Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, CT13 9NJ, UK
Known, past or suspected breast cancer.
Previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism).
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction).
Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Porphyria.
Before initiating or reinstituting therapy, a complete personal and family medical history should be taken. Physical (including pelvic) examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman, but may include, if judged appropriate by the clinician, abdominal and pelvic examination. Women should be encouraged to participate in the national breast cancer screening programme (mammography) and the national cervical screening programme (cervical cytology) as appropriate for their age.
The possibility of genital tract pathology should be considered before commencing treatment in women with abnormal uterine bleeding, especially in women over 45, who may require gynaecological investigation.
A negative pregnancy test should be demonstrated before starting therapy (see section 4.6).
Doses of up to 30 mg a day may not suppress ovulation and patients should be advised to take adequate contraceptive measures, where appropriate.
If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with Provera, in particular:
Rare cases of thrombo-embolism have been reported with use of Provera, especially at higher doses. Causality has not been established.
History or emergence of the following conditions requires careful consideration and appropriate investigation: signs of a blood clot; migraine or unusually severe headaches or acute visual disturbances of any kind.
Provera, especially in high doses, may cause weight gain and fluid retention. With this in mind, caution should be exercised in treating any patient with a pre-existing medical condition, such as epilepsy, migraine, asthma, cardiac or renal dysfunction, that might be adversely affected by weight gain or fluid retention.
Some patients receiving Provera may exhibit a decreased glucose tolerance. The mechanism for this is not known. This fact should be borne in mind when treating all patients and especially known diabetics.
This product contains lactose and sucrose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Patients with a history of treatment for mental depression should be carefully monitored while receiving Provera therapy. Some patients may complain of premenstrual like depression while on Provera therapy.
Therapy should be discontinued in case a contraindication is discovered and in the following situations:
Aminoglutethimide administered concurrently with Provera may significantly depress the bioavailability of Provera.
Interactions with other medicinal treatments (including oral anti-coagulants) have rarely been reported, but causality has not been determined. The possibility of interaction should be borne in mind in patients receiving concurrent treatment with other drugs.
The metabolism of progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4 inducers or inhibitors on MPA have not been conducted and therefore the clinical effects of CYP3A4 inducers or inhibitors are unknown.
Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John’s wort (Hypericum perforatum) may induce the metabolism of progestogens.
Clinically, an increased metabolism of progestogens may lead to decreased effect.
Provera is not indicated during pregnancy. If pregnancy occurs during medication with Provera, treatment should be withdrawn immediately.
The results of most epidemiological studies to date relevant to inadvertent foetal exposure to progestogens indicate no teratogenic or foetotoxic effect.
Provera is not indicated during lactation.
Medroxyprogesterone acetate and its metabolites are secreted in breast milk, but there is no evidence to suggest that this presents any hazard to the child.
No adverse effect has been reported.
The table below provides a listing of adverse drug reactions with frequency based on all-causality data from Phase 3 clinical studies that evaluated efficacy and safety of DMPA in gynaecology. Those most frequently (>5%) reported adverse drug reactions were dysfunctional uterine bleeding (19%), headache (12%) and nausea (10%).
The following lists of adverse reactions are listed within the organ system classes, under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Common: Drug hypersensitivity
Not known: Anaphylactic reaction, Anaphylactoid reaction, Angioedema
Not known: Anovulation
Common: Depression, Insomnia, Nervousness
Very common: Headache
Common: Dizziness
Not known: Somnolence
Not known: Embolism and thrombosis
Very common: Nausea
Common: Alopecia, Acne, Urticaria Pruritus
Uncommon: Hirsutism
Not known: Rash
Very common: Dysfunctional uterine bleeding (irregular, increase, decrease, spotting)
Common: Cervical discharge, Breast pain, Breast tenderness
Uncommon: Galactorrhoea
Not known: Amenorrhoea, Uterine cervical erosion
Common: Temperature elevation, Fatigue
Uncommon: Oedema, Fluid retention
Common: Weight increased
Not known: Glucose tolerance decreased, Weight decreased
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Not applicable.
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