Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s

METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

beneficial effect in a wide variety of neoplastic

RX diseases, alone and in combination with other
cytotoxic agents.
METHOTREXATE
Choriocarcinoma and Similar Trophoblastic
INJECTION USP Diseases
50MG/2ML Methotrexate is administered orally or
intramuscularly in doses of 15-30 mg daily for a
1.NAME OF THE MEDICINAL 5 day course. Such courses may be repeated 3-5
PRODUCT times as required, with rest periods of one or
more weeks interposed between courses until
Methotrexate 50mg/ 2ml Injection any manifesting toxic symptoms subside.
2. QUALITATIVE AND The effectiveness of therapy can be evaluated by
QUANTITATIVE COMPOSITION 24 hours quantitative analysis of urinary
chorionic gonadotrophin hormone (HCG).
Each ml of solution contains 25 mg Combination therapy with other cytotoxic drugs,
methotrexate (sodium salt formed in situ) has also been reported as useful.
Each vial of 2 ml of solution contains 50 mg
methotrexate (sodium salt formed in situ) Hydatidiform mole may precede or be followed
For excipients, see 6.1. by choriocarcinoma, and methotrexate has been
used in similar doses for the treatment of
3. PHARMACEUTICAL FORM hydatidiform mole and chorioadenoma
Solution for Injection destruens.

Vials containing a clear yellow solution Breast Carcinoma

Prolonged cyclic combination with
4. CLINICAL PARTICULARS
cyclophosphamide, methotrexate and
4.1 Therapeutic indications fluorouracil has given good results when used as
Methotrexate is indicated in the treatment of adjuvant treatment to radical mastectomy in
neoplastic disease, such as trophoblastic primary breast cancer with positive axillary
neoplasms and leukaemia, and the symptomatic lymph nodes. Methotrexate dosage was 40
treatment of severe recalcitrant disabling mg/m2intravenously on the first and eighth days.
psoriasis which is not adequately responsive to Leukaemia
other forms of therapy.
Acute granulocytic leukaemia is rare in children
4.2 Posology and method of administration but common in adults and this form of
Adults and children leukaemia responds poorly to chemotherapy.
Antineoplastic Chemotherapy Methotrexate is not generally a drug of choice
for induction of remission of lymphoblastic
Methotrexate is active orally and parenterally. leukaemia. Oral methotrexate dosage 3.3
Methotrexate Injection may be given by the mg/m2 daily, and prednisolone 40-60
intramuscular, intravenous, intraarterial or mg/m2 daily for 4-6 weeks has been used. After
intrathecal routes. a remission is attained, methotrexate in a
Note: Only the 50 mg/2 ml presentation maintenance dosage of 20-30 mg/m2 orally or by
should be used for the intrathecal route of intramuscular injection has been administered
administration to prevent accidental twice weekly. Twice weekly doses appear to be
overdose. more effective than daily drug administration.
Alternatively, 2.5 mg/kg has been administered
Dosage is related to the patient's body weight or intravenously every 14 days.
surface area. Methotrexate has been used with
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

