Clomifene 50mg Tablets (Wockhardt UK Ltd)

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

Pituitary or ovarian 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.

Hyperstimulation of the ovary, with excessive ovarian enlargement, may occur rarely. Patients undergoing therapy with clomifene, particularly those with polycystic ovary syndrome, should receive the lowest possible doses to minimise ovarian enlargement or cyst formation. The patient should be instructed to report any abdominal or pelvic pain and should be evaluated for the presence of ovarian cysts before each cycle of treatment. Pelvic examination, which should be carried out with care, will reveal the diagnosis. The dose of clomifene should be reduced. Further courses should not be given until the ovaries have returned to pre-treatment size.

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 visual symptoms particularly blurring of vision occasionally 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.

Eye: Visual disturbances, including after-images and blurred vision may occur. Ocular side effects usually disappear within a few days or weeks after withdrawal of clomifene (see 4.4 Special warnings and precautions for use).

Gastro-intestinal: Nausea, vomiting.

General: Dizziness, lightheadedness, fatigue and insomnia.

Hepato-biliary: Jaundice

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.

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.

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

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 dose 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 And Other Handling

None

7. Marketing Authorisation Holder

Wockhardt UK Ltd,

Ash Road North,

Wrexham,

LL13 9UF,

UK.

8. Marketing Authorisation Number(S)

PL29831/0037

9. Date Of First Authorisation/Renewal Of The Authorisation

24 July 2007

10. Date Of Revision Of The Text

09 /11/2010