post-title portfolio-title Tamoxifen Citrate Film Coated Tablets IP 20mg Taj Pharma 2020-03-19 12:08:58 no no

Tamoxifen Citrate Film Coated Tablets IP 20mg Taj Pharma

Tamoxifen Citrate Film Coated Tablets IP 20mg Taj Pharma

Overview

INTRODUCTION

Tamoxifen citrate 20mg Tablet is an anti-estrogens. It is used in the treatment of breast cancer. It is also used to reduce the risk of breast cancer in women with a high chance of developing it. This medicine helps to slow down the growth and multiplication of cancer cells.

Tamoxifen citrate 20mg Tablet is also helpful in the treatment of infertility. It can be taken with or without food, but take it at the same time to get the most benefit. It should be taken as your doctor’s advice. The dose and how often you take it depends on what you are taking it for. Your doctor will decide how much you need to improve your symptoms. Swallow the tablets whole with a drink of water. You should take this medicine for as long as it is prescribed for you.

The most common side effects of this medicine include nausea, skin rash, hot flushes, thinning of hair and tiredness. If these bother you or appear serious, let your doctor know. There may be ways of reducing or preventing them. Some side effects may mean you should inform your doctor immediately include vaginal bleeding, irregular menstrual period and vaginal discharge. It makes birth control pills less effective, hence use a condom and other preventive measures to avoid pregnancy.

Before taking this medicine, tell your doctor if you are on treatment of infertility or had a blood clot disorder. Your doctor should also know about all other medicines you are taking as many of these may make this medicine less effective or change the way it works. Tell your doctor if you are pregnant or breastfeeding. Your doctor may perform some blood tests to check liver function and calcium level in the body.

USES OF TAMOXIFEN CITRATE TABLET

  • Breast cancer

SIDE EFFECTS OF TAMOXIFEN CITRATE TABLET

Common

  • Nausea
  • Skin rash
  • Hot flashes
  • Thinning of hair
  • Vaginal discharge
  • Swelling

HOW TO USE TAMOXIFEN CITRATE TABLET

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Tamoxifen citrate 20mg Tablet may be taken with or without food, but it is better to take it at a fixed time.

HOW TAMOXIFEN CITRATE TABLET WORKS

Tamoxifen citrate 20mg Tablet is a hormone-based medication. It works by binding to estrogen receptors and blocking the effects of estrogen (a natural female hormone) in the breast tissue. This slows down the growth and multiplication of breast cancer cells.

SAFETY ADVICE

warningsAlcohol

UNSAFE

It is unsafe to consume alcohol with Tamoxifen citrate 20mg Tablet.

warningsPregnancy

UNSAFE

Tamoxifen citrate 20mg Tablet is highly unsafe to use during pregnancy. Seek your doctor’s advice as studies on pregnant women and animals have shown significant harmful effects to the developing baby.

warningsBreastfeeding

CONSULT YOUR DOCTOR

Tamoxifen citrate 20mg Tablet is probably unsafe to use during breastfeeding. Limited human data suggests that the drug may pass into the breastmilk and harm the baby.

warningsDriving

UNSAFE

Tamoxifen citrate 20mg Tablet may cause side effects which could affect your ability to drive.
Tamoxifen citrate 20mg Tablet may cause tiredness. This may affect your driving ability.

warningsKidney

SAFE IF PRESCRIBED

Tamoxifen citrate 20mg Tablet is probably safe to use in patients with kidney disease. Limited data available suggests that dose adjustment of Tamoxifen citrate 20mg Tablet may not be needed in these patients. Please consult your doctor.

warningsLiver

CONSULT YOUR DOCTOR

There is limited information available on the use of Tamoxifen citrate 20mg Tablet in patients with liver disease. Please consult your doctor.

Tamoxifen Citrate Film Coated Tablets IP 20mg Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

a) Tamoxifen citrate Film Coated Tablets IP 10mg Taj Pharma
b) Tamoxifen citrate Film Coated Tablets IP 20mg Taj Pharma

2.QUALITATIVE AND QUANTITATIVE COMPOSITION??????????????????????????????

a) Each film-coated tablet contains:
Tamoxifen (as citrate)? IP??? 10mg
Excipients? ????q.s.

b) Each film-coated tablet contains:
Tamoxifen (as citrate)? IP??? 20mg
Excipients????? q.s.

3.PHARMACEUTICAL FORM
Tablet
White to off-white, round, biconvex, tablets.

4.CLINICAL PARTICULARS

4.1 Therapeutic indications

  1. The treatment of breast cancer
  2. The treatment of anovulatory infertility

4.2 Posology and method of administration

Posology

  1. Breast cancer

Adults

The recommended daily dose of Tamoxifen is normally 20 mg. No additional benefit, in terms of delayed recurrence or improved survival in patients, has been demonstrated with higher doses. Substantive evidence supporting the use of treatment with 30-40 mg per day is not available, although these doses have been used in some patients with advanced disease.

