Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Contraindications

Children under 18 years
History of angioedema associated with aliskiren
Breastfeeding
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal impairment - eGFR below 30ml/minute/1.73m sq

Precautions and Warnings

Allergic disposition
Females of childbearing potential
Cardiac disorder
Diabetes mellitus
Electrolyte depletion
Hepatic disorder
History of angioedema
Hypovolaemia
Nephrotic syndrome
New York Heart Association class III failure
New York Heart Association class IV failure
Renal artery stenosis
Renal dialysis
Renal impairment
Renovascular hypertension

Advise ability to drive/operate machinery may be affected by side effects
Advise patient that first dose hypotension may occur
Correct volume and/or salt depletion before initiating therapy
Monitor renal function regularly
Monitor serum potassium in patients with renal impairment
Advise patient to report symptoms of allergic type hypersensitivity
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Advise patient to seek advice at first indications of pregnancy
Discontinue if allergic reaction occurs
Discontinue if angioedema occurs
Discontinue if renal failure develops
Discontinue if severe and persistent diarrhoea develops
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
Advise patient to avoid fruit juices (grapefruit, apple and orange)
Female: Ensure adequate contraception during treatment

The concomitant use of aliskiren with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists is contraindicated in patients with diabetes mellitus or renal impairment eGFR below 60 ml/minute/1.73 metre squared.

Acute renal failure, reversible upon discontinuation of treatment, has been observed in at-risk patients taking aliskiren. Therefore caution should be used when treating patients with conditions pre-disposing them to kidney dysfunction.

Other substances that act directly on the renin angiotensin system (RAS) have been associated with serious foetal malformations and neonatal death. Healthcare professionals prescribing any agent which acts on the RAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy.

Pregnancy and Lactation

Pregnancy

Aliskiren is contraindicated in pregnancy and in women who are trying to conceive. There is little data concerning the use of aliskiren in humans, but reproductive toxicity studies in rats and rabbits did not reveal any teratogenicity at doses less than or equal to 20 and less than or equal to 7 times the maximum human daily dose respectively.The use of aliskiren during the second and third trimesters may cause teratogenicity, severe foetal and neonatal toxicity. Foetal toxic effects may include anuria, oligohydramnios, foetal hypocalvaria, intrauterine growth restriction, prematurity and patent ductus arteriosus (Briggs, 2011).

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

Aliskiren is contraindicated in breastfeeding.

It is not known whether aliskiren is excreted in human milk however, due to its high molecular weight and low oral absorption (3%), it is unlikely that an infant would absorb enough to receive a therapeutic dose from breast milk. Aliskiren has been found in the milk of lactating rats. The lack of data regarding aliskiren and other renin inhibitors prevents a proper assessment of the safety of this drug. Aliskiren should therefore not be used during breastfeeding, particularly in premature infants, as nephrons of the kidney are undeveloped (Hale, 2010).

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

Acute renal failure
Anaemia
Anaphylactic reaction
Angioedema
Arthralgia
Cough
Decrease in haematocrit
Decrease in haemoglobin
Diarrhoea
Dizziness
Erythema
Headache
Hepatic disorders
Hepatic failure
Hepatitis
Hives
Hyperkalaemia
Hypersensitivity reactions
Hypotension
Increases in hepatic enzymes
Jaundice
Oral mucosal blistering
Palpitations
Peripheral oedema
Pruritus
Rash
Renal impairment
Serum creatinine increased
Severe cutaneous skin eruptions
Stevens-Johnson syndrome
Swelling
Swelling of lips and face
Throat swelling
Tongue swelling
Toxic epidermal necrolysis
Urticaria

Presentation

Oral formulations of aliskiren (as hemifumarate)

Drugs List

Therapeutic Indications

Uses

Treatment of essential hypertension

Dosage

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
History of angioedema associated with aliskiren
Breastfeeding
Hereditary angioneurotic oedema
Idiopathic angioneurotic oedema
Pregnancy
Renal impairment - eGFR below 30ml/minute/1.73m sq

