Consumer medicine information

Clomid

Clomifene citrate

BRAND INFORMATION

Brand name

Clomid

Active ingredient

Clomifene citrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Clomid.

What is in this leaflet

This leaflet answers some common questions about Clomid.

It does not contain all the available information.

It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Clomid against the benefits he/she expects it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Clomid is used for

About 20% of couples who experience difficulty in conceiving, do so because the woman's ovaries are not producing and releasing an egg each menstrual cycle (anovulation). Your doctor has prescribed Clomid to treat this.

Clomid acts by causing a gland in the brain (the anterior pituitary) to release hormones which stimulate ovulation.

It must be remembered that there are many causes of anovulation, so Clomid may not be effective in all cases.

When taking Clomid there should be 28-32 days from the beginning of one period to the next. Your ovaries should release an egg 6-12 days after a course of Clomid. You should have intercourse around this time to maximise your chances of conception.

If your period does not arrive after the 35th day there are two likely possibilities:

  • the dose of Clomid has not been sufficient to produce ovulation,
    or
  • you are pregnant

If your period is overdue, contact your doctor/fertility unit and they will advise you what steps to take.

This medicine is available only with a doctor's prescription.

Before you take Clomid

Your doctor will perform a pelvic examination on you before you begin to take Clomid. This is to check that you have no physical conditions which may stop you falling pregnant or which might indicate that Clomid is not a suitable drug for you.

When you must not take it

Do not take Clomid if you have an allergy to Clomid or any of the ingredients listed at the end of this leaflet.

Do not take Clomid if you are pregnant. Like most fertility medicines, Clomid should not be taken during pregnancy.

To avoid inadvertently taking Clomid during early pregnancy, you should perform tests during each treatment cycle to determine whether ovulation occurs. You should have a pregnancy test before the next course of Clomid therapy.

Do not take Clomid if you have any of the following conditions:

  • liver disease or a history of liver problems
  • hormone-dependent tumours
  • abnormal uterine bleeding of undetermined origin
  • ovarian cysts, with the exception of polycystic ovary

Do not take Clomid after the expiry date (EXP) printed on the pack. If you take this medicine after the expiry date has passed, it may not work as well.

Do not take Clomid if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking Clomid, contact your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Tell your doctor or pharmacist if you have pre-existing or a family history of hyperlipidemia (high cholesterol levels) or hypertriglyceridemia (high triglyceride levels in blood).

Tell your doctor or pharmacist if you are breast-feeding. Like most fertility medicines, Clomid is not recommended while you are breast-feeding.

The chances of multiple pregnancies are higher when you use Clomid. You should be aware of the potential complications of multiple pregnancy before taking Clomid. Discuss this with your doctor.

How to take Clomid

How much to take

The recommended dose for the first course of Clomid is one tablet per day for five days at the beginning of your cycle. If ovulation does not occur, your doctor may advise you to increase the dose of Clomid in subsequent treatment cycles.

Do not take an increased dose unless instructed to do so by your doctor. Taking more than your doctor prescribes may overstimulate your ovaries, possibly damaging your ovaries and endangering your health.

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

When to take it

Your doctor will advise you on which day of your cycle to begin to take Clomid. If you do not have regular periods your doctor may prescribe other tablets e.g., norethisterone for a number of days, after which a period may start. Use this bleeding to time your Clomid course.

Take Clomid at about the same time each day. This will help you remember when to take the tablets.

How long to use it

Clomid tablets are usually taken daily for five consecutive days at the beginning of your cycle.

Your doctor will advise you on how many courses of Clomid, you should take.

Long term therapy with Clomid is not recommended. Your doctor will tell you for how long you should take Clomid.

If you forget to take it

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26) or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Clomid. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Clomid Progress Checks

It will be necessary to monitor your response to Clomid. Methods used to do this include:

  • basal body temperature chart
  • urine testing
  • blood tests
  • mucus testing

The most appropriate method for you will be discussed by your doctor.

While you are using Clomid

Things you must not do

Do not give Clomid to anyone else, even if they have the same condition as you.