Elderly

Similar dosing regimens of ‘Tamoxifen’ have been used in elderly patients with breast cancer and in some of these patients it has been used as sole therapy.

  1. Anovulatory Infertility

Before commencing any course of treatment, whether initial or subsequent, the possibility of pregnancy must be excluded. In women who are menstruating regularly, but with anovular cycles, the initial course of treatment consists of 20 mg given daily on the second, third, fourth and fifth days of the menstrual cycle. If unsatisfactory basal temperature records or poor pre-ovulatory cervical mucus indicate that this initial course of treatment has been unsuccessful, further courses may be given during subsequent menstrual periods, increasing the dosage to 40 mg and then to 80 mg daily.

In women who are not menstruating regularly, the initial course may begin on any day. If no signs of ovulation are demonstrable, then a subsequent course of treatment may start 45 days later, with dosage increased as above. If a patient responds with menstruation, then the next course of treatment is commenced on the second day of the cycle.

Paediatric population

The use of Tamoxifen is not recommended in children, as safety and efficacy have not been established (see sections 5.1 and 5.2).

Method of administration

For administration by the oral route

4.3 Contraindications

Tamoxifen Tablets should not be used in the following:

  • pregnancy: Pre-menopausal patients must be carefully examined before treatment for breast cancer or infertility to exclude the possibility of pregnancy (see also Section 4.6).
  • hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
  • Concurrent anastrozole therapy (see section 4.5).
  • treatment for infertility: Patients with a personal or family history of confirmed idiopathic venous thromboembolic events or a known genetic defect.

4.4 Special warnings and precautions for use

Menstruation is suppressed in a proportion of pre-menopausal women receiving Tamoxifen for the treatment of breast cancer.

An increased incidence of endometrial changes including hyperplasia, polyps, cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours), has been reported in association with Tamoxifen treatment. The underlying mechanism is unknown but may be related to the oestrogen-like effect properties of Tamoxifen. Any patient receiving or having previously received Tamoxifen who report abnormal gynaecological symptoms, especially vaginal bleeding, or who presents with menstrual irregularities, vaginal discharge and symptoms such as pelvic pain or pressure should be promptly investigated.

A number of second primary tumours, occurring at sites other than the endometrium and the opposite breast, have been reported in clinical trials, following the treatment of breast cancer patients with tamoxifen. No causal link has been established and the clinical significance of these observations remains unclear.

Venous thromboembolism

  • A 2-3-fold increase in the risk for VTE has been demonstrated in healthy tamoxifen-treated women (see section 4.8).
  • In patients with?breast cancer, prescribers should obtain careful histories with respect to the patient’s personal and family history of VTE. If suggestive of a prothrombotic risk, patients should be screened for thrombophilic factors. Patients who test positive should be counselled regarding their thrombotic risk. The decision to use tamoxifen in these patients should be based on the overall risk to the patient. In selected patients, the use of tamoxifen with prophylactic anticoagulation may be justified (cross-reference section 4.5)
  • The risk of VTE is further increased by severe obesity, increasing age and all other risk factors for VTE. The risks and benefits should be carefully considered for?allpatients before treatment with tamoxifen. In patients with?breast cancer, this risk is also increased by concomitant chemotherapy (see section 4.5). Long-term anti-coagulant prophylaxis may be justified for some patients with?breast cancerwho have multiple risk factors for VTE.
  • Surgery and immobility: For patients being treated for?infertility, tamoxifen should be stopped at least 6 weeks before surgery or long-term immobility (when possible) and re-started only when the patient is fully mobile. For patients with?breast cancer, tamoxifen treatment should only be stopped if the risk of tamoxifen-induced thrombosis clearly outweighs the risks associated with interrupting treatment. All patients should receive appropriate thrombosis prophylactic measures and should include graduated compression stockings for the period of hospitalisation, early ambulation, if possible, and anti-coagulant treatment.
  • If?anypatient presents with VTE, tamoxifen should be stopped immediately and appropriate anti-thrombosis measures initiated. In patients being treated for?infertility, tamoxifen should not be re-started unless there is a compelling alternative explanation for their thrombotic event. In patients receiving tamoxifen for?breast cancer, the decision to re-start tamoxifen should be made with respect to the overall risk for the patient. In selected patients with?breast cancer, the continued use of tamoxifen with prophylactic anticoagulation may be justified.
  • Allpatients should be advised to contact their doctors immediately if they become aware of any symptoms of VTE.

In delayed microsurgical breast reconstruction Tamoxifen may increase the risk of microvascular flap complications.

In an uncontrolled trial in 28 girls aged 2?10 years with McCune Albright Syndrome (MAS), who received 20 mg once a day for up to 12 months duration, mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. While this finding is in line with the pharmacodynamic properties of tamoxifen, a causal relationship has not been established (see section 5.1).

