Drugs List

Therapeutic Indications

Uses

Essential hypertension when stabilised on same ingreds.in same proportions
Stable coronary artery disease when stabilised on same ingreds. & strengths

Contraindications

Children under 18 years
Desensitisation therapy
Within 36 hours of discontinuing a sacubitril containing product
Breastfeeding
Cardiac failure within 1 month of a myocardial infarction
Cardiogenic shock
Haemodialysis with high flux membranes
Haemodynamic instability
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Left ventricular outflow obstruction
Pregnancy
Renal artery stenosis
Renal impairment - creatinine clearance below 60ml/minute
Severe aortic stenosis
Severe hypotension
Unstable angina

Precautions and Warnings

Elderly
Immunosuppression
Aortic stenosis
Atherosclerosis
Cardiac failure
Cerebral ischaemia
Collagen vascular disease
Dehydration
Diabetes mellitus
Electrolyte depletion
Hepatic impairment
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Ischaemic heart disease
Metabolic acidosis
Mitral stenosis
Peripheral vascular disease
Renovascular disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaphylactoid reactions possible with highly permeable dialysis membranes
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Place patient in supine position if severe hypotension occurs
Evaluate renal function before and during treatment
Exclude pregnancy prior to initiation of treatment
Monitor serum electrolytes before and during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure regularly
Monitor patients with renovascular disease
Monitor serum potassium regularly
Reduce dose/discontinue if serum creatinine or blood urea increases
Advise patients at risk of neutropenia to report any signs of infection
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue temporarily in LDL apheresis or desensitisation therapy
Discontinue treatment 24 hours prior to surgery
Discontinue at first signs of jaundice,cholestasis,hepatitis
Discontinue immediately if angioedema of the tongue/glottis/larynx occurs
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise on problems of salt substitutes/high intake of potassium-rich food
Grapefruit prod increase dihydropyridine Ca channel blocker bioavailability
Female: Ensure adequate contraception during treatment

Systematic testing should be carried out for clinical signs of water and electrolyte depletion, which may occur with an intercurrent episode of diarrhoea or vomiting. Marked hypotension may require the implementation of an intravenous infusion of isotonic saline.
Transient hypotension is not a contraindication to continuation of treatment. After re-establishment of a satisfactory blood volume and blood pressure, treatment can be started again either at a reduced dose or with only one of the constituents.

Elevated potassium levels may occur during ACE inhibitor therapy. Those especially at risk of hyperkalaemia include renal impairment, worsening of renal function, age (greater than 70 years), diabetes mellitus, inter-current events, in particular dehydration, acute cardiac decompensation and metabolic acidosis.

If renovascular hypertension is present there may be an increased risk of severe hypotension and renal impairment.

Perindopril treatment should be stopped immediately if the patient develops angioedema of the face, extremities, lips, tongue, glottis and/or larynx. This may occur at any time during treatment. In such cases, the patient should be monitored until the oedema has disappeared. When confined to the face and lips, angioedema usually resolves without treatment. However antihistamines have been used. Angioedema involving the tongue, glottis or larynx may be fatal.
Appropriate emergency therapy should be given (e.g. adrenaline/maintenance of patent airway). The patient should be hospitalised and observed for at least 12 to 24 hours and should not be discharged until complete resolution of symptoms has occurred.
Patients with a history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema while receiving an ACE inhibitor. Intestinal angioedema can occur in patients treated with ACE inhibitors, and should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Symptomatic hypotension is more likely to occur in patients who have been volume-depleted and salt-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension. Patients at risk should be closely supervised during initiation of therapy and during dose adjustment. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

A persistent, non-productive cough may occur which usually resolves itself after therapy is discontinued. An iatrogenic aetiology should be considered in the event of this symptom. If the prescription of an ACE inhibitor is still preferred, continuation of treatment may be considered.