Do not use Clomid to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how Clomid affects you. Clomid may cause visual disturbances in some people. Make sure you know how you react to Clomid before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or have blurred vision.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Clomid. Clomid helps many people with infertility, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious; most of the time they are not. You may need medical treatment if you get some of the side effects.

Tell your doctor or pharmacist if you notice any of the following:

  • hot flushes
  • intermenstrual ("between period") spotting or heavy menstrual periods
  • nausea or vomiting
  • breast discomfort
  • headache
  • insomnia, nervousness, depression, fatigue, dizziness or light-headedness, fainting
  • rash itching or skin irritations
  • increased frequency of urination
  • hair loss
  • fever
  • vaginal discharge
  • seizures
  • visual problems
  • increased heart rate
  • palpitations

If you experience any of the following symptoms of allergic reaction, contact your doctor or other healthcare professional immediately or go to the nearest hospital emergency room right away:

  • difficulty breathing
  • shortness of breath
  • swelling of the face, lips, throat or tongue
  • cold, clammy skin

If any of the following happen, stop taking Clomid and tell your doctor or pharmacist immediately:

  • blurred vision, spots or flashes
  • abdominal discomfort or pelvic pain, soreness or a "bloated" feeling
  • weight gain

The chances of ectopic pregnancies (foetus growing outside the womb) are higher if you conceive on Clomid.

Clomid may cause uterine fibroids to grow in size.

Skin condition (known as erythema multiforme), that may affect the mouth and other parts of the body.

Symptoms may include red, often itchy spots, which start on the limbs and sometimes on the face and the rest of the body. The spots may blister or may progress to form raised, red, pale-centered marks. Those affected may have fever, sore throat, headache and/or diarrhea. If you experience these symptoms, contact your doctor or other healthcare professional.

Prolonged Clomid use may be associated with a small increase in the risk of ovarian cancer.

Hypertriglyceridemia (high triglyceride levels in blood) has been observed in patients who have pre-existing or a family history of hypertriglyceridaemia.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Clomid

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they will not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store Clomid or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor or pharmacist tells you to stop taking Clomid or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Clomid tablets are beige, round, flat faced bevel edged with a score line on one side and M into two concentric circles engraved on the other side.

The 50mg strength is available in boxes of 10 tablets.

Ingredients

Each Clomid tablet contains clomifene citrate (50mg), sucrose, lactose monohydrate, maize starch, pregelatinized maize starch, magnesium stearate and iron oxide yellow.

Manufacturer

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

AUST R 313131

Date of preparation: December 2020.

clomid-ccdsv8-cmiv4-22dec20

Published by MIMS March 2021

BRAND INFORMATION

Brand name

Clomid

Active ingredient

Clomifene citrate

Schedule

S4

 

1 Name of Medicine

Clomifene citrate.

2 Qualitative and Quantitative Composition

Each Clomid tablet contains the active ingredient 50 mg clomifene citrate.

Excipients with known effect.

Sugars (sucrose, lactose monohydrate). For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablet, 50 mg (beige, scored on one side and M into two concentric circles engraved on the other side).

4 Clinical Particulars

4.1 Therapeutic Indications

Clomid is indicated for the treatment of ovulatory failure in carefully selected infertile women who wish to become pregnant.

4.2 Dose and Method of Administration

The recommended dose for the first course of Clomid is 50 mg (one tablet) daily for five days. When ovulation occurs at this dosage there is no advantage in increasing the dose in subsequent cycles of treatment. If ovulation occurs at this dosage but is not followed by pregnancy, subsequent courses for a total maximum of six cycles of Clomid treatment may be administered.
If ovulation appears not to have occurred after the first course of therapy, a second course of 100 mg daily (two 50 mg tablets given as a single daily dose) for five days should be given. Increase of the dosage or duration of therapy beyond 100 mg daily for five days should not be undertaken. If ovulatory menses do not occur, this dose may be repeated for two additional cycles, but failure to induce ovulation after three consecutive cycles at this dosage should constitute an adequate therapeutic trial. If, however, ovulation does occur at this dosage but is not followed by pregnancy, subsequent courses for a total maximum of 6 cycles of Clomid treatment may be administered.
Therapy may be started at any time in a patient who has had no recent uterine bleeding, but if progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the course of Clomid 50 mg daily for five days should be started on or about the fifth day of the cycle.
The majority of patients who are going to respond will respond to the first course of therapy. If ovulatory menses have not occurred after 3 courses, the diagnosis should be re-evaluated. Treatment beyond this is not recommended in the patient who does not exhibit evidence of ovulation.

