1. Name of the medicinal product
a) Medroxyprogesterone Acetate Tablets USP 2.5mg TajPharma
b) Medroxyprogesterone Acetate Tablets USP 5mg TajPharma
c) Medroxyprogesterone Acetate Tablets USP 10mg TajPharma
2. Qualitative and quantitative composition
a) Each tablet contains:
Medroxyprogesterone USP 2.5mg,
Excipients q.s.
b) Each tablet contains:
Medroxyprogesterone USP 5mg,
Excipients q.s.
c) Each tablet contains:
Medroxyprogesterone USP 10mg,
Excipients q.s.
3. Pharmaceutical form
Tablet
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
Posology
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. Breakthrough bleeding, which is self-limiting, may occur. No additional hormonal therapy is recommended for the management of this bleeding.
Elderly: Not applicable
Paediatric population: Not applicable
Method of administration
For oral use.
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
Hypersensitivity to the active substance or to any of the excipients
Porphyria
4.4 Special warnings and precautions for use
Medical Examination/Follow-Up
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.
Conditions which need Supervision
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 Medroxyprogesterone Acetate, in particular:
– A history of, or risk factors for, thromboembolic disorders (see below)
– Risk factors for oestrogen dependent tumours, e.g. 1 degree heredity for breast cancer
– Hypertension
– Liver disorders (e.g. liver adenoma)
– Diabetes mellitus with or without vascular involvement
– Cholelithiasis
– Migraine or (severe) headache
– Systemic lupus erythematosus.
– Epilepsy
– Asthma
– Otosclerosis
Rare cases of thrombo-embolism have been reported with use of Medroxyprogesterone Acetate, 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.
Medroxyprogesterone Acetate, 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 Medroxyprogesterone Acetate 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 Medroxyprogesterone Acetate therapy. Some patients may complain of premenstrual like depression while on Medroxyprogesterone Acetate therapy.
Reasons for Immediate Withdrawal of Therapy:
Therapy should be discontinued in case a contraindication is discovered and in the following situations:
– Jaundice or deterioration in liver function
– Significant increase in blood pressure
– New onset of migraine-type headache
4.5 Interaction with other medicinal products and other forms of interaction
Aminoglutethimide administered concurrently with Medroxyprogesterone Acetate may significantly depress the bioavailability of Medroxyprogesterone Acetate.
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.
4.6 Fertility, pregnancy and lactation
Pregnancy
Medroxyprogesterone Acetate is not indicated during pregnancy. If pregnancy occurs during medication with Medroxyprogesterone Acetate, 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.
Breast-feeding
Medroxyprogesterone Acetate 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 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).
| System Organ Class | 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 | Frequency Not Known (cannot be estimated from available data) |
| Immune system disorders | Drug hypersensitivity | Anaphylactic reaction, Anaphylactoid reaction, Angioedema | ||||
| Endocrine disorders | Anovulation | |||||
| Psychiatric disorders | Depression, Insomnia, Nervousness | |||||
| Nervous system disorders | Headache | Dizziness | Somnolence | |||
| Vascular disorders | Embolism and thrombosis | |||||
| Gastrointestinal disorders | Nausea | |||||
| Skin and subcutaneous tissue disorders | Alopecia, Acne, Urticaria Pruritus | Hirsutism | Rash | |||
| Reproductive system and breast disorders | Dysfunctional uterine bleeding (irregular, increase, decrease, spotting) | Cervical discharge, Breast pain, Breast tenderness | Galactorrhoea | Amenorrhoea, Uterine cervical erosion | ||
| General disorders and administration site conditions | Temperature elevation, Fatigue | Oedema, Fluid retention | ||||
| Investigations | Weight increased | Glucose tolerance decreased, Weight decreased |
Reporting of suspected adverse reactions
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.
