SIDE EFFECTS
Clinical Events
Trial Adverse: 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 visual complaints, 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.
Postmarketing Adverse Events
The following adverse experiences were reported spontaneously with clomiphene citrate tablets USP. The cause and effect relationship of the listed events to the administration of clomiphene citrate tablets USP is not known.
Dermatologic: Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus
Central Nervous System: Migraine headache, paresthesia, seizure, stroke, syncope
Psychiatric: Anxiety, irritability, mood changes, psychosis
Visual Disorders: Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, temporary loss of vision
Cardiovascular: Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis
Musculoskeletal: Arthralgia, back pain, myalgia
Hepatic: Transaminases increased, hepatitis
Neoplasms: Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma); breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous system (astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma); trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin’s lymphoma, tongue carcinoma, bladder carcinoma); and neoplasms of offspring (neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia)
Genitourinary: Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage
Body as a Whole: Fever, tinnitus, weakness
Other: Leukocytosis, th roid disorder.
Fetal/Neoastal Anomalies
The following fetal abnormalities have also been reported during postmarketing surveillance: delayed development; abnormal bone development including skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot, and joints; tissue malformations including imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, renal agenesis and dysgenesis, and malformations of the eye and lens (cataract), ear, lung, heart (ventricular septal defect and tetralogy of Fallot), and genitalia; as well as dwarfism, deafness, mental retardation, chromosomal disorders, and neural tube defects (including anencephaly).
