Duinum Adverse Reactions

Symptoms/Signs/Conditions: Adverse effects appeared to be dose-related, occurring more frequently at the higher dose and with the longer courses of treatment used in investigational studies. At recommended dosage, adverse effects are not prominent and infrequently interfere with treatment.
During the investigational studies, the more common reported adverse effects included ovarian enlargement (13.6%), vasomotor flushes (10.4%), abdominal-pelvic discomfort (distension, bloating) (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%).
Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Tumours/neoplasms: Isolated reports have been received on the occurrence of endocrine-related or dependent neoplasms or their aggravation. Ovarian cancer: See Precautions.
Endocrine disorders: Ovarian enlargement: At recommended dosage, abnormal ovarian enlargement is infrequent although the usual cyclic variation in ovarian size may be exaggerated. Similarly, cyclic ovarian pain may be accentuated. With higher or prolonged dosage, more frequent ovarian enlargement and cyst formation may occur, and the luteal phase of the cycle may be prolonged.
Rare instances of massive ovarian enlargement are recorded. Such an instance has been described in a patient with polycystic ovary syndrome whose Duinum therapy consisted of 100 mg daily for 14 days. Abnormal ovarian enlargement usually regresses spontaneously; most of the patients with this condition should be treated conservatively.
Metabolism and nutrition disorders: Hypertriglyceridemia (frequency: not known), 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.
Nervous system disorders: Convulsions have been reported; patients with a history of seizures may be predisposed. In investigational patients, CNS symptoms/signs, conditions of dizziness, light-headedness/vertigo (0.9%), nervous tension/insomnia (0.8%) and fatigue/depression (0.7%) were reported. After prescription availability, there were isolated additional reports of these conditions and also reports of other conditions such as syncope/fainting, cerebrovascular accident, cerebral thrombosis, psychotic reactions including paranoid psychosis, neurologic impairment, disorientation and speech disturbance.
Eye disorders: 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 bright-light environment.
Ophthalmologically definable scotomata, phosphenes and reduced visual acuity have been reported.
There are rare reports of cataracts and optic neuritis.
These visual disturbances are usually reversible. However, cases of prolonged visual disturbance have been reported, including after Duinum have been discontinued. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy.
Cardiac disorders: Tachycardia, (frequency not known) palpitations (frequency not known).
Gastrointestinal disorders: Pancreatitis (frequency not known).
Hepatobiliary disorders: Bromsulphalein (BSP) retention of greater than 5% was reported in 32 of 141 patients in whom it was measured, including 5 of 43 patients who took approximately the dose of clomifene now recommended. Retention was usually minimal unless associated with prolonged continuous clomifene administration or with apparently unrelated liver disease. Other liver function tests were usually normal. In a later study in which patients were given 6 consecutive monthly courses of clomifene (50 or 100 mg daily for 3 days) or matching placebo, BSP tests were done on 94 patients. Values in excess of 5% retention were recorded in 11 patients, 6 of whom had taken drug and 5 placebo.
In a separate report, one patient taking 50mg of clomifene daily developed jaundice on the 19th day of treatment; liver biopsy revealed bile stasis without evidence of hepatitis.
Skin and subcutaneous tissue disorders: Dermatitis and rash were reported by investigational patients. Conditions such as rash and urticaria were the most common ones reported after prescription availability but also reported were conditions such as allergic reaction, erythema multiforme, ecchymosis and angioneurotic oedema. Hair thinning (alopecia) has been reported very rarely.
Reproductive system and breast disorders: There are reports of new cases of endometriosis and exacerbation of pre-existing endometriosis during clomifene therapy.
Multiple pregnancies, including simultaneous intrauterine and extrauterine pregnancies, have been reported. There is an increased chance of ectopic pregnancy in women who conceive following clomifene therapy.
Reduced endometrial thickness (frequency not known).