mph Bangladesh


Methotrexate

(meth'' oh trex' ate) 

PCI / LCI  : Contraindicated in pregnancy and lactation (breast feeding)

Molecule Info

| See TERMINOLOGY & ABBREVIATIONS |
WARNING

METHOTREXATE SHOULD BE USED ONLY BY PHYSICIANS WHOSE KNOWLEDGE AND EXPERIENCE INCLUDE THE USE OF ANTIMETABOLITE THERAPY.

BECAUSE OF THE POSSIBILITY OF SERIOUS TOXIC REACTIONS (WHICH CAN BE FATAL):

METHOTREXATE SHOULD BE USED ONLY IN LIFE THREATENING NEOPLASTIC DISEASES, OR IN PATIENTS WITH PSORIASIS OR RHEUMATOID ARTHRITIS WITH SEVERE, RECALCITRANT, DISABLING DISEASE WHICH IS NOT ADEQUATELY RESPONSIVE TO OTHER FORMS OF THERAPY.

DEATHS HAVE BEEN REPORTED WITH THE USE OF METHOTREXATE IN THE TREATMENT OF MALIGNANCY, PSORIASIS, AND RHEUMATOID ARTHRITIS.

PATIENTS SHOULD BE CLOSELY MONITORED FOR BONE MARROW, LIVER, LUNG AND KIDNEY TOXICITIES.

PATIENTS SHOULD BE INFORMED BY THEIR PHYSICIAN OF THE RISKS INVOLVED AND BE UNDER A PHYSICIAN'S CARE THROUGHOUT THERAPY.

Methotrexate has been reported to cause fetal death and/or congenital anomalies. Therefore, it is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant women with psoriasis or rheumatoid arthritis should not receive methotrexate.

Methotrexate elimination is reduced in patients with impaired renal function, ascites, or plural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration.

Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs). (See PRECAUTIONS: Drug Interactions.)

Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population. (See PRECAUTIONS: Organ System Toxicity: Hepatic )

Methotrexate-induced lung disease is a potentially dangerous lesion, which may occur acutely at any time during therapy and which has been reported at doses as low as 7.5 mg/week. It is not always fully reversible. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.

Diarrhea and ulcerative stomatitis require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.

Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue methotrexate first and, if the lymphoma does not regress, appropriate treatment should be instituted.

Like other cytoxic drugs, methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors. Appropriate supportive and pharmacologic measures may prevent or alleviate this complication.

Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy.

Potentially fatal opportunistic infections, especially Pneumocystis carinii pneumonia, may occur with methotrexate therapy.

Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.

Content(s) & Description

Methotrexate.

Methotrexate BP and sodium hydroxide BP in water for injections.
Sodium chloride BP is added to the 50 mg/2 mL presentation to render it isotonic. Methotrexate 1000 mg/10 mL is hypertonic.
Methotrexate is (S)-2-[4-[[(2,4-diaminopteridin-6-yl) methyl] methylamino] benzoylamino] pentanedioic acid. It is a yellow or orange, crystalline powder, practically insoluble in water, alcohol, ether and ethylene chloride. It dissolves in dilute solutions of mineral acids and dilute solutions of alkali hydroxides and carbonates.
Molecular Formula: C20H22N8O5; molecular weight: 454.4.

Indication(s)
Antineoplastic Chemotherapy: Treatment of breast cancer, gestational choriocarcinoma and in patients with chorioadenoma destruens and hydatidiform mole. Palliation of acute and subacute lymphocytic and meningeal leukaemia. Greatest effect has been observed in palliation of acute lymphoblastic (stem cell) leukaemias. In combination with corticosteroids, methotrexate may be used for induction of remission. Methotrexate is now most commonly used for the maintenance of induced remissions. It is also effective in the treatment of the advanced stages (III and IV, Peters Staging System) of lymphosarcoma, particularly in children and in advanced cases of mycosis fungoides.
High-Dose Therapy: The use of very high doses is made possible by vials for injection containing 500 mg and 1000 mg (See Precautions). Diseases treated with these doses administered in the form of single-drug or combination therapy, include osteogenic sarcoma, acute leukaemia, bronchogenic carcinoma and epidermoid carcinoma of the head and neck.
Psoriasis Chemotherapy (See Warnings and Precautions): Because of the high risk attending to its use, Methotrexate is only indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultations.
Dosage & Administration
Because of its potential to cause severe toxicity, methotrexate therapy requires close supervision with particular caution to distinguish between daily and weekly dosage regimens. Weekly dosage prescriptions should specify a particular day of the week.
Antineoplastic Chemotherapy: Methotrexate may be administered by IM, IV or intrathecal routes.
Methotrexate 1000 mg/10 mL should not be used intrathecally as the solution is hypertonic.
For intrathecal injection, Methotrexate should be diluted to a strength of 1 mg/mL with an appropriate preservative-free medium eg, sodium chloride injection 0.9%.
For conversion of mg/kg body weight to mg/m2 of body surface area or the reverse, a ratio of 1:30 is given as a guideline. The conversion factor varies between 1:20 and 1:40 depending on age and body build.
Breast Carcinoma: 40 mg/m2 IV on only the 1st and 8th days. Prolonged cyclic combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil has given good results when used as adjuvant treatment to radical mastectomy in primary breast cancer with positive axillary lymph nodes.
Choriocarcinoma and Similar Trophoblastic Diseases: 15-30 mg IM daily for a 5-day course. Such courses are usually repeated 3-5 times as required with a rest period of ≥1 week interposed between courses, until any manifesting toxic symptoms subside. The effectiveness of therapy is ordinarily evaluated by 24-hr quantitative analysis of urinary chorionic gonadotrophin hormone (βHCG), which should return to normal or <50 units/24 hrs usually after the 3rd or 4th course and usually followed by a complete resolution of measurable lesions in 4-6 weeks. One to two courses of methotrexate after normalisation of βHCG is usually recommended. Before each course of methotrexate, careful clinical assessment is essential. Cyclic combination therapy of methotrexate with other antitumour drugs has been reported as being useful. Since hydatidiform mole may precede or be followed by choriocarcinoma, prophylactic chemotherapy with methotrexate has been recommended.
Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrexate is administered in these disease states in doses similar to those recommended for choriocarcinoma.
Leukaemia: Induction: 3.3 mg/m2 in combination with prednisolone 60 mg/m2given daily, remission occurred in 50% of patients treated, usually within a period of 4-6 weeks.
Acute lymphatic (lymphoblastic) leukaemia in children and young adolescents is the most responsive to present day chemotherapy. In young adults and older patients, clinical remission is more difficult to obtain and early relapse is more common. In chronic lymphatic leukaemia, the prognosis for adequate response is less encouraging. Methotrexate alone or in combination with steroids was used initially for induction of remission of lymphoblastic leukaemias. More recently, corticosteroid therapy in combination with other antileukaemic drugs or in cyclic combination therapy including methotrexate, has produced rapid and effective remissions.
Maintenance Therapy: 30 mg/m2 2 times weekly IM or 2.5 mg/kg IV every 14 days.
Methotrexate alone or in combination with other agents, appears to be the drug of choice for securing maintenance of drug-induced remissions. When remission is achieved and supportive care has produced general clinical improvement, maintenance therapy is initiated. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen.
Meningeal Leukaemia: Patients with leukaemia are subject to leukaemic invasion of the central nervous system. This may manifest characteristic signs or symptoms or may remain silent and be diagnosed only by examination of the cerebrospinal fluid, which contains leukaemic cells in such cases. Therefore, the cerebrospinal fluid should be examined in all leukaemic patients. Since passage of methotrexate from blood serum to the cerebrospinal fluid is minimal, for adequate therapy methotrexate is administered intrathecally.
It is now common practice to administer methotrexate intrathecally as prophylaxis in all cases of lymphocytic leukaemia.
By intrathecal injection, the distribution of methotrexate is in the cerebrospinal fluid, the volume of which is dependent on age and not body surface area. The cerebrospinal fluid is at 40% of adult volume at birth and reaches adult volume in several years.
Recommended Doses: Children ≥3 years: 12 mg; 2 years: 10 mg; 1 year: 8 mg; <1 year: 6 mg.
There is some indication that infants <4 months and adults ≥70 years may have increased acute toxicity with doses recommended and dose reduction may be indicated. The solution is made in a strength of 1 mg/mL with an appropriate, sterile, preservative-free medium eg, sodium chloride injection BP 0.9%.
For the treatment of meningeal leukaemia, intrathecal methotrexate may be given at intervals of 2-5 days however, there is some indication that doses given at intervals of <1 week may result in increased toxicity.
Methotrexate is administered until the cell count of the cerebrospinal fluid returns to normal. At this point, 1 additional dose is advisable.
For prophylaxis against meningeal leukaemia, the dosage is the same as for treatment except for the intervals of administration. On this subject, it is advisable for the physician to consult the medical literature.
Large doses may cause convulsions. Untoward side effects may occur with any given intrathecal injection and are commonly neurological in character.
Methotrexate given by intrathecal route appears significantly in the systemic circulation and may cause systemic methotrexate toxicity. Therefore, systemic antileukaemic therapy with methotrexate should be appropriately adjusted, reduced or discontinued. Focal leukaemic involvement of the central nervous system may not respond to intrathecal chemotherapy and is best treated with radiotherapy.
Lymphomas: Recommended Dosage: 10-25 mg/day orally for 4-8 days. In Burkitt's tumour, stages I-II, methotrexate has produced prolonged remission in some cases. In stage III, methotrexate is commonly given concomitantly with other antitumour agents. Treatment in all stages usually consists of several courses of the drug interposed with 7- to 10-day rest periods.
Stage III Lymphosarcomas: Combined Drug Therapy with Methotrexate: 0.625-2.5 mg/kg daily.
Hodgkin's disease responds poorly to methotrexate and to most types of chemotherapy.
Mycosis Fungoides: 50 mg IM weekly or 25 mg IM twice weekly as an alternative to oral therapy may be given.
High-Dose Therapy (See Precautions): Dosage regimens have varied considerably in different studies, the nature and severity of the disease and the previous experience of the investigator are some of the factors influencing the choice of dosage and the duration of therapy. It must be emphasised that high dosages should be used only by qualified specialists and in hospitals where the necessary facilities are available.
Psoriasis Chemotherapy: The patient should be fully informed of the risks involved and should be under constant supervision of the physician. Assessment of renal function, liver function and blood elements should be made by history, physical examination and laboratory tests (eg, full blood count, urinalysis, serum creatinine, liver function studies and liver biopsy if indicated) before beginning methotrexate, periodically during methotrexate therapy and before reinstituting methotrexate therapy after a rest period. Appropriate steps should be taken to avoid conception during and for at least 3 months following methotrexate therapy.
The commonly used injectable dosage schedule is by weekly parenteral intermittent large doses. The schedules should be continually tailored to the individual patient. Dose schedules cited as follows pertain to an average 70-kg adult. An initial test dose 1 week prior to initiation of therapy is recommended to detect any idiosyncrasy. A suggested dose range is 5-10 mg parenterally.
Recommended Starting Dose: Adults 70 kg: Weekly Single IM or IV Dose Schedules: 10-25 mg/week until adequate response is achieved. With this dosage schedule, 50 mg/week should ordinarily not be exceeded.
Dosage may be gradually adjusted to achieve optimal clinical response, but not to exceed the maximum stated for each schedule. Once optimal clinical response has been achieved, the dosage schedule should be reduced to the lowest possible amount of drug and to the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy, which should be encouraged.
Overdose
Discontinue methotrexate at the 1st sign of ulceration or bleeding, diarrhoea or marked depression of the haematopoietic system.
Symptoms commonly reported following oral overdose include those symptoms and signs reported at pharmacological doses, particularly haematological and gastrointestinal reactions. For example, leucopenia, thrombocytopenia, anaemia, pancytopenia, bone marrow suppression, mucositis, oral ulceration, nausea, vomiting, gastrointestinal ulceration and bleeding. In some cases, no symptoms were reported. There have been reports of death following overdose. In these cases, events eg, sepsis or septic shock, renal failure and aplastic anaemia were also reported.
As soon as possible after an inadvertent overdosage of methotrexate, calcium folinate (leucovorin calcium) should be given at 10 mg/m2 IV or IM every 6 hrs until the serum methotrexate levels are <10-8 M. In the presence of gastric stasis or obstruction leucovorin should be administered parenterally. Concomitant hydration (3 L/day) and urinary alkalinisation with sodium bicarbonate should be employed. The bicarbonate dose should be adjusted to maintain a urinary pH ≥7. Serum samples should be assayed for creatinine levels and methotrexate levels at 24-hr intervals. If the 24-hr serum creatinine level has increased 50% over baseline or if the 24-hr methotrexate level is >5 x 10-6 M or the 48-hr methotrexate level is ≥9 x 10-7 M, the doses of calcium folinate should be increased to 100 mg/m2 IV every 3 hrs until the methotrexate level is <10-8 M. The infusion rate of calcium folinate should not exceed 16 mL (calcium folinate 160 mg)/minute. Patients with significant 3rd space accumulations should be considered high-risk and monitored until serum methotrexate levels are <10-8 M regardless of their 24-hr serum concentration.
The previously mentioned statements on calcium folinate dosage do not apply with high-dosage methotrexate therapy. The dosages of calcium folinate have varied in different studies and the published literature on high-dosage methotrexate should be consulted.
Neither standard haemodialysis nor peritoneal dialysis has been shown to significantly improve methotrexate elimination. Some clearance of methotrexate may be obtained by haemodialysis if the patient is totally anuric and no other therapeutic options are available. Effective clearance of methotrexate has been reported with acute, intermittent haemodialysis using a high-flux dialyser.
Contraindications
Pregnant patients with psoriasis. Psoriasis patients with severe hepatic disorders and renal impairment; alcoholism or alcoholic liver disease; overt or laboratory evidence of immunodeficiency; bone marrow depression or preexisting blood dyscrasias eg bone marrow hypoplasia, leucopenia, thrombocytopenia or anaemia; serious infections; peptic ulcer disease or ulcerative colitis; known hypersensitivity to methotrexate or to any of the excipients of Methotrexate Pfizer.
Radiotherapy to the central nervous system should not be given concurrently with intrathecal methotrexate.
During lactation: Methotrexate passes into breast milk and is contraindicated during breastfeeding. The highest breast milk to plasma concentration ratio reached was 0.08:1. Because of the potential for serious adverse reactions from methotrexate in breastfed infants, it is contraindicated in nursing mothers.
Special Precautions
Close monitoring for toxicity is mandatory, particularly in high dose therapy or where drug elimination could be impaired (renal impairment, pleural effusion, ascites). Deaths have been reported with use of methotrexate in the treatment of malignancy and psoriasis.
Methotrexate should be used with extreme caution in the presence of debility and in extreme youth or age. Due to diminished hepatic and renal functions as well as decreased folate states in elderly patients, relatively low doses should be considered and these patients should be closely monitored.
The risk of developing acute hepatitis and chronic hepatotoxicity in psoriatic patients seems to be correlated not only to the cumulative dose of methotrexate but also to the presence of concurrent conditions eg, alcoholism, obesity, diabetes, advanced age and arsenical compounds. Chronic toxicity is potentially fatal; it generally occurs after prolonged use (generally ≥2 years) and after a total cumulative dose of at least 1.5 g.
In patients with malignant disease who have preexisting bone marrow aplasia, leucopenia, thrombocytopenia or anaemia, methotrexate should be used with caution, if at all.
Methotrexate given concomitantly with radiation may increase the risk of soft tissue necrosis and osteonecrosis.
High-Dose Therapy: Methotrexate has been used in very high dosage followed by leucovorin rescue in the experimental treatment of certain neoplastic disease. This procedure is investigational and hazardous. It should not be attempted outside of facilities where the necessary expertise and resources have been assembled. The recent published literature should be consulted. Large doses should not be used in patients with impaired renal function or a 3rd-space reservoir eg, ascites or large pleural effusion, because rapid drug excretion is important in limiting toxicity. Careful monitoring of renal function and methotrexate serum levels is required in order to reveal impending toxicity. Administration of calcium folinate is mandatory in high-dose methotrexate therapy. The administration of calcium folinate, hydration and urine alkalinisation should be carried out with constant monitoring of the toxic effects and the elimination of methotrexate.
Check the following before and during use: Methotrexate may cause renal damage that may lead to acute renal failure. Close attention to renal function including adequate hydration, urine alkalinisation and measurement of serum methotrexate and renal function are recommended.
Methotrexate is excreted principally by the kidneys. Its use in the presence of impaired renal function may result in accumulation of toxic amounts or even additional renal damage. The patient's renal status should be determined prior to and periodically during methotrexate therapy and proper caution exercised should significant renal impairment be disclosed. Drug dosage should be reduced or discontinued until renal function is improved or restored. The urine should be kept alkaline throughout therapy with methotrexate (methotrexate is a weak acid and tends to precipitate at urine pH <6).
High doses of methotrexate used in the treatment of osteosarcoma may cause renal damage leading to acute renal failure. Nephrotoxicity is due primarily to the precipitation of methotrexate and 7-hydroxymethotrexate in the renal tubules. Close attention to renal function including adequate hydration, using alkalinisation and measurement of serum methotrexate and creatinine levels are essential for safe administration.
Vomiting, diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy; otherwise, haemorrhagic enteritis and death from intestinal perforation may occur. Pulmonary symptoms (especially a dry non-productive cough) or a nonspecific pneumonitis occurring during methotrexate therapy may be indicative of a potentially dangerous lesion and require interruption of treatment and careful investigation. Although clinically variable, the typical patient with methotrexate-induced lung disease presents with fever, cough, chest pain, dyspnoea, hypoxaemia and an infiltrate on x-ray. This lesion can occur at all dosages. Infection (including pneumonia) needs to be excluded.
Systemic high doses or intrathecal administration of methotrexate may cause significant central nervous system toxicity. Patients should be closely monitored for neurologic symptoms and if these occur, treatment should be discontinued and appropriate therapy instituted.
Methotrexate has the potential for serious toxicity. Toxic effects may be related in frequency and severity to dose or frequency of administration, but have been seen at all doses. Because the toxic effects can occur at any time during therapy, it is necessary to follow the patients on methotrexate therapy very closely. When such reactions do occur, methotrexate should be reduced in dosage or discontinued and appropriate corrective measures should be taken. If methotrexate therapy is reinstituted, it should be carried out with utmost caution, with adequate consideration of further need for methotrexate and with increased alertness as to possible recurrence of toxicity.
Pre-treatment and periodic haematologic studies are essential to the use of methotrexate in chemotherapy because of its common effect of haematopoietic suppression, manifesting as anaemia, aplastic anaemia, pancytopenia, leukopenia, neutropenia and/or thrombocytopenia. This may occur abruptly and on apparent safe dosage and any profound drop in blood cell count indicates immediate stoppage of methotrexate and appropriate therapy. If profound leucopenia occurs during therapy, bacterial infection may occur or become a threat. Cessation of methotrexate and appropriate antibiotic therapy is usually indicated. In severe bone marrow depression, blood or platelet transfusions may be necessary.
Methotrexate causes hepatotoxicity, liver fibrosis and cirrhosis, but generally only after prolonged use. Liver enzyme elevations are frequently seen. These are usually transient and asymptomatic and do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histological changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. Periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment.
In psoriasis, liver damage and function tests, including serum albumin and prothrombin time, should be performed several times prior to dosing. Liver function tests are often normal in developing fibrosis or cirrhosis. These lesions may be detectable only by biopsy. It is recommended to obtain a liver biopsy at: Before start of therapy or shortly after initiation of therapy (2-4 months); after a total cumulative dose of 1.5 g; and after each additional 1-1.5 g. In case of moderate fibrosis or any cirrhosis, discontinue methotrexate; mild fibrosis normally suggests a repeat biopsy in 6 months. Milder histologic findings eg, fatty change and low-grade portal inflammation are relatively common before the start of therapy. Although these mild changes are normally not a reason to avoid or discontinue methotrexate therapy, it should be used with caution.
In general, the following laboratory tests are recommended as part of essential clinical evaluation and appropriate monitoring of patients chosen for or receiving methotrexate therapy; a full blood count, haematocrit; urinalysis; renal function tests; liver function tests. A chest x-ray is also recommended. The tests should be performed prior to therapy, at appropriate periods during therapy and after termination of therapy. During initial or changing doses, or during periods of increased risk of elevated methotrexate blood levels (eg, dehydration), more frequent monitoring may also be indicated. During therapy for psoriasis, monitoring of these parameters is recommended: Haematology at least monthly, and liver and renal function every 1-2 months. More frequent monitoring is usually indicated during antineoplastic therapy. It may be useful or important to perform liver biopsy or bone marrow aspiration studies where high dose or long-term therapy is being followed.
Methotrexate exits slowly from the 3rd-space compartments (eg, pleural effusions or ascites). This results in a prolonged terminal phase t½ and unexpected toxicity. In patients with significant 3rd-space accumulation, it is advisable to evacuate the fluid before treatment and to monitor plasma methotrexate levels.
Information for Patients: Patients should be informed of the early signs and symptoms of toxicity, of the need to see a physician promptly if they occur and the need for close follow-up, including periodic laboratory tests to monitor toxicity.
Patients should be informed of the potential benefit and risk in the use of methotrexate. The risk of effects on reproduction should be discussed with both male and female patients taking methotrexate.
Patients receiving methotrexate should avoid excessive unprotected exposure to sun or sunlamps because of possible photosensitivity reactions.
Infection or Immunological States: Methotrexate should be used with extreme caution in the presence of active infection, peptic ulcer and ulcerative colitis. Methotrexate therapy has immunosuppressive activity which can potentially lead to serious or even fatal infections. This factor must be taken into consideration in evaluating the use of methotrexate where immune responses in a patient may be important or essential.
Pneumonia (in some cases leading to respiratory failure) may occur. Potentially fatal opportunistic infections, especially Pneumocystis cariniipneumonia, may occur with methotrexate therapy. When a patient presents with pulmonary symptoms, the possibility of Pneumocystis carinii pneumonia should be considered.
It is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency (see Contraindications).
Immunisation may be ineffective when given during methotrexate therapy. Immunisation with live virus vaccines is generally not recommended. There have been reports of disseminated vaccinia infections after smallpox immunisation in patients receiving methotrexate therapy.
Effects on the Ability to Drive or Operate Machinery: Adverse reactions to methotrexate eg, dizziness and fatigue may affect the ability to drive or operate machinery.
Carcinogenicity and Mutagenicity: No controlled human data exist regarding the risk of neoplasia with methotrexate. Methotrexate has been evaluated in a number of animal studies for carcinogenic potential with inconclusive results.
There is evidence that methotrexate causes chromosomal damage to animal somatic cells and human bone marrow cells. In vitro, methotrexate caused chromosomal aberrations in Chinese hamster A(T1) C1-3 cells, induced morphological transformation in mouse C3H/10T½ clone 8 cells and was associated with an increased incidence of large colony mutants at the tk locus in L5178Y/tk± mouse lymphoma cells. In vivo, it caused an increased incidence of polychromatic erythrocytes in mice and a transient and reversible increase in chromosomal aberrations in human bone marrow cells. The clinical significance of these findings is uncertain.
Benefit should be weighed against this potential risk before using methotrexate alone or in combination with other drugs, especially in children or young adults. Methotrexate causes embryotoxicity, abortion and fetal defects in humans. It has also been reported to cause impairment of fertility, oligospermia and menstrual dysfunction in humans, during and for a short period after cessation of therapy.
During pregnancy: Pregnancy Category D: Methotrexate has caused fetal death and/or congenital abnormalities; therefore, it is not recommended in women of childbearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant psoriatic women should not receive methotrexate (see Contraindications). Women of childbearing potential should not be started on methotrexate until pregnancy is excluded and should be fully counselled on the serious risk to the fetus should they become pregnant while undergoing treatment.
Pregnancy should be avoided if either partner is receiving methotrexate, during and for a minimum of 3 months after therapy has ceased, although the optimal time interval between the cessation of methotrexate treatment of either partner and pregnancy, has not been clearly established.
Adverse Drug Reaction(s)
The major toxic effects of methotrexate occur on normal, rapidly proliferating tissues, particularly the bone marrow and gastrointestinal tract. Ulcerations of the oral mucosa are usually the earliest signs of toxicity. The most common adverse reactions include ulcerative stomatitis, leucopenia, nausea and abdominal distress. Others reported are malaise, undue fatigue, chills and fever, headaches, dizziness, drowsiness, tinnitus, blurred vision, eye discomfort and decreased resistance to infection. In general, the incidence and severity of side effects are considered to be dose and frequency related. Adverse reactions as reported for the various systems are as follows: Dermatological and Hypersensitivity: Dermatitis, erythematous rashes, pruritus, urticaria, photosensitivity, depigmentation/hyperpigmentation, alopecia, vasculitis, petechiae, ecchymosis, telangiectasia, acne, folliculitis, furunculosis, nail changes. Burning and erythema may appear in psoriatic areas for 1-2 days following each dose. Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Skin ulceration has been reported in psoriatic patients and a few cases of anaphylactoid reactions have been reported. 
Severe, occasionally fatal, dermatological reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin ulceration/necrosis and erythema multiforme have been reported in children and adults within days of methotrexate administration. Reactions were noted after single or multiple doses of methotrexate in patients with neoplastic and non-neoplastic diseases.
Haematological and Lymphatic System: Bone marrow depression, leucopenia, neutropenia, thrombocytopenia, decrease in serum albumin, anaemia (including aplastic anaemia), eosinophilia, pancytopenia, agranulocytosis, hypogammaglobulinaemia, lymphadenopathy and proliferative disorders. Clinical sequelae eg, fever, infections, haemorrhage from various sites and septicaemia may be expected. Megaloblastic anaemia has also been reported, mainly in elderly patients receiving long-term methotrexate therapy. Folate supplementation may permit continuation of methotrexate therapy with resolution of anaemia.
Gastrointestinal: Mucositis (gingivitis, pharyngitis, stomatitis, glossitis), anorexia, nausea, vomiting, diarrhoea, abdominal distress, haematemesis, melaena, gastrointestinal tract ulceration and bleeding, intestinal perforation, enteritis, acute and chronic hepatic toxicity resulting in acute liver atrophy, necrosis, fatty metamorphosis, acute hepatitis, periportal fibrosis, hepatic cirrhosis, pancreatitis, elevated liver enzymes, decreased serum albumin and hepatic failure. In rare cases, the effect of methotrexate on the intestinal mucosa has led to malabsorption or toxic megacolon. Alteration of liver function tests (increases in transaminases and LDH levels) is commonly reported but usually resolves within 1 month after cessation of therapy.
Urogenital: Renal failure, dysuria, azotaemia, cystitis, haematuria, defective oogenesis or spermatogenesis, transient oligospermia, urogenital or menstrual dysfunction, infertility, abortion, fetal defects, fetal death, severe nephropathy, vaginitis, vaginal discharge.
Cardiovascular: Pericarditis, vasculitis, pericardial effusion, hypotension and thromboembolic events (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis and pulmonary embolism).
Neurological: Headaches, drowsiness, blurred vision, lethargy, motor dysfunction, cranial nerve palsies, leukoencephalopathy, encephalopathy and coma have been reported. Aphasia, hemiparesis, paresis, convulsions and Guillain-Barre syndrome, increased cerebrospinal fluid pressures have followed intrathecal administration.
Following low doses, occasional patients have reported transient subtle cognitive dysfunction, mood alteration or unusual cranial sensations. Cognitive impairment has been recorded in children who received intrathecal methotrexate together with cranial irradiation. There have been reports of leucoencephalopathy following IV administration of methotrexate in high doses to patients who have had craniospinal irradiation.
After the intrathecal or high-dose use of methotrexate, the central nervous system toxicity which may occur can be classified as follows: Chemical arachnoiditis manifested by symptoms eg, headache, back pain, nuchal rigidity and fever; paresis, usually transient, manifested by paraplegia and increased cerebrospinal fluid pressure associated with involvement with ≥1 spinal nerve roots; a delayed syndrome occurring months to years after treatment characterised by necrotising leucoencephalopathy and manifested by confusion, stupor, irritability, somnolence, ataxia, dementia, occasionally major convulsions and rarely, death. The effects are dose-related and occur particularly when intrathecal methotrexate is given at doses >50 mg in combination with cranial irradiation and systemic methotrexate therapy.
Pulmonary: Interstitial pneumonitis deaths, interstitial fibrosis and reversible eosinophilic pulmonary infiltrates have been reported and chronic interstitial