Drugs List

Therapeutic Indications

Uses

Replacement therapy for oestrogen deficiency symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

All strengths
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women.

625 micrograms and 1.25 mg tablets only
Prevention of osteoporosis in postmenopausal women at a high risk of fractures and who are intolerant or contraindicated for drugs indicated for the prevention of osteoporosis.

Contraindications

Children under 18 years
Abnormal liver function test
Acute hepatic disorder
Breast cancer
Breastfeeding
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hereditary fructose intolerance
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder without anticoagulant therapy
History of venous thromboembolism
Lupus anticoagulant
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Protein C deficiency disease
Protein S deficiency disease
Pulmonary embolism
Recent arterial thromboembolic disorder
Thrombophilia
Thrombophlebitis
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of breast cancer
Family history of venous thromboembolism
History of recurrent spontaneous abortion
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic impairment
History of chloasma
History of endometrial hyperplasia
History of thromboembolic disorder
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Lactose intolerance
Malignant melanoma
Migraine
Multiple sclerosis
Otosclerosis
Renal impairment
Sickle cell disease
Systemic lupus erythematosus
Uterine fibroids

Patients on thyroid replacement therapy may require increased doses
Risk of pancreatitis in individuals with hypertriglyceridaemia
Add progestogen for 12-14 days each cycle for those with an intact uterus
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Not all available strengths are licensed for all indications
Contains lactose
Preparation contains sucrose
Some formulations contain sunset yellow (E110); may cause allergic reaction
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
Monitor hepatic function in patients with hepatic impairment
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient that changes in their breasts should be reported to Dr/nurse
Discontinue at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
Uterine fibroids may increase in size
May interfere with certain laboratory measurements
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if cholestasis develops
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if severe abdominal symptoms develop
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden pain in the chest occurs
Discontinue if symptoms due to endometriosis are exacerbated
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT
Intolerance to contact lenses may occur

Only for use in the treatment of menopausal symptoms which adversely affect the quality of life. Treatment should be reviewed annually and only continued if the benefits outweigh the risks.

Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

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 sequential administration of a progestogen to protect the endometrium. The addition of a progestogen for at least 12 days of the cycle in non-hysterectomised women greatly reduces this risk. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.

Patients with end stage renal disease should be closely monitored since the circulating level of the active ingredients will be increased.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

An increase in the expected frequency of cardiovascular defects, eye and ear abnormalities and Down's syndrome has been found with oestrogens as a group in the newborn when exposed to these in the womb (Briggs, 2011). However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations.

Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males who have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally.

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

Hormone replacement therapy is contraindicated during breastfeeding.

Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breastfeed (Hale, 2010). Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2011). Even though the extent of these changes is low, the changes in milk production and composition may be of nutritional importance in malnourished mothers. Because of the reasons mentioned above the use of this medication during breastfeeding should be avoided.

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
Aggravation of porphyria
Alopecia
Anaphylactoid reaction
Angioedema
Anxiety
Arthralgia
Bloating
Breakthrough bleeding
Breast enlargement
Breast pain
Breast secretion
Breast tenderness
Cervical erosion
Change in amount of cervical secretion
Change in carbohydrate metabolism
Change in menstrual flow
Changes in libido
Chloasma
Cholestatic jaundice
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Dementia
Depression
Dizziness
Dysmenorrhoea
Endometrial hyperplasia
Enlargement of hepatic haemangiomas
Erythema multiforme
Erythema nodosum
Exacerbation of chorea
Exacerbation of epilepsy
Exacerbation of hypocalcaemia
Exacerbation of otosclerosis
Exacerbation of pre-existing asthma
Fibrocystic breast changes
Fluid retention
Galactorrhoea
Gallbladder disease
Gynaecomastia in older men
Haemorrhagic eruption
Headache
Hirsutism
Hypersensitivity reactions
Hypertension
Increase in plasma triglyceride concentration
Increased blood pressure
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased risk of oestrogen-dependent neoplasms
Increased size of uterine fibroids
Intolerance to contact lenses
Irregular uterine bleeding
Irritability
Ischaemic colitis
Leg cramps
Leukorrhoea
Melasma
Meningioma
Migraine
Mood changes
Myocardial infarction
Nausea
Nervousness
Oedema
Ovarian cancer
Pancreatitis
Pelvic pain
Porphyria
Premenstrual-like syndrome
Pruritus
Pulmonary embolism
Rash
Retinal vascular thrombosis
Sodium retention
Stroke
Thromboembolism
Thrombophlebitis
Urticaria
Uterine bleeding
Vaginal candidiasis
Vaginitis
Vascular purpura
Venous thrombosis
Vomiting
Weight changes

Presentation

Tablets containing conjugated oestrogens, equine

Drugs List

Therapeutic Indications

Uses

Replacement therapy for oestrogen deficiency symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

All strengths
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women.

625 micrograms and 1.25 mg tablets only
Prevention of osteoporosis in postmenopausal women at a high risk of fractures and who are intolerant or contraindicated for drugs indicated for the prevention of osteoporosis.

