SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Clomifene 50mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contain 50mg of Clomifene Citrate

Excipient: Also contains lactose

For full list of excipients, see section 6.1”

3    PHARMACEUTICAL FORM

Tablet

White, round tablets with HG C50 on one side and a breakline on the other side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

The treatment of anovulatory infertility in women.

4.2    Posology and method of administration

Route of administration : Oral (i) Dosage Schedule

The recommended dose for the first course of treatment is 50mg (one tablet) daily for five days, starting within the first five days of spontaneous or induced menstrual bleeding. Therapy may be started as an arbitrary time in patients who have had no recent menstrual bleeding.

If ovulation occurs but is not followed by pregnancy, subsequent courses at the same dosage may be given up to a maximum of three cycles.

The majority of patients who are going to respond will respond to the first course of therapy, and three courses should constitute an adequate therapeutic trial. If ovulatory menses have not yet occurred, the diagnosis should be re-evaluated. Treatment beyond this is not recommended in the patient who does not exhibit evidence of ovulation.

Long-term cyclic therapy: Not recommended.

The relative safety of long-term cyclic therapy has not been conclusively demonstrated and, since the majority of patients will ovulate following three courses, long-term cyclic therapy is not recommended, i.e. beyond a total of about six cycles (including three ovulatory cycles).

(ii) Types of Patient

Not intended for children.

Not intended for elderly patients.

Only for women of reproductive age with anovulatory infertility.

4.3 Contraindications

Hypersensitivity to clomifene

Pregnancy

Liver disease or a history of liver dysfunction

Abnormal uterine bleeding until the cause has been determined

Hormone dependent tumours

Ovarian cysts (other than in association with polycystic ovary syndrome)

4.4 Special warnings and precautions for use

There have been rare reports of ovarian cancer with fertility drugs; infertility itself is a primary risk factor. Epidemiological data suggest that prolonged use of clomifene 50mg tablets may increase this risk. Therefore the recommended duration of treatment should not be exceeded (see section 4.2).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Causes of infertility other than ovarian dysfunction should be excluded before the start of treatment.

Ovarian Hyperstimulation Syndrome (OHSS) has been reported in patients receiving clomifene therapy for ovulation induction. In some cases, OHSS occurred following the cyclic use of clomifene therapy or when clomifene was used in combination with gonadotropins. The following symptoms have been reported in association with this syndrome during clomifene therapy: pericardial effusion, anasarca, hydrothorax, acute abdomen, renal failure, pulmonary oedema, ovarian haemorrhage, deep venous thrombosis, torsion of the ovary and acute respiratory distress. If conception results, rapid progression to the severe form of the syndrome may occur.

To minimise the hazard of the abnormal ovarian enlargement associated with clomifene therapy, the lowest dose consistent with expectation of good results should be used. The patient should be instructed to inform the physician of any abdominal or pelvic pain, weight gain, discomfort or distension after taking clomifene. Maximal enlargement of the ovary may not occur until several days after discontinuation of the course of clomifene. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomifene.

The patient who complains of abdominal or pelvic pain, discomfort, or distension after taking clomifene should be examined because of the possible presence of an ovarian cyst or other cause. Due to fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously. If abnormal enlargement occurs clomifene should not be given until the ovaries have returned to pre-treatment size. Ovarian enlargement and cyst formation associated with clomifene therapy usually regress spontaneously within a few days or weeks after discontinuing treatment. Most of these patients should be managed conservatively. The dosage and/or duration of the next course of treatment should be reduced

The patient should be evaluated for the presence of ovarian cysts before each cycle of treatment.

The incidence of multiple pregnancies is increased when conception takes place during a clomifene-stimulated cycle.

In order to avoid inadvertent administration of clomifene in early pregnancy, the basal body temperature should be monitored. In the absence of expected menses, a sensitive pregnancy test should be performed and only if negative should the patient be given the course of clomifene.

