Drugs List

Therapeutic Indications

Uses

Menopausal symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Contraindications

Predisposition to thromboembolic disease
Abnormal liver function test
Breast cancer
Breastfeeding
Cerebral ischaemia
Galactosaemia
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Ischaemic heart disease
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage
Venous thromboembolism

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of venous thromboembolism
Major surgery
Prolonged immobilisation
Risk factor for oestrogen-dependent neoplasm
Severe headache
Severe trauma
Within 1 year of last natural menstrual period
Asthma
Cardiac impairment
Cholelithiasis
Cholestatic jaundice
Diabetes mellitus
Endometriosis
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic disorder
History of endometrial hyperplasia
History of hepatic disorder
Hypercholesterolaemia
Hypertension
Hypertriglyceridaemia
Lactose intolerance
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Contains lactose
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Abnormal and/or irregular bleeding should be investigated
Advise patients of risks/benefits & review need for treatment regularly
Discontinue treatment if patient develops seizures
Advise patient that changes in their breasts should be reported to Dr/nurse
Advise patient to contact a doctor if symptoms of thromboembolism develop
Avoid immobilisation-treatment may cause increased risk of thromboembolism
Increased risk of VTE during travel involving >5hr immobilisation
May affect results of some laboratory tests
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue if cholestatic jaundice occurs
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if significant rise in blood pressure occurs
Discontinue if symptoms due to endometriosis are exacerbated
Discontinue if venous thromboembolism develops
Advise patient not to take St John's wort concurrently
Female: Not for contraception.Use non-hormonal contraception, if required

For the treatment of menopausal symptoms the benefits of short-term HRT are considered to outweigh the risks in the majority of women.
In all cases, it is good practice to use the lowest effective dose for the shortest possible time and to review the need to continue treatment at least annually.
For postmenopausal women over 50 years who are at an increased risk of bone fracture, HRT should be used to prevent osteoporosis only in those who are intolerant of, or contraindicated for, other osteoporosis therapies.

Physical examination should be guided by this and a knowledge of the contraindications and precautions and warnings for use of the product. Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

There is an increased risk of breast cancer in women currently or recently using Hormone Replacement Therapy (HRT). The risk of breast cancer increases with the duration of treatment and, after stopping HRT, the risk will decrease with time. When HRT lasts for more than 5 years, the risk may persist for 10 years or more.

Ovarian cancer is much rarer than breast cancer. Evidence suggests a slight increased risk in women taking oestrogen-only or combined oestrogen and progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.

Examinations to rule out endometrial abnormalities should be undertaken at regular intervals. Prolonged monotherapy with oestrogens increases the risk of endometrial hyperplasia and carcinoma in postmenopausal women unless supplemented by administration of a progestogen to protect the endometrium. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.

Pregnancy and Lactation

Pregnancy

Tibolone is contraindicated in pregnancy.

Discontinue therapy if pregnancy occurs.

Animal studies have shown reproductive toxicity in mice and rats. The potential risk to humans is unknown.

The accidental administration has no risk-based reason for a termination of pregnancy. A detailed ultrasound examination could verify a normal morphologic development of the foetus.

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

Tibolone is contraindicated in breastfeeding.

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

"Spotting" bleeding
Abdominal pain
Abnormal liver function
Acne
Amnesia
Arthralgia
Breast pain
Cervical dysplasia
Chloasma
Dementia
Depression
Dizziness
Endometrial hyperplasia
Erythema multiforme
Erythema nodosum
Fungal infection
Gallbladder disease
Gastric upset
Genital pruritus
Hair growth abnormal
Headache
Increased risk of breast cancer
Increased risk of oestrogen-dependent neoplasms
Leukorrhoea
Migraine
Myalgia
Myocardial infarction
Oedema
Pruritus
Rash
Risk of endometrial carcinoma
Seborrhoeic dermatitis
Stroke
Vaginal bleeding
Vaginal discharge
Vaginitis
Vascular purpura
Venous thrombosis
Visual disturbances
Weight changes

Presentation

Tablets containing tibolone

Drugs List

Therapeutic Indications

Uses

Menopausal symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Dosage

For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used.

