Drugs List

Therapeutic Indications

Uses

Angina pectoris
Hypertension
Migraine (prophylaxis)
Myocardial infarction - early convalescence phase to reduce re-infarction

Contraindications

Children under 18 years
Asthma
Breastfeeding
Cardiogenic shock
Chronic obstructive pulmonary disease
History of asthma
History of bronchospasm
Hypotension
Metabolic acidosis
Non-paced sinus node dysfunction
Pregnancy
Prinzmetal's angina
Second degree atrioventricular block
Severe peripheral circulatory disorder
Severe peripheral vascular disease
Severe Raynaud's syndrome
Sinus bradycardia
Third degree atrioventricular block
Uncontrolled cardiac failure
Uncontrolled phaeochromocytoma

Precautions and Warnings

History of allergies including anaphylaxis
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
History of non-asthmatic obstructive pulmonary disease
Intermittent claudication
Myasthenia gravis
Portal hypertension
Psoriasis
Raynaud's syndrome
Renal impairment
Stable cardiac failure

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
Betablockers may mask symptoms of thyrotoxicosis
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
HR < 50-55bpm at rest and symptomatic, review dose
Monitor antidiabetic drug treatment
Monitor for cardiac failure: if occurs withdraw gradually
Beta blockers may reduce the response to adrenaline in anaphylaxis
Consider slow discontinuation if dry eyes and skin rashes occur
May cause bronchospasm
May exacerbate psoriasis
May increase sensitivity to/seriousness of allergic reactions
Abrupt withdrawal may induce angina or myocardial infarction
Gradually withdraw over 2 weeks
If discontinuing before surgery, do this at least 24 hours beforehand
Advise patient to moderate alcohol intake during treatment

All patients should be observed for evidence of cardiac failure and, if it occurs, treatment with timolol should be gradually withdrawn. If it is not possible to withdraw timolol then digitalisation and diuretic therapy should be considered.

Pregnancy and Lactation

Pregnancy

The manufacturer states that timolol is contraindicated in pregnancy.

Reproductive studies in mice, rats and rabbits at doses up to about 40 times the maximum recommended daily human dose (MRHD) based on patient weight of 50 kg found no evidence of teratogenicity. However, foetal toxicity (resorptions) was observed in rabbits at this dose and in mice exposed to 830 times the MRHD (a maternal-toxic dose).

All beta-blockers cross the placenta. There is no clear evidence to suggest beta-blocker are teratogens. There has been reports of congenital anomalies following in utero exposure to this class of drug, but no causal relationship has been proven. Beta-blockers may cause intra-uterine growth restriction and reduced placenta weight. There is a theoretical risk of neonatal beta-blockade, however the symptoms are usually mild and improve within 48 hours of delivery. There is conflicting opinions regarding the safety of stopping beta-blockers 24 - 48 hours before delivery (Briggs, 2011).

Some guidance recommends that hypertension in pregnancy is treated with other beta-blockers (such as labetalol) which have been extensively used without reports of adverse effects on the foetus. It comments further that patients with gestational hypertension or pre-eclampsia should only be offered antihypertensive treatment other than labetalol after considering the side-effect profiles for the foetus and neonate. Schaefer (2007) comments that treatment with timolol is not an indication for invasive diagnostic procedures or for termination of pregnancy and highlights the importance of awareness of pharmacological effects such as decrease heart rate, hypoglycaemia and respiratory problems, particularly in premature neonates, when treatment with beta-blockers continues until birth.

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 ).

Recommended for use in pregnancy? - No

Crosses placenta? - Yes

Other information - If administer to the mother, monitor neonate for bradycardia for 24 - 48 hours.

Lactation

Timolol is contraindicated during breastfeeding.

Timolol appears in breast milk (milk: plasma ratio 0.8). No untoward effects on the infant have been reported, but beta-blocker drugs with similar breast milk excretion characteristics have caused adverse effects. Information on LactMed suggests that with less than 10% protein binding, 20% renal excretion and a relatively short half-life, timolol presents a moderate risk of accumulation in infants, especially neonates. Other agents may be preferred, especially while nursing a newborn or preterm infant. The manufacturer does not recommend the use of timolol during breastfeeding. Schaefer (2007) comments that if timolol has been taken, there is no need to limit breastfeeding but the medication should be changed. Briggs (2011) suggests that infants should be observed for signs of beta-blockade (e.g. bradycardia) and Hale suggests the infant should be observed for hypotension, weakness, hypoglycaemia, sedation and depression.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - No

Side Effects

Aggravation of angina
Allergic skin reactions
Arthralgia
Bradycardia
Bronchospasm
Cardiac failure
Cold extremities
Conduction disturbances
Confusion
Cyanosis of extremities
Depression
Diarrhoea
Disorientation
Dizziness
Dry eyes
Dyspepsia
Dyspnoea
Erectile dysfunction
Erythematous rash
Exacerbation of intermittent claudication
Exacerbation of psoriasis
Exacerbation of Raynaud's disease
Fatigue
Hallucinations
Headache
Hypoglycaemia
Hypotension
Increase in antinuclear antibodies (ANA)
Increased atrioventricular block
Insomnia
Nausea
Nightmares
Paraesthesia
Psoriasiform rash
Psychoses
Rash
Retroperitoneal fibrosis
Sleep disturbances
Somnolence
Vertigo
Visual disturbances
Vomiting
Weakness

Presentation

Oral formulations of timolol maleate.

Drugs List

Therapeutic Indications

Uses

Angina pectoris
Hypertension
Migraine (prophylaxis)
Myocardial infarction - early convalescence phase to reduce re-infarction

Dosage

Initially administer lowest possible dose in order to identify cardiac decompensation or bronchospasm at an early stage. This is particularly important in the elderly.
Subsequent increases in dose should occur slowly, for example, once weekly.