Meningeal Leukaemia 10 mg daily by mouth for weeks or months and

dosage should be adjusted according to the
Some patients with leukaemia are subject to patient's response and haematological
leukaemic invasions of the central nervous monitoring. Methotrexate has also been given
system and the CSF should be examined in all intramuscularly in doses of 50 mg once weekly
leukaemia patients. or 25 mg twice weekly.
Passage of methotrexate from blood to the
Psoriasis Chemotherapy
cerebrospinal fluid is minimal and for adequate
therapy the drug should be administered Cases of severe uncontrolled psoriasis,
intrathecally. Methotrexate may be given in a unresponsive to conventional therapy, have
prophylactic regimen in all cases of lymphocytic responded to weekly single, oral, intramuscular
leukaemia. The dose of intrathecal Methotrexate or intravenous doses of 10-25 mg per week, and
is constant regardless of age or body surface adjusted according to the patient's response. An
area in patients over the age of 3 years of age, initial test dose one week prior to initiation of
the maximum intrathecal dose should be 12 mg therapy is recommended to detect any
in such patients. Patients under the age of 3 idiosyncrasy. A suggested dose range is 5-10
years should be treated in accordance with mg.
combination chemotherapy protocols. The
administration is at weekly intervals and is An alternative dosage schedule consists of 2.5 to
usually repeated until the cell count of 5 mg of methotrexate administered orally at 12
cerebrospinal fluid returns to normal. At this hour intervals for 3 doses each week or at 8-hour
point one additional dose is advised. Large doses intervals for 4 doses each week; weekly dosages
should not exceed 30 mg.
may cause convulsions and untoward side
effects may occur as with any intrathecal A daily oral dosage schedule of 2 to 5 mg
injection, and are commonly neurological in administered orally for 5 days followed by a rest
character. period of at least 2 days may also be used. The
daily dose should not exceed 6.25 mg.
Note: Only the 50 mg/2 ml presentation
should be used for the intrathecal route of The patient should be fully informed of the risks
administration to prevent accidental involved and the clinician should pay particular
overdose. attention to the appearance of liver toxicity by
carrying out liver function tests before starting
Lymphomas
methotrexate treatment, and repeating these at 2
In Burkitt's Tumour, stages 1-2, methotrexate to 4 month intervals during therapy. The aim of
has prolonged remissions in some cases. therapy should be to reduce the dose to the
Recommended dosage is 10-25 mg per day lowest possible level with the longest possible
orally for 4 to 8 days. In stage 3, methotrexate is rest period. The use of methotrexate may permit
commonly given concomitantly with other the return to conventional topical therapy which
antitumour agents. Treatment in all stages should be encouraged.
usually consists of several courses of the drug
interposed with 7 to 10 day rest periods, and in Use in the elderly
stage 3 they respond to combined drug therapy Methotrexate should be used with extreme
with methotrexate given in doses of 0.625 mg to caution in elderly patients. A reduction in
2.5 mg/kg daily. Hodgkin's disease responds dosage should be considered.
poorly to methotrexate and to most types of
chemotherapy. 4.3 Contraindications
Methotrexate is contraindicated in:
Mycosis Fungoides
Patients with significantly impaired renal
Therapy with methotrexate appears to produce function.
clinical remissions in one half of the cases
treated. Recommended dosage is usually 2.5 to
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

Patients with significantly impaired hepatic infection. If methotrexate induced lung disease
function is suspected treatment with corticosteroids
should be initiated and treatment with
Patients with pre-existing blood dyscrasias, such methotrexate should not be restarted.
as significant marrow hypoplasia, leukopenia,
thrombocytopenia or anaemia. When a patient presents with pulmonary
symptoms, the possibility of Pneumocystis
Patients with active infections. carinii pneumonia should be considered.
Patients with overt or laboratory evidence of Methotrexate has the potential for serious,
immunodeficiency syndrome(s). sometimes fatal toxicity. The toxic effects may
Methotrexate is contraindicated in pregnancy. be related in frequency and severity to the dose
or frequency of administration but have been
Because of the potential for serious adverse seen at all doses. Because the toxic reactions can
reactions from methotrexate in breast fed occur at any time during therapy, the patients
infants, breast feeding is contraindicated in have to be observed closely and must be
women taking methotrexate. informed of early signs and symptoms of
Patients with a known allergic hypersensitivity toxicity.
to methotrexate or any of the other ingredients Use caution when administering high-dose
should not receive methotrexate. methotrexate to patients receiving proton pump
4.4 Special Warnings and precautions for inhibitor (PPI) therapy. Case reports and
published population pharmacokinetic studies
use
suggest that concomitant use of some PPIs, such
WARNINGS as omeprazole, esomeprazole, and pantoprazole,
with methotrexate (primarily at high dose), may
Methotrexate must be used only by physicians elevate and prolong serum levels of
experienced in antimetabolite chemotherapy. methotrexate and/or its metabolite
Because of the possibility of fatal or severe toxic hydroxymethotrexate, possibly leading to
reactions, the patient should be fully informed methotrexate toxicities. In two of these cases,
by the physician of the risks involved and be delayed methotrexate elimination was observed
under his constant supervision. when high-dose methotrexate was co-
administered with PPIs, but was not observed
Only the 50 mg/2 ml presentation Methotrexate when methotrexate was co-administered with
25 mg/ml Injection should be used for the ranitidine. However, no formal drug interaction
intrathecal route of administration. Larger studies of methotrexate with ranitidine have
presentations are not suitable due to the risk of been conducted.
accidental overdose.
Deaths have been reported with the use of
Acute or chronic interstitial pneumonitis, often methotrexate in the treatment of psoriasis.
associated with blood eosinophilia, may occur
and deaths have been reported. Symptoms In the treatment of psoriasis, methotrexate
typically include dyspnoea, cough (especially a should be restricted to severe recalcitrant,
dry non-productive cough) thoracic pain and disabling psoriasis which is not adequately
fever for which patients should be monitored at responsive to other forms of therapy, but only
each follow-up visit. Patients should be when the diagnosis has been established by
informed of the risk of pneumonitis and advised biopsy and/or after dermatological consultation.
to contact their doctor immediately should they 1. Full blood counts should be closely monitored
develop persistent cough or dyspnoea. before, during and after treatment. If a clinically
Methotrexate should be withdrawn from patients significant drop in white-cell or platelet count
with pulmonary symptoms and a thorough develops, methotrexate should be withdrawn
investigation should be made to exclude immediately. Patients should be advised to
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

