Special Warning : אזהרת שימוש

4.4    Special Warnings and Precautions for Use

Warnings:
In the treatment of carcinoma of breast occasional cases of hypercalcaemia have been reported.

Unexpected vaginal bleeding during therapy with medroxyprogesterone acetate should be investigated.

Medication should not be readministered pending examination if there is sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilloedema or retinal vascular lesions, medication should not be readministered.

Medroxyprogesterone acetate may produce Cushingoid symptoms.

Some patients receiving medroxyprogesterone acetate may exhibit suppressed adrenal function. Medroxyprogesterone acetate may decrease ACTH and hydrocortisone blood levels.

Treatment with medroxyprogesterone acetate should be discontinued in the event of: • jaundice or deterioration in liver function
• significant increase in blood pressure
• new onset of migraine-type headache

Precautions:

Animal studies show that Provera possesses adrenocorticoid activity. This has also been reported in man, therefore patients receiving large doses continuously and for long periods should be observed closely for signs normally associated with adrenocorticoid therapy, such 
as hypertension, sodium retention, oedema, etc. Care is needed in treating patients with diabetes and/or arterial hypertension.

Before using Provera the general medical condition of the patient should be carefully evaluated.

This product should be used under the supervision of a specialist and the patient kept under regular surveillance.

Patients with the following conditions should be carefully monitored while taking progestogens:
•   Conditions which may be influenced by potential fluid retention o Epilepsy o Migraine o Asthma o Cardiac dysfunction o Renal dysfunction
•   History of mental depression
•   Diabetes (a decrease in glucose tolerance has been observed in some patients).
•   Hyperlipidaemia

The pathologist (laboratory) should be informed of the patient’s use of medroxyprogesterone acetate if endometrial or endocervical tissue is submitted for examination.

The physician/laboratory should be informed that medroxyprogesterone acetate may decrease the levels of the following endocrine biomarkers:
•   Plasma/urinary steroids (e.g., cortisol, oestrogen, pregnanediol, progesterone, testosterone)
•   Plasma/urinary gonadotrophins (e.g., LH and FSH)
•   Sex-hormone-binding-globulin

The use of medroxyprogesterone acetate in oncology indications may also cause partial adrenal insufficiency (decrease in pituitary-adrenal axis response) during Metyrapone testing.
Thus the ability of adrenal cortex to respond to ACTH should be demonstrated before metyrapone is administered.

Although medroxyprogesterone acetate has not been causally associated with the induction of thromboembolic disorders, MPA is not recommended in any patient with a history of venous thromboembolism (VTE). Discontinuation of medroxyprogesterone acetate is recommended in patients who develop VTE while undergoing therapy with MPA.

Risk of venous thromboembolism (VTE)

The risk of VTE has not been assessed for progesterone alone. However, VTE is a known risk factor of oestrogen-only and combined hormone replacement therapy. When prescribing medroxyprogesterone acetate for oncology indications the following precautions and risk factors should be considered in the light of the patient’s condition, the dose of medroxyprogesterone acetate and the duration of therapy:
•   Generally recognised risk factors for VTE include a personal or family history of VTE or known thromboembolic states, severe obesity (BMI > 30 kg/m2) and systemic lupus erythematosus
•   The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery.
•   If VTE develops after initiating therapy, medroxyprogesterone acetate should be discontinued. Patients should be told to contact their doctor immediately if they become aware of a symptom suggestive of potential thromboembolism (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

Effects on Driving

4.7    Effects on Ability to Drive and Use Machines

The effect of MPA on the ability to drive and use machines has not been systematically evaluated.