More than 640 patients have been treated with Vagifem in clinical trials, including >200 patients treated from 28 weeks and up to 64 weeks. Well-known oestrogen-related adverse events which occurred with a higher frequency in the treated group as compared with the placebo group, are presented as "common (>1/100,<1/10)".
The spontaneous reporting rate on Vagifem corresponds to approximately 1 case per 10,000 patient years. Adverse events for which an increased frequency has not been observed in clinical trials, but which have been spontaneously reported and which on an overall judgement are considered possibly related to Vagifem treatment, are therefore presented as "very rare (<1/10,000)".
Post-marketing experience is subject to under-reporting especially with regard to trivial and well known adverse drug reactions. The presented frequencies should be interpreted in that light.
The most commonly reported adverse drug reactions are: Vaginal discharge and vaginal discomfort.
Oestrogen-related adverse events eg, breast pain, peripheral oedema and postmenopausal bleedings are most likely present at the beginning of Vagifem treatment.
Common (>1/100, <1/10): Infections and Infestations: Genital candidiasis or vaginitis.
Nervous System Disorders: Headache.
Gastrointestinal Disorders: Nausea, abdominal pain, abdominal distension or abdominal discomfort, dyspepsia, vomiting, flatulence.
Reproductive System and Breast Disorders: Vaginal haemorrhage, vaginal discharge or vaginal discomfort, breast oedema, breast enlargement, breast pain or breast tenderness.
General Disorders and Administration Site Conditions: Peripheral oedema.
Very Rare (<1/10,000): Neoplasms Benign and Malignant (including cysts and polyps): Breast cancer, endometrial cancer.
Immune System Disorders: Hypersensitivity, not otherwise specified (NOS).
Metabolism and Nutrition Disorders: Fluid retention.
Psychiatric Disorders: Insomnia, depression.
Nervous System Disorders: Aggravated migraine.
Vascular Disorders: Deep venous thrombosis.
Gastrointestinal Disorders: Diarrhoea.
Skin and Subcutaneous Tissue Disorders: Urticaria, erythematosus rash, rash NOS, pruritic rash, genital pruritus.
Reproductive System and Breast Disorders: Endometrial hyperplasia, vaginal irritation, vaginal pain, vaginismus, vaginal ulceration.
General Disorders and Administration Site Conditions: Ineffective drug.
Investigations: Increased weight, increased blood oestrogen.
The following adverse reactions have been reported in association with other oestrogen treatment: Myocardial infarction, congestive heart disease.
Gall bladder disease.
Skin and Subcutaneous Disorders: Chloasma, erythema multiforme, erythema nodosum, vascular purpura, pruritus.
Risk of developing endometrial cancer, endometrial hyperplasia or increase in size of uterine fibroids*. Insomnia; epilepsy; libido disorder NOS; deterioration of asthma; probable dementia.
* In non-hysterectomised women.