report all symptoms or signs suggestive of 6. Methotrexate affects gametogenesis during

infection. the period of its administration and may result in
decreased fertility which is thought to be
2. Methotrexate may be hepatotoxic, particularly reversible on discontinuation of therapy.
at high dosage or with prolonged therapy. Liver Conception should be avoided during the period
atrophy, necrosis, cirrhosis, fatty changes, and of methotrexate administration and for at least 6
periportal fibrosis have been reported. Since months thereafter. Patients and their partners
changes may occur without previous signs of should be advised to this effect.
gastrointestinal or haematological toxicity, it is
imperative that hepatic function be determined 7. Methotrexate has some immunosuppressive
prior to initiation of treatment and monitored activity and immunological responses to
regularly throughout therapy. If substantial concurrent vaccination may be decreased. The
hepatic function abnormalities develop, immunosuppressive effect of methotrexate
methotrexate dosing should be suspended for at should be taken into account when immune
least 2 weeks. Special caution is indicated in the responses of patients are important or essential.
presence of pre-existing liver damage or Immunisation with live virus vaccines is
impaired hepatic function. Concomitant use of generally not recommended.
other drugs with hepatotoxic potential (including
alcohol) should be avoided. 8. Pleural effusions and ascites should be
drained prior to initiation of methotrexate
3. Methotrexate has been shown to be therapy.
teratogenic; it has caused foetal death and/or
congenital anomalies. Therefore it is not 9. Deaths have been reported with the use of
methotrexate. Serious adverse reactions
recommended in women of childbearing
including deaths have been reported with
potential unless there is appropriate medical
evidence that the benefits can be expected to concomitant administration of methotrexate
outweigh the considered risks. Pregnant (usually in high doses) along with some non-
psoriatic patients should not receive steroidal anti-inflammatory drugs (NSAIDs).
methotrexate. 10. Concomitant administration of folate
4. Renal function should be closely monitored antagonists such as
before, during and after treatment. Caution trimethoprim/sulphamethoxazole has been
should be exercised if significant renal reported to cause an acute megaloblastic
pancytopenia in rare instances.
impairment is disclosed. Reduce dose of
methotrexate in patients with renal impairment. 11. Systemic toxicity may occur following
High doses may cause the precipitation of intrathecal administration. Blood counts should
methotrexate or its metabolites in the renal be monitored closely.
tubules. A high fluid throughput and
alkalinisation of the urine to pH 6.5 – 7.0, by 12. A chest X-ray is recommended prior to
oral or intravenous administration of sodium initiation of methotrexate therapy.
bicarbonate (5 x 625 mg tablets every three 13. If acute methotrexate toxicity occurs,
hours) or acetazolamide (500 mg orally four patients may require folinic acid.
times a day) is recommended as a preventative
measure. Methotrexate is excreted primarily by 14. Severe, occasionally fatal, cutaneous or
the kidneys. Its use in the presence of impaired sensitivity reactions (e.g., toxic epidermic
renal function may result in accumulation of necrolysis, Stevens-Johnson syndrome,
toxic amounts or even additional renal damage. exfoliative dermatitis, skin necrosis, erythema
multiforme, vasculitis and extensive herpetiform
5. Diarrhoea and ulcerative stomatitis are skin eruptions) may occur after the
frequent toxic effects and require interruption of administration of methotrexate and recovery
therapy, otherwise haemorrhagic enteritis and ensured mostly after discontinuation of the
death from intestinal perforation may occur. therapy.
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

