Drugs List

Therapeutic Indications

Uses

Hypertension

Contraindications

Children under 18 years
Addison's disease
Anuria
Asthma
Bradycardia
Breastfeeding
Cardiogenic shock
Chronic obstructive pulmonary disease
History of bronchospasm
Hypercalcaemia
Hyponatraemia
Hypotension
Metabolic acidosis
Non-paced sinus node dysfunction
Pregnancy
Prinzmetal's angina
Refractory hypokalaemia
Second degree atrioventricular block
Severe hepatic impairment
Severe peripheral circulatory disorder
Severe renal impairment
Symptomatic hyperuricaemia
Third degree atrioventricular block
Uncontrolled cardiac failure
Uncontrolled phaeochromocytoma

Precautions and Warnings

Disorder of fluid balance
Elderly
Bradycardia with pulse rate at rest < 50 beats per minute
Diabetes mellitus
Electrolyte imbalance
First degree atrioventricular block
Gout
Hepatic cirrhosis
Hepatic impairment
History of obstructive pulmonary disease
History of psoriasis
Hyperaldosteronism
Hypoglycaemia
Intermittent claudication
Ischaemic heart disease
Malnutrition
Myasthenia gravis
Nephrotic syndrome
Portal hypertension
Psoriasis
Raynaud's syndrome
Renal impairment
Systemic lupus erythematosus

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Control cardiac failure before starting treatment
May exacerbate or activate systemic lupus erythematosus
May mask symptoms of hyperthyroidism
May mask symptoms of thyrotoxicosis
May unmask the symptoms of myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
Monitor fluid and electrolyte status
Monitor for cardiac failure: if occurs withdraw gradually
Monitor lung function in patients with respiratory disorders
Monitor patients with existing or tendency towards diabetes mellitus
Monitor renal function
Reduce dose if bradycardia develops
Beta blockers may reduce the response to adrenaline in anaphylaxis
Consider slow discontinuation if dry eyes and skin rashes occur
Excess consumption of liquorice may increase the risk of hypokalaemia
May aggravate symptoms of peripheral arterial circulatory disorders
May exacerbate psoriasis
May increase sensitivity to/seriousness of allergic reactions
May precipitate gout
Do not withdraw this drug suddenly
Gradually withdraw over 2 weeks

The continued sympathetic effect of beta-blockade may result in cardiac failure. Monitor patients for evidence of cardiac failure, and if it occurs, treatment with beta blockers should be gradually withdrawn. If beta blocker treatment cannot be withdrawn then digitalisation and diuretic therapy should be considered.

Pregnancy and Lactation

Pregnancy

Timolol maleate and bendroflumethiazide is contraindicated in pregnancy.

Both constituents cross the placenta. Beta blockers reduce placental perfusion, which may result in immature/premature deliveries and intrauterine foetal death. Adverse effects (especially hypoglycaemia and bradycardia) may occur in the foetus and neonate. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period.
Beta blockers can cause intrauterine growth restriction and reduced placental weight. Treatment beginning in the second trimester results in the greatest weight reductions. Treatment in the third trimester results in decreased weight of the placenta only. Although intrauterine growth restriction is a serious concern, the benefits to the mother might outweigh the risk to the foetus. Newborns exposed to beta blockers in utero must be observed for the first 48 hours after birth for bradycardia and other symptoms of beta blockade (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

Timolol and bendroflumethiazide is contraindicated during breastfeeding.

Both timolol and bendroflumethiazide pass into breast milk. The manufacturer does not recommend the use of this product during breastfeeding.

Schaefer (2015) suggests that the use of beta blockers during breastfeeding is allowed. Consider changing therapy to one of the preferred beta blockers (metoprolol, oxprenolol, pindolol, propranolol, labetalol). Infants exposed to timolol via breast milk should be monitored for signs of beta blockade (Briggs, 2015).

LactMed notes that if bendroflumethiazide is required by the mother, it is not a reason to discontinue breastfeeding. LactMed also suggests that due to the variability in excretion of timolol into breast milk, other agents may be preferred, especially while 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

Aggravation of angina
Aggravation of pre-existing myopia
Allergic dermatitis
Anaemia
Arthralgia
Atrioventricular block
Blood dyscrasias
Blood urea increased
Bradycardia
Bronchospasm
Cardiac failure
Cold extremities
Coma
Confusion
Cyanosis
Dehydration
Depression
Diarrhoea
Disorientation
Dizziness
Dry eyes
Dyspepsia
Dyspnoea
Erectile dysfunction
Erythematous rash
Exacerbation of intermittent claudication
Exacerbation of psoriasis
Exacerbation of Raynaud's disease
Exacerbation of systemic lupus erythematosus
Fatigue
Fluid and electrolyte disturbances
Glycosuria
Gout
Granulocytopenia
Hallucinations
Headache
Hyperglycaemia
Hyperuricaemia
Hypokalaemia
Hypotension
Impaired vision
Increase in antinuclear antibodies (ANA)
Insomnia
Muscle pain
Nausea
Necrotising vasculitis
Nightmares
Oliguria
Pancreatitis
Paraesthesia
Photosensitivity
Psoriasiform rash
Rash
Retroperitoneal fibrosis
Sedation
Thirst
Thrombocytopenia
Vertigo
Vomiting
Weakness
Withdrawal symptoms

