Clomiphene - Warnings and 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.

Postmarketing surveillance of adverse events has also revealed other visual signs and symptoms during clomiphene citrate therapy (see ADVERSE REACTIONS ).

While the etiology of these visual symptoms is not yet understood, patients with any visual symptoms should discontinue treatment and have a complete ophthalmological evaluation carried out promptly.

Ovarian Hyperstimulation Syndrome The ovarian hyperstimulation syndrome (OHSS) has been reported to occur in patients receiving clomiphene citrate therapy for ovulation induction.

OHSS may progress rapidly (within 24 hours to several days) and become a serious medical disorder.

In some cases, OHSS occurred following cyclic use of clomiphene citrate therapy or when clomiphene citrate was used in combination with gonadotropins.

Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with OHSS.

OHSS is a medical event distinct from uncomplicated ovarian enlargement.

The clinical signs of this syndrome in severe cases can include gross ovarian enlargement, gastrointestinal symptoms, ascites, dyspnea, oliguria, and pleural effusion.

In addition, the following symptoms have been reported in association with this syndrome: pericardial effusion, anasarca, hydrothorax, acute abdomen, hypotension, renal failure, pulmonary edema, intraperitoneal and ovarian hemorrhage, deep venous thrombosis, torsion of the ovary, and acute respiratory distress.

The early warning signs of OHSS are abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain.

Elevated urinary steroid levels, varying degrees of electrolyte imbalance, hypovolemia, hemoconcentration, and hypoproteinemia may occur.

Death due to hypovolemic shock, hemoconcentration, or thromboembolism has occurred.

Due to fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously.

If conception results, rapid progression to the severe form of the syndrome may occur.