Clinical medicine profile
Clomiphene
Therapeutic agent (verify pharmacological class)
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CONTRAINDICATIONS Hypersensitivity Clomiphene citrate is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients.
- Pregnancy Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate does not offer benefit in this population.
- Available human data do not suggest an increased risk for congenital anomalies above the background population risk when used as indicated.
- However, animal reproductive toxicology studies showed increased embryo-fetal loss and structural malformations in offspring.
- If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks to the fetus.
- (See PRECAUTIONS: Pregnancy .) Liver Disease.
- Clomiphene citrate therapy is contraindicated in patients with liver disease or a history of liver dysfunction (see also INDICATIONS AND USAGE and ADVERSE REACTIONS ).
- Abnormal Uterine Bleeding.
- Clomiphene citrate is contraindicated in patients with abnormal uterine bleeding of undetermined origin (see INDICATIONS AND USAGE ).
- Ovarian Cysts.
- Clomiphene citrate is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome (see INDICATIONS AND USAGE and WARNINGS ).
- Clomiphene citrate is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor (see INDICATIONS AND USAGE ).
Precautions
- WARNINGS Visual Symptoms Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during therapy with clomiphene citrate.
- These visual symptoms increase in incidence with increasing total dose or therapy duration.
- These visual disturbances are usually reversible
- however, cases of prolonged visual disturbance have been reported with some occurring after clomiphene citrate discontinuation.
- The visual disturbances may be irreversible, especially with increased dosage or duration of therapy.
- Patients should be warned that these visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting.
- These visual symptoms appear to be due to intensification and prolongation of after images.
- Symptoms often first appear or are accentuated with exposure to a brightly lit environment.
- While measured visual acuity usually has not been affected, a study patient taking 200 mg clomiphene citrate daily developed visual blurring on the 7th day of treatment, which progressed to severe diminution of visual acuity by the 10th day.
- No other abnormality was found, and the visual acuity returned to normal on the 3rd day after treatment was stopped.
- Ophthalmologically definable scotomata and retinal cell function (electroretinographic) changes have also been reported.
- A patient treated during clinical studies developed phosphenes and scotomata during prolonged clomiphene citrate administration, which disappeared by the 32 nd day after stopping therapy.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE & ADMINISTRATION General Considerations The workup and treatment of candidates for clomiphene citrate therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with clomiphene citrate only after careful diagnostic evaluation (see INDICATIONS AND USAGE ). The plan of therapy should be outlined in advance. Impediments to achieving the goal of therapy must be excluded or adequately treated before beginning clomiphene citrate. The therapeutic objective should be balanced with potential risks and discussed with the patient and others involved in the achievement of a pregnancy. Ovulation most often occurs from 5 to 10 days after a course of clomiphene citrate. Coitus should be timed to coincide with the expected time of ovulation. Appropriate tests to determine ovulation may be useful during this time. Recommended Dosage Treatment of the selected patient should begin with a low dose, 50 mg daily (1 tablet) for 5 days. The dose should be increased only in those patients who do not ovulate in response to cyclic 50 mg clomiphene citrate. A low dosage or duration of treatment course is particularly recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in patients with polycystic ovary syndrome (see WARNINGS; Ovarian Hyperstimulation Syndrome ). The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle. If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the regimen of 50 mg daily for 5 days should be started on or about the 5 th day of the cycle. Therapy may be started at any time in the patient who has had no recent uterine bleeding. When ovulation occurs at this dosage, there is no advantage to increasing the dose in subsequent cycles of treatment. If ovulation does not appear to occur after the first course of therapy, a second course of 100 mg daily (two 50 mg tablets given as a single daily dose) for 5 days should be given. This course may be started as early as 30 days after the previous one after precautions are taken to exclude the presence of pregnancy. Increasing the dosage or duration of therapy beyond 100 mg/day for 5 days is not recommended. The majority of patients who are going to ovulate will do so after the first course of therapy. If ovulation does not occur after three courses of therapy, further treatment with clomiphene citrate is not recommended and the patient should be reevaluated. If three ovulatory responses occur, but pregnancy has not been achieved, further treatment is not recommended. If menses does not occur after an ovulatory response, the patient should be reevaluated. Long-term cyclic therapy is not recommended beyond a total of about six cycles (see PRECAUTIONS ).
See label paediatric section if present; otherwise use paediatric formulary — do not extrapolate adult doses.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS & USAGE Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy.
- Impediments to achieving pregnancy must be excluded or adequately treated before beginning clomiphene citrate therapy.
- Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome (see WARNINGS: Ovarian Hyperstimulation Syndrome ), amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.
- Properly timed coitus in relationship to ovulation is important.
- A basal body temperature graph or other appropriate tests may help the patient and her physician determine if ovulation occurred.
- Once ovulation has been established, each course of clomiphene citrate should be started on or about the 5 th day of the cycle.
- Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles).
- (See DOSAGE AND ADMINISTRATION and PRECAUTIONS .) Clomiphene citrate is indicated only in patients with demonstrated ovulatory dysfunction who meet the conditions described below: Patients who are not pregnant.
- Patients without ovarian cysts.
- Clomiphene citrate should not be used in patients with ovarian enlargement except those with polycystic ovary syndrome.
- Pelvic examination is necessary prior to the first and each subsequent course of clomiphene citrate treatment.
- Patients without abnormal vaginal bleeding.
Adverse effects
- ADVERSE REACTIONS Clinical Trial Adverse Events.
- Clomiphene citrate, at recommended dosages, is generally well tolerated.