Clomifene should be used with caution:

• in patients with uterine fibroids, because of the risk of further enlargement of the fibroids

in patients suffering from mental depression, because of the risk of exacerbation in patients with or susceptible to thrombophlebitis.

Clomifene therapy should be withdrawn if the patient experiences visual disturbances and a full ophthalmologic examination should be performed.

4.5 Interaction with other medicinal products and other forms of interaction

None known.

4.6 Pregnancy and lactation

Use during pregnancy is contraindicated.

It is not known whether clomifene is distributed into breast milk However, the drug may suppress lactation.

4.7 Effects on ability to drive and use machines

Drowsiness or sedation do not occur, but patients should be warned that dizziness, lightheadedness or visual disturbances, particularly blurring of vision, may occur during clomifene therapy and may affect their ability to drive or operate machinery. Onset is gradual.

4.8 Undesirable effects

Side effects, when they occur, are generally mild. They are dose related.

Side effects are reversible on drug withdrawal.

Ear Disorders: Vertigo

Eye disorders: Symptoms described usually as “blurring” or spots or flashes (scintillating scotomata) increase in incidence with increasing total dose.

These symptoms appear to be due to intensification and prolongation of afterimages. After-images as such have also been reported. Symptoms often first appear or are accentuated with exposure to bright-light environment. Ophthalmologically definable scotomata, phosphenes and reduced visual acuity have been reported.

There are rare reports of cataracts and optic neuritis.

These visual disturbances are usually reversible (see 4.4 Special warnings and precautions for use). However, cases of prolonged visual disturbance have been reported, including after clomifene has been discontinued. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy

Gastro-intestinal: Nausea, vomiting.

General: Dizziness, light-headedness, fatigue and insomnia.

Hepato-biliary: Jaundice, Abnormalities in liver function tests may occur Metabolic: Weight gain

Neurological: Headache. Convulsions have been reported. Patients with a history of seizures may be predisposed.

Pregnancy: Ectopic or heterotopic pregnancies have occurred following treatment with clomifene. Patients should be warned that there is a risk of multiple pregnancies (rarely more than twins).

Psychiatric: Depression. Nervousness. Acute psychotic reactions with paranoid tendencies have occurred rarely.

Reproductive: Among those reported, which are of low frequency at the recommended doses are ovarian hyperstimulation syndrome with ovarian enlargement and ovarian cyst formation (see 4.4 Special warnings and precautions for use), intermenstrual bleeding, menorrhagia, endometriosis, abdominal pelvic discomfort, hot flushes, breast tenderness or discomfort.

Very rarely and only at much higher doses than those recommended, massive ovarian enlargement has been reported.

Skin: Rash, alopecia, urticaria

Tumours/neoplasms: Isolated reports have been received on the occurrence of endocrine-related or dependent neoplasms or their aggravation. Ovarian cancer: see section 4.4

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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

There is no experience with overdosage

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Clomifene is used to induce ovulation in women with anovulatory cycles. This agent is an anti-oestrogen and is believed to act by binding to oestrogen receptors in the hypothalamus and allowing follicle stimulating hormone (FSH) to rise in order to stimulate follicular development and ultimately result in ovulation.

It is probable that clomifene additionally exerts a direct effect on ovarian function.

5.2 Pharmacokinetic properties

Clomifene is absorbed from the gastrointestinal tract and slowly excreted through the liver into the bile. The biological half life is reported to be about five days. Enterohepatic recirculation takes place.

5.3 Preclinical safety data

Nothing of relevance to the prescriber which does not appear elsewhere in the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Magnesium stearate

Maize starch Lactose

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Five years

6.4 Special precautions for storage

Do not store above 25°C.

Store in original packaging.

6.5 Nature and contents of container

Blister packs of 10 tablets manufactured from 250 micron white opaque PVC and 20 micron hard temper aluminium foil.

Pack Sizes: 10, 20, 30, 100 tablets (1,2,3 or 10 strips) in an outer carton.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 29831/0037

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

21/04/1992 / 03/06/2005

10 DATE OF REVISION OF THE TEXT

27/08/2015