PRECAUTIONS haematological studies are essential to the use of

methotrexate in chemotherapy because of its
Methotrexate has a high potential toxicity, common effect of haematopoietic suppression.
usually dose related, and should be used only by This may occur abruptly and on apparent safe
physicians experienced in antimetabolite dosage, and any profound drop in blood cell
chemotherapy, in patients under their constant count indicates immediate stopping of the drug
supervision. The physician should be familiar and appropriate therapy. In patients with
with the various characteristics of the drug and
malignant disease who have pre-existing bone
its established clinical usage.
marrow aplasia, leukopenia, thrombocytopenia
Before beginning methotrexate therapy or or anaemia, methotrexate should be used with
reinstituting methotrexate after a rest period, caution, if at all.
assessment of renal function, liver function and In general, the following laboratory tests are
blood elements should be made by history, recommended as part of essential clinical
physical examination and laboratory tests.
evaluation and appropriate monitoring of
It should be noted that intrathecal doses are patients chosen for or receiving methotrexate
transported into the cardiovascular system and therapy: complete haemogram; haematocrit;
may give rise to systemic toxicity. Systemic urinalysis; renal function tests; liver function
toxicity of methotrexate may also be enhanced tests and chest X-ray.
in patients with renal dysfunction, ascites, or The purpose is to determine any existing organ
other effusions due to prolongation of serum dysfunction or system impairment. The tests
half-life.
should be performed prior to therapy, at
In rare cases, following intrathecal appropriate periods during therapy and after
administration, a tumour lysis syndrome has termination of therapy.
been observed.
Liver biopsy may be considered after cumulative
Carcinogenesis, mutagenesis, and impairment doses >1.5 g have been given, if hepatic
of fertility: Animal carcinogenicity studies have impairment is suspected.
demonstrated methotrexate to be free of
Methotrexate is bound in part to serum albumin
carcinogenic potential. Although methotrexate after absorption, and toxicity may be increased
has been reported to cause chromosomal damage because of displacement by certain drugs such as
to animal somatic cells and bone marrow cells in salicylates, sulphonamides, phenytoin, and some
humans, these effects are transient and antibacterials such as tetracycline,
reversible. In patients treated with methotrexate, chloramphenicol and para-aminobenzoic acid.
evidence is insufficient to permit conclusive These drugs, especially salicylates and
evaluation of any increased risk of neoplasia.
sulphonamides, whether antibacterial,
Methotrexate has been reported to cause hypoglycaemic or diuretic, should not be given
impairment of fertility, oligospermia, menstrual concurrently until the significance of these
dysfunction and amenorrhoea in humans, during findings is established.
and for a short period after cessation of therapy. Vitamin preparations containing folic acid or its
In addition, methotrexate causes embryotoxicity, derivatives may alter response to methotrexate.
abortion and foetal defects in humans. Therefore
the possible risks of effects on reproduction Methotrexate should be used with extreme
should be discussed with patients of caution in the presence of infection, peptic ulcer,
childbearing potential (see 'Warnings'). ulcerative colitis, debility, and in extreme youth
and old age. If profound leukopenia occurs
Patients undergoing therapy should be subject to during therapy, bacterial infection may occur or
appropriate supervision so that signs or become a threat. Cessation of the drug and
symptoms of possible toxic effects or adverse appropriate antibiotic therapy is usually
reactions may be detected and evaluated with
minimal delay. Pretreatment and periodic
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