- Adverse reactions usually have been mild and transient and most have disappeared promptly after treatment has been discontinued.
- Adverse experiences reported in patients treated with clomiphene citrate during clinical studies are shown in Table 2.
- Table 2.
- Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n = 8029*) Adverse Event % Ovarian Enlargement 13.6 Vasomotor Flushes 10.4 Abdominal-Pelvic Discomfort/Distention/Bloating 5.5 Nausea and Vomiting 2.2 Breast Discomfort 2.1 Visual Symptoms Blurred vision, lights, floaters, waves, unspecified visualcomplaints, photophobia, diplopia, scotomata, phosphenes 1.5 Headache 1.3 Abnormal Uterine Bleeding Intermenstrual spotting, menorrhagia 1.3 *Includes 498 patients whose reports may have been duplicated in the event totals and could not be distinguished as such.
- Also, excludes 47 patients who did not report symptom data.
- The following adverse events have been reported in fewer than 1% of patients in clinical trials: Acute abdomen, appetite increase, constipation, dermatitis or rash, depression, diarrhea, dizziness, fatigue, hair loss/dry hair, increased urinary frequency/volume, insomnia, light-headedness, nervous tension, vaginal dryness, vertigo, weight gain/loss.
- Patients on prolonged clomiphene citrate therapy may show elevated serum levels of desmosterol.
- This is most likely due to a direct interference with cholesterol synthesis.
- However, the serum sterols in patients receiving the recommended dose of clomiphene citrate are not significantly altered.
- Ovarian cancer has been infrequently reported in patients who have received fertility drugs.
- Infertility is a primary risk factor for ovarian cancer
- however, epidemiology data suggest that prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
An anti-oestrogen that exerts its effects by competing with estrogen for binding sites at the hypothalamic level.
Read complete mechanism
An anti-oestrogen that exerts its effects by competing with estrogen for binding sites at the hypothalamic level. In effect, the gonadotrophins, follicle-stimulating hormone [FSH] and luteinizing hormone [LH] secretions are increased. This results in ovarian follicle maturation, followed by the preovulatory LH surge, ovulation, and the subsequent development of the corpus luteum. Its effectiveness in male infertility may be related to the increases in FSH and LH secretions.
Product-specific
Product-specific
See product SmPC
of the 14 C averaged about 50% of the oral dose and 37% of an intravenous dose after 5 days. Mean urinary excretion was approximately 8% with fecal excretion of about 42%. Some 14 C label was still present in the feces 6 weeks after administration. Subsequent single-dose studies...
than enclomiphene (trans). Detectable levels of zuclomiphene persisted for longer than a month in these subjects. This may be suggestive of stereo-specific enterohepatic recycling or sequestering of the zuclomiphene. Thus, it is possible that some active drug may remain in the bo...
Pregnancy, lactation & diet
PREGNANCY Fetal Risk Summary Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate treatment does not offer benefit in this population. Available human data do not suggest an increased risk for congenital anomalies above the background population risk. However, animal reproductive toxicology studies showed increased embryo-fetal loss and structural malformations in offspring. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks to the fetus. Clinical Considerations To avoid inadvertent clomiphene citrate administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation and/or pregnancy occurs. Patients should be evaluated carefully to exclude ovarian enlargement or ovarian cyst formation between each treatment cycle. The next course of clomiphene citrate therapy should be delayed until these conditions have been excluded. Human Data The available human data from epidemiologic studies do not show any apparent cause and effect relationship between clomiphene citrate periconceptual exposure and an increased risk of overall birth defects, or any specific anomaly. However, due to the small number of cases of congenital anomalies occurring in clomiphene citrate treated women, these epidemiologic studies were only able to rule out large differences in risk. The studies did not consider factors associated with female subfertility and were unable to adjust for other important confounders. In addition, available data do not support an increased rate of spontaneous abortion among subfertile women treated with clomiphene citrate for ovulation induction. Animal Data Oral administration of clomiphene citrate to pregnant rats during organogenesis at doses of 1 to 2 mg/kg/day resulted in hydramnion and weak, edematous fetuses with wavy ribs and other temporary bone changes. Doses of 8 mg/kg/day or more also caused increased resorptions and dead fetuses, dystocia, and delayed parturition, and 40 mg/kg/day resulted in increased maternal mortality. Single doses of 50 mg/kg caused fetal cataracts, while 200 mg/kg caused cleft palate. Following injection of clomiphene citrate 2 mg/kg to mice and rats during pregnancy, the offspring exhibited metaplastic changes of the reproductive tract. Newborn mice and rats injected during the first few days of life also developed metaplastic changes in uterine and vaginal mucosa, as well as premature vaginal opening and anovulatory ovaries. These findings are similar to the abnormal reproductive behavior and sterility described with other estrogens and antiestrogens. In rabbits, some temporary bone alterations were seen in fetuses from dams given oral doses of 20 or 40 mg/kg/day during pregnancy, but not following 8 mg/kg/day. No permanent malformations were observed in those studies. Also, rhesus monkeys given oral doses of 1.5 to 4.5 mg/kg/day for various periods during pregnancy did not have any abnormal offspring.
NURSING MOTHERS It is not known whether clomiphene citrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if clomiphene citrate is administered to a nursing woman. In some patients, clomiphene citrate may reduce lactation. Ovarian Cancer Prolonged use of clomiphene citrate tablets may increase the risk of a borderline or invasive ovarian tumor (see ADVERSE REACTIONS ).
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| PRACLOMIDE | MEDCURE HEALTHCARE | Tablet | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.