Dosage

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Abnormal liver function test
Acute hepatic disorder
Breast cancer
Breastfeeding
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hereditary fructose intolerance
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder without anticoagulant therapy
History of venous thromboembolism
Lupus anticoagulant
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Protein C deficiency disease
Protein S deficiency disease
Pulmonary embolism
Recent arterial thromboembolic disorder
Thrombophilia
Thrombophlebitis
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of breast cancer
Family history of venous thromboembolism
History of recurrent spontaneous abortion
Predisposition to thromboembolic disease
Prolonged immobilisation
Recent surgery
Recent trauma
Severe headache
Asthma
Cardiac impairment
Cholelithiasis
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
Hepatic adenoma
Hepatic impairment
History of chloasma
History of endometrial hyperplasia
History of thromboembolic disorder
Hypertension
Hypertriglyceridaemia
Hypocalcaemia
Lactose intolerance
Malignant melanoma
Migraine
Multiple sclerosis
Otosclerosis
Renal impairment
Sickle cell disease
Systemic lupus erythematosus
Uterine fibroids

Patients on thyroid replacement therapy may require increased doses
Risk of pancreatitis in individuals with hypertriglyceridaemia
Add progestogen for 12-14 days each cycle for those with an intact uterus
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Not all available strengths are licensed for all indications
Contains lactose
Preparation contains sucrose
Some formulations contain sunset yellow (E110); may cause allergic reaction
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
Monitor hepatic function in patients with hepatic impairment
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient that changes in their breasts should be reported to Dr/nurse
Discontinue at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
Uterine fibroids may increase in size
May interfere with certain laboratory measurements
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if cholestasis develops
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if severe abdominal symptoms develop
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden pain in the chest occurs
Discontinue if symptoms due to endometriosis are exacerbated
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT
Intolerance to contact lenses may occur

Only for use in the treatment of menopausal symptoms which adversely affect the quality of life. Treatment should be reviewed annually and only continued if the benefits outweigh the risks.

Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

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 sequential administration of a progestogen to protect the endometrium. The addition of a progestogen for at least 12 days of the cycle in non-hysterectomised women greatly reduces this risk. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.

Patients with end stage renal disease should be closely monitored since the circulating level of the active ingredients will be increased.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

An increase in the expected frequency of cardiovascular defects, eye and ear abnormalities and Down's syndrome has been found with oestrogens as a group in the newborn when exposed to these in the womb (Briggs, 2011). However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations.

Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males who have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally.

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

Hormone replacement therapy is contraindicated during breastfeeding.

Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breastfeed (Hale, 2010). Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2011). Even though the extent of these changes is low, the changes in milk production and composition may be of nutritional importance in malnourished mothers. Because of the reasons mentioned above the use of this medication during breastfeeding should be avoided.

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

Counselling

Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age. Breast awareness should also be encouraged and patients advised to report any changes in their breasts to their doctor or nurse.

Advise patients to contact their doctor if they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

Patients should be advised of the increased risks of diagnosis of breast cancer versus the benefits of HRT.

Advise patients not to self-medicate with St John's Wort during HRT.

Advise patient grapefruit products may increase the plasma level of the drug.

Side Effects

"Spotting" bleeding
Abdominal pain
Aggravation of porphyria
Alopecia
Anaphylactoid reaction
Angioedema
Anxiety
Arthralgia
Bloating
Breakthrough bleeding
Breast enlargement
Breast pain
Breast secretion
Breast tenderness
Cervical erosion
Change in amount of cervical secretion
Change in carbohydrate metabolism
Change in menstrual flow
Changes in libido
Chloasma
Cholestatic jaundice
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Dementia
Depression
Dizziness
Dysmenorrhoea
Endometrial hyperplasia
Enlargement of hepatic haemangiomas
Erythema multiforme
Erythema nodosum
Exacerbation of chorea
Exacerbation of epilepsy
Exacerbation of hypocalcaemia
Exacerbation of otosclerosis
Exacerbation of pre-existing asthma
Fibrocystic breast changes
Fluid retention
Galactorrhoea
Gallbladder disease
Gynaecomastia in older men
Haemorrhagic eruption
Headache
Hirsutism
Hypersensitivity reactions
Hypertension
Increase in plasma triglyceride concentration
Increased blood pressure
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased risk of oestrogen-dependent neoplasms
Increased size of uterine fibroids
Intolerance to contact lenses
Irregular uterine bleeding
Irritability
Ischaemic colitis
Leg cramps
Leukorrhoea
Melasma
Meningioma
Migraine
Mood changes
Myocardial infarction
Nausea
Nervousness
Oedema
Ovarian cancer
Pancreatitis
Pelvic pain
Porphyria
Premenstrual-like syndrome
Pruritus
Pulmonary embolism
Rash
Retinal vascular thrombosis
Sodium retention
Stroke
Thromboembolism
Thrombophlebitis
Urticaria
Uterine bleeding
Vaginal candidiasis
Vaginitis
Vascular purpura
Venous thrombosis
Vomiting
Weight changes

Effects on Laboratory Tests

Hormone replacement therapy, especially oestrogen-progestogen combined treatment may increase the density of mammographic images and adversely effect the detection of breast cancer.

The use of oestrogen may influence the laboratory results of certain endocrine tests and liver enzymes.

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: August 2014

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.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on August 14, 2014.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Premarin 0.3 mg tablets. Pfizer Ltd. Revised August 2016.
Summary of Product Characteristics: Premarin 0.625 mg tablets. Pfizer Ltd. Revised August 2016.
Summary of Product Characteristics: Premarin 1.25 mg tablets. Pfizer Ltd. Revised August 2016.

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

MHRA Drug Safety Update: Hormone-replacement therapy. Dated: September 2007. https://www.mhra.gov.uk/Publications/Safetyguidence/DrugsSafetyUpdate/CON046451
Last accessed: 19 December 2011

NAPOS. The drug database for acute porphyria.
Available at: https://www.drugs-porphyria.org Conjugated estrogens.
Last revised: September 2009
Last accessed: August 19, 2014