indicated. In severe bone marrow depression, use of NSAIDs and salicylates has been
blood or platelet transfusions may be necessary. associated with fatal methotrexate toxicity.
Since it is reported that methotrexate may have However, patients using constant dosage
an immunosuppressive action, this factor must regimens of NSAIDs have received concurrent
be taken into consideration in evaluating the use doses of methotrexate without problems
of the drug where immune responses in a patient observed.
may be important or essential.
Treatment with more than one DMARD in
In all instances where the use of methotrexate is various regimens is being tried but there is little
considered for chemotherapy, the physician evidence available to assess benefit. A meta-
must evaluate the need and usefulness of the analysis of 5 different combinations of
drug against the risks of toxic effects or adverse DMARDs demonstrated that although efficacy
reactions. Most such adverse reactions are might be greater than single DMARDs, toxicity
reversible if detected early. When such effects or was also increased.
reactions do occur, the drug should be reduced
in dosage or discontinued and appropriate Renal tubular transport is also diminished by
probenecid and penicillins; use of these with
corrective measures should be taken according
methotrexate should be carefully monitored.
to the clinical judgement of the physician.
Reinstitution of methotrexate therapy should be A potential interaction may exist between
carried out with caution, with adequate methotrexate and proton-pump inhibitors (e.g.
consideration of further need for the drug and omeprazole, pantoprazole). Omeprazole may
alertness as to the possible recurrence of inhibit methotrexate clearance resulting in
toxicity. potentially toxic methotrexate levels.
Methotrexate given concomitantly with Severe bone marrow depression has been
radiotherapy may increase the risk of soft tissue reported following the concurrent use of
necrosis and osteonecrosis. methotrexate and co-trimoxazole or
trimethoprim. Concurrent use should probably
4.5 Interaction with other medicinal be avoided.
products and other forms of interaction
The use of nitrous oxide anaesthesia potentiates
Methotrexate is extensively protein bound and the effect of methotrexate on folate metabolism,
may be displaced by certain drugs such as yielding increased toxicity such as severe
salicylates, hypoglycaemics, diuretics, unpredictable myelosuppression, stomatitis and
sulphonamides, diphenylhydantoins, neurotoxicity. Severe neurotoxicity has
tetracyclines, chloramphenicol and p- particularly been reported with intrathecal
aminobenzoic acid, and the acidic anti- administration of methotrexate following nitrous
inflammatory agents, so causing a potential for oxide anaesthesia.
increased toxicity when used concurrently.
An increased risk of hepatitis has been reported
Concomitant use of other drugs with following the use of methotrexate and the
nephrotoxic or hepatotoxic potential (including acitretin metabolite, etretinate. Consequently,
alcohol) should be avoided. the concomitant use of methotrexate and
Vitamin preparations containing folic acid or its acitretin should be avoided.
derivatives may decrease the effectiveness of Methotrexate may increase the bioavailability of
methotrexate. mercaptopurine by interference with first-pass
Caution should be used when NSAIDs and metabolism.
salicylates are administered concomitantly with Concomitant application of methotrexate and
methotrexate. These drugs have been reported to theophylline can reduce theophylline clearance.
reduce the tubular secretion of methotrexate and
thereby may enhance its toxicity. Concomitant 4.6 Pregnancy and lactation
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

