Drugs List

Therapeutic Indications

Uses

Hypertension
Treatment of cardiac failure (adjunct)

Cardiac failure in combination with a diuretic

Hypertension (as monotherapy or combination therapy with other antihypertensive agents)

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Breastfeeding
Cardiogenic shock
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis

Precautions and Warnings

Desensitisation therapy
Immunosuppression
Aortic stenosis
Atherosclerosis
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Hyponatraemia
Hypotension
Hypovolaemia
Lactose intolerance
Left ventricular outflow obstruction
Mitral stenosis
Peripheral vascular disease
Renal dialysis
Renal impairment
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
Monitor serum electrolytes before and during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood pressure regularly
Monitor patients with renovascular disease
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
Discontinue before parathyroid function tests
May affect results of some laboratory tests
Discontinue treatment 24 hours prior to surgery
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
Discontinue or reduce dose if renal impairment worsens
Advise patient not to take NSAIDs unless advised by clinician
Avoid antacids within 2 hours of dose
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

Initiate treatment in hospital for patients with severe cardiac failure (NYHA IV) and those at high risk of first dose hypotension e.g. those on multiple or high dose diuretics, hypovolaemia, hyponatraemia (serum sodium below 130 meq/l), pre-existing hypotension (systolic BP below 90 mmHg), unstable cardiac failure and those on high dose vasodilator therapy.

Pregnancy and Lactation

Pregnancy

The use of fosinopril during pregnancy is contraindicated.

The use of fosinopril during the first trimester is not recommended. There is limited data regarding fosinopril use during pregnancy, however, foetal toxicity should be similar to that seen with other ACE inhibitors. Foetal hypocalvaria and severe renal defects have been observed when these agents have been administered during the second and third trimesters. The cause of this toxicity is thought to be related to foetal hypotension and decreased renal blood flow. Fosinopril prevents the conversion of angiotensin l to angiotensin ll and this can lead to in utero renal failure. As the primary method of removal of this drug is via the kidneys, impairment of this system in the newborn prevents elimination of fosinopril which in turn leads to prolonged hypotension.

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).

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

The use of fosinopril during breastfeeding is contraindicated.

Fosinopril has been detected in human milk after a daily dose of 20 mg given for 3 days. Due to insufficient information available regarding the use of the drug during breastfeeding and the information given by the MHRA below, this drug should not be used whilst breastfeeding.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not all absolutely contraindicated and some may be prescribed if treatment is considered essential, however 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. The MHRA has stated that fosinopril is not recommended during breastfeeding. 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.

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

Accelerated erythrocyte sedimentation
Agranulocytosis
Anaphylactoid reaction
Angina
Angioedema
Arrhythmias
Arthritis
Asthenia
Blood urea increased
Bronchitis
Bronchospasm
Cardiac arrest
Cerebrovascular accident
Chest pain
Cholestatic jaundice
Conduction disturbances
Confusion
Cough
Decrease in haematocrit
Decreased appetite
Depression
Dermatitis
Disorientation
Dizziness
Dry mouth
Dysphagia
Dysphasia
Dysphonia
Dyspnoea
Ear pain
Ecchymosis
Eosinophilia
Epistaxis
Fatigue
Fever
Flushing
Fulminant hepatic necrosis
Gastro-intestinal disturbances
Gout
Haemoglobin decrease
Haemorrhage
Headache
Hepatic impairment
Hepatitis
Hoarseness
Hyperhidrosis
Hyperkalaemia
Hypertension
Hypertensive crisis
Hypoglycaemia
Hypotension
Increases in hepatic enzymes
Laryngitis
Leucocytosis
Leukopenia
Lymphadenopathy
Memory disturbances
Micturition disorders
Mood changes
Myalgia
Myocardial infarction
Neutropenia
Oral lesions
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Peripheral oedema
Peripheral vascular disorders
Photosensitivity
Pneumonia
Positive anti-nuclear antibodies (not associated with SLE)
Prostate abnormalities
Proteinuria
Pruritus
Pulmonary congestion
Rash
Renal failure
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sexual dysfunction
Shock
Sinusitis
Sleep disturbances
Somnolence
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Tremor
Upper respiratory symptoms
Urticaria
Vasculitis
Vertigo
Visual disturbances
Weight changes

Presentation

Oral formulations of fosinopril.