4.3 Contraindications

Liver disease.

Clomid is contraindicated in patients with known liver disease or a history of liver dysfunction.

Hormone-dependent tumours or abnormal uterine bleeding.

Clomid is contraindicated in patients with hormone-dependent tumours or in patients with abnormal uterine bleeding of undetermined origin.

Pregnancy.

Clomid should not be administered during pregnancy. To avoid inadvertent Clomid administration during early pregnancy, appropriate tests should be utilised during each treatment cycle to determine whether ovulation occurs. The patient should have a pregnancy test before the next course of Clomid therapy.

Ovarian cyst.

Clomid should not be given in the presence of an ovarian cyst, except polycystic ovary, since further enlargement of the cyst may occur. Patients should be evaluated for the presence of ovarian cyst prior to each course of treatment.

4.4 Special Warnings and Precautions for Use

Careful evaluation and selection of patients and close attention to dosage instructions, contraindications and side effects are mandatory. Since Clomid is indicated only in patients with ovarian dysfunction, other possible causes of infertility should be excluded or treated before giving Clomid.
A pelvic examination should be made before each course of Clomid is given.
As the relative safety of long-term cyclic therapy with Clomid has not been conclusively demonstrated, and as the majority of patients will ovulate following 3 courses, long-term cyclic therapy beyond a total of about 6 cycles (including 3 ovulatory cycles) is not recommended.

Ovarian hyperstimulation syndrome (OHSS).

Ovarian hyperstimulation syndrome (OHSS) has been reported in patients receiving Clomid therapy alone or in combination with gonadotrophins. Rare cases of severe forms of OHSS have been reported where the following symptoms have occurred: 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 abnormal ovarian enlargement associated with Clomid therapy, patients should be given the smallest dose possible of Clomid consistent with an expectation of good results. It should be borne in mind that maximal ovarian enlargement may not occur until several days after the treatment cycle is completed. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotrophin may have an exaggerated response to the usual doses of Clomid.
The patient should be instructed to inform the physician of any abdominal or pelvic pain, weight gain, discomfort or distension after taking Clomid.
Patients who complain of abdominal or pelvic pain, discomfort or distension after receiving Clomid should be examined for the presence of an ovarian cyst or other cause. Due to the fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously. If abnormal enlargement of the ovary occurs, additional courses of Clomid should not be given until the ovaries have returned to pre-treatment size, and then a shorter course or smaller dose should be administered. Ovarian enlargement and cyst formation that is associated with Clomid therapy usually regresses spontaneously within a few days or weeks after discontinuing treatment. Unless surgical indication for laparotomy exists, such cystic enlargement should be managed conservatively. The dosage and/or duration of the next course of treatment should be reduced.

Risk of ovarian cancer.

Available data indicate that the use of clomifene citrate may increase the risk of ovarian cancer, especially in nulligravid women (see Section 4.8 Adverse Effects (Undesirable Effects)).
Patients should be evaluated for the presence of ovarian neoplasia before the start of treatment (see Section 4.3 Contraindications).

Visual symptoms.

Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during or shortly after Clomid therapy. These visual disturbances are usually reversible; however, cases of prolonged visual disturbance have been reported including after Clomid discontinuation. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy. The significance of these symptoms is not yet understood. If they do occur Clomid should be discontinued and a complete ophthalmological evaluation should be made. No further courses of Clomid should be administered.
Patients should be warned that visual symptoms may render such activities as driving a car or operating machinery hazardous, particularly under conditions of variable lighting. The patient should be instructed to inform the physician whenever any unusual visual symptoms occur.

Hypersensitivity reactions.

