Drugs List

Therapeutic Indications

Uses

Hypertension
Lactation - suppression of
Oedema
Premenstrual oedema

Contraindications

Addison's disease
Galactosaemia
Hypercalcaemia
Hyponatraemia
Long QT syndrome
Refractory hypokalaemia
Severe hepatic impairment
Severe renal impairment
Symptomatic hyperuricaemia
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Anuria
Breastfeeding
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepatic cirrhosis
History of torsade de pointes
Hyperaldosteronism
Lactose intolerance
Malnutrition
Mild hepatic impairment
Mild renal impairment
Nephrotic syndrome
Pregnancy
Systemic lupus erythematosus

Correct electrolyte disorders before treatment
May cause hepatic encephalopathy in patients with hepatic disease
May exacerbate or activate systemic lupus erythematosus
Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Monitor antidiabetic drug treatment
Monitor fluid and electrolyte status
Monitor patients at risk of gout
Monitor patients with existing or tendency towards diabetes mellitus
Monitor renal function
Excess consumption of liquorice may increase the risk of hypokalaemia
Potassium supplements may be required
Discontinue before parathyroid function tests
May affect results of some laboratory tests
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol

Potassium supplements should not be given to patients with renal insufficiency that is complicated by hyperkalaemia. Potassium supplements alone may not be sufficient to correct hypokalaemia in patients who are deficient in magnesium.

Pregnancy and Lactation

Pregnancy

Use bendroflumethiazide with caution during pregnancy.

The use of bendroflumethiazide during pregnancy may increase the risk of acute haemorrhagic pancreatitis, reductions in maternal blood volume may decrease placental perfusion. Newborn infants have been reported to experience jaundice, thrombocytopenia and severe electrolyte imbalances. Cases are rare and should not prevent the use of bendroflumethiazide when indicated in pregnancy.

Hydrochlorothiazide is the thiazide of choice during pregnancy. If bendroflumethiazide is used, a risk-based termination or invasive diagnostic interventions are not necessary (Schaefer, 2015).

Thiazide diuretics may have an effect on smooth muscle and inhibit labour (Briggs, 2015).

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

Use bendroflumethiazide with caution during breastfeeding.

Bendroflumethiazide is expressed in breast milk, therefore breastfeeding should be avoided. Treatment with large doses of thiazides may suppress lactation.

Schaefer (2015) comments that during breastfeeding, diuretics should not normally be prescribed for treating hypertension. However, when such a drug is urgently needed, moderately dosed treatment with hydrochlorothiazide can be undertaken. Single doses of bendroflumethiazide do not require limitation of breastfeeding, but the therapy should be changed.

LactMed suggests that it is not necessary to discontinue breastfeeding if bendroflumethiazide is required by the mother. Breast milk product may be decreased in intense diuresis with large doses of bendroflumethiazide, especially during the neonatal period. Shorter-acting diuretics in low doses are preferred over bendroflumethiazide.

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

Agranulocytosis
Anaphylaxis
Anorexia
Aplastic anaemia
Blood disorders
Blood dyscrasias
Blood lipid changes
Cardiac arrhythmias
Cholecystitis
Cholestasis
Constipation
Cutaneous lupus erythematosus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Electrolyte disturbances
Erythema multiforme
Exacerbation of diabetes
Exacerbation of latent gout
Exacerbation of systemic lupus erythematosus
Exfoliative dermatitis
Gastric irritation
Gastro-intestinal symptoms
Gout
Headache
Hypercalcaemia
Hyperglycaemia
Hypersensitivity reactions
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypotension
Impotence
Interstitial nephritis
Intrahepatic cholestasis
Leucopenia
Lichen planus
Malaise
Muscle weakness
Muscular cramps
Nausea
Neutropenia
Oliguria
Pancreatitis
Paraesthesia
Photosensitivity
Pneumonitis
Polyuria
Postural hypotension
Pseudoporphyria
Pulmonary oedema
Rash
Reduced carbohydrate tolerance
Reduced libido
Skin reactions
Systemic lupus erythematosus
Thirst
Thrombocytopenia
Toxic epidermal necrolysis
Urolithiasis
Vasculitis
Vomiting

Presentation

Oral formulations containing bendroflumethiazide.