Adults

Elderly

Additional Dosage Information

Contraindications

Predisposition to thromboembolic disease
Abnormal liver function test
Breast cancer
Breastfeeding
Cerebral ischaemia
Galactosaemia
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Ischaemic heart disease
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage
Venous thromboembolism

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of venous thromboembolism
Major surgery
Prolonged immobilisation
Risk factor for oestrogen-dependent neoplasm
Severe headache
Severe trauma
Within 1 year of last natural menstrual period
Asthma
Cardiac impairment
Cholelithiasis
Cholestatic jaundice
Diabetes mellitus
Endometriosis
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic disorder
History of endometrial hyperplasia
History of hepatic disorder
Hypercholesterolaemia
Hypertension
Hypertriglyceridaemia
Lactose intolerance
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Contains lactose
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Abnormal and/or irregular bleeding should be investigated
Advise patients of risks/benefits & review need for treatment regularly
Discontinue treatment if patient develops seizures
Advise patient that changes in their breasts should be reported to Dr/nurse
Advise patient to contact a doctor if symptoms of thromboembolism develop
Avoid immobilisation-treatment may cause increased risk of thromboembolism
Increased risk of VTE during travel involving >5hr immobilisation
May affect results of some laboratory tests
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue if cholestatic jaundice occurs
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if significant rise in blood pressure occurs
Discontinue if symptoms due to endometriosis are exacerbated
Discontinue if venous thromboembolism develops
Advise patient not to take St John's wort concurrently
Female: Not for contraception.Use non-hormonal contraception, if required

For the treatment of menopausal symptoms the benefits of short-term HRT are considered to outweigh the risks in the majority of women.
In all cases, it is good practice to use the lowest effective dose for the shortest possible time and to review the need to continue treatment at least annually.
For postmenopausal women over 50 years who are at an increased risk of bone fracture, HRT should be used to prevent osteoporosis only in those who are intolerant of, or contraindicated for, other osteoporosis therapies.

Physical examination should be guided by this and a knowledge of the contraindications and precautions and warnings for use of the product. Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

There is an increased risk of breast cancer in women currently or recently using Hormone Replacement Therapy (HRT). The risk of breast cancer increases with the duration of treatment and, after stopping HRT, the risk will decrease with time. When HRT lasts for more than 5 years, the risk may persist for 10 years or more.

Ovarian cancer is much rarer than breast cancer. Evidence suggests a slight increased risk in women taking oestrogen-only or combined oestrogen and progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.

Examinations to rule out endometrial abnormalities should be undertaken at regular intervals. Prolonged monotherapy with oestrogens increases the risk of endometrial hyperplasia and carcinoma in postmenopausal women unless supplemented by administration of a progestogen to protect the endometrium. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.

Pregnancy and Lactation

Pregnancy

Tibolone is contraindicated in pregnancy.

Discontinue therapy if pregnancy occurs.

Animal studies have shown reproductive toxicity in mice and rats. The potential risk to humans is unknown.

The accidental administration has no risk-based reason for a termination of pregnancy. A detailed ultrasound examination could verify a normal morphologic development of the foetus.

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

Tibolone is contraindicated in breastfeeding.

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

"Spotting" bleeding
Abdominal pain
Abnormal liver function
Acne
Amnesia
Arthralgia
Breast pain
Cervical dysplasia
Chloasma
Dementia
Depression
Dizziness
Endometrial hyperplasia
Erythema multiforme
Erythema nodosum
Fungal infection
Gallbladder disease
Gastric upset
Genital pruritus
Hair growth abnormal
Headache
Increased risk of breast cancer
Increased risk of oestrogen-dependent neoplasms
Leukorrhoea
Migraine
Myalgia
Myocardial infarction
Oedema
Pruritus
Rash
Risk of endometrial carcinoma
Seborrhoeic dermatitis
Stroke
Vaginal bleeding
Vaginal discharge
Vaginitis
Vascular purpura
Venous thrombosis
Visual disturbances
Weight changes

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: July 2016

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.

Summary of Product Characteristics: Livial 2.5mg tablets. Merck Sharp & Dohme Limited. Revised September 2020.