The treatment of renovascular hypertension is revascularisation. Nonetheless, ACE inhibitors can be beneficial in patients with renovascular hypertension who are awaiting corrective surgery or when such a surgery is not possible. Treatment should be started in a hospital setting at a low dose and renal function and potassium levels should be monitored, since some patients have developed a functional renal insufficiency which was reversed when treatment was stopped.

Pregnancy and Lactation

Pregnancy

Perindopril with amlodipine is contraindicated during the second and third trimesters of pregnancy and should be avoided during the first trimester.

Perindopril
It is not known if perindopril or its metabolite perindoprilat crosses the human placenta. The molecular weights (about 368 for the free acid and 442 for the salt form) suggest that transfer to the foetus will occur (Briggs, 2011).

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy as exposure during these trimesters is known to induce human foetal toxicity (renal dysfunction, oligohydramnios, pulmonary hypoplasia, patent ductus arteriosus, delay in skull ossification, neonatal toxicity and even death). Severe and sometimes fatal anuria in the foetus and in the newborn have been observed and is thought to be caused by the compromise of the foetal renal system. Foetal renal failure resulting from in utero exposure to ACE inhibitors has been reported where dialysis has been required shortly after birth. Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA recommends that a risk cannot be excluded. Recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. Unless treatment with an ACE inhibitor is considered absolutely essential, women who are planning to become pregnant should be switched to an alternative drug with an established safety record. If exposure has occurred in the first trimester a detailed ultrasound diagnosis is advisable. Exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. In cases involving long term prenatal therapy in the second and/ or third trimesters, the foetus should be monitored for the potential development of oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans (Schaefer, 2007).

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension.

Amlodipine
Some dihydropyridine compounds have been found to be teratogenic in animals. However, amlodipine was found not to be teratogenic or embryotoxic in rats and rabbits up to 8 and 23 times, respectively, the maximum human dose based on BSA (MRHD) during their respective periods of major organogenesis. Effects on reproduction in animals were found at high dosages (including delayed parturition, difficult labour and impaired foetal and pup survival) (Briggs, 2011). There is no adequate data for the use of amlodipine in pregnant women. The molecular weight of amlodipine is low enough that passage to the foetus should be expected. Calcium channel blockers may inhibit labour (Schaefer,2007). In the first trimester, calcium antagonists are considered to be second-line therapy. Manufacturers advise amlodipine should not be administered during pregnancy or to women of childbearing potential unless effective contraception is used unless clearly needed. Schaefer (2007) suggests that if exposure to amlodipine has occurred during the first trimester, a detailed ultrasound diagnosis is advisable. Overall exposure to a calcium antagonist during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Perindopril with amlodipine is contraindicated during breastfeeding.

Perindopril
The effect of perindopril treatment on nursing infants has not been determined, however, due to its molecular size it is likely that perindopril and the active metabolite perindoprilat are excreted in breast milk, lactating mothers are advised not to breast feed while taking perindopril.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not absolutely contraindicated and may be prescribed if treatment is considered essential. The MHRA state that ACE inhibitors should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension particularly in preterm infants. If ACE inhibitor therapy is considered essential for the mother the use of captopril, enalapril or quinapril may be considered when the infant is older. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary.

