Drugs List

Therapeutic Indications

Uses

Essential hypertension in patients with secondary hyperaldosteronism
Resistant oedema in patients with secondary hyperaldosteronism

Resistant oedema or essential hypertension in patients with secondary hyperaldosteronism.

This fixed ratio combination should only be used if titration with the component drugs separately indicates that this product is appropriate.

Contraindications

Children under 18 years
Addison's disease
Anuria
Breastfeeding
Dehydration
Galactosaemia
Hyperkalaemia
Hypovolaemia
Long QT syndrome
Porphyria
Renal damage secondary to nephrotoxic agents
Renal impairment - creatinine clearance below 30ml/minute/1.73m sq
Renal impairment associated with hepatic coma
Renal impairment secondary to hepatotoxic agents
Severe hypokalaemia
Severe hyponatraemia
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Hypoproteinaemia
Predisposition to hypotension
Predisposition to hypovolaemia
Predisposition to radio-contrast induced nephropathy
Predisposition towards electrolyte imbalance
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepato-renal syndrome
History of torsade de pointes
Hypotension
Lactose intolerance
Pregnancy
Prostate cancer
Renal impairment - creatinine clearance 30-60ml/minute/1.73m sq
Systemic lupus erythematosus
Urinary obstruction

Correct electrolyte disorders before treatment
Correct hypotension before initiating treatment
May decrease glucose tolerance in patients with diabetes mellitus
May exacerbate or activate systemic lupus erythematosus
Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Contains lactose
Monitor serum electrolytes before and during treatment
Consider monitoring ECG in patients at risk of QT prolongation
Investigate any sustained increase in PSA during treatment
Monitor closely patient with urinary obstruction
Monitor serum potassium regularly
Excess consumption of liquorice may increase the risk of hypokalaemia
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
May cause vocal changes. Discuss with patient where job may be affected
May precipitate diabetes mellitus
Discontinue if evidence of significant bone marrow depression
Temporarily suspend therapy if fluid/electrolyte imbalance occurs
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food

Some patients with metastatic castration resistant prostate cancer, tumour progression has been observed during spironolactone treatment. Spironolactone binds to the androgen receptor and can increase the prostate specific antigen (PSA) value.

Pregnancy and Lactation

Pregnancy

Use spironolactone with furosemide with caution in pregnancy.

Avoid use during pregnancy if possible. Diuretics are no longer used as standard therapy during pregnancy and should only be used for particular indications. Furosemide may be used when treatment of cardiac or renal failure requires a diuretic. Spironolactone should only be chosen if therapy with an aldosterone antagonist is absolutely necessary.

Antiandrogenic effects have been seen in humans and feminisation in male rat foetuses has been observed with spironolactone. In one study, rat offspring of both sexes exposed in utero in late gestation exhibited permanent dose related changes in their reproductive tracts. In animal experiments carcinogenic effects have been seen, although as yet, there are no indications of any clinical relevance of this finding to humans. No reports associating spironolactone to congenital defects (cardiovascular defects, spina bifida, polydactyly, limb reduction defects and hypospadias) in human pregnancies have been found (Briggs, 2011).

Furosemide crosses the placenta. Following oral doses of 25 to 40 mg, peak concentrations in cord serum were seen at 9 hours. Increased foetal urine production after maternal furosemide therapy has been observed (Briggs, 2011).

Diuretics are not recommended for use during pregnancy because of theoretical concerns that they may further reduce the circulatory blood volume in women with pre-eclampsia. If therapy is essential, the development of oligohydramnios should be ruled out in long term treatment. Hypoglycaemia in the newborn should also be determined. Schaefer (2007) concludes that therapy with a diuretic is not an indication for interrupting the pregnancy. The manufacturers state that spironolactone and furosemide tablets must not be used during pregnancy unless there are compelling medical reasons. Careful monitoring of foetal growth should be performed if used during 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

Spironolactone with furosemide is contraindicated in breastfeeding.

It is not known whether unmetabolised spironolactone is excreted into breast milk. Canrenone, which is the principal metabolite, is excreted into human milk and has been found with a milk: plasma ratio of 0.72 at 2 hours, and 0.51 at 14.5 hours. These amounts would provide an estimated maximum of 0.2% of the mother's daily dose to the infant. Briggs (2011) consider these amounts to be clinically insignificant. The effects of spironolactone on the nursing infant are unknown. Schaefer (2007) concludes that single doses of spironolactone do not require limitation of breastfeeding, however, the therapy should be changed.

Furosemide passes into breast milk and may inhibit lactation.

Theoretically, intense diuresis may decrease lactation and therefore, an alternative drug may be preferred, especially whilst nursing a newborn or preterm infant.

