UTOVLAN Tablet Ref.[7887] Active ingredients: Norethisterone

If menstrual bleeding should fail to follow a course of Utovlan, the possibility of pregnancy must be excluded before a further course is given.

Therapy should be discontinued if the following occur:

• Jaundice or deterioration in liver function
• Significant increase in blood pressure
• New onset of migraine-type headache

Progestogens may cause fluid retention. Special care should be taken when prescribing norethisterone in patients with conditions which might be aggravated by this factor:

• Epilepsy
• Migraine
• Asthma
• Cardiac dysfunction
• Renal dysfunction

Risk of venous thromboembolism (VTE)

Long term use of low dose progestogens as part of combined oral contraception or combined hormone replacement therapy has been associated with an increased risk of venous thromboembolism, although the role of progestogens in this aetiology is uncertain. A patient who develops symptoms suggestive of thromboembolic complications should have her status and need for treatment carefully assessed before continuing therapy.

Any patient who develops an acute impairment of vision, proptosis, diplopia or migraine headache should be carefully evaluated ophthalmologically to exclude papilloedema or retinal vascular lesions before continuing medication.

Generally recognised risk factors for VTE include a personal history or family history, severe obesity (BMI >30 kg/m2) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.

Treatment with steroid hormones may add to these risk factors. Personal or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophillic predisposition. Until a thorough evaluation of thrombophillic factors has been made or anticoagulant treatment initiated, use of progestogens in these patients should be viewed as contraindicated. Where a patient is already taking anticoagulants, the risks and benefits of progestogen therapy should be carefully considered.

The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all post-operative patients, scrupulous attention should be given to prophylactic measures to prevent VTE. Where prolonged immobilisation is likely to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to stopping progestogen therapy 4-6 weeks pre-operatively. Treatment should not be restarted until the patient is fully remobilised.

If VTE develops after initiating therapy the drug should be withdrawn. Patients should be advised to contact their doctor immediately if they become aware of a potential thromboembolic symptom (e.g., painful swelling in the leg, sudden pain in the chest, dyspnoea).

Hepatic adenoma – In very rare cases, hepatic adenomas may be associated with progesterone-only pill (POP) use. In some cases the hepatic adenoma may decrease in size or become undetectable after discontinuation of norethisterone. Rupture of hepatic adenomas may cause death through intra-abdominal haemorrhage. In extremely rare cases, hepatocellular carcinoma may be associated with combined oral contraceptives use.

Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.

Interaction with other medicines

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes. These compounds include anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g., rifampicin, rifabutin, nevirapine, efavirenz, tetracyclines, ampicillin, oxacillin and cotrimoxazole)

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John’s wort (Hypericum perforatum) may induce the metabolism of progestogens. Progestogen levels may therefore be reduced.

Aminoglutethimide has been reported to decrease plasma levels of some progestogens.

Concurrent administration of cyclosporin and norethisterone has been reported to lead to increased plasma cyclosporin levels and/or decreased plasma norethisterone levels.

When used in combination with cytotoxic drugs, it is possible that progestogens may reduce the haematological toxicity of chemotherapy.

Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.

Other forms of interaction

Progestogens can influence certain laboratory tests (e.g., tests for hepatic function, thyroid function and coagulation).

Contraindicated in pregnancy.

Utovlan has no influence on the ability to drive and use machines.

Progestogens given alone at low doses have been associated with the following undesirable effects:

Genitourinary: breakthrough bleeding, spotting, amenorrhoea, abnormal uterine bleeding, (irregular, increase, decrease), alterations of cervical secretions, cervical erosions, prolonged anovulation

Reproductive system and breast disorders: galactorrhoea, mastodynia, tenderness

Central Nervous System: depression, headache, dizziness, fatigue, insomnia, nervousness, somnolence, confusion, euphoria, loss of concentration, vision disorders

Gastrointestinal/Hepatobiliary: nausea, vomiting, cholestatic icterus/jaundice, constipation, diarrhoea, dry mouth, disturbed liver function

Neoplasms benign, malignant and unspecified (incl cysts and polyps): hepatic adenoma

Metabolic & Nutritional: altered serum lipid and lipoprotein profiles, increased fasting glucose levels, increased fasting insulin levels, decreased glucose tolerance, adrenergic-like effects (e.g., fine hand tremors, sweating, cramps in calves at night), corticoid-like effects (e.g., Cushingoid syndrome), diabetic cataract, exacerbation of diabetes mellitus, glycosuria

Cardiovascular: thrombo-embolic disorders, cerebral and myocardial infarction, congestive heart failure, increased blood pressure, palpitations, pulmonary embolism, retinal thrombosis, tachycardia, thrombophlebitis

Skin & Mucous Membranes: acne, hirsutism, alopecia, pruritis, rash, urticaria

Allergy: hypersensitivity reactions (e.g., anaphylaxis & anaphylactoid reactions, angioedema)

Miscellaneous: oedema/fluid retention, bloating, weight gain, pyrexia, change in appetite, change in libido, hypercalcaemia, malaise

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.