4.9 Overdose
In animals Medroxyprogesterone Acetate 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 Medroxyprogesterone Acetate 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
Pharmacotherapeutic group: Progestogens – Pregnen (4) derivatives
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
Lactose
Sucrose
Maize starch
Liquid Paraffin
Talc
Calcium Stearate
Purified Wate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
5 years.
6.4 Special precautions for storage
Glass bottles: None
Blister packs: Store below 25°C
6.5 Nature and contents of container
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.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
None.
7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com
Medroxyprogesterone Acetate Tablets USP 10mg TajPharma
Package leaflet: Information for the patient
a) Medroxyprogesterone Acetate Tablets USP 2.5mg Taj Pharma
b) Medroxyprogesterone Acetate Tablets USP 5mg Taj Pharma
c) Medroxyprogesterone Acetate Tablets USP 10mg Taj Pharma
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
What is in this leaflet
1. What Medroxyprogesterone acetate Tablets are and what they are used for
2. What you need to know before you take Medroxyprogesterone acetate Tablets
3. How to take Medroxyprogesterone acetate Tablets
4. Possible side effects
5. How to store Medroxyprogesterone acetate Tablets
6. Contents of the pack and other information
1. WHAT MEDROXYPROGESTERONE ACETATE TABLETS ARE AND WHAT THEY ARE USED FOR
· The active substance Medroxyprogesterone Acetate tablet, is one of a group of medicines called ‘progestogens’. Progestogens are similar to the natural female hormone, progesterone.
- Medroxyprogesterone Acetate tablet has several uses. You can take Medroxyprogesterone Acetate tablet to treat or manage:
o Heavy periods
o Painful periods o Irregular periods or periods that are more frequent than normal
o Absence of periods
o Mild to moderate endometriosis (where tissue from your womb is found outside your womb)
You must talk to a doctor if you do not feel better or if you feel worse.
2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE MEDROXYPROGESTERONE ACETATE TABLETS
Medroxyprogesterone Acetate tablet may not be suitable for all women. Please read the following list carefully to see if any of these apply to you. Consult your doctor if you are not sure.
Do not take Medroxyprogesterone Acetate tablet if you:
o are allergic to Medroxyprogesterone Acetate tablet or other similar hormone medicines, or to any of the other ingredients of this medicine
o are pregnant, or think you might be pregnant. Your doctor may give you a pregnancy test before starting treatment or if you miss a period during treatment
o have now or have had in the past breast cancer
o have now or have had in the past blood clots forming in your veins (venous thrombosis)
o have now or have had in the past blood clots forming in your arteries (arterial thrombosis)
o have liver problems
o have porphyria where your body lacks the ability to correctly produce certain enzymes and it manifests with either neurological complications or with skin problems (or occasionally both)
Warnings and precautions
Talk to your doctor or pharmacist before taking Medroxyprogesterone Acetate Tablets if you have any of the following conditions to help them decide if Medroxyprogesterone Acetate tablet is suitable for you:
· Epilepsy
· Migraine headaches
· Asthma
· Heart problems
· Kidney problems
· Diabetes
· Depression or a history of depression
· High blood pressure
· Liver problems
· Gallstones
· Systemic lupus erythematosus (SLE) = an allergic condition which causes joint
· pain, skin rashes and fever Hearing problems
· Medroxyprogesterone Acetate tablet, especially in high doses, may cause weight gain and fluid retention.
Risk of Venous Thromboembolism (VTE)
All women have a small chance of having a blood clot in the veins of the leg, in the lung or other part of the body. The chances of getting a clot are very slightly higher if you are taking a hormone medicine like Medroxyprogesterone Acetate tablet. You are more likely to get a clot whether or not you are taking Medroxyprogesterone Acetate tablet if you:
·are very overweight
· have had a blood clot in the veins or lungs before
· have relatives who have had blood clots
· are unable to move for long periods of time (for example after an operation)
· have a serious injury or have major surgery
· have a history of repeated miscarriage
· Tell your doctor if you have just had an operation or if you are going to have an operation while taking Medroxyprogesterone Acetate tablet.
Other medicines and Medroxyprogesterone Acetate tablet
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
The effect of Medroxyprogesterone Acetate tablet may be altered when taken at the same time as any of the following medicines:
o Aminoglutethimide, sometimes used in Cushing’s syndrome
o Medicines for thinning the blood (e.g. warfarin)
o Medicines for treating convulsions (e.g. phenobarbital, phenytoin and carbamazepine)
o Ritonavir and nelfinavir, sometimes used to treat HIV and AIDS
o Medicines for treating infections (e.g. rifampicin, rifabutin, nevirapine, efavirenz)
o St John’s wort, a herbal treatment for depression
Pregnancy, breast-feeding and fertility Pregnancy
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Medroxyprogesterone Acetate tablet must not be taken if you are pregnant as hormonal medicines can affect the developing baby. It is important you use another method of contraception (e.g. a condom) while taking Medroxyprogesterone Acetate tablet, as it is not a contraceptive.
Breast-feeding
If you are breast-feeding, speak to your doctor who will advise whether you should use an alternative method of feeding your baby. Driving and using machines
No effect on the ability to drive or use machines has been seen with Medroxyprogesterone Acetate tablet.
Medroxyprogesterone Acetate tablet contain lactose monohydrate, sucrose and sunset yellow (E110)
Lactose monohydrate and sucrose are types of sugar. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Medroxyprogesterone Acetate tablet 2.5 mg Tablets also contain sunset yellow (E110) which may cause allergic reactions
3. HOW TO TAKE MEDROXYPROGESTERONE ACETATE TABLETS
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The number of tablets will depend on the condition you are being treated for. This information can also be found on the label on the box the tablets come in. The following information will help you see what the usual dose is for a particular problem.
Taking Medroxyprogesterone Acetate tablet for heavy or irregular bleeding and other period problems
You will usually take 2.5mg-10mg for 5-10 days beginning 16 days to 21 days after your last period began. Treatment should be given for 2 consecutive cycles.
In some cases, your doctor may also prescribe oestrogen to be taken at the same time as Medroxyprogesterone Acetate tablet at doses of 5-10mg for 10 days. A few days after you stop taking the tablets you may have bleeding like a period (breakthrough bleeding).
Taking Medroxyprogesterone Acetate tablet when you have amenorrhoea (when you are not having periods)
You will usually take 2.5mg-10mg for 5-10 days beginning on a day which has been calculated or assumed to represent Day 16 to Day 21 of your menstrual cycle. Repeat the treatment for 3 consecutive cycles.
In some cases, your doctor may also prescribe oestrogen to be taken at the same time as Medroxyprogesterone Acetate tablet for 10 days. A few days after you stop taking the tablets, you may have bleeding like a period (breakthrough bleeding).
Taking Medroxyprogesterone Acetate tablet for endometriosis (where tissue from your womb is found outside your womb)
You will usually take 10mg 3 times a day (30mg) for 3 months (90 days) starting on the first day of your period. If you have any irregular spotting or bleeding during treatment this is normal and nothing to worry about.
If you do not have a period after you finish a course of Medroxyprogesterone Acetate tablet, check with your doctor in case you are pregnant.
If you forget to take Medroxyprogesterone Acetate tablet
Take the tablet as soon as you remember, and carry on taking the tablets at the normal times. Do not take a double dose to make up for a forgotten dose.
If you take more Medroxyprogesterone Acetate tablet than you should
If you take too many tablets, contact your doctor straight away.