Amlodipine
There is no adequate data for the use of amlodipine in breastfeeding. Hale (2010) comments that because most calcium channel blockers readily transfer into milk, that the same should be assumed for this drug. The molecular weight of amlodipine is low enough that excretion into breast milk should be expected. No paediatric concerns have been reported but the infant should be observed for bradycardia or hypotension upon prolonged use. Guidelines from NICE recommend that women who still need antihypertensive treatment in the postnatal period are told that there is insufficient evidence on the safety in babies receiving breast milk of amlodipine. Some manufacturers advise patients to stop breast feeding during treatment with amlodipine as it is not known whether amlodipine is excreted in breast milk. Schaefer (2007) comments that individual doses of amlodipine do not require limitation of breastfeeding, but therapy should be changed. An alternative drug may be preferred.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal failure
Agranulocytosis
Allergic reaction
Alopecia
Altered bowel habit
Angina pectoris
Angioedema
Anxiety
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bradycardia
Bronchospasm
Chest pain
Cholestatic jaundice
Confusion
Constipation
Cough
Decrease in haemoglobin and haematocrit
Depression
Diarrhoea
Diplopia
Dizziness
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Eosinophilic pneumonia
Erythema multiforme
Exanthema
Exfoliative dermatitis
Fatigue
Flushing
Gastritis
Gingival hyperplasia
Gynaecomastia
Haemolytic anaemia
Headache
Hepatitis
Hyperglycaemia
Hyperkalaemia
Hypertonia
Hypoaesthesia
Hypoglycaemia
Hypotension
Impotence
Increase in blood urea or creatinine
Increased sweating
Increased urinary frequency
Increases in hepatic enzymes
Insomnia
Leucopenia
Malaise
Micturition disorders
Mood changes
Muscular cramps
Myalgia
Myocardial infarction
Nausea
Neutropenia
Nocturia
Oedema
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Photosensitivity
Pruritus
Purpura
Quincke's oedema
Rash
Renal impairment
Rhinitis
Serum bilirubin increased
Skin discolouration
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Stroke
Syncope
Thrombocytopenia
Tinnitus
Tremor
Urticaria
Vasculitis
Ventricular tachycardia
Vertigo
Visual disturbances
Vomiting
Weight changes

Presentation

Oral formulations of perindopril erbumine with amlodipine.

Drugs List

Therapeutic Indications

Uses

Essential hypertension when stabilised on same ingreds.in same proportions
Stable coronary artery disease when stabilised on same ingreds. & strengths

Dosage

Adults

Elderly

Patients with Renal Impairment

Contraindications

Children under 18 years
Desensitisation therapy
Within 36 hours of discontinuing a sacubitril containing product
Breastfeeding
Cardiac failure within 1 month of a myocardial infarction
Cardiogenic shock
Haemodialysis with high flux membranes
Haemodynamic instability
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Left ventricular outflow obstruction
Pregnancy
Renal artery stenosis
Renal impairment - creatinine clearance below 60ml/minute
Severe aortic stenosis
Severe hypotension
Unstable angina

Precautions and Warnings

Elderly
Immunosuppression
Aortic stenosis
Atherosclerosis
Cardiac failure
Cerebral ischaemia
Collagen vascular disease
Dehydration
Diabetes mellitus
Electrolyte depletion
Hepatic impairment
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Ischaemic heart disease
Metabolic acidosis
Mitral stenosis
Peripheral vascular disease
Renovascular disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaphylactoid reactions possible with highly permeable dialysis membranes
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Place patient in supine position if severe hypotension occurs
Evaluate renal function before and during treatment
Exclude pregnancy prior to initiation of treatment
Monitor serum electrolytes before and during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure regularly
Monitor patients with renovascular disease
Monitor serum potassium regularly
Reduce dose/discontinue if serum creatinine or blood urea increases
Advise patients at risk of neutropenia to report any signs of infection
Higher incidence of angioedema in black patients
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue temporarily in LDL apheresis or desensitisation therapy
Discontinue treatment 24 hours prior to surgery
Discontinue at first signs of jaundice,cholestasis,hepatitis
Discontinue immediately if angioedema of the tongue/glottis/larynx occurs
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise on problems of salt substitutes/high intake of potassium-rich food
Grapefruit prod increase dihydropyridine Ca channel blocker bioavailability
Female: Ensure adequate contraception during treatment

Systematic testing should be carried out for clinical signs of water and electrolyte depletion, which may occur with an intercurrent episode of diarrhoea or vomiting. Marked hypotension may require the implementation of an intravenous infusion of isotonic saline.
Transient hypotension is not a contraindication to continuation of treatment. After re-establishment of a satisfactory blood volume and blood pressure, treatment can be started again either at a reduced dose or with only one of the constituents.

