Drugs List

Therapeutic Indications

Uses

Intermittent treatment of uterine fibroids: not eligible for surgery

Intermittent treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age who have not reached menopause when uterine fibroid embolisation or surgical treatment options are not suitable or have failed.

Contraindications

Children under 18 years
Breast cancer
Breastfeeding
Cervical cancer
Hepatic disorder
Ovarian carcinoma
Pregnancy
Severe uncontrolled asthma
Undiagnosed gynaecological haemorrhage
Uterine neoplasm

Precautions and Warnings

Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Exclude pregnancy prior to initiation of treatment
Perform liver function tests before commencing therapy
Monitor hepatic function 2 to 4 weeks after discontinuation
Monitor liver function tests monthly during treatment
Perform annual endometrial ultrasound
Advise patient/carer to contact GP immediately if signs of liver disorder
Discontinue if jaundice or other clinical symptoms of hepatic injury
Suspend treatment if transaminases >3 times upper limit of normal
Inform pathology lab of this medicine if endometrial/cervical tissue sent
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Barrier or non-hormonal contraception advised during treatment

Cases of liver injury and hepatic failure some requiring liver transplantation have been reported. Do not initiate ulipristal acetate in women with baseline alanine transaminase (ALT) or aspartate aminotransferase (AST) more than 2 times the upper limit of normal, this is either in isolation or combination with bilirubin more than 2 times the upper limit of normal.

Ulipristal acetate has a specific pharmacodynamic action on the endometrium. Changes in the histology of the endometrium may be observed in patients treated with ulipristal acetate. These changes are reversible after treatment cessation. These histological changes are denoted as Progesterone Receptor Modulator Associated Endometrial changes (PAEC) and should not be mistaken for endometrial hyperplasia. A reversible increase in the thickness of the endometrium may occur.

In repeated intermittent treatment periodic monitoring of the endometrium is recommended. This includes annual ultrasound to be performed after resumption of menstruation during off treatment period. If endometrial thickening is noted and persists after the return of menstruations during off-treatment periods or beyond 3 months following the end of treatment and/or an altered bleeding pattern is noted, investigate to exclude other underlying conditions, including endometrial malignancy.

In case of hyperplasia (without atypia), monitoring as per usual clinical practice would be recommended. In case of atypical hyperplasia, investigation and management as per usual clinical practice should be performed.

Ulipristal acetate use usually leads to a significant reduction in menstrual blood loss or amenorrhoea within the first 10 days of treatment. Should excessive bleeding persist, patients should notify their physician. Menstrual periods will generally return within 4 weeks after the end of each treatment course. If, during repeated treatment, after the initial reduction in bleeding or amenorrhoea, an altered persistent or unexpected bleeding pattern occurs such as inter-menstrual bleeding, investigation of the endometrium including endometrial biopsy should be performed to exclude other underlying conditions, including endometrial malignancy.

Pregnancy and Lactation

Pregnancy

Ulipristal acetate is contraindicated during pregnancy.

The manufacturer states that there is limited data regarding the use of ulipristal acetate in pregnant women. No teratogenic potential was observed however animal data is insufficient with regards to reproductive toxicity.

Lactation

Ulipristal acetate is contraindicated during breastfeeding.

The manufacturer states that ulipristal acetate is excreted in human milk. The effects on newborns and infants has not been studied, therefore a risk cannot be excluded.

Side Effects

Abdominal pain
Acne
Alopecia
Amenorrhoea
Angioedema
Anorexia
Anxiety
Asthenia
Back pain
Breast discomfort
Breast pain
Breast swelling
Breast tenderness
Constipation
Dizziness
Dry mouth
Dry skin
Dyspepsia
Elevated triglyceride levels
Emotional disorder
Endometrial hyperplasia
Epistaxis
Fatigue
Flatulence
Headache
Hepatic failure
Hot flushes
Hyperhidrosis
Hypersensitivity reactions
Increase in plasma cholesterol
Jaundice
Metrorrhagia
Musculoskeletal pain
Nausea
Oedema
Ovarian cysts
Pelvic pain
Urinary incontinence
Uterine haemorrhage
Vaginal discharge
Vertigo
Vomiting
Weight gain

Presentation

Oral formulations of ulipristal acetate.

Drugs List

Therapeutic Indications

Uses

Intermittent treatment of uterine fibroids: not eligible for surgery

Intermittent treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age who have not reached menopause when uterine fibroid embolisation or surgical treatment options are not suitable or have failed.