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

Abnormal vision
Acute generalised exanthematous pustulosis
Agranulocytosis
Allergic reaction
Anaphylactic reaction
Anaphylactoid reaction
Androgen type effects
Aplastic anaemia
Ataxia
Blood urea increased
Bone marrow depression
Bullous pemphigoid
Bullous reactions
Cardiac arrhythmias
Confusion
Decrease in blood pressure
Decrease in plasma calcium
Decreased glucose tolerance
Dehydration
Diarrhoea
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Elevated triglyceride levels
Eosinophilia
Erythema multiforme
Exacerbation of systemic lupus erythematosus
Exfoliative dermatitis
Fever
Fluctuating serum potassium levels
Fluid and electrolyte disturbances
Gastro-intestinal symptoms
Gout
Gynaecomastia
Haemolytic anaemia
Headache
Hearing disturbances
Hepatic encephalopathy
Hirsutism
Hyperglycaemia
Hypochloraemic alkalosis
Hyponatraemia
Hypotension
Hypovolaemia
Impaired concentration
Increase in plasma cholesterol
Increase of liver transaminases
Increased uric acid level
Interstitial nephritis
Intrahepatic cholestasis
Itching
Leucopenia
Lichenoid rash
Light-headedness
Maculopapular rash
Malaise
Mastodynia
Menstrual disturbances
Metabolic alkalosis
Muscle cramps
Muscle weakness
Nausea
Nephrocalcinosis
Nephrolithiasis
Nipple discomfort
Orthostatic hypotension
Pancreatitis
Paraesthesia
Peptic ulceration
Photosensitivity
Precipitation of diabetes
Purpura
Rash
Reduction of male potency
Sensation of pressure
Serum creatinine increased
Stevens-Johnson syndrome
Systemic lupus erythematosus
Tetany
Thirst
Thrombocytopenia
Thrombosis
Tinnitus
Toxic epidermal necrolysis
Urinary retention
Urticaria
Vasculitis
Voice changes
Vomiting
Weakness

Presentation

Oral formulations of spironolactone and furosemide.

Drugs List

Therapeutic Indications

Uses

Essential hypertension in patients with secondary hyperaldosteronism
Resistant oedema in patients with secondary hyperaldosteronism

Resistant oedema or essential hypertension in patients with secondary hyperaldosteronism.

This fixed ratio combination should only be used if titration with the component drugs separately indicates that this product is appropriate.

Dosage

Treatment with this medication should only be used in patients who don't respond to therapy with a diuretic alone at conventional doses.

Titrate to dose required using the component drugs separately. The fixed combination product can then be used if appropriate.

Adults

Contraindications

Children under 18 years
Addison's disease
Anuria
Breastfeeding
Dehydration
Galactosaemia
Hyperkalaemia
Hypovolaemia
Long QT syndrome
Porphyria
Renal damage secondary to nephrotoxic agents
Renal impairment - creatinine clearance below 30ml/minute/1.73m sq
Renal impairment associated with hepatic coma
Renal impairment secondary to hepatotoxic agents
Severe hypokalaemia
Severe hyponatraemia
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Hypoproteinaemia
Predisposition to hypotension
Predisposition to hypovolaemia
Predisposition to radio-contrast induced nephropathy
Predisposition towards electrolyte imbalance
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepato-renal syndrome
History of torsade de pointes
Hypotension
Lactose intolerance
Pregnancy
Prostate cancer
Renal impairment - creatinine clearance 30-60ml/minute/1.73m sq
Systemic lupus erythematosus
Urinary obstruction

Correct electrolyte disorders before treatment
Correct hypotension before initiating treatment
May decrease glucose tolerance in patients with diabetes mellitus
May exacerbate or activate systemic lupus erythematosus
Advise ability to drive/operate machinery may be affected by side effects
Correct hypovolaemia prior to administration
Contains lactose
Monitor serum electrolytes before and during treatment
Consider monitoring ECG in patients at risk of QT prolongation
Investigate any sustained increase in PSA during treatment
Monitor closely patient with urinary obstruction
Monitor serum potassium regularly
Excess consumption of liquorice may increase the risk of hypokalaemia
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
May cause vocal changes. Discuss with patient where job may be affected
May precipitate diabetes mellitus
Discontinue if evidence of significant bone marrow depression
Temporarily suspend therapy if fluid/electrolyte imbalance occurs
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food

Some patients with metastatic castration resistant prostate cancer, tumour progression has been observed during spironolactone treatment. Spironolactone binds to the androgen receptor and can increase the prostate specific antigen (PSA) value.

Pregnancy and Lactation

Pregnancy

Use spironolactone with furosemide with caution in pregnancy.