Hypersensitivity reaction including anaphylaxis and angioedema have been reported with Clomid use. In case of allergic reactions, treatment with Clomid must be discontinued and appropriate symptomatic treatment initiated (see Section 4.8 Adverse Effects (Undesirable Effects)).

Uterine fibroids.

Caution should be exercised when using Clomid in patients with uterine fibroids due to the potential for further enlargement of the fibroids.

Hypertriglyceridemia.

Cases of hypertriglyceridemia have been reported (see Section 4.8 Adverse Effects (Undesirable Effects)) in the postmarketing experience with Clomid. Pre-existing or family history of hyperlipidemia and use of higher than recommended dose and/or longer duration of treatment with Clomid are associated with risk of hypertriglyceridemia. Periodic monitoring of plasma triglycerides may be indicated in these patients.

Carcinogenicity/ mutagenicity.

Epidemiological case control studies reported an increased relative risk for both ovarian cancer and ovarian tumours of low malignant potential in infertile women who used fertility drugs compared to women without a history of infertility. However, because infertility is a primary risk factor for ovarian cancer, and because of other limitations such as small sample sizes, it cannot be determined from these studies whether the use of fertility drugs increases the risk of ovarian cancer beyond the effect of infertility. Therefore, prolonged use of Clomid may increase the risk of developing a borderline or invasive ovarian tumour.
Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic potential of Clomid.
The mutagenic potential of Clomid has not been evaluated.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions with other drugs have not been documented.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Multiple pregnancy.

The incidence of multiple pregnancy is increased when conception takes place during a cycle in which Clomid is given. The potential complications and hazards of multiple pregnancy should be discussed with the patient.
In a large series of closely monitored patients who became pregnant after receiving Clomid, there were 6.9% (165) twins, 0.5% (11) triplets, 0.3% (7) quadruplets, and 0.13% (3) quintuplets. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic to dizygotic twins was 1:5.
Of these multiple pregnancies, 357 live infants were born of 165 multiple births. After excluding 60 neonatal deaths, 297 survived, including 27 of 61 live infants from triplet, quadruplet, and quintuplet pregnancies. In addition, one sextuplet pregnancy has been reported in a patient treated with Clomid. Patients (and their husbands) should be advised of the possibility and potential complications and hazards of multiple pregnancy associated with Clomid therapy.

Ectopic pregnancy.

There is an increased chance of ectopic pregnancy (including tubal and ovarian sites) in women who conceive following Clomid therapy.
(Category B3)
See Section 4.3 Contraindications, Pregnancy. Clomid was found to damage rat and rabbit foetuses when given in high doses to the pregnant animal. Clomid should not be used during pregnancy.

Pregnancy wastage.

The experience from patients of all diagnoses during clinical investigation of Clomid shows a pregnancy (single and multiple) wastage or fetal loss rate of 21.4% (abortion rate of 19.0%), 1.18% ectopic pregnancies, 0.17% hydatidiform mole, 0.04% foetus papyraceous and 1.01% of pregnancies with one or more stillbirths.
It is not known whether Clomid is excreted in milk. Clomid may reduce lactation.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned that visual symptoms, dizziness, seizures or fatigue (see Section 4.8 Adverse Effects (Undesirable Effects)), may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting. The patient should be instructed to inform the physician whenever any unusual visual symptoms occur.

