindicated

Linked to perindopril

• The use of perindopril/ amlodipine is contraindicated during pregnancy
• Pregnant women shoμld be informed of the potential hazards to the foetus and must not take perindopril/ amlodipine during pregnancy
• Patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with perindopril/ amlodipine should be stopped immediately and if appropriate, alternative therapy should be started
• Foetal exposure to ACE inhibitors during the first trimester of pregnancy has been reported to be associated with an increased risk of malformations of the cardiovascular (atrial and/or ventricular septal defect, pulmonic stenosis, patent ductus arteriosus) and central nervous system (microcephaly spina bifida) and of kidney malformations
• Perindopril/ amlodipine passes through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms
• Oligohydramnios as well as hypotension, oliguria and anuria in new-borns, have been reported after administration of perindopril/ amlodipine during the second and third trimester
• Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur

Linked to amlodipine

• The safety of amlodipine in human pregnancy has not been established
• In animal studies, reproductive toxicity was observed at high doses

Recommendations in other jurisdictions

• First trimester: Caution; not recommended
• Second and third trimester: Contraindicated
• Given the effects of the individual components in this combination product on pregnancy, perindopril/ amlodipine is not recommended during the first trimester of pregnancy
• Perindopril/ amlodipine is contraindicated during the second and third trimesters of pregnancy

Linked to perindopril

• The use of ACE inhibitors is not recommended during the first trimester of pregnancy
• The use of ACE inhibitors is contraindicated during the second and third trimester of pregnancy
• Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded
• Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started
• Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia)
• Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension

Linked to amlodipine

• The safety of amlodipine in human pregnancy has not been established
• Data on a limited number of exposed pregnancies do not indicate that amlodipine or other calcium receptor antagonists have a harmful effect on the health of the foetus. However, there may be a risk of prolonged delivery. In animal studies, reproductive toxicity was observed at high doses
• Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus

Breastfeeding

South African recommendations

• Contraindicated

Linked to perindopril

• Because no information is available regarding the use of perindopril during lactation, perindopril is contraindicated

Linked to amlodipine

• Safety of amlodipine during lactation has not been established. It is not known whether amlodipine is excreted in breast milk

Recommendations in other jurisdictions

• Caution; not recommended

Linked to perindopril

• Because no information is available regarding the use of perindopril during breastfeeding, perindopril/ amlodipine is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant

Linked to amlodipine

• Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3-7%, with a maximum of 15%. The effect of amlodipine on infants is unknown
• A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breastfeeding to the child and the benefit of amlodipine therapy to the mother

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

Linked to perindopril

• There was no effect on reproductive function or fertility

Linked to amlodipine

• Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility

South African recommendations

• CrCl≥60ml/min: No dose adjustment recommended
• CrCl<60ml/min: Caution; not recommended
  Elimination of perindoprilat is decreased in patients with renal failure. Therefore, the usual medical follow-up will include frequent monitoring of creatinine and potassium
  Perindopril/ amlodipine can be administered in patients with CrCl≥60ml/min, and is not suitable for patients with CrCl<60 ml/min. In these patients, an individual dose titration with the monocomponents is recommended
  Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment
  Amlodipine is not dialysable
• CrCl≤30ml/min: Contraindicated

Recommendations in other jurisdictions

• CrCl≥60ml/min: No dose adjustment recommended
• CrCl<60ml/min: Caution; not recommended
  Elimination of perindoprilat is decreased in patients with renal failure. Therefore, the usual medical follow-up will include frequent monitoring of creatinine and potassium
  Perindopril/ amlodipine can be administered in patients with CrCl≥60ml/min, and is not suitable for patients with CrCl<60 ml/min. In these patients, an individual dose titration with the monocomponents is recommended
  Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment
  Amlodipine is not dialysable

Recommendations below are applicable to South Africa and other jurisdictions

• Mild to moderate: Caution; dose adjustment recommended
  Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautious and should start at the lower end of the dosing range
  To find the optimal starting dose and maintenance dose of patients with hepatic impairment, the patients should be individually titrated using the free combination of amlodipine and perindopril
• Caution; no information available
  The pharmacokinetics of amlodipine have not been studied in severe hepatic impairment
  Amlodipine should be initiated at the lowest dose and titrated slowly in patients with severe hepatic impairment

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  Elimination of perindoprilat is decreased in the elderly. Therefore, the usual medical follow-up will include frequent monitoring of creatinine and potassium
  Normal dosage regimens are recommended in the elderly

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Perindopril
Central Nervous System Disorders

• Mood disturbances
• Sleep disorder
• Dizziness
• Headache
• Paraesthesia
• Vertigo
• Somnolence
• Syncope
• Confusion
• Malaise

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Angina pectoris
• Arrhythmia
• Myocardial infarction
• Hypotension
• Vasculitis
• Stroke 
• Chest pain
• Peripheral oedema
• Orthostatic effects

Respiratory Disorders

• Cough
• Dyspnoea
• Bronchospasm
• Eosinophilic pneumonia
• Rhinitis
• Asthenia
• Sinusitis

Gastrointestinal Disorders

• Abdominal pain
• Constipation
• Diarrhoea
• Dysgeusia
• Dyspepsia
• Nausea and vomiting
• Dry mouth
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis 
• Increased serum bilirubin 
• Increased serum hepatic enzymes

