Clomifene Citrate

Registered South African indications:

• Ovulation induction

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Hepatic impairment
• Porphyria
• Hormone-dependent tumours
• Abnormal uterine bleeding of undetermined origin
• Ovarian cyst (except polycystic ovary)

Cautions 

• Breastfeeding
• Pre-existing hypertriglyceridemia
• Family history of hypertriglyceridemia
• Prolonged therapy
• Higher doses
• Uterine fibroids
• History of seizures
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Ovulatory failure in women desiring pregnancy in whom ovulatory dysfunction is demonstrated 

• Oral (tab): 50mg, dly; Treatment duration: 5 days ;If no response, repeat course: 100mg, dly for 5 days at least 30 days after the first course; Max duration: 6 cycles (including 3 ovulatory cycles)

Other causes of infertility must be excluded or adequately treated before initiating therapy

If no recent bleeding, the course may be initiated at any time; If spontaneous bleeding/progestin-induced bleeding, then initiate therapy on day 5 of the menstrual cycle; Each subsequent course should be administered cyclically on day 5 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

Increase of the dosage or duration of therapy beyond 100 mg/day for 5 days should not be undertaken

The majority of patients who are going to respond will respond to the first course of therapy, and 3 courses should constitute an adequate therapeutic trial; If ovulatory menses have not yet occurred, the diagnosis should be re-evaluated

Ovulation normally occurs from days 6-12 after a course of clomifene and the importance of correctly timing coitus must be emphasized to patients

Special care with lower dosage or duration of treatment is recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in patients with polycystic ovary syndrome

Clomifene therapy is ineffective in patients with primary pituitary or primary ovarian failure

Clomifene therapy cannot be expected to substitute for specific treatment of other causes of ovulatory failure, such as thyroid or adrenal disorders

For hyperprolactinaemia, there is other preferred specific treatment

Clomifene is not first-line treatment for low weight-related amenorrhoea, with infertility. Clomifene also has no value if a high follicle-stimulating hormone blood level is observed following early menopause

Not indicated for use in children

Pregnancy 

• Contraindicated
• Clomifene is not indicated during pregnancy. Although there is no evidence that clomifene has a harmful effect on the human foetus, there is evidence that clomifene has a deleterious effect on rat and rabbit foetuses when given in high doses to the pregnant animal. To avoid inadvertent clomifene administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation occurs. The patient should have a pregnancy test before the next course of clomifene therapy

Breastfeeding

• Caution 
• It is not known whether clomifene citrate is excreted in human milk. Clomifene may reduce production of breast milk

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Seizures
• Transient paraesthesia
• Dizziness
• Vertigo
• Nervous tension
• Insomnia
• Depression
• Fatigue
• Syncope
• Cerebrovascular accident
• Cerebral thrombosis
• Psychotic reactions, including paranoid psychosis
• Neurologic impairment
• Disorientation
• Speech disturbance
• Anxiety
• Mood disturbance
  - Altered mood
  - Mood swings
  - Irritability

Cardiovascular Disorders

• Vasomotor flushes
• Cerebral thrombosis
• Tachycardia
• Palpitations

Gastrointestinal Disorders

• Pancreatitis
• Abdominal-pelvic discomfort
  - Distention
  - Bloating
• Nausea and vomiting

Hepatobiliary Disorders

• Bromsulphalein retention
• Jaundice
• Increased transaminases

Genitourinary Disorders

• Ovarian enlargement
• Interrmenstrual spotting
• Menorrhagia
• Increased cyclic ovarian pain (mittelschmerz)
• Cyst formation (higher and/or prolonged dose)
• Prolonged luteal phase (higher and/or prolonged dose)
• Endometriosis or exacerbation thereof
• Multiple pregnancies
• Extrauterine pregnancies
• Ectopic pregnancy
• Reduced endometrial thickness
• Increased risk of ovarian cancer
• Breast discomfort
• Ovarian hyperstimulation syndrome
  - Pericardial effusion
  - Anasarca
  - Hydrothorax
  - Acute abdomen
  - Renal failure
  - Pulmonary oedema
  - Ovarian haemorrhage
  - Deep venous thrombosis
  - Torsion of the ovary
  - Acute respiratory distress

Endocrine and Metabolic Disorders

• Hypertriglyceridaemia
• Endocrine-related or dependent neoplasms or exacerbation thereof

Skin and Subcutaneous Tissue Disorders

• Dermatitis
• Rash
• Allergic reaction
• Erythema multiforme
• Urticaria
• Ecchymosis
• Angioneurotic oedema
• Alopecia

Sensory Disorders

• Blurred vision
• Scintillating scotomata
• Scotoma
• Phosphenes
• Decreased visual acuity
• Optic neuritis
• Cataracts

No information available

• Gynaecological examination
• Pregnancy test
• Oestrogen levels

None routine. Specific cases may require

• Serum triglycerides
• Thyroid function

Clomifene is a triarylethylene compound (related to chlorotrianisene and triparanol). It is a non-steroidal agent which stimulates ovulation in a high percentage of appropriately selected anovulatory women. The ovulatory response to cyclic clomifene therapy is mediated through increased output of pituitary gonadotrophins, which in turn stimulates the maturation and endocrine activity of the ovarian follicle.

Tablet 50mg

• Clomid (Adcock Ingram)
• Clomihexal (Sandoz)
• Fertab (Gulf Drug)
• Fertomid (Cipla)
• Rubitab 50 (Ruby)