4.8 Adverse Effects (Undesirable Effects)

Side effects are dose-related, being more frequent and more severe when higher doses of Clomid are administered.
During clinical trials, the more common side effects included ovarian enlargement (13.6%), vasomotor flushes (10.4%), abdominal-pelvic discomfort (distension, bloating, pain or soreness) (5.5%), nausea and vomiting (2.2%), breast discomfort (2.1%), visual symptoms (1.5%), headache (1.3%) and intermenstrual spotting or menorrhagia (1.3%).
Vasomotor symptoms resembling menopausal hot flushes are not usually severe and disappear soon after treatment is discontinued. Abdominal symptoms are most often related to ovulatory (Mittelschmerz) or pre-menstrual phenomena, or to ovarian enlargement. At recommended dosage, the normal variation in ovarian size may be exaggerated. Rare instances of massive ovarian enlargement and rupture of a lutein cyst with haemoperitoneum have been reported.
Neoplasm, benign, malignant and unspecified (including cysts and polyps): Ovarian malignancies (frequency not known).
Visual 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 after-images. After-images as such have also been reported. Symptoms often first appear or are accentuated with exposure to a more brightly lit environment.
Immune system disorders, anaphylaxis, angioedema have been reported, frequency not known (see Section 4.4 Special Warnings and Precautions for Use).
Ophthalmologically definable scotomata, phosphenes, reduced visual acuity and retinal cell function (electroretinographic) changes have also been reported. There have been rare reports of cataracts and optic neuritis.
These visual disturbances are usually reversible; however cases of prolonged visual disturbances have been reported including after Clomid discontinuation. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy.
Other less frequently reported symptoms included increased nervous tension, depression, fatigue, dizziness or lightheadedness, insomnia, heavier menses, weight gain, skin and subcutaneous tissue disorders, urticaria and allergic dermatitis/ rash, increased urinary frequency, alopecia or moderate reversible hair loss, the frequency of erythema multiforme is not known.
Anxiety, nervousness and mood disturbances including altered mood, mood swings and irritability have been reported.
There have been reports of new cases of endometriosis and exacerbation of pre-existing endometriosis during Clomid therapy.
Isolated reports have been received of the occurrence of endocrine-related or dependent tumours/ neoplasms or the aggravation of such growths.
Hypertriglyceridemia, in some cases with pancreatitis, has been observed in patients with pre-existing or a family history of hypertriglyceridemia and/or with dose and duration of treatment exceeding the label recommendations.
Seizures have been rarely reported. Transient paraesthesia has been reported.
Tachycardia, palpitations and pancreatitis have been reported.
Multiple pregnancies, including simultaneous intrauterine and extrauterine pregnancies, have been reported.
There is an increased chance of ectopic pregnancy (including tubal and ovarian sites) in women who conceive following Clomid therapy.
Reduced endometrial thickness has been reported.
Defects at birth have been reported in 58 infants from 2,369 delivered pregnancies in mothers treated with Clomid. Four of the infants were in the abortion/ stillbirth category, 14 were from multiple pregnancies, and the remaining were single births. The defects have included Down's syndrome (5 infants), congenital heart lesions (8 infants), microcephaly (2 infants), harelip and cleft palate (2 infants), hypospadias (3 infants), undescended testes (2 infants), club foot (4 infants), gastrointestinal malformations (4 infants), congenital hip (2 infants) and polydactyly (both of twins).
Eight of the total of 58 infants were born to 7 of 158 mothers who received (inadvertently) a course of Clomid during the first 6 weeks after conception.
Clomid, when given continuously for prolonged periods, may interfere with cholesterol synthesis. Serum from patients treated in this way appears to have elevated desmosterol levels. In patients taking recommended doses of Clomid, serum sterol patterns are not significantly altered.
Bromsulphophthalein (BSP) retention of greater than 5% has been reported in 32 of 141 patients in whom it was measured. Increased transaminases have been reported. Other liver function tests were usually normal. Retention was usually minimal unless associated with prolonged continuous Clomid administration or with apparently unrelated liver disease.
In some patients, pre-existing BSP retention decreased even though Clomid therapy was continued. One patient developed jaundice on the 14th day of Clomid therapy; liver biopsy revealed bile stasis without evidence of hepatitis. Clomid has not been reported to cause significant abnormality in the haematopoietic or renal system, the protein bound iodine or in serum cholesterol.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Toxic effects of acute overdosage of Clomid have not been reported, but the number of overdose cases recorded is small. In the event of an overdose, appropriate supportive measures should be employed.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Ovulation stimulants, ATC code: G03BG02.
Commonly associated diagnoses include polycystic ovary syndrome, lactation amenorrhoea syndrome, psychogenic amenorrhoea, certain cases of secondary amenorrhoea of undetermined aetiology, and post-oral contraceptive amenorrhoea. In such patients, approximately 70% will ovulate and (provided that there is no other cause of infertility in them or in their partners) about 30% will become pregnant. It is worthwhile to note that the data from which these percentages were derived included patients who were single and some who either did not desire pregnancy at the time of treatment or had impediments to achievement of pregnancy other than ovulatory dysfunction.
Good levels of endogenous oestrogen (estimated from vaginal smears, endometrial biopsy, assay or urinary oestrogen, or from bleeding in response to progesterone) are a favourable prognosis for treatment with Clomid, but reduced oestrogen levels do not always rule out the possibility of successful therapy.
Some anovulatory patients that appear to respond to Clomid but either do not actually ovulate or whose luteal phases are so short that the opportunity to conceive is limited may benefit by having, following Clomid courses, injections of human chorionic gonadotrophin (HCG) at about the expected time of ovulation.
Clomid therapy is ineffective in patients in whom primary pituitary or ovarian failure precludes the possibility of stimulating normal function.