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Breast cancer
Breastfeeding
Cervical cancer
Hepatic disorder
Ovarian carcinoma
Pregnancy
Severe uncontrolled asthma
Undiagnosed gynaecological haemorrhage
Uterine neoplasm

Precautions and Warnings

Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Exclude pregnancy prior to initiation of treatment
Perform liver function tests before commencing therapy
Monitor hepatic function 2 to 4 weeks after discontinuation
Monitor liver function tests monthly during treatment
Perform annual endometrial ultrasound
Advise patient/carer to contact GP immediately if signs of liver disorder
Discontinue if jaundice or other clinical symptoms of hepatic injury
Suspend treatment if transaminases >3 times upper limit of normal
Inform pathology lab of this medicine if endometrial/cervical tissue sent
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Barrier or non-hormonal contraception advised during treatment

Cases of liver injury and hepatic failure some requiring liver transplantation have been reported. Do not initiate ulipristal acetate in women with baseline alanine transaminase (ALT) or aspartate aminotransferase (AST) more than 2 times the upper limit of normal, this is either in isolation or combination with bilirubin more than 2 times the upper limit of normal.

Ulipristal acetate has a specific pharmacodynamic action on the endometrium. Changes in the histology of the endometrium may be observed in patients treated with ulipristal acetate. These changes are reversible after treatment cessation. These histological changes are denoted as Progesterone Receptor Modulator Associated Endometrial changes (PAEC) and should not be mistaken for endometrial hyperplasia. A reversible increase in the thickness of the endometrium may occur.

In repeated intermittent treatment periodic monitoring of the endometrium is recommended. This includes annual ultrasound to be performed after resumption of menstruation during off treatment period. If endometrial thickening is noted and persists after the return of menstruations during off-treatment periods or beyond 3 months following the end of treatment and/or an altered bleeding pattern is noted, investigate to exclude other underlying conditions, including endometrial malignancy.

In case of hyperplasia (without atypia), monitoring as per usual clinical practice would be recommended. In case of atypical hyperplasia, investigation and management as per usual clinical practice should be performed.

Ulipristal acetate use usually leads to a significant reduction in menstrual blood loss or amenorrhoea within the first 10 days of treatment. Should excessive bleeding persist, patients should notify their physician. Menstrual periods will generally return within 4 weeks after the end of each treatment course. If, during repeated treatment, after the initial reduction in bleeding or amenorrhoea, an altered persistent or unexpected bleeding pattern occurs such as inter-menstrual bleeding, investigation of the endometrium including endometrial biopsy should be performed to exclude other underlying conditions, including endometrial malignancy.

Pregnancy and Lactation

Pregnancy

Ulipristal acetate is contraindicated during pregnancy.

The manufacturer states that there is limited data regarding the use of ulipristal acetate in pregnant women. No teratogenic potential was observed however animal data is insufficient with regards to reproductive toxicity.

Lactation

Ulipristal acetate is contraindicated during breastfeeding.

The manufacturer states that ulipristal acetate is excreted in human milk. The effects on newborns and infants has not been studied, therefore a risk cannot be excluded.

Side Effects

Abdominal pain
Acne
Alopecia
Amenorrhoea
Angioedema
Anorexia
Anxiety
Asthenia
Back pain
Breast discomfort
Breast pain
Breast swelling
Breast tenderness
Constipation
Dizziness
Dry mouth
Dry skin
Dyspepsia
Elevated triglyceride levels
Emotional disorder
Endometrial hyperplasia
Epistaxis
Fatigue
Flatulence
Headache
Hepatic failure
Hot flushes
Hyperhidrosis
Hypersensitivity reactions
Increase in plasma cholesterol
Jaundice
Metrorrhagia
Musculoskeletal pain
Nausea
Oedema
Ovarian cysts
Pelvic pain
Urinary incontinence
Uterine haemorrhage
Vaginal discharge
Vertigo
Vomiting
Weight gain

Effects on Laboratory Tests

Endometrial thickening
If hysterectomy or endometrial biopsy specimens are sent for histology, the laboratory should be aware of the treatment.

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: March 2021

Reference Sources

Summary of Product Characteristics: Esmya 5 mg Tablets. Gedeon Richter (UK) Ltd. Revised January 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 March 2021

MHRA Drug Safety Update February 2021
Available at: https://www.mhra.gov.uk
Last accessed: 17 March 2021