Abortion, foetal death, and/or congenital and severity of side effects are considered to be
anomalies have occurred in pregnant women dose-related. Adverse reactions as reported for
receiving methotrexate, especially during the the various systems are as follows:
first trimester of pregnancy. Methotrexate is
contraindicated in the management of psoriasis Skin: Severe, occasionally fatal, dermatologic
or rheumatoid arthritis in pregnant women. reactions including erythema multiforme,
Women of childbearing potential should not Stevens-Johnson syndrome, skin necrosis,
exfoliative dermatitis, epidermal necrolysis.
receive methotrexate until pregnancy is
Erythematous rashes, pruritus, urticaria,
excluded. For the management of psoriasis or
rheumatoid arthritis, methotrexate therapy in dermatitis, photosensitivity, pigmentary
women should be started immediately following changes, alopecia, ecchymosis, telangiectasia,
a menstrual period and appropriate measures acne, furunculosis. Lesions of psoriasis may be
should be taken in men or women to avoid aggravated by concomitant exposure to
conception during and for at least 6 months ultraviolet radiation. Skin ulceration in psoriatic
following cessation of methotrexate therapy. patients and rarely painful erosion of psoriatic
plaques have been reported. The recall
Both men and women receiving methotrexate phenomenon has been reported in both radiation
should be informed of the potential risk of and solar damaged skin.
adverse effects on reproduction. Women of
childbearing potential should be fully informed Blood: Bone marrow depression, leukopenia,
of the potential hazard to the foetus should they thrombocytopenia, anaemia
hypogammaglobulinaemia, haemorrhage from
become pregnant during methotrexate therapy.
various sites, septicaemia.
In cancer chemotherapy, methotrexate should
not be used in pregnant women or women of Alimentary System: Gingivitis, pharyngitis,
childbearing potential who might become stomatitis, mucostitis, anorexia, vomiting,
pregnant unless the potential benefits to the diarrhoea, haematemesis, melaena,
mother outweigh the possible risks to the foetus. gastrointestinal ulceration and bleeding,
pancreatitis, enteritis, hepatic toxicity resulting
Defective oogenesis or spermatogenesis,
transient oligospermia, menstrual dysfunction, in active liver atrophy, necrosis, fatty
and infertility have been reported in patients metamorphosis, periportal fibrosis, or hepatic
receiving methotrexate. cirrhosis. In rare cases the effect of methotrexate
on the intestinal mucosa has led to
Methotrexate is distributed into breast milk. malabsorption or toxic megacolon.
Because of the potential for serious adverse
Hepatic: Hepatic toxicity resulting in significant
reactions to methotrexate in nursing infants, a
elevations of liver enzymes, acute liver atrophy,
decision should be made whether to discontinue
nursing or the drug, taking into account the necrosis, fatty metamorphosis, hepatitis,
importance of the drug to the woman. periportal fibrosis, or cirrhosis or death may
occur, usually following chronic administration.
4.7 Effects on ability to drive and use
Urogenital System: Renal failure, azotaemia,
machines cystitis, haematuria, defective oogenesis or
spermatogenesis, transient oligospermia,
Not applicable menstrual dysfunction, infertility, abortion,
4.8 Undesirable Effects foetal defects, severe nephropathy. Vaginitis,
The most common adverse reactions include vaginal ulcers, cystitis, haematuria and
ulcerative stomatitis, leukopenia, nausea and nephropathy have also been reported.
abdominal distress. Although very rare, Pulmonary System: Acute or chronic
anaphylactic reactions to methotrexate have interstitial pneumonitis, often associated with
occurred. Others reported are malaise, undue blood eosinophilia, may occur and deaths have
fatigue, chills and fever, dizziness and decreased been reported (see Section 4.4 Special warnings
resistance to infection. In general, the incidence
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