Elevated potassium levels may occur during ACE inhibitor therapy. Those especially at risk of hyperkalaemia include renal impairment, worsening of renal function, age (greater than 70 years), diabetes mellitus, inter-current events, in particular dehydration, acute cardiac decompensation and metabolic acidosis.

If renovascular hypertension is present there may be an increased risk of severe hypotension and renal impairment.

Perindopril treatment should be stopped immediately if the patient develops angioedema of the face, extremities, lips, tongue, glottis and/or larynx. This may occur at any time during treatment. In such cases, the patient should be monitored until the oedema has disappeared. When confined to the face and lips, angioedema usually resolves without treatment. However antihistamines have been used. Angioedema involving the tongue, glottis or larynx may be fatal.
Appropriate emergency therapy should be given (e.g. adrenaline/maintenance of patent airway). The patient should be hospitalised and observed for at least 12 to 24 hours and should not be discharged until complete resolution of symptoms has occurred.
Patients with a history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema while receiving an ACE inhibitor. Intestinal angioedema can occur in patients treated with ACE inhibitors, and should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Symptomatic hypotension is more likely to occur in patients who have been volume-depleted and salt-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension. Patients at risk should be closely supervised during initiation of therapy and during dose adjustment. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

A persistent, non-productive cough may occur which usually resolves itself after therapy is discontinued. An iatrogenic aetiology should be considered in the event of this symptom. If the prescription of an ACE inhibitor is still preferred, continuation of treatment may be considered.

The treatment of renovascular hypertension is revascularisation. Nonetheless, ACE inhibitors can be beneficial in patients with renovascular hypertension who are awaiting corrective surgery or when such a surgery is not possible. Treatment should be started in a hospital setting at a low dose and renal function and potassium levels should be monitored, since some patients have developed a functional renal insufficiency which was reversed when treatment was stopped.

Pregnancy and Lactation

Pregnancy

Perindopril with amlodipine is contraindicated during the second and third trimesters of pregnancy and should be avoided during the first trimester.

Perindopril
It is not known if perindopril or its metabolite perindoprilat crosses the human placenta. The molecular weights (about 368 for the free acid and 442 for the salt form) suggest that transfer to the foetus will occur (Briggs, 2011).

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy as exposure during these trimesters is known to induce human foetal toxicity (renal dysfunction, oligohydramnios, pulmonary hypoplasia, patent ductus arteriosus, delay in skull ossification, neonatal toxicity and even death). Severe and sometimes fatal anuria in the foetus and in the newborn have been observed and is thought to be caused by the compromise of the foetal renal system. Foetal renal failure resulting from in utero exposure to ACE inhibitors has been reported where dialysis has been required shortly after birth. Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA recommends that a risk cannot be excluded. Recent data published does associate first trimester ACE inhibitor exposure with congenital CNS and cardiovascular defects. Unless treatment with an ACE inhibitor is considered absolutely essential, women who are planning to become pregnant should be switched to an alternative drug with an established safety record. If exposure has occurred in the first trimester a detailed ultrasound diagnosis is advisable. Exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. In cases involving long term prenatal therapy in the second and/ or third trimesters, the foetus should be monitored for the potential development of oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans (Schaefer, 2007).

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension.

Amlodipine
Some dihydropyridine compounds have been found to be teratogenic in animals. However, amlodipine was found not to be teratogenic or embryotoxic in rats and rabbits up to 8 and 23 times, respectively, the maximum human dose based on BSA (MRHD) during their respective periods of major organogenesis. Effects on reproduction in animals were found at high dosages (including delayed parturition, difficult labour and impaired foetal and pup survival) (Briggs, 2011). There is no adequate data for the use of amlodipine in pregnant women. The molecular weight of amlodipine is low enough that passage to the foetus should be expected. Calcium channel blockers may inhibit labour (Schaefer,2007). In the first trimester, calcium antagonists are considered to be second-line therapy. Manufacturers advise amlodipine should not be administered during pregnancy or to women of childbearing potential unless effective contraception is used unless clearly needed. Schaefer (2007) suggests that if exposure to amlodipine has occurred during the first trimester, a detailed ultrasound diagnosis is advisable. Overall exposure to a calcium antagonist during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Perindopril with amlodipine is contraindicated during breastfeeding.