Presentation

Oral formulations containing timolol maleate and bendroflumethiazide

Drugs List

Therapeutic Indications

Uses

Hypertension

Dosage

Adults

Elderly

Patients with Renal Impairment

Contraindications

Children under 18 years
Addison's disease
Anuria
Asthma
Bradycardia
Breastfeeding
Cardiogenic shock
Chronic obstructive pulmonary disease
History of bronchospasm
Hypercalcaemia
Hyponatraemia
Hypotension
Metabolic acidosis
Non-paced sinus node dysfunction
Pregnancy
Prinzmetal's angina
Refractory hypokalaemia
Second degree atrioventricular block
Severe hepatic impairment
Severe peripheral circulatory disorder
Severe renal impairment
Symptomatic hyperuricaemia
Third degree atrioventricular block
Uncontrolled cardiac failure
Uncontrolled phaeochromocytoma

Precautions and Warnings

Disorder of fluid balance
Elderly
Bradycardia with pulse rate at rest < 50 beats per minute
Diabetes mellitus
Electrolyte imbalance
First degree atrioventricular block
Gout
Hepatic cirrhosis
Hepatic impairment
History of obstructive pulmonary disease
History of psoriasis
Hyperaldosteronism
Hypoglycaemia
Intermittent claudication
Ischaemic heart disease
Malnutrition
Myasthenia gravis
Nephrotic syndrome
Portal hypertension
Psoriasis
Raynaud's syndrome
Renal impairment
Systemic lupus erythematosus

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Control cardiac failure before starting treatment
May exacerbate or activate systemic lupus erythematosus
May mask symptoms of hyperthyroidism
May mask symptoms of thyrotoxicosis
May unmask the symptoms of myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
Monitor fluid and electrolyte status
Monitor for cardiac failure: if occurs withdraw gradually
Monitor lung function in patients with respiratory disorders
Monitor patients with existing or tendency towards diabetes mellitus
Monitor renal function
Reduce dose if bradycardia develops
Beta blockers may reduce the response to adrenaline in anaphylaxis
Consider slow discontinuation if dry eyes and skin rashes occur
Excess consumption of liquorice may increase the risk of hypokalaemia
May aggravate symptoms of peripheral arterial circulatory disorders
May exacerbate psoriasis
May increase sensitivity to/seriousness of allergic reactions
May precipitate gout
Do not withdraw this drug suddenly
Gradually withdraw over 2 weeks

The continued sympathetic effect of beta-blockade may result in cardiac failure. Monitor patients for evidence of cardiac failure, and if it occurs, treatment with beta blockers should be gradually withdrawn. If beta blocker treatment cannot be withdrawn then digitalisation and diuretic therapy should be considered.

Pregnancy and Lactation

Pregnancy

Timolol maleate and bendroflumethiazide is contraindicated in pregnancy.

Both constituents cross the placenta. Beta blockers reduce placental perfusion, which may result in immature/premature deliveries and intrauterine foetal death. Adverse effects (especially hypoglycaemia and bradycardia) may occur in the foetus and neonate. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period.
Beta blockers can cause intrauterine growth restriction and reduced placental weight. Treatment beginning in the second trimester results in the greatest weight reductions. Treatment in the third trimester results in decreased weight of the placenta only. Although intrauterine growth restriction is a serious concern, the benefits to the mother might outweigh the risk to the foetus. Newborns exposed to beta blockers in utero must be observed for the first 48 hours after birth for bradycardia and other symptoms of beta blockade (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

Timolol and bendroflumethiazide is contraindicated during breastfeeding.

Both timolol and bendroflumethiazide pass into breast milk. The manufacturer does not recommend the use of this product during breastfeeding.

Schaefer (2015) suggests that the use of beta blockers during breastfeeding is allowed. Consider changing therapy to one of the preferred beta blockers (metoprolol, oxprenolol, pindolol, propranolol, labetalol). Infants exposed to timolol via breast milk should be monitored for signs of beta blockade (Briggs, 2015).

LactMed notes that if bendroflumethiazide is required by the mother, it is not a reason to discontinue breastfeeding. LactMed also suggests that due to the variability in excretion of timolol into breast milk, other agents may be preferred, especially while 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

Aggravation of angina
Aggravation of pre-existing myopia
Allergic dermatitis
Anaemia
Arthralgia
Atrioventricular block
Blood dyscrasias
Blood urea increased
Bradycardia
Bronchospasm
Cardiac failure
Cold extremities
Coma
Confusion
Cyanosis
Dehydration
Depression
Diarrhoea
Disorientation
Dizziness
Dry eyes
Dyspepsia
Dyspnoea
Erectile dysfunction
Erythematous rash
Exacerbation of intermittent claudication
Exacerbation of psoriasis
Exacerbation of Raynaud's disease
Exacerbation of systemic lupus erythematosus
Fatigue
Fluid and electrolyte disturbances
Glycosuria
Gout
Granulocytopenia
Hallucinations
Headache
Hyperglycaemia
Hyperuricaemia
Hypokalaemia
Hypotension
Impaired vision
Increase in antinuclear antibodies (ANA)
Insomnia
Muscle pain
Nausea
Necrotising vasculitis
Nightmares
Oliguria
Pancreatitis
Paraesthesia
Photosensitivity
Psoriasiform rash
Rash
Retroperitoneal fibrosis
Sedation
Thirst
Thrombocytopenia
Vertigo
Vomiting
Weakness
Withdrawal symptoms

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 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: timolol maleate/bendroflumethiazide. Beechmere Pharmaceuticals Ltd. Revised 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
Bendroflumethiazide. Last revised: March 10, 2015
Last accessed: January 13, 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
Timolol. Last revised: March 10, 2015
Last accessed: January 13, 2017