Drugs List

Therapeutic Indications

Uses

Congestive heart failure (adjunct)
Treatment of essential hypertension

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
History of angioneurotic oedema
Idiopathic angioneurotic oedema
Left ventricular outflow obstruction
Pregnancy
Renal artery stenosis

Precautions and Warnings

Desensitisation therapy
Females of childbearing potential
Immunosuppression
Patients over 70 years
Aortic stenosis
Atherosclerosis
Breastfeeding
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Electrolyte depletion
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypotension
Hypovolaemia
Lactose intolerance
Peripheral vascular disease
Renal impairment - creatinine clearance below 40ml/minute
Renovascular disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Advise patient that first dose hypotension may occur
Afro-Caribbean or black patients may show reduced response
Consider stopping diuretic 2-3 days prior to therapy if appropriate
Correct volume and/or salt depletion before initiating therapy
Exclude renovascular disorder before treatment
Contains lactose
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 dose reduction if BUN and serum creatinine rise during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood pressure regularly
Monitor patients with renovascular disease
Monitor plasma sodium in patients at risk of hyponatraemia
Monitor serum potassium regularly
Profound hypotension can occur,especially after initial dose-monitor
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
Withdraw before apheresis
Withdraw before desensitisation
Advise patient to seek advice at first indications of pregnancy
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
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

In patients with uncomplicated hypertension, symptomatic hypotension has been observed rarely after the initial dose of quinapril as well as after increasing the dose of quinapril. It is more likely to occur in patients who have been volume and salt-depleted by prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhoea, vomiting or patients with severe cardiac failure. Therefore, in these patients, diuretic therapy should be discontinued and volume and/or salt depletion should be corrected before initiating therapy with quinapril.

In patients undergoing surgery or during anaesthesia with agents producing hypotension, quinapril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Agranulocytosis and bone marrow depression, as well as a reduction in red cell count, haemoglobin content and platelet count have been seen rarely in patients on ACE inhibitors. These are more frequent in patients with renal impairment, especially if they have a collagen vascular disease. Regular monitoring of white blood cell counts and protein levels in urine should be considered in patients with collagen vascular disease (e.g. lupus erythematosus and scleroderma), especially associated with impaired renal function and concomitant therapy particularly with corticosteroids and anti-metabolites. Patients on allopurinol, immunosuppressants and other substances that may change the blood picture also have increased likelihood of other blood picture changes.

Pregnancy and Lactation

Pregnancy

The use of quinapril during pregnancy is contraindicated.

Quinapril appears to be a human teratogen. Two reviews have indicated that both renal perfusion and glomerular plasma flow are low during gestation. In order for the foetus to maintain glomerular filtration at low pressures high levels of angiotensin ll may be necessary. Briggs (2011) states that as quinapril prevents the conversion of angiotensin I to angiotensin II, the utero renal blood flow is adversely effected causing decreased renal blood flow and foetal hypotension. Sustained and prolonged hypotension may be seen as the main cause to drug build up and prevention of drug elimination. As a result the drug produces foetal calvarial hypoplasia and renal defects.

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).

If pregnancy occurs this drug should be discontinued immediately.

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 14-17 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

Quinapril may be considered for use during breastfeeding in older infants, but monitor the infant for hypotensive effects.

Quinapril is excreted into breast milk. The authors of one study, where a 20mg oral dose of quinapril was given to 6 healthy mothers who had been breastfeeding for 2 weeks, have estimated the infant dose as 1.6% of the mother's weight adjusted dose.

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.

LactMed state that the low levels found in breast milk would not be expected to cause any adverse effects in the newborn and Briggs (2011) recommends that quinapril is probably compatible with breastfeeding.

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
Accelerated erythrocyte sedimentation
Agranulocytosis
Alopecia
Amblyopia
Anaphylactoid reaction
Angina pectoris
Angioedema
Arthralgia
Arthritis
Asthenia
Back pain
Blood urea increased
Blurred vision
Bronchitis
Bronchospasm
Cerebral haemorrhage
Cerebrovascular accident
Chest pain
Cholestatic jaundice
Confusion
Constipation
Cough
Decrease in haematocrit
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Elevation of liver enzymes
Eosinophilia
Eosinophilic pneumonia
Epidermal necrolysis
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flatulence
Glossitis
Haemoglobin decrease
Haemolytic anaemia
Headache
Hepatitis
Hyperkalaemia
Hypoglycaemia
Hyponatraemia
Hypotension
Ileus
Impotence
Insomnia
Intestinal angioedema
Leucocytosis
Leucopenia
Loss of balance
Myalgia
Myocardial infarction
Nausea
Nervousness
Neutropenia
Oedema
Oliguria
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Peripheral oedema
Perspiration
Pharyngitis
Photosensitivity
Positive ANA titre
Postural hypotension
Proteinuria
Pruritus
Psoriasis like symptoms
Rash
Renal impairment
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sinusitis
Somnolence
Stevens-Johnson syndrome
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vasculitis
Vasodilatation
Vertigo
Vomiting

Presentation

Oral formulations of quinapril (as quinapril hydrochloride).