Perindopril
The effect of perindopril treatment on nursing infants has not been determined, however, due to its molecular size it is likely that perindopril and the active metabolite perindoprilat are excreted in breast milk, lactating mothers are advised not to breast feed while taking perindopril.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not absolutely contraindicated and may be prescribed if treatment is considered essential. The MHRA state that ACE inhibitors should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension particularly in preterm infants. If ACE inhibitor therapy is considered essential for the mother the use of captopril, enalapril or quinapril may be considered when the infant is older. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary.

Amlodipine
There is no adequate data for the use of amlodipine in breastfeeding. Hale (2010) comments that because most calcium channel blockers readily transfer into milk, that the same should be assumed for this drug. The molecular weight of amlodipine is low enough that excretion into breast milk should be expected. No paediatric concerns have been reported but the infant should be observed for bradycardia or hypotension upon prolonged use. Guidelines from NICE recommend that women who still need antihypertensive treatment in the postnatal period are told that there is insufficient evidence on the safety in babies receiving breast milk of amlodipine. Some manufacturers advise patients to stop breast feeding during treatment with amlodipine as it is not known whether amlodipine is excreted in breast milk. Schaefer (2007) comments that individual doses of amlodipine do not require limitation of breastfeeding, but therapy should be changed. An alternative drug may be preferred.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal failure
Agranulocytosis
Allergic reaction
Alopecia
Altered bowel habit
Angina pectoris
Angioedema
Anxiety
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bradycardia
Bronchospasm
Chest pain
Cholestatic jaundice
Confusion
Constipation
Cough
Decrease in haemoglobin and haematocrit
Depression
Diarrhoea
Diplopia
Dizziness
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Eosinophilic pneumonia
Erythema multiforme
Exanthema
Exfoliative dermatitis
Fatigue
Flushing
Gastritis
Gingival hyperplasia
Gynaecomastia
Haemolytic anaemia
Headache
Hepatitis
Hyperglycaemia
Hyperkalaemia
Hypertonia
Hypoaesthesia
Hypoglycaemia
Hypotension
Impotence
Increase in blood urea or creatinine
Increased sweating
Increased urinary frequency
Increases in hepatic enzymes
Insomnia
Leucopenia
Malaise
Micturition disorders
Mood changes
Muscular cramps
Myalgia
Myocardial infarction
Nausea
Neutropenia
Nocturia
Oedema
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Photosensitivity
Pruritus
Purpura
Quincke's oedema
Rash
Renal impairment
Rhinitis
Serum bilirubin increased
Skin discolouration
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Stroke
Syncope
Thrombocytopenia
Tinnitus
Tremor
Urticaria
Vasculitis
Ventricular tachycardia
Vertigo
Visual disturbances
Vomiting
Weight changes

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: June 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on June 18, 2014.

Summary of Product Characteristics: Perindopril/Amlodipine 4mg/10mg tablets. Consilient Health Ltd. Revised July 2011.
Summary of Product Characteristics: Perindopril/Amlodipine 4mg/5mg tablets. Consilient Health Ltd. Revised July 2011.
Summary of Product Characteristics: Perindopril/Amlodipine 8mg/10mg tablets. Consilient Health Ltd. Revised July 2011.
Summary of Product Characteristics: Perindopril/Amlodipine 8mg/5mg tablets. Consilient Health Ltd. Revised July 2011.

MHRA Drug Safety Update: Volume 1, Issue 5, December 2007
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON2033216
Last accessed: June 18, 2014

MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: June 18, 2014

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Amlodipine Last revised: December 6, 2013
Last accessed: June 18, 2014

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Perindopril Last revised: September 7, 2013
Last accessed: June 18, 2014