Thursday, September 29, 2016

Provera Tablets 2.5 mg, Provera Tablets 5 mg & Provera Tablets 10 mg





1. Name Of The Medicinal Product



Provera Tablets 2.5 mg



Provera Tablets 5 mg



Provera Tablets 10 mg


2. Qualitative And Quantitative Composition



Each tablet contains 2.5 mg medroxyprogesterone acetate Ph. Eur.



Each tablet contains 5 mg medroxyprogesterone acetate Ph. Eur.



Each tablet contains 10 mg medroxyprogesterone acetate Ph. Eur.



3. Pharmaceutical Form



Tablets for oral use



4. Clinical Particulars



4.1 Therapeutic Indications



Progestogen. Indicated for dysfunctional (anovulatory) uterine bleeding, secondary amenorrhoea and for mild to moderate endometriosis.



4.2 Posology And Method Of Administration



Oral.



Adults:



Dysfunctional (anovulatory) uterine bleeding: 2.5 - 10 mg daily for 5 - 10 days commencing on the assumed or calculated 16th - 21st day of the cycle. Treatment should be given for two consecutive cycles. When bleeding occurs from a poorly developed proliferative endometrium, conventional oestrogen therapy may be employed in conjunction with medroxyprogesterone acetate in doses of 5 - 10 mg for 10 days.



Secondary amenorrhoea: 2.5 - 10 mg daily for 5 - 10 days beginning on the assumed or calculated 16th to 21st day of the cycle. Repeat the treatment for three consecutive cycles. In amenorrhoea associated with a poorly developed proliferative endometrium, conventional oestrogen therapy may be employed in conjunction with medroxyprogesterone acetate in doses of 5 - 10 mg for 10 days.



Mild to moderate endometriosis: Beginning on the first day of the menstrual cycle, 10 mg three times a day for 90 consecutive days.



5 mg & 10 mg only



Breakthrough bleeding, which is self-limiting, may occur. No additional hormonal therapy is recommended for the management of this bleeding.



All strengths



Elderly: Not applicable



Children: Not applicable



4.3 Contraindications



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;



Known hypersensitivity to the active substances or to any of the excipients;



Porphyria



4.4 Special Warnings And Precautions For Use



Whether administered alone or in conjunction with oestrogens, Provera should not be employed in patients with abnormal uterine bleeding until a definite diagnosis has been established and the possibility of genital malignancy eliminated.



Rare cases of thrombo-embolism have been reported with use of Provera, especially at higher doses. Causality has not been established.



Doses of up to 30 mg a day may not suppress ovulation and patients should be advised to take adequate contraceptive measures, where appropriate.



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.



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.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



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).



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.



4.6 Pregnancy And Lactation



Pregnancy



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.



Lactation



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.



4.7 Effects On Ability To Drive And Use Machines



No adverse effect has been reported.



4.8 Undesirable Effects



The following medical events have been occasionally to rarely associated with the use of progestogens:


























MEDDRA SOC




EVENT




Immune System disorders




Hypersensitivity reactions (e.g., anaphylaxis & anaphylactoid reactions, angioedema)




Metabolism and nutritional disorders




Weight change, oedema/fluid retention




Psychiatric disorders




Depression, insomnia, nervousness




Nervous system disorders




Dizziness, headache, somnolence




Vascular disorders




Thromboembolic disorders




Gastrointestinal disorders




Nausea




Skin and subcutaneous tissue disorders




Acne, alopecia, hirsutism, pruritus, rash, urticaria




Reproductive system and breast disorders




Galactorrhoea, breast tenderness, breast pain.




General disorders and administration site conditions




Fatigue




Investigations




Decreased glucose tolerance



4.9 Overdose



In animals Provera has been shown to be capable of exerting an adreno-corticoid effect, but this has not been reported in the human, following usual dosages. The oral administration of Provera at a rate of 100 mg per day has been shown to have no effect on adrenal function.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Medroxyprogesterone acetate has actions and uses similar to those of progesterone.



MPA has minimal androgenic activity compared to progesterone and virtually no oestrogenic activity.



Progestogens are used in the treatment of dysfunctional uterine bleeding, secondary amenorrhoea and endometriosis.



5.2 Pharmacokinetic Properties



MPA is rapidly absorbed from the G-I tract with a single oral dose of 10-250 mg. The time taken to reach the peak serum concentration (Tmax) was 2-6 hours and the average peak serum concentration (Cmax) was 13-46.89 mg/ml.



Unmetabolised MPA is highly plasma protein bound. MPA is metabolised in the liver.



MPA is primarily metabolised by faecal excretion as glucuronide conjugated metabolite.



Metabolised MPA is excreted more rapidly and in a greater percentage following oral doses than after aqueous intramuscular injection



5.3 Preclinical Safety Data



None stated



6. Pharmaceutical Particulars



6.1 List Of Excipients










2.5 mg:




Lactose Ph.Eur., Sucrose Ph.Eur., Maize starch Ph.Eur., Liquid Paraffin Ph.Eur., Talc Ph.Eur., Calcium Stearate NF, E110, Purified Water Ph.Eur.




5 mg:




Lactose Ph.Eur., Starch Ph.Eur., Sucrose Ph.Eur., Liquid Paraffin Ph.Eur., Calcium Stearate NF, Talc, FD & C Blue No. 2 Aluminium Lake, Purified Water Ph.Eur.




10 mg:




Lactose Ph.Eur., Sucrose Ph.Eur., Maize starch Ph.Eur., Liquid Paraffin Ph.Eur., Talc Ph.Eur., Calcium Stearate NF, Purified Water Ph.Eur.



6.2 Incompatibilities



None known.



6.3 Shelf Life










2.5 mg:




36 months




5 mg:




24 months if stored in blister strips



60 months if stored in either amber glass bottles with screw caps of HDPE bottles with tamper evident caps.




10 mg




5 years



6.4 Special Precautions For Storage



2.5mg & 5mg: Store bottle pack at controlled room temperature (15-30°C)



Store blister pack below 25°C








10mg:




Glass bottles: None




 




Blister packs: Store below 25°C



6.5 Nature And Contents Of Container










2.5 mg:




HDPE tamper-evident bottles with LDPE push-fit tamper evident caps, containing 100 tablets.



Aluminium foil/PVC blisters, containing 10, 30, 50 or 100 tablets.




5 mg:




Blister strips of 250 micron opaque PVC/20 micron aluminium foil containing 10, 20 or 100 tablets or amber glass bottles with screw caps or HDPE bottles with tamper evident caps containing 100 tablets.




10 mg:




HDPE tamper-evident bottles with LDPE push-fit tamper evident caps, containing 50 tablets.



Aluminium foil/PVC blisters, containing 10, 20, 30, 50, 90 or 100 tablets.



6.6 Special Precautions For Disposal And Other Handling



None.



7. Marketing Authorisation Holder



Pfizer Limited



Ramsgate Road



Sandwich



Kent



CT13 9NJ



United Kingdom



8. Marketing Authorisation Number(S)



2.5 mg: PL 0057/1034



5 mg: PL 0057/1037



10 mg: PL 0057/1033



9. Date Of First Authorisation/Renewal Of The Authorisation













2.5 mg




Date of first authorisation:




22 September 2010




5 mg:




Date of first authorisation:




23 September 2010




10 mg:




Date of first authorisation:




21 September 2010



10. Date Of Revision Of The Text



November 2011



Ref: PV 4_1




No comments:

Post a Comment