Drugs List

Therapeutic Indications

Uses

Congestive heart failure (adjunct)
Treatment of essential hypertension

Dosage

Adults

Elderly

Patients with Renal Impairment

Patients with Hepatic Impairment

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
History of angioneurotic oedema
Idiopathic angioneurotic oedema
Left ventricular outflow obstruction
Pregnancy
Renal artery stenosis

Precautions and Warnings

Desensitisation therapy
Females of childbearing potential
Immunosuppression
Patients over 70 years
Aortic stenosis
Atherosclerosis
Breastfeeding
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Electrolyte depletion
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment
Hyperkalaemia
Hypertrophic cardiomyopathy
Hypotension
Hypovolaemia
Lactose intolerance
Peripheral vascular disease
Renal impairment - creatinine clearance below 40ml/minute
Renovascular disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Anaphylaxis possible with concomitant hyposensitisation to wasp/bee venom
Advise ability to drive/operate machinery may be affected by side effects
Advise patient that first dose hypotension may occur
Afro-Caribbean or black patients may show reduced response
Consider stopping diuretic 2-3 days prior to therapy if appropriate
Correct volume and/or salt depletion before initiating therapy
Exclude renovascular disorder before treatment
Contains lactose
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 dose reduction if BUN and serum creatinine rise during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood pressure regularly
Monitor patients with renovascular disease
Monitor plasma sodium in patients at risk of hyponatraemia
Monitor serum potassium regularly
Profound hypotension can occur,especially after initial dose-monitor
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
Withdraw before apheresis
Withdraw before desensitisation
Advise patient to seek advice at first indications of pregnancy
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
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment

In patients with uncomplicated hypertension, symptomatic hypotension has been observed rarely after the initial dose of quinapril as well as after increasing the dose of quinapril. It is more likely to occur in patients who have been volume and salt-depleted by prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhoea, vomiting or patients with severe cardiac failure. Therefore, in these patients, diuretic therapy should be discontinued and volume and/or salt depletion should be corrected before initiating therapy with quinapril.

In patients undergoing surgery or during anaesthesia with agents producing hypotension, quinapril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Agranulocytosis and bone marrow depression, as well as a reduction in red cell count, haemoglobin content and platelet count have been seen rarely in patients on ACE inhibitors. These are more frequent in patients with renal impairment, especially if they have a collagen vascular disease. Regular monitoring of white blood cell counts and protein levels in urine should be considered in patients with collagen vascular disease (e.g. lupus erythematosus and scleroderma), especially associated with impaired renal function and concomitant therapy particularly with corticosteroids and anti-metabolites. Patients on allopurinol, immunosuppressants and other substances that may change the blood picture also have increased likelihood of other blood picture changes.

Pregnancy and Lactation

Pregnancy

The use of quinapril during pregnancy is contraindicated.

Quinapril appears to be a human teratogen. Two reviews have indicated that both renal perfusion and glomerular plasma flow are low during gestation. In order for the foetus to maintain glomerular filtration at low pressures high levels of angiotensin ll may be necessary. Briggs (2011) states that as quinapril prevents the conversion of angiotensin I to angiotensin II, the utero renal blood flow is adversely effected causing decreased renal blood flow and foetal hypotension. Sustained and prolonged hypotension may be seen as the main cause to drug build up and prevention of drug elimination. As a result the drug produces foetal calvarial hypoplasia and renal defects.

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).

If pregnancy occurs this drug should be discontinued immediately.

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 14-17 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

Quinapril may be considered for use during breastfeeding in older infants, but monitor the infant for hypotensive effects.

Quinapril is excreted into breast milk. The authors of one study, where a 20mg oral dose of quinapril was given to 6 healthy mothers who had been breastfeeding for 2 weeks, have estimated the infant dose as 1.6% of the mother's weight adjusted dose.

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.

LactMed state that the low levels found in breast milk would not be expected to cause any adverse effects in the newborn and Briggs (2011) recommends that quinapril is probably compatible with breastfeeding.

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
Accelerated erythrocyte sedimentation
Agranulocytosis
Alopecia
Amblyopia
Anaphylactoid reaction
Angina pectoris
Angioedema
Arthralgia
Arthritis
Asthenia
Back pain
Blood urea increased
Blurred vision
Bronchitis
Bronchospasm
Cerebral haemorrhage
Cerebrovascular accident
Chest pain
Cholestatic jaundice
Confusion
Constipation
Cough
Decrease in haematocrit
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Elevation of liver enzymes
Eosinophilia
Eosinophilic pneumonia
Epidermal necrolysis
Erythema multiforme
Exfoliative dermatitis
Fatigue
Fever
Flatulence
Glossitis
Haemoglobin decrease
Haemolytic anaemia
Headache
Hepatitis
Hyperkalaemia
Hypoglycaemia
Hyponatraemia
Hypotension
Ileus
Impotence
Insomnia
Intestinal angioedema
Leucocytosis
Leucopenia
Loss of balance
Myalgia
Myocardial infarction
Nausea
Nervousness
Neutropenia
Oedema
Oliguria
Palpitations
Pancreatitis
Paraesthesia
Pemphigus
Peripheral oedema
Perspiration
Pharyngitis
Photosensitivity
Positive ANA titre
Postural hypotension
Proteinuria
Pruritus
Psoriasis like symptoms
Rash
Renal impairment
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sinusitis
Somnolence
Stevens-Johnson syndrome
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vasculitis
Vasodilatation
Vertigo
Vomiting

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: May 2013

Reference Sources

British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

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.

Medications and Mother's Milk, 14th edition (2010) Hale, T.W. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Accupro Tablets 5mg. Pfizer Ltd. Revised October 2017.

Summary of Product Characteristics: Accupro Tablets 10mg. Pfizer Ltd. Revised October 2017.

Summary of Product Characteristics: Accupro Tablets 20mg. Pfizer Ltd. Revised October 2017.

Summary of Product Characteristics: Accupro Tablets 40mg. Pfizer Ltd. Revised October 2017.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

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
Quinapril, Last revised: December 27, 2007.
Last accessed: May 7, 2013.

MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: May 7, 2013.

MHRA: Drug Safety Update: Volume 2 Issue 12, July 2009
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON051770
Last accessed: May 7, 2013.