In the literature it has been shown that CYP2D6 poor metabolisers have a lowered plasma level of endoxifen, one of the most important active metabolites of tamoxifen (see section 5.2).

Concomitant medications that inhibit (CYPD2D6 may lead to reduced concentrations of the active metabolite endoxifen. Therefore, potent inhibitors of CYP2D6 (e.g. paroxetine, fluoxetine, quinidine, cinacalcet or bupropion) should whenever possible be avoided during tamoxifen treatment (see section 4.5 and 5.2).

Radiation recall has been reported rarely in patients on Tamoxifen who have received prior radiotherapy. The reaction is usually reversible upon temporary cessation of therapy and re-challenge may result in a milder reaction. Treatment with Tamoxifen was continued in most cases.

4.5 Interaction with other medicinal products and other forms of interaction

When Tamoxifen Tablets are used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant effect may occur. Where such co-administration is initiated, careful monitoring of the patient is recommended.

When Tamoxifen is used in combination with cytotoxic agents for the treatment of breast cancer, there is increased risk of thromboembolic events occurring. (See also Sections 4.4 and 4.8). Because of this increase in risk of VTE, thrombosis prophylaxis should be considered for these patients for the period of concomitant chemotherapy.

The use of tamoxifen in combination with anastrozole as adjuvant therapy has not shown improved efficacy compared with tamoxifen alone.

As tamoxifen is metabolised by cytochrome P450 3A4, care is required when co- administering with drugs, such as rifampicin, known to induce this enzyme as tamoxifen levels may be reduced. The clinical relevance of this reduction is unknown.

Pharmacokinetic interaction with CYP2D6 inhibitors, showing a reduction in plasma level of an active tamoxifen metabolite, 4-hydroxy-Ndesmethyltamoxifen (endoxifen), has been reported in the literature.

Pharmacokinetic interaction with CYP2D6 inhibitors, showing a 65-75% reduction in plasma levels of one of the more active forms of the drug, i.e. endoxifen, has been reported in the literature.

Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants (e.g. paroxetine) in some studies. As a reduced effect of tamoxifen cannot be excluded, co-administration with potent CYP2D6 inhibitors (e.g. paroxetine, fluoxetine, quinidine, cinacalcet or bupropion) should whenever possible be avoided (see section 4.4 and 5.2).

4.6 Fertility, pregnancy and lactation

Pregnancy

Tamoxifen Tablets must not be administered during pregnancy. There have been a small number of reports of spontaneous abortions, birth defects and foetal deaths after women have taken tamoxifen, although no causal relationship has been established.

Reproductive toxicology studies in rats, rabbits and monkeys have shown no teratogenic potential.

In rodent models of foetal reproductive tract development, tamoxifen was associated with changes similar to those caused by oestradiol, ethynyloestradiol, clomiphene and diethylstilboestrol (DES). Although the clinical relevance of these changes is unknown, some of them, especially vaginal adenosis, are similar to those seen in young women who were exposed to DES?in utero?and who have a 1 in 1000 risk of developing clear-cell carcinoma of the vagina or cervix. Only a small number of pregnant women have been exposed to tamoxifen. Such exposure has not been reported to cause subsequent vaginal adenosis or clear-cell carcinoma of the vagina or cervix in young women exposed?in utero?to tamoxifen.

Women should be advised not to become pregnant whilst taking Tamoxifen 10mg Tablets and should use barrier or other non-hormonal contraceptive methods if sexually active. Pre-menopausal patients must be carefully examined before treatment to exclude pregnancy. Women should be informed of the potential risks to the foetus, should they become pregnant whilst taking Tamoxifen 10mg Tablets or within two months of cessation of therapy.

Breast-feeding

It is not known if Tamoxifen Tablets is excreted in human milk and therefore the drug is not recommended during breast-feeding. The decision either to discontinue nursing or discontinue Tamoxifen Tablets should take into account the importance of the drug to the mother.

4.7 Effects on ability to drive and use machines

Tamoxifen is unlikely to impair the ability of patients to drive or operate machinery. However, fatigue has been reported with the use of Tamoxifen and caution should be observed when driving or using machinery while such symptoms persist.

4.8 Undesirable effects

ADR Unless specified, the following frequency categories were calculated from the number of adverse events reported in a large phase III study conducted in 9366 postmenopausal women patients with operable breast cancer treated for 5 years and unless specified, no account was taken of the frequency within the comparative treatment group or whether the investigator considered it to be related to study medication.