Drugs List

Therapeutic Indications

Uses

Hypertension
Lactation - suppression of
Oedema
Premenstrual oedema

Dosage

Adults

Children

Patients with Renal Impairment

Contraindications

Addison's disease
Galactosaemia
Hypercalcaemia
Hyponatraemia
Long QT syndrome
Refractory hypokalaemia
Severe hepatic impairment
Severe renal impairment
Symptomatic hyperuricaemia
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Anuria
Breastfeeding
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Gout
Hepatic cirrhosis
History of torsade de pointes
Hyperaldosteronism
Lactose intolerance
Malnutrition
Mild hepatic impairment
Mild renal impairment
Nephrotic syndrome
Pregnancy
Systemic lupus erythematosus

Correct electrolyte disorders before treatment
May cause hepatic encephalopathy in patients with hepatic disease
May exacerbate or activate systemic lupus erythematosus
Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Monitor antidiabetic drug treatment
Monitor fluid and electrolyte status
Monitor patients at risk of gout
Monitor patients with existing or tendency towards diabetes mellitus
Monitor renal function
Excess consumption of liquorice may increase the risk of hypokalaemia
Potassium supplements may be required
Discontinue before parathyroid function tests
May affect results of some laboratory tests
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol

Potassium supplements should not be given to patients with renal insufficiency that is complicated by hyperkalaemia. Potassium supplements alone may not be sufficient to correct hypokalaemia in patients who are deficient in magnesium.

Pregnancy and Lactation

Pregnancy

Use bendroflumethiazide with caution during pregnancy.

The use of bendroflumethiazide during pregnancy may increase the risk of acute haemorrhagic pancreatitis, reductions in maternal blood volume may decrease placental perfusion. Newborn infants have been reported to experience jaundice, thrombocytopenia and severe electrolyte imbalances. Cases are rare and should not prevent the use of bendroflumethiazide when indicated in pregnancy.

Hydrochlorothiazide is the thiazide of choice during pregnancy. If bendroflumethiazide is used, a risk-based termination or invasive diagnostic interventions are not necessary (Schaefer, 2015).

Thiazide diuretics may have an effect on smooth muscle and inhibit labour (Briggs, 2015).

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

Use bendroflumethiazide with caution during breastfeeding.

Bendroflumethiazide is expressed in breast milk, therefore breastfeeding should be avoided. Treatment with large doses of thiazides may suppress lactation.

Schaefer (2015) comments that during breastfeeding, diuretics should not normally be prescribed for treating hypertension. However, when such a drug is urgently needed, moderately dosed treatment with hydrochlorothiazide can be undertaken. Single doses of bendroflumethiazide do not require limitation of breastfeeding, but the therapy should be changed.

LactMed suggests that it is not necessary to discontinue breastfeeding if bendroflumethiazide is required by the mother. Breast milk product may be decreased in intense diuresis with large doses of bendroflumethiazide, especially during the neonatal period. Shorter-acting diuretics in low doses are preferred over bendroflumethiazide.

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

Agranulocytosis
Anaphylaxis
Anorexia
Aplastic anaemia
Blood disorders
Blood dyscrasias
Blood lipid changes
Cardiac arrhythmias
Cholecystitis
Cholestasis
Constipation
Cutaneous lupus erythematosus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Electrolyte disturbances
Erythema multiforme
Exacerbation of diabetes
Exacerbation of latent gout
Exacerbation of systemic lupus erythematosus
Exfoliative dermatitis
Gastric irritation
Gastro-intestinal symptoms
Gout
Headache
Hypercalcaemia
Hyperglycaemia
Hypersensitivity reactions
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypotension
Impotence
Interstitial nephritis
Intrahepatic cholestasis
Leucopenia
Lichen planus
Malaise
Muscle weakness
Muscular cramps
Nausea
Neutropenia
Oliguria
Pancreatitis
Paraesthesia
Photosensitivity
Pneumonitis
Polyuria
Postural hypotension
Pseudoporphyria
Pulmonary oedema
Rash
Reduced carbohydrate tolerance
Reduced libido
Skin reactions
Systemic lupus erythematosus
Thirst
Thrombocytopenia
Toxic epidermal necrolysis
Urolithiasis
Vasculitis
Vomiting

Effects on Laboratory Tests

Bendroflumethiazide may interfere with laboratory tests including estimation of serum protein bound iodine and parathyroid function tests.

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 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Aprinox / Bendroflumethiazide 2.5 and 5mg Tablets. Sovereign Medical. Revised March 2013.

Summary of Product Characteristics: Bendroflumethiazide tablets BP 2.5mg. Actavis UK Ltd. Revised March 2015.

Summary of Product Characteristics: Bendroflumethiazide tablets BP 5mg. Actavis UK Ltd. Revised March 2015.

Summary of Product Characteristics: Bendroflumethiazide tablets BP 2.5mg. Wockhardt UK Ltd. Revised February 2017.

Summary of Product Characteristics: Bendroflumethiazide tablets BP 5mg. Actavis UK Ltd. Revised February 2017.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 June 2017

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
Bendroflumethiazide. Last revised: 10 March 2015
Last accessed: 26 May 2017