Drugs List

Therapeutic Indications

Uses

Hypertension
Treatment of cardiac failure (adjunct)

Cardiac failure in combination with a diuretic

Hypertension (as monotherapy or combination therapy with other antihypertensive agents)

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Within 36 hours of discontinuing a sacubitril containing product
Breastfeeding
Cardiogenic shock
Galactosaemia
Haemodialysis with high flux membranes
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal artery stenosis

Precautions and Warnings

Desensitisation therapy
Immunosuppression
Aortic stenosis
Atherosclerosis
Cerebral ischaemia
Collagen vascular disease
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of angioedema
Hyperkalaemia
Hypertrophic cardiomyopathy
Hyponatraemia
Hypotension
Hypovolaemia
Lactose intolerance
Left ventricular outflow obstruction
Mitral stenosis
Peripheral vascular disease
Renal dialysis
Renal impairment
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
Monitor serum electrolytes before and during treatment
Consider monitoring white blood cell counts in collagen vascular disease
Monitor blood pressure regularly
Monitor patients with renovascular disease
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
Discontinue before parathyroid function tests
May affect results of some laboratory tests
Discontinue treatment 24 hours prior to surgery
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
Discontinue or reduce dose if renal impairment worsens
Advise patient not to take NSAIDs unless advised by clinician
Avoid antacids within 2 hours of dose
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

Initiate treatment in hospital for patients with severe cardiac failure (NYHA IV) and those at high risk of first dose hypotension e.g. those on multiple or high dose diuretics, hypovolaemia, hyponatraemia (serum sodium below 130 meq/l), pre-existing hypotension (systolic BP below 90 mmHg), unstable cardiac failure and those on high dose vasodilator therapy.

Pregnancy and Lactation

Pregnancy

The use of fosinopril during pregnancy is contraindicated.

The use of fosinopril during the first trimester is not recommended. There is limited data regarding fosinopril use during pregnancy, however, foetal toxicity should be similar to that seen with other ACE inhibitors. Foetal hypocalvaria and severe renal defects have been observed when these agents have been administered during the second and third trimesters. The cause of this toxicity is thought to be related to foetal hypotension and decreased renal blood flow. Fosinopril prevents the conversion of angiotensin l to angiotensin ll and this can lead to in utero renal failure. As the primary method of removal of this drug is via the kidneys, impairment of this system in the newborn prevents elimination of fosinopril which in turn leads to prolonged hypotension.

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).

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

The use of fosinopril during breastfeeding is contraindicated.

Fosinopril has been detected in human milk after a daily dose of 20 mg given for 3 days. Due to insufficient information available regarding the use of the drug during breastfeeding and the information given by the MHRA below, this drug should not be used whilst breastfeeding.

The MHRA has stated that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not all absolutely contraindicated and some may be prescribed if treatment is considered essential, however 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. The MHRA has stated that fosinopril is not recommended during breastfeeding. 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.

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

Accelerated erythrocyte sedimentation
Agranulocytosis
Anaphylactoid reaction
Angina
Angioedema
Arrhythmias
Arthritis
Asthenia
Blood urea increased
Bronchitis
Bronchospasm
Cardiac arrest
Cerebrovascular accident
Chest pain
Cholestatic jaundice
Conduction disturbances
Confusion
Cough
Decrease in haematocrit
Decreased appetite
Depression
Dermatitis
Disorientation
Dizziness
Dry mouth
Dysphagia
Dysphasia
Dysphonia
Dyspnoea
Ear pain
Ecchymosis
Eosinophilia
Epistaxis
Fatigue
Fever
Flushing
Fulminant hepatic necrosis
Gastro-intestinal disturbances
Gout
Haemoglobin decrease
Haemorrhage
Headache
Hepatic impairment
Hepatitis
Hoarseness
Hyperhidrosis
Hyperkalaemia
Hypertension
Hypertensive crisis
Hypoglycaemia
Hypotension
Increases in hepatic enzymes
Laryngitis
Leucocytosis
Leukopenia
Lymphadenopathy
Memory disturbances
Micturition disorders
Mood changes
Myalgia
Myocardial infarction
Neutropenia
Oral lesions
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Peripheral oedema
Peripheral vascular disorders
Photosensitivity
Pneumonia
Positive anti-nuclear antibodies (not associated with SLE)
Prostate abnormalities
Proteinuria
Pruritus
Pulmonary congestion
Rash
Renal failure
Rhinitis
Serum bilirubin increased
Serum creatinine increased
Sexual dysfunction
Shock
Sinusitis
Sleep disturbances
Somnolence
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Transient ischaemic attack
Tremor
Upper respiratory symptoms
Urticaria
Vasculitis
Vertigo
Visual disturbances
Weight changes

Effects on Laboratory Tests

May cause false low measurements of serum digoxin levels with assays using the charcoal absorption method. Other kits using the antibody coated-tube method should be used instead.

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: March 2013

Reference Sources

British National Formulary, 64th Edition (2012) 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.

Summary of Product Characteristics: Fosinopril Sodium 10mg Tablets. Actavis UK Ltd. Revised September 2012.

Summary of Product Characteristics: Fosinopril Sodium 20mg Tablets. Actavis UK Ltd. Revised September 2012.

Summary of Product Characteristics: Fosinopril Sodium 10mg Tablets. Aurobindo Pharma Milpharm Ltd. Revised October 2011.

Summary of Product Characteristics: Fosinopril Sodium 20mg Tablets. Aurobindo Pharma Milpharm Ltd. Revised October 2011.

MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: March 19, 2013.

MHRA Drug Safety Update: Volume 1, Issue 5, December 2007
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON2033216
Last accessed: March 19, 2013.

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
Fosinopril. Last revised: January 4, 2011.
Last accessed: March 19, 2013.