Avoid use during pregnancy if possible. Diuretics are no longer used as standard therapy during pregnancy and should only be used for particular indications. Furosemide may be used when treatment of cardiac or renal failure requires a diuretic. Spironolactone should only be chosen if therapy with an aldosterone antagonist is absolutely necessary.

Antiandrogenic effects have been seen in humans and feminisation in male rat foetuses has been observed with spironolactone. In one study, rat offspring of both sexes exposed in utero in late gestation exhibited permanent dose related changes in their reproductive tracts. In animal experiments carcinogenic effects have been seen, although as yet, there are no indications of any clinical relevance of this finding to humans. No reports associating spironolactone to congenital defects (cardiovascular defects, spina bifida, polydactyly, limb reduction defects and hypospadias) in human pregnancies have been found (Briggs, 2011).

Furosemide crosses the placenta. Following oral doses of 25 to 40 mg, peak concentrations in cord serum were seen at 9 hours. Increased foetal urine production after maternal furosemide therapy has been observed (Briggs, 2011).

Diuretics are not recommended for use during pregnancy because of theoretical concerns that they may further reduce the circulatory blood volume in women with pre-eclampsia. If therapy is essential, the development of oligohydramnios should be ruled out in long term treatment. Hypoglycaemia in the newborn should also be determined. Schaefer (2007) concludes that therapy with a diuretic is not an indication for interrupting the pregnancy. The manufacturers state that spironolactone and furosemide tablets must not be used during pregnancy unless there are compelling medical reasons. Careful monitoring of foetal growth should be performed if used during 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

Spironolactone with furosemide is contraindicated in breastfeeding.

It is not known whether unmetabolised spironolactone is excreted into breast milk. Canrenone, which is the principal metabolite, is excreted into human milk and has been found with a milk: plasma ratio of 0.72 at 2 hours, and 0.51 at 14.5 hours. These amounts would provide an estimated maximum of 0.2% of the mother's daily dose to the infant. Briggs (2011) consider these amounts to be clinically insignificant. The effects of spironolactone on the nursing infant are unknown. Schaefer (2007) concludes that single doses of spironolactone do not require limitation of breastfeeding, however, the therapy should be changed.

Furosemide passes into breast milk and may inhibit lactation.

Theoretically, intense diuresis may decrease lactation and therefore, an alternative drug may be preferred, especially whilst nursing a newborn or preterm infant.

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

Abnormal vision
Acute generalised exanthematous pustulosis
Agranulocytosis
Allergic reaction
Anaphylactic reaction
Anaphylactoid reaction
Androgen type effects
Aplastic anaemia
Ataxia
Blood urea increased
Bone marrow depression
Bullous pemphigoid
Bullous reactions
Cardiac arrhythmias
Confusion
Decrease in blood pressure
Decrease in plasma calcium
Decreased glucose tolerance
Dehydration
Diarrhoea
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Elevated triglyceride levels
Eosinophilia
Erythema multiforme
Exacerbation of systemic lupus erythematosus
Exfoliative dermatitis
Fever
Fluctuating serum potassium levels
Fluid and electrolyte disturbances
Gastro-intestinal symptoms
Gout
Gynaecomastia
Haemolytic anaemia
Headache
Hearing disturbances
Hepatic encephalopathy
Hirsutism
Hyperglycaemia
Hypochloraemic alkalosis
Hyponatraemia
Hypotension
Hypovolaemia
Impaired concentration
Increase in plasma cholesterol
Increase of liver transaminases
Increased uric acid level
Interstitial nephritis
Intrahepatic cholestasis
Itching
Leucopenia
Lichenoid rash
Light-headedness
Maculopapular rash
Malaise
Mastodynia
Menstrual disturbances
Metabolic alkalosis
Muscle cramps
Muscle weakness
Nausea
Nephrocalcinosis
Nephrolithiasis
Nipple discomfort
Orthostatic hypotension
Pancreatitis
Paraesthesia
Peptic ulceration
Photosensitivity
Precipitation of diabetes
Purpura
Rash
Reduction of male potency
Sensation of pressure
Serum creatinine increased
Stevens-Johnson syndrome
Systemic lupus erythematosus
Tetany
Thirst
Thrombocytopenia
Thrombosis
Tinnitus
Toxic epidermal necrolysis
Urinary retention
Urticaria
Vasculitis
Voice changes
Vomiting
Weakness

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 2015

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.

Summary of Product Characteristics: Lasilactone capsules. Sanofi. Revised, July 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 September 2018

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
Furosemide: 10 March, 2015
Last accessed: 8 June, 2015

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
Spironolactone: 10 March, 2015
Last accessed: 8 June, 2015