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Asthma
Breastfeeding
Cardiogenic shock
Chronic obstructive pulmonary disease
History of asthma
History of bronchospasm
Hypotension
Metabolic acidosis
Non-paced sinus node dysfunction
Pregnancy
Prinzmetal's angina
Second degree atrioventricular block
Severe peripheral circulatory disorder
Severe peripheral vascular disease
Severe Raynaud's syndrome
Sinus bradycardia
Third degree atrioventricular block
Uncontrolled cardiac failure
Uncontrolled phaeochromocytoma

Precautions and Warnings

History of allergies including anaphylaxis
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
History of non-asthmatic obstructive pulmonary disease
Intermittent claudication
Myasthenia gravis
Portal hypertension
Psoriasis
Raynaud's syndrome
Renal impairment
Stable cardiac failure

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
Betablockers may mask symptoms of thyrotoxicosis
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
HR < 50-55bpm at rest and symptomatic, review dose
Monitor antidiabetic drug treatment
Monitor for cardiac failure: if occurs withdraw gradually
Beta blockers may reduce the response to adrenaline in anaphylaxis
Consider slow discontinuation if dry eyes and skin rashes occur
May cause bronchospasm
May exacerbate psoriasis
May increase sensitivity to/seriousness of allergic reactions
Abrupt withdrawal may induce angina or myocardial infarction
Gradually withdraw over 2 weeks
If discontinuing before surgery, do this at least 24 hours beforehand
Advise patient to moderate alcohol intake during treatment

All patients should be observed for evidence of cardiac failure and, if it occurs, treatment with timolol should be gradually withdrawn. If it is not possible to withdraw timolol then digitalisation and diuretic therapy should be considered.

Pregnancy and Lactation

Pregnancy

The manufacturer states that timolol is contraindicated in pregnancy.

Reproductive studies in mice, rats and rabbits at doses up to about 40 times the maximum recommended daily human dose (MRHD) based on patient weight of 50 kg found no evidence of teratogenicity. However, foetal toxicity (resorptions) was observed in rabbits at this dose and in mice exposed to 830 times the MRHD (a maternal-toxic dose).

All beta-blockers cross the placenta. There is no clear evidence to suggest beta-blocker are teratogens. There has been reports of congenital anomalies following in utero exposure to this class of drug, but no causal relationship has been proven. Beta-blockers may cause intra-uterine growth restriction and reduced placenta weight. There is a theoretical risk of neonatal beta-blockade, however the symptoms are usually mild and improve within 48 hours of delivery. There is conflicting opinions regarding the safety of stopping beta-blockers 24 - 48 hours before delivery (Briggs, 2011).

Some guidance recommends that hypertension in pregnancy is treated with other beta-blockers (such as labetalol) which have been extensively used without reports of adverse effects on the foetus. It comments further that patients with gestational hypertension or pre-eclampsia should only be offered antihypertensive treatment other than labetalol after considering the side-effect profiles for the foetus and neonate. Schaefer (2007) comments that treatment with timolol is not an indication for invasive diagnostic procedures or for termination of pregnancy and highlights the importance of awareness of pharmacological effects such as decrease heart rate, hypoglycaemia and respiratory problems, particularly in premature neonates, when treatment with beta-blockers continues until birth.

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 ).

Recommended for use in pregnancy? - No

Crosses placenta? - Yes

Other information - If administer to the mother, monitor neonate for bradycardia for 24 - 48 hours.

Lactation

Timolol is contraindicated during breastfeeding.

Timolol appears in breast milk (milk: plasma ratio 0.8). No untoward effects on the infant have been reported, but beta-blocker drugs with similar breast milk excretion characteristics have caused adverse effects. Information on LactMed suggests that with less than 10% protein binding, 20% renal excretion and a relatively short half-life, timolol presents a moderate risk of accumulation in infants, especially neonates. Other agents may be preferred, especially while nursing a newborn or preterm infant. The manufacturer does not recommend the use of timolol during breastfeeding. Schaefer (2007) comments that if timolol has been taken, there is no need to limit breastfeeding but the medication should be changed. Briggs (2011) suggests that infants should be observed for signs of beta-blockade (e.g. bradycardia) and Hale suggests the infant should be observed for hypotension, weakness, hypoglycaemia, sedation and depression.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - No

Side Effects

Aggravation of angina
Allergic skin reactions
Arthralgia
Bradycardia
Bronchospasm
Cardiac failure
Cold extremities
Conduction disturbances
Confusion
Cyanosis of extremities
Depression
Diarrhoea
Disorientation
Dizziness
Dry eyes
Dyspepsia
Dyspnoea
Erectile dysfunction
Erythematous rash
Exacerbation of intermittent claudication
Exacerbation of psoriasis
Exacerbation of Raynaud's disease
Fatigue
Hallucinations
Headache
Hypoglycaemia
Hypotension
Increase in antinuclear antibodies (ANA)
Increased atrioventricular block
Insomnia
Nausea
Nightmares
Paraesthesia
Psoriasiform rash
Psychoses
Rash
Retroperitoneal fibrosis
Sleep disturbances
Somnolence
Vertigo
Visual disturbances
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: May 2013

Reference Sources

British National Formulary, 65th Edition (March - September 2013) 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.

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: Betim 10mg tablets. Meda Pharmaceuticals. Revised December 2012.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

National Institute for Health and Care Excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107/Guidance/pdf/English
Last accessed: May 8, 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
Timolol Last revised: April 3, 2012
Last accessed: May 8, 2013