Table 1 Adverse Drug Reactions (ADR) seen with Tamoxifen

FrequencySystem Organ Class (SOC)ADR
Very common

(? 10%)

Gastrointestinal disorders

Metabolism and nutrition disorders

Reproductive system and breast disorders

 

Skin and subcutaneous tissue disorders

Vascular disorders

General disorders and administration site conditions

? Nausea

? Fluid retention

? Vaginal bleeding

? Vaginal discharge

? Skin Rash

? Hot flushes

? Fatigue

Common

(? 1% and <10%)

Blood and lymphatic system disorders

Eye disorders

 

Immune system disorders

Investigations

Musculoskeletal and connective tissue disorders

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Nervous system disorders

 

 

 

Reproductive system and breast disorders

 

Skin and subcutaneous tissue disorders

Gastrointestinal disorders

 

 

Hepatobiliary disorders

 

Multiple SOC Terms

? Anaemia

? Cataracts

? Retinopathy

? Hypersensitivity reactions

? Elevated triglycerides

? Leg cramp

? Myalgia

? Uterine fibroids
? Ischaemic cerebrovascular events

? Headache

? Light headedness

? Sensory disturbances (including paraesthesia and dysgeusia)

? Pruritus valvae

? Endometrial changes (including hyperplasia and polyps)

? Alopecia

? Vomiting

? Diarrhoea

? Constipation

? Changes in liver enzymes

? Fatty liver

? Thromboembolic events (including deep vein thrombosis and pulmonary embolism)

Uncommon

(? 0.1% and <1%)

Blood and lymphatic system disorders

 

Eye disorders

Gastrointestinal disorders

Metabolism and nutrition disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Respiratory, thoracic and mediastinal disorders

Hepatobiliary disorders

? Thrombocytopenia

? Leukopenia

? Visual disturbances

? Pancreatitis

? Hypercalcaemia (in patients with bony metastases)

? Endometrial cancer
? Interstitial pneumonitis

? Cirrhosis of the liver

Rare

(? 0.01% and <0.1%)

Blood and lymphatic system disorders

 

Eye disorders

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

 

Nervous system

Hepatobiliary disorders

 

 

 

 

Skin and subcutaneous tissue disorders

 

 

 

 

Reproductive system and breast disorders

? Neutropeniaa

? Agranulocytosisa

? Corneal changes

? Optic neuropathya

? Uterine Sarcoma (mostly malignant mixed Mullerian tumours)a

? Tumour Flarea

? Optic neuritis

? Hepatitis

? Cholestasisa

? Hepatic failurea

? Hepatocellular injurya

? Hepatic necrosisa

? Angioedema

? Steven-Johnsons syndromea

? Cutaneous vasculitisa

? Bullous pemphigoida

? Erythema multiformea

? Endometriosisa

? Cystic ovarian swellinga

? Vaginal polyps

Very Rare

(<0.01%)

Skin and subcutaneous tissue disorders

Congenital, familial and genetic disorders

Injury, poisoning and procedural complications

? Cutaneous lupus erythematosusb

? Porphyria cutanea tardab

? Radiation Recallb

a?This adverse drug reaction was?not?reported in the tamoxifen arm (n= 3094) of the above study; however, it has been reported in other trials or from other sources. The frequency has been calculated using the upper limit of the 95% confidence interval for the point estimate (based on 3/X, where X represents the total sample size e.g. 3094). This is calculated as 3/3094 which equates to a frequency category of ‘rare’.

b?The event was not observed in other major clinical studies. The frequency has been calculated using the upper limit of the 95% confidence interval for the point estimate (based on 3/X, where X represents the total sample size of 13,357 patients in the major clinical studies). This is calculated as 3/13,357 which equates to a frequency category of ‘very rare’.

Side effects can be classified as either due to the pharmacological action of the drug, e.g., hot flushes, vaginal bleeding, vaginal discharge, pruritus vulvae and tumour flare, or as more general side effects, e.g., gastro-intestinal intolerance, headache, light-headedness and occasionally, fluid retention and alopecia.

When side effects are severe, it may be possible to control them by a simple reduction of dosage (to not less than 20 mg/day) without loss of control of the disease. If side effects do not respond to this measure, it may be necessary to stop the treatment.

Skin rashes (including isolated reports of erythema multiforme, Stevens- Johnson syndrome and bullous pemphigoid) and rare hypersensitivity reactions including angioedema have been reported.

Uncommonly, of patients with bony metastases have developed hypercalcaemia on initiation of therapy.

Cases of visual disturbance including reports of corneal changes and common reports of retinopathy have been described in patients receiving tamoxifen therapy. Cataracts have been reported commonly in association with the administration of Tamoxifen.

Cases of optic neuropathy and optic neuritis have been reported in patients receiving Tamoxifen and, in a small number of cases, blindness has occurred.

Sensory disturbances (including paraesthesia and dysgeusia) have been reported commonly in patients receiving Tamoxifen.

Uterine fibroids and endometrial changes including hyperplasia and polyps have been reported.

Falls in platelet count, usually to 80,000 to 90,000 per cu mm but occasionally lower, have been reported in patients taking Tamoxifen for breast cancer.