Mechanism of action.

The ovulatory response to cyclic Clomid therapy appears to be mediated through increased output of pituitary gonadotrophins, which in turn stimulates the maturation and endocrine activity of the ovarian follicle and the subsequent development and function of the corpus luteum. The role of the pituitary is indicated by increased urinary excretion of gonadotrophins and the response of the ovary, as manifested by increased urinary oestrogen excretion.
Ovulation most often occurs from 6-12 days after a course of Clomid. With this in mind, coitus should be timed to coincide with the expected time of ovulation.
Although there is no evidence of a 'carry over effect' of Clomid, spontaneous ovulatory menses have been noted after Clomid therapy in some patients.
Infertile patients with the polycystic ovary syndrome who have not responded to wedge resection of the ovary may respond to Clomid.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Orally administered 14C labelled clomifene citrate was readily absorbed when administered to humans.

Excretion.

Cumulative excretion of the 14C label in urine and faeces averaged about 50% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 7.8% and mean faecal excretion of 42.4%. Less than 1% per day was excreted in faecal and urine samples collected from 31 to 53 days after clomifene citrate 14C administration. Some clomifene and/or its metabolites (here measured as 14C) may therefore remain in the body during early pregnancy in women who conceive in the menstrual cycle of Clomid treatment.

5.3 Preclinical Safety Data

Genotoxicity.

Clomifene citrate did not induce gene mutations in bacteria (Ames test) or chromosome aberrations in cultured human peripheral blood lymphocytes. Clomifene citrate at oral doses up to 2000 mg/kg/day did not induce genotoxic effects in rats.
The mutagenic potential of Clomid has not been evaluated. See Section 4.4 Special Warnings and Precautions for Use.

Carcinogenicity.

Epidemiological case control studies reported an increased relative risk for both ovarian cancer and ovarian tumours of low malignant potential in infertile women who used fertility drugs compared to women without a history of infertility. However, because infertility is a primary risk factor for ovarian cancer, and because of other limitations such as small sample sizes, it cannot be determined from these studies whether the use of fertility drugs increases the risk of ovarian cancer beyond the effect of infertility.
Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic potential of Clomid.
See Section 4.4 Special Warnings and Precautions for Use.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sucrose, lactose monohydrate, pregelatinised maize starch, maize starch and magnesium stearate, iron oxide yellow.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25 degrees Celsius.

6.5 Nature and Contents of Container

Clomid is available in PVC/Al blister packs of 5 or 10* tablets.
* Marketed pack.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Clomifene citrate is a white to pale yellow powder.

Chemical structure.

Clomid contains clomifene citrate, a triarylethylene compound (related to chlorotrianisene and triparanol).
2-[4-(2-chloro-1,2-diphenylethenyl)phenoxyl]- N,N-diethylethanamine 2-hydroxy-1,2,3-propanetricarboxylate (1:1) or 2-[p-(2-chloro-1,2-diphenylvinyl) phenoxy] triethylamine citrate (1:1).
The empirical formula is C26H28ClNO,C6H8O7 (MW = 598.09).
The structural formula appears:

CAS number.

50-41-9.

7 Medicine Schedule (Poisons Standard)

Prescription Medicine (Schedule 4).

Summary Table of Changes