Precautions and Warnings

Allergic disposition
Females of childbearing potential
Cardiac disorder
Diabetes mellitus
Electrolyte depletion
Hepatic disorder
History of angioedema
Hypovolaemia
Nephrotic syndrome
New York Heart Association class III failure
New York Heart Association class IV failure
Renal artery stenosis
Renal dialysis
Renal impairment
Renovascular hypertension

Advise ability to drive/operate machinery may be affected by side effects
Advise patient that first dose hypotension may occur
Correct volume and/or salt depletion before initiating therapy
Monitor renal function regularly
Monitor serum potassium in patients with renal impairment
Advise patient to report symptoms of allergic type hypersensitivity
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Advise patient to seek advice at first indications of pregnancy
Discontinue if allergic reaction occurs
Discontinue if angioedema occurs
Discontinue if renal failure develops
Discontinue if severe and persistent diarrhoea develops
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
Advise patient to avoid fruit juices (grapefruit, apple and orange)
Female: Ensure adequate contraception during treatment

The concomitant use of aliskiren with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists is contraindicated in patients with diabetes mellitus or renal impairment eGFR below 60 ml/minute/1.73 metre squared.

Acute renal failure, reversible upon discontinuation of treatment, has been observed in at-risk patients taking aliskiren. Therefore caution should be used when treating patients with conditions pre-disposing them to kidney dysfunction.

Other substances that act directly on the renin angiotensin system (RAS) have been associated with serious foetal malformations and neonatal death. Healthcare professionals prescribing any agent which acts on the RAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy.

Pregnancy and Lactation

Pregnancy

Aliskiren is contraindicated in pregnancy and in women who are trying to conceive. There is little data concerning the use of aliskiren in humans, but reproductive toxicity studies in rats and rabbits did not reveal any teratogenicity at doses less than or equal to 20 and less than or equal to 7 times the maximum human daily dose respectively.The use of aliskiren during the second and third trimesters may cause teratogenicity, severe foetal and neonatal toxicity. Foetal toxic effects may include anuria, oligohydramnios, foetal hypocalvaria, intrauterine growth restriction, prematurity and patent ductus arteriosus (Briggs, 2011).

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

Aliskiren is contraindicated in breastfeeding.

It is not known whether aliskiren is excreted in human milk however, due to its high molecular weight and low oral absorption (3%), it is unlikely that an infant would absorb enough to receive a therapeutic dose from breast milk. Aliskiren has been found in the milk of lactating rats. The lack of data regarding aliskiren and other renin inhibitors prevents a proper assessment of the safety of this drug. Aliskiren should therefore not be used during breastfeeding, particularly in premature infants, as nephrons of the kidney are undeveloped (Hale, 2010).

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

Acute renal failure
Anaemia
Anaphylactic reaction
Angioedema
Arthralgia
Cough
Decrease in haematocrit
Decrease in haemoglobin
Diarrhoea
Dizziness
Erythema
Headache
Hepatic disorders
Hepatic failure
Hepatitis
Hives
Hyperkalaemia
Hypersensitivity reactions
Hypotension
Increases in hepatic enzymes
Jaundice
Oral mucosal blistering
Palpitations
Peripheral oedema
Pruritus
Rash
Renal impairment
Serum creatinine increased
Severe cutaneous skin eruptions
Stevens-Johnson syndrome
Swelling
Swelling of lips and face
Throat swelling
Tongue swelling
Toxic epidermal necrolysis
Urticaria

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: January 2014

Reference Sources

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.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [January 15, 2014]].

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

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Rasilez 150mg and 300mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised June 2016.

Summary of Product Characteristics: Rasilez 300mg film coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2016.

MHRA drug safety advice for aliskiren (Volume 5 - Issue 8)
https://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON146526
Date issued: March, 2012.
Last accessed: January 15, 2014.