Leucopenia has been observed following the administration of Tamoxifen, sometimes in association with anaemia and/or thrombocytopenia. Neutropenia has been reported on rare occasions; this can sometimes be severe, and very rarely cases of agranulocytosis have been reported.

There is evidence of ischaemic cerebrovascular events and thromboembolic events, including deep vein thrombosis, microvascular thrombosis and pulmonary embolism have been reported during tamoxifen therapy (see sections 4.3, 4.4 and 4.5. When tamoxifen is used in combination with cytotoxic agents, there is an increased risk of thrombo-embolic events occuring.

Leg cramps and myalgia have been reported commonly in patients receiving Tamoxifen.

Uncommonly, cases of interstitial pneumonitis have been reported.

Tamoxifen has been associated with changes in liver enzyme levels and on rare occasions with a spectrum of more severe liver abnormalities including fatty liver, cholestasis and hepatitis,, liver failure, cirrhosis, and, hepatocellular injury (including hepatic necrosis).

Commonly, elevation of serum triglyceride levels, in some cases with pancreatitis, may be associated with the use of Tamoxifen.

Cystic ovarian swellings have occasionally been observed in pre-menopausal women receiving Tamoxifen.

Vaginal polyps have rarely been observed in women receiving Tamoxifen.

Cutaneous lupus erythematosus has been observed very-rarely in patients receiving Tamoxifen.

Porphyria cutanea tarda has been observed very-rarely in patients receiving Tamoxifen.

Fatigue has been reported very commonly in patients taking Tamoxifen.

Radiation recall has been observed very rarely in patients receiving Tamoxifen.

Uncommonly incidence of endometrial cancer and rare instances of uterine sarcoma (mostly malignant mixed Mullerian tumours) has been reported in association with Tamoxifen treatment.

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

On theoretical grounds, an overdosage would be expected to cause enhancement of the pharmacological side effects mentioned above. Observations in animals show that extreme overdosage (100 – 200 times recommended daily dose) may produce oestrogenic effects.

There have been reports in the literature that Tamoxifen given at several times the standard dose may be associated with prolongation of the QT interval of the ECG.

There is no specific antidote to overdosage, and treatment must be symptomatic.

5.PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-estrogens.

Mechanism of action:

Tamoxifen is a non-steroidal, triphenylethylene-based drug, which displays a complex spectrum of oestrogen antagonist and oestrogen agonist-like pharmacological effects in different tissues. In breast cancer patients, at the tumour level, tamoxifen acts primarily as an antioestrogen, preventing oestrogen binding to the oestrogen receptor. However, clinical studies have shown some benefit in oestrogen receptor negative tumours, which may indicate other mechanisms of action. In the clinical situation, it is recognised that tamoxifen leads to reductions in levels of blood total cholesterol and low density lipoproteins in postmenopausal women of the order of 10 – 20%. Tamoxifen does not adversely affect bone mineral density.

Paediatric population:

An uncontrolled trial was undertaken in a heterogenous group of 28 girls aged 2 to 10 years with McCune Albright Syndrome (MAS), who received 20 mg once a day for up to 12 months duration. Among the patients who reported vaginal bleeding during the pre-study period, 62% (13 out of 21 patients) reported no bleeding for a 6-month period and 33% (7 out of 21 patients) reported no vaginal bleeding for the duration of the trial. Mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. While this finding is in line with the pharmacodynamic properties of tamoxifen, a causal relationship has not been established (see section 4.4). There are no long-term safety data in children. In particular, the long-term effects of tamoxifen on growth, puberty and general development have not been studied.

CYP2D6 polymorphism:

CYP2D6 polymorphism status may be associated with variability in clinical response to tamoxifen. The poor metaboliser status may be associated with reduced response. The consequences of the findings for the treatment of CYP2D6 poor metabolisers have not been fully elucidated (see sections 4.4, 4.5 and 5.2).

CYP2D6 genotype:

Available clinical data suggest that patients, who are homozygote for non-functional CYP2D6 alleles, may experience reduced effect of tamoxifen in the treatment of breast cancer.

The available studies have mainly been performed in postmenopausal women (see sections 4.4 and 5.2).

5.2 Pharmacokinetic properties

Absorption:

After oral administration, tamoxifen is absorbed rapidly with maximum serum concentrations attained within 4 – 7 hours. Steady state concentrations (about 300 mg/ml) are achieved after four weeks treatment with 40 mg daily.

Distribution:

The drug is highly protein bound to serum albumin (> 99%).

Biotransformation:

Metabolism is by hydroxylation, demethylation and conjugation, giving rise to several metabolites, which have a similar pharmacological profile to the parent compound and thus contribute to the therapeutic effect. An elimination half-life of approximately seven days has been calculated for the drug itself, whereas that for N-desmethyltamoxifen, the principal circulating metabolite, is 14 days.