and special precautions for use). Acute Adverse reactions following intrathecal
pulmonary oedema has also been reported after methotrexate are generally classified into three
oral and intrathecal use. Pulmonary fibrosis is groups, acute, subacute, and chronic. The acute
rare. A syndrome consisting of pleuritic pain and form is a chemical arachnoiditis manifested by
pleural thickening has been reported following headache, back or shoulder pain, nuchal rigidity,
high doses. and fever. The subacute form may include
paresis, usually transient, paraplegia, nerve
Central Nervous System: Headaches,
palsies, and cerebellar dysfunction. The chronic
drowsiness, blurred vision, aphasia, cognitive
form is a leukoencephalopathy manifested by
disorder, hemiparesis and convulsions have irritability, confusion, ataxia, spasticity,
occurred possibly related to haemorrhage or to occasionally convulsions, dementia,
complications from intraarterial catheterization. somnolence, coma, and rarely, death. There is
Convulsion, paresis, Guillain-Barre syndrome evidence that the combined use of cranial
and increased cerebrospinal fluid pressure have radiation and intrathecal methotrexate increases
followed intrathecal administration. the incidence of leukoencephalopathy.
Other reactions related to, or attributed to the use Additional reactions related to or attributed to
of methotrexate such as pneumonitis, metabolic the use of methotrexate such as osteoporosis,
changes, precipitation of diabetes, osteoporotic abnormal (usually 'megaloblastic') red cell
effects, abnormal changes in tissue cells and morphology, precipitation of diabetes, other
even sudden death have been reported. metabolic changes, and sudden death have been
There have been reports of leukoencephalopathy reported.
following intravenous methotrexate in high
4.9 Overdose
doses, or low doses following cranial-spinal
Calcium folinate (calcium leucovorin) is a
radiation.
potent agent for neutralizing the immediate toxic
Cardiac disorders: Pericarditis, pericardial effects of methotrexate on the haematopoietic
effusion system. Where large doses or overdoses are
given, calcium folinate may be administered by
Ear disorders: Tinnitus intravenous infusion in doses up to 75 mg within
Eye disorders: Conjunctivitis 12 hours, followed by 12 mg intramuscularly
every 6 hours for 4 doses. Where average doses
Infections and infestations: Opportunistic of methotrexate appear to have an adverse effect
infections (sometimes fatal e.g. fatal sepsis) 6-12 mg of calcium folinate may be given
have also been reported in patients receiving intramuscularly every 6 hours for 4 doses. In
methotrexate therapy for neoplastic and non- general, where overdosage is suspected, the dose
neoplastic diseases, Pneumocystis carinii of calcium folinate should be equal to or higher
pneumonia being the most common. Other than, the offending dose of methotrexate and
reported infections include, pneumonia, should be administered as soon as possible;
nocardiosis, histoplasmosis, cryptococcosis, preferably within the first hour and certainly
Herpes Zoster, Herpes Simplex, hepatitis and within 4 hours after which it may not be
cytomegalovirus infection, including effective.
cytomegaloviral pneumonia.
Other supporting therapy such as blood
Musculoskeletal and connective tissue transfusion and renal dialysis may be required.
disorders: Arthralgia/myalgia Effective clearance of methotrexate has been
Psychiatric disorders: Mood altered reported with acute, intermittent haemodialysis
using a high flux dialyser.
Vascular disorder: Vasculitis, hypotension,
thromboembolic events (e.g. thrombophlebitis,
pulmonary embolism, arterial, cerebral, deep
vein or retinal vein thrombosis).
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
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5. PHARMACOLOGICAL administration. Following oral doses of 0.06