Genitourinary Disorders

• Renal insufficiency
• Acute renal failure
• Uraemia
• Oliguria
• Anuria
• Increased serum urea 
• Increased serum creatinine 

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Hyperkalaemia
• Hyponatraemia
• Erectile dysfunction

Musculoskeletal Disorders

• Muscle cramps
• Arthralgia
• Myalgia
• Asthenia

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Rash
• Urticaria
• Angioedema 
• Photosensitivity 
• Pemphigoid
• Hyperhidrosis
• Erythema multiforme
• Psoriasis aggravation
• Diaphoresis
• Alopecia
• Psoriasis
• Pemphigus
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome

Immune, Blood and Lymphatic System Disorders

• Eosinophilia
• Agranulocytosis
• Pancytopenia
• Increased haemoglobin 
• Increased haematocrit 
• Leucopenia
• Neutropenia
• Haemolytic anaemia
• Thrombocytopenia
• Pyrexia

Sensory Disorders

• Visual disturbances
• Tinnitus

Amlodipine
Central Nervous System Disorders

• Dizziness
• Headache
• Tremor
• Dysgeusia
• Syncope
• Hypoaesthesia
• Paraesthesia
• Hypertonia
• Peripheral neuropathy
• Extrapyramidal disorder
• Depression
• Mood changes
• Insomnia
• Confusion
• Fatigue
• Asthenia
• Malaise

Cardiovascular Disorders

• Palpitations
• Arrhythmia
• Myocardial infarction
• Flushing
• Hypotension
• Vasculitis
• Chest pain

Respiratory Disorders

• Dyspnoea
• Cough
• Rhinitis

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Dyspepsia
• Altered bowel habits 
• Dry mouth
• Pancreatitis
• Gastritis
• Gingival hyperplasia

Hepatobiliary Disorders

• Hepatitis
• Jaundice 
• Increased hepatic enzymes 

Genitourinary Disorders

• Impotence
• Micturition disorder
• Nocturia
• Increased urinary frequency

Endocrine and Metabolic Disorders

• Weight gain
• Hyperglycaemia
• Gynecomastia

Musculoskeletal Disorders

• Ankle swelling
• Muscle cramps
• Arthralgia
• Myalgia
• Back pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Purpura
• Skin discolouration
• Hyperhidrosis
• Pruritus
• Rash
• Exanthema
• Urticaria
• Angioedema
• Erythema multiforme
• Exfoliative dermatitis
• Stevens-Johnson syndrome
• Quincke oedema
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Leukocytopenia
• Thrombocytopenia
• Immune system disorders
• Allergic reactions

Sensory Disorders

• Tinnitus
• Visual disturbance

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Perindopril

• Sacubitril/ valsartan
• Potassium sparing diuretics
• Spironolactone
• Triamterene
• Amiloride
• Fluoroquinolones
• Diuretics
• Antihypertensive agents
• Agents that increase serum potassium
• Lithium
• Antidiabetic agents
• Sympathomimetics
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers 
• Aliskiren
• Racecadotril
• Non-steroidal anti-inflammatory drugs
• Heparins
• Immunosuppressant agents 
• mTOR inhibitors
• Estramustine
• Baclofen
• Gliptins
• Anaesthetic agents
• Tricyclic antidepressants
• Antipsychotics
• Gold

Amlodipine

• CYP3A4 inhibitors
• CYP314 inducers
• Dantrolene
• Tacrolimus
• Cyclosporine
• Simvastatin 

None routine. Specific cases may require

• Electrolytes
• Renal function 
• Full blood count

Perindopril
Perindopril is an angiotensin-converting enzyme inhibitor. Inhibition of this enzyme results in a reduction of angiotensin II levels, which leads to increased plasma renin activity and reduced secretion of aldosterone. It also causes an increase in the activity of circulating and local kallikrein-kinin systems.

Amlodipine
Amlodipine is a calcium ion influx inhibitor and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. Amlodipine dialtes peripheral arterioles and thus reduces afterload, it also dilates coronary arteries and arterioles which increases myocardial oxygen delivery. 

COMBINATION PREPARATIONS

Perindopril/ Amlodipine

Tablet 4mg/5mg

• Pearloc (Pharma Dynamics)

Tablet 5mg/5mg

• Coveram (Servier Laboratories SA) originator
• Mixanval 5/5 (Servier Laboratories SA)
• Reaptan (Servier Laboratories SA)

Tablet 4mg/10mg

• Pearloc (Pharma Dynamics)

Tablet 10mg/5mg

• Coveram (Servier Laboratories SA) originator
• Mixanval 10/5 (Servier Laboratories SA)
• Reaptan (Servier Laboratories SA)

Tablet 8mg/5mg

• Pearloc (Pharma Dynamics)

Tablet 5mg/10mg

• Coveram (Servier Laboratories SA) originator
• Mixanval 5/10 (Servier Laboratories SA)
• Reaptan (Servier Laboratories SA)

Tablet 8mg/10mg

• Pearloc (Pharma Dynamics)

Tablet 10mg/10mg

• Coveram (Servier Laboratories SA) originator
• Mixanval 10/10 (Servier Laboratories SA)
• Reaptan (Servier Laboratories SA)