If you stop taking Medroxyprogesterone Acetate tablet
Do not stop taking your medicine or alter the dose you are currently taking without seeing your doctor first. It is important to keep taking your medicine.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everyone gets them. Reasons for stopping Medroxyprogesterone Acetate tablet treatment immediately
Rarely, Medroxyprogesterone Acetate tablet may cause a severe allergic reaction which can be life-threatening in some cases. You can get some or all of the following symptoms: wheezing, difficulty breathing, feeling faint, swelling of the face or tongue, hands and feet, intense itchy skin rash. If you think you are reacting badly to the medicine, get emergency medical help immediately.
If you get any of the following symptoms, you should stop taking the tablets and see your doctor immediately.
These are symptoms of a blood clot in the lungs which may all occur together:
§ Sudden, severe, sharp pain in your chest
§ Coughing up blood
§ You suddenly become short of breath
§ Your heart beats more rapidly
These can be symptoms of a blood clot in the brain (‘a stroke’):
§ You have an unusually severe or long headache
§ Your sight is affected in any way
§ You find it difficult to speak
§ You collapse or faint
§ Any part of your body feels weak or numb
These are symptoms of a deep-vein thrombosis (DVT):
§ You have severe pain, tenderness or swelling in your calf, ankle or foot
§ You have purple discolouration of the skin of the leg or the skin becomes red and
warm to touch
Tell your doctor if you get any other side effects reported with Medroxyprogesterone Acetate tablet which may include the following:
Very common: may affect more than 1 in 10 people
·headache
· feeling sick
· unexpected or unusual vaginal bleeding or spotting
Common: may affect up to 1 in 10 people ·severe allergic reaction to the drug (e.g. wheezing, difficulty breathing)
· depression
· difficulty sleeping
· nervousness
· dizziness
· hair loss
· acne
· nettle rash or hives
· itchy skin
· vaginal discharge
· breast pain
· breast tenderness
· fever
·tiredness weight increase
Uncommon: may affect up to 1 in 100 people ·Facial hair growth
· milky discharge from the breast when not pregnant or breastfeeding
· oedema/fluid retention
Not known: frequency cannot be estimated from the available data
·severe allergic reaction (anaphylactic reaction)
· swelling in face/throat which may cause difficulty breathing
· delayed egg release with longer menstrual cycle (periods)
· drowsiness
· swelling in the veins due to blood clots
· tenderness or swelling in your calf, ankle or foot
· rash
· stopping or extended break of your periods
· abnormality of cervix
· decreased sugar tolerance
· weight decrease
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine
5.HOW TO STORE MEDROXYPROGESTERONE ACETATE TABLETS
Keep this medicine out of the sight and reach of children.
Medroxyprogesterone Acetate tablet tablets should not be used after the expiry date which is stated on the carton, blister strip or bottle label after EXP. The expiry date refers to the last day of that month.
For the blister and carton presentation, do not store your tablets above 25°C.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Further Information
What Medroxyprogesterone acetate Soluble Tablets contain
The active substance is Medroxyprogesterone Acetate tablet.
a) Each tablet contains: Medroxyprogesterone Acetate USP 2.5mg
b) Each tablet contains: Medroxyprogesterone Acetate USP 5mg
c) Each tablet contains: Medroxyprogesterone Acetate USP 10mg
The other ingredients are:
5 mg: Lactose monohydrate, starch, sucrose, liquid paraffin, calcium stearate, talc, the colour FD & C Blue No. 2 Aluminium Lake, purified water.
10 mg: Lactose monohydrate, sucrose, maize starch, liquid paraffin, talc, calcium stearate, purified water.
Medroxyprogesterone Acetate tablet contain lactose monohydrate, sucrose and sunset yellow (E110).
What Medroxyprogesterone acetate Tablets look like and contents of the pack
Medroxyprogesterone Acetate tablet 5mg tablets are blue and are available in packs of 10, 20 or 100 tablets or in bottles containing 100 tablets.
Medroxyprogesterone Acetate tablet 10mg tablets are white and are available in packs of 10, 20, 30, 50, 90 or 100 tablets or in bottles containing 50 tablets.
Not all pack sizes may be marketed.
7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com