PROPERTIES mg/kg or more, the drug had a serum half-life of
2-4 hours, but the serum half-life was reported to
5.1 Pharmacodynamic properties be increased to 8-10 hours when oral doses of
0.037 mg/kg were given.
Methotrexate is an antimetabolite which acts
principally by competitively inhibiting the Methotrexate does not appear to be appreciably
enzyme, dihydrofolate reductase. In the process metabolised. The drug is excreted primarily by
of DNA synthesis and cellular replication, folic the kidneys via glomerular filtration and active
acid must be reduced to tetrahydrofolic acid by transport. Small amounts are excreted in the
this enzyme, and inhibition by methotrexate faeces, probably via the bile. Methotrexate has a
interferes with tissue cell reproduction. Actively biphasic excretion pattern. If methotrexate
proliferating tissues such as malignant cells are excretion is impaired accumulation will occur
generally more sensitive to this effect of more rapidly in patients with impaired renal
methotrexate. It also inhibits antibody synthesis. function. In addition, simultaneous
administration of other weak organic acids such
Methotrexate also has immunosuppressive as salicylates may suppress methotrexate
activity, in part possibly as a result of inhibition clearance.
of lymphocyte multiplication. The mechanism(s)
of action in the management of rheumatoid 5.3 Preclinical safety data
arthritis of the drug is not known, although Not applicable.
suggested mechanisms have included
immunosuppressive and/or anti-inflammatory 6. PHARMACEUTICAL
effect. PARTICULARS
5.2 Pharmacokinetic properties
6.1 List of excipients
In doses of 0.1 mg (of methotrexate) per kg, Sodium chloride, sodium hydroxide and Water
methotrexate is completely absorbed from the for Injections
gastrointestinal tract; larger oral doses may be
incompletely absorbed. Peak serum 6.2 Incompatibilities
concentrations are achieved within 0.5 - 2 hours Immediate precipitation or turbidity results when
following intravenous, intramuscular or combined with certain concentrations of
intraarterial administration. Serum droperidol, heparin sodium, metoclopramide
concentrations following oral administration of hydrochloride, ranitidine hydrochloride in
methotrexate may be slightly lower than those syringe.
following intravenous injection.
Methotrexate is actively transported across cell 6.3 Shelf life
membranes. The drug is widely distributed into As packaged for sale – 2 years
body tissues with highest concentrations in the After dilution – Chemical and physical in-use
kidneys, gall bladder, spleen, liver and skin. stability has been demonstrated in dextrose 5%
Methotrexate is retained for several weeks in the and sodium chloride 0.9% infusion solutions for
kidneys and for months in the liver. Sustained 30 days at 4°C in PVC containers when
serum concentrations and tissue accumulation protected from light.
may result from repeated daily doses.
Methotrexate crosses the placental barrier and is From a microbiological point of view the
distributed into breast milk. Approximately 50% product should be used immediately. If not used
of the drug in the blood is bound to serum immediately, in-use storage times and conditions
proteins. prior to use are the responsibility of the user and
would normally not be longer than 24 hours at 2-
In one study, methotrexate had a serum half-life 8°C, unless dilution has taken place in controlled
of 2-4 hours following intramuscular and validated aseptic conditions.
Methotrexate 50mg/ 2ml Injection SMPC, Taj P harma ceutical s
METHOT REX ATE Taj Phar ma : U ses, Side E ffe cts, Intera ctions , Picture s, Warni ngs, METH OTRE XATE Dosage & Rx Info | METH OTRE XATE Uses , Side Effects -: Indications, Side E ffe cts, War nings, ME THOT REX ATE - Dr ug Informati on - Taj P harma, M ETHOT REXATE dose Taj pharma ceuti cals METH OTRE XATE interactions, Taj Phar mace utical METH OTRE XATE contraindications, METH OT REXATE price, METH OTREXATE Taj P harma M ethotrexate 2 mg, 5 mg Tabl ets. SMPC- Taj Phar ma . Stay connecte d to all update d on MET HOT REXATE Taj Phar ma ceuticals Taj phar mace uticals Hydera bad. Cancer

6.4 Special precautions for storage

As packaged for sale –
For the 50 mg/2 ml, 250 mg/10 ml and 500
mg/20 ml presentations: Do not store above
25°C. Do not freeze. Keep container in the outer
carton.
For the 1 g/40 ml presentation : Store at 2°C -
8°C. Keep container in the outer carton.
After dilution – see 6.3.
6.5 Nature and contents of container
50 mg/2 ml - Conventional or Onco-Tain® Type
I glass vial with rubber stopper, aluminium seal
and plastic 'flip-off' top. Packs containing 5
vials.
6.6 Special precautions for disposal and
other handling
Single use only. Discard any unused contents.
Onco-Vials® should be used with an appropriate
Faulding administration device.
7. MANUFACTURER:

Manufactured in India by:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Survey No.188/1 to 189/1,190/1 to 4,
Athiyawad, Dabhel,
Daman- 396210 (INDIA)