Elimination:

Excretion occurs primarily via the faeces.

Paediatric population:

In a clinical study where girls between 2 and 10 years with McCune Albright Syndrome (MAS) received 20 mg tamoxifen once a day for up to 12 months duration, there was an age-dependent decrease in clearance and an increase in exposure (AUC), (with values up to 50% higher in the youngest patients) compared with adults.

CYP2D6 polymorphism:

Tamoxifen is metabolised mainly via CYP3A4 to N-desmethyl-tamoxifen, which is further metabolised by CYP2D6 to another active metabolite endoxifen. In patients who lack the enzyme CYP2D6 endoxifen concentrations are approximately 75% lower than in patients with normal CYP2D6 activity. Administration of strong CYP2D6 inhibitors reduces endoxifen circulating levels to a similar extent.

5.3 Preclinical safety data

Tamoxifen was not mutagenic in a range of in-vitro and in-vivo mutagenicity tests. Tamoxifen was genotoxic in some in-vitro and in-vivo genotoxicity tests in rodents. Gonadal tumours in mice and liver tumours in rats receiving tamoxifen have been reported in long-term studies. The clinical relevance of these findings has not been established.

Tamoxifen is a drug on which extensive clinical experience has been obtained. Relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.

6.PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Calcium hydrogen phosphate
Microcrystalline cellulose
Sodium starch glycollate (Type A)

Povidone K25
Magnesium stearate
Colloidal anhydrous silica

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

48 months.

6.4 Special precautions for storage

Do not store above 25?C.

Store in original container.

6.5 Nature and contents of container

The tablets are packed in blisters constituted from a PVC and aluminium foil.

6.6 Special precautions for disposal and other handling

None

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
Mumbai, India
Survey No.188/1 to 189/1,190/1 to 4,
Athiyawad, Dabhel,
Daman- 396210 (INDIA)

Tamoxifen Citrate Film Coated Tablets IP 20mg Taj Pharma
Package leaflet: Information for the patient

Tamoxifen

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. See section 4.

What is in this leaflet:

  1. What Tamoxifen is and what it is used for
  2. What you need to know before you take Tamoxifen
  3. How to take Tamoxifen
  4. Possible side effects
  5. How to store Tamoxifen
  6. Contents of the pack and other information
1 WHAT TAMOXIFEN IS AND WHAT IT IS USED FOR

Tamoxifen Tablets contain a medicine called tamoxifen. This belongs to a group of medicines called ?anti-oestrogens?.

What Tamoxifen Tablets are used for
? Tamoxifen Tablets are used to treat breast cancer.
? Tamoxifen Tablets also to treat infertility in women caused by a failure to produce and release eggs (ovulate) properly.
? Tamoxifen Tablets can also reduce the risk of developing breast cancer occurring in those women who have an increased likelihood of developing breast cancer (your risk).
It is important that your healthcare professional calculates your risk of developing breast cancer and discusses the result with you before commencing treatment.
There are a number of specific tools available to calculate breast cancer risk, based on information such as your age, family history, genetics, reproductive factors (e.g. age when periods started and stopped, had children or not, taken or taking hormonal replacement therapy and/or oral contraceptive pill) and history of breast disease. Although the tools can estimate your risk, it doesn?t mean you will get breast cancer, being at increased risk means you have a higher chance of developing breast cancer. If you and your healthcare professional are considering using Tamoxifen Tablets for this, it is important to understand the benefits as well as the side effects of taking Tamoxifen Tablets because you don’t currently have breast cancer and tamoxifen reduces, but does not stop the risk of developing breast cancer.

If you want to know more about how to decide whether tamoxifen is right for you, there is more information for patients on the National Institute for Health and Care Excellence website. Ask your doctor to talk to you about the information which is available for patients.

How Tamoxifen Tablets work
Oestrogen is a natural substance in your body known as a ?sex hormone?. Some breast cancers need oestrogen to grow and tamoxifen works by blocking the effects of oestrogen.

2 WHAT YOU NEED TO KNOW BEFORE YOU TAKE TAMOXIFEN

Do not take Tamoxifen Tablets:
? if you are allergic to tamoxifen or any of the other ingredients of this medicine (listed in section 6)
? if you are pregnant or think you might be pregnant (see the section on ?Pregnancy? below).
? if you are taking anastrozole.
? if you are taking any treatment for infertility.
? if you have had blood clots in the past and the doctor did not know what caused them.
? if someone in your family has had blood clots with the cause not known.
? if your doctor has told you that you have an illness which runs in the family that increases the risk of blood clots.
? if you are taking medicines used to prevent blood clots such as warfarin.

Do not take Tamoxifen Tablets if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Tamoxifen Tablets.

Warnings and precautions
Talk to your doctor or pharmacist before taking Tamoxifen Tablets.
In delayed breast reconstruction operation (weeks to years after the primary breast operation when your own tissue is moved to shape a new breast) Tamoxifen Tablets may increase the risk of the formation of blood clots in the small vessels of the tissue flap which may lead to complications.
Tamoxifen therapy may be used to reduce the risk of breast cancer and it can be associated with serious side effects such as blood clots in the veins of your leg (deep vein thrombosis), blood clots in your lungs (pulmonary embolus) and uterine cancer, all of which can be fatal. Other less serious side effects such as hot flushes, vaginal discharge, menstrual irregularities and pelvis pain may also occur.

Whether the benefits of treatment outweigh the risks depends on your age, health history, your level of breast cancer risk and on your personal judgement. Tamoxifen therapy to reduce the risk of breast cancer may not be appropriate for all women at increased risk. All assessments with your healthcare professional of the potential benefits and risks prior to starting therapy are essential. You should understand that tamoxifen reduces, but does not eliminate the risk of breast cancer.

Operations
If you are to undergo planned surgery, you should tell your doctor or pharmacist as they may wish to consider stopping your treatment for a short period.

Children
This medicine is not for use in children.

Other medicines and Tamoxifen Tablets
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines you buy without a prescription and herbal medicines. This is because Tamoxifen Tablets can affect the way some other medicines work and some medicines can have an effect on Tamoxifen Tablets.
In particular, you should tell your doctor or pharmacist if you are taking any of the following medicines:
? Oral contraceptives
? Hormone replacement therapy (HRT)
? Antidepressants (e.g. paroxetine, fluoxetine).
? Bupropion (used as antidepressant or aid to smoking cessation).
? Quinidine (for example used in the treatment of cardiac arrhythmia).
? Cincalet/Cinacalcet (for treatment of disorders of the parathyroid gland).
? Blood thinning medicines such as warfarin. These are known as ?anti-coagulants?.
? Rifampicin, which is used for tuberculosis (TB).
? Medicines known as ?aromatase inhibitors? that are used to treat breast cancer. These include anastrozole, letrozole and exemestane.

Contraception
Women who can become pregnant should use adequate non-hormonal contraception (e.g., barrier contraception) during treatment with tamoxifen and for an additional two months after stopping treatment.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
? Do not take Tamoxifen Tablets if you are pregnant. This is because it may affect your unborn baby.
? You should not become pregnant while taking Tamoxifen Tablets. Please see your doctor for advice on what contraceptive precautions you should take, as some may be affected by Tamoxifen Tablets.
? You should see your doctor immediately if you think you may have become pregnant after starting to take Tamoxifen Tablets.

Breast-feeding
Talk to your doctor before taking Tamoxifen Tablets if you are breast-feeding.

Driving and using machines
Tamoxifen Tablets are not likely to affect your ability to drive or use any tools or machines. However, tiredness has been reported with the use of Tamoxifen Tablets and caution should be observed when driving or operating machinery while such symptoms persist.

Tamoxifen Tablets contain lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product as it contains lactose.

3 HOW TO TAKE TAMOXIFEN

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Breast cancer treatment
The recommended dose for breast cancer is 20mg daily.

Infertility
The dose for infertility depends on your periods (menstrual cycle).
? If you are having regular periods, the recommended dose is one 20mg tablet daily on the 2nd, 3rd, 4th and 5th days of your period.
? If this does not work, your doctor may suggest that you take a higher dose of Tamoxifen Tablets during your next period. If this happens, the recommended dose is 40mg or 80mg daily on the 2nd, 3rd, 4th and 5th days of your period.
? If you are not having regular periods, you can start taking the tablets on any day of the month.

Reducing the risk of breast cancer
The recommended dose for reducing the risk of breast cancer is 20 mg daily for 5 years.
Your healthcare professional will calculate your risk of breast cancer occurring using information about you, your medical history and any family history of breast cancer.

If you take more Tamoxifen Tablets than you should
If you take more Tamoxifen Tablets than you should, talk to a doctor or pharmacist straight away.

If you forget to take Tamoxifen Tablets
If you forget to take a dose, take another as soon as you remember. However, if it is nearly time for the next dose skip the missed dose. Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

Stopping treatment with Tamoxifen Tablets
You should continue to take Tamoxifen Tablets for as long as your doctor tells you to. Do not stop taking the medicine without talking to your doctor first.
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 everybody gets them.

Stop taking Tamoxifen Tablets and tell your doctor straight away if you notice any of the following side effects ? you may need urgent medical treatment:
? Symptoms of a blood clot. These include swelling of the calf or leg, chest pain, being short of breath or suddenly feeling weak.
? Symptoms of a stroke. These include sudden onset of the following: weakness or paralysis of the arms or legs, being unable to move the arms or legs, sudden difficulty with speaking, walking, difficulty in holding things or difficulty in thinking. These symptoms are caused by a reduced blood supply in the brain.
? Difficulty in breathing.
? Swelling of the face, lips, tongue or throat which may make it difficult to swallow.
? Swelling of the hands, feet or ankles.
? Nettle rash (also called ?hives? or ?urticaria?). Tell your doctor straight away if you notice any of the following:
? Unusual bleeding from your vagina.
? Irregular periods, especially if associated with heavier bleeding as this could be a warning sign for a certain type of cancer affecting the lining of your womb (endometrial cancer).
? Vaginal discharge.
? A feeling of discomfort in the lower tummy (pelvis) such as pain or pressure. These effects may mean that there have been changes to the lining of your womb (the endometrium). Sometimes these effects are serious and could include cancer. They can happen during or after treatment with Tamoxifen Tablets.

Other possible side effects:
Very common: may affect more than 1 in 10 people
? Nausea.
? Fluid retention.
? Skin rash.
? Hot flushes.
? Tiredness.

Common: may affect up to 1 in 10 people
? Anaemia (a blood problem which means you have too few red blood cells).
? Changes in vision due to cataracts or changes to the retina of your eye.
? Increased amounts of fats in your blood (shown by blood tests).
? Allergic reactions.
? Leg cramp.
? Changes in the womb (including changes to its lining and benign growths).
? Headache.
? Feeling light-headed.
? Itching of the genitals.
? Thinning of the hair.
? Vomiting.
? Diarrhoea.
? Constipation.
? Changes in blood tests of liver function.
? Formation of fatty liver cells.
? Muscle pain.
? Sensory changes (including taste disorder and numbness or tingling in the skin).
? Increased risk of blood clots (including clots in small vessels).

Uncommon: may affect up to 1 in 100 people
? Blood problems. This can make you bruise more easily, get serious infections, or feel very tired or breathless.
? Changes to your vision and difficulty seeing.
? Swelling of the pancreas. This may cause moderate to severe pain in the stomach.
? Changes in the amount of calcium in your blood. The signs may include feeling very sick, being sick a lot or being thirsty.

Tell your doctor if this happens because he or she may want you to have blood tests.
? Inflammation of the lungs. The symptoms may be like pneumonia (such as feeling short of breath and coughing).
? Liver cirrhosis (problems with your liver).

Rare: may affect up to 1 in 1,000 people
? Severe blood problems. This can make you bruise more easily, get serious infections, or feel very tired or breathless.
? Changes to the cornea of your eye.
? Problems with the nerve that connects your retina to your brain.
? Swelling of the optic nerve.
? On occasions more severe liver diseases have occurred from which some patients have died. These liver diseases include inflammation of the liver, liver cirrhosis, liver cell damage, reduced bile formation, and failure of the liver. Symptoms may include a general feeling of being unwell, with or without jaundice (yellowing of the skin and eyes).
? A severe rash with blisters or peeling of the skin and possibly blisters in the mouth and nose (Stevens-Johnson syndrome).
? Damage to blood vessels causing red or purple dots in the skin.
? Severe skin disorder. The symptoms include redness, blistering and peeling.
? Cells normally only found in the lining of the womb found elsewhere in your body, cysts on the ovaries, and cancer (the signs of this are given above).
? Non-cancerous mass in the inner lining of the vagina (called vaginal polyp).
? At the beginning of treatment, a worsening of the symptoms of your breast cancer such as an increase in pain and/or an increase in the size of the affected tissue may occur (known as tumour flare).

Very rare: may affect up to 1 in 10,000 people
? Inflammation of the skin characterized by rash or erythema, very often on areas exposed to light (a condition called cutaneous lupus erythematosus)
? A skin condition characterised by skin blisters in areas exposed to the light, this is due to the increased liver production of a special group of cell pigments (called porphyrins)
? Radiation recall – skin rash involving redness, swelling, and/or blistering (like severe sunburn) of the skin after receiving radiation therapy.

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 STORETAMOXIFEN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and foil. The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration such as discoloration.
Do not store above 25?C.
Store in the original container or package in order to protect from light and moisture. Do not transfer the tablets to another container.
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 CONTENTS OF THE PACK AND OTHER INFORMATION

What Tamoxifen contains
The active substance is Tamoxifen citrate.

a) Each film-coated tablet contains:
Tamoxifen (as citrate)? IP??? 10mg
Excipients? ????q.s.

b) Each film-coated tablet contains:
Tamoxifen (as citrate)? IP??? 20mg
Excipients????? q.s.

Contents of the pack
Tamoxifen 10mg, 20mg Tablets are white, circular, uncoated tablets
Tamoxifen Tablets are available in blister strip packs of 30 tablets.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
Mumbai, India
at SURVEY NO. 188/1, 190/1TO 4, ATHIYAWAD , DABHEL,
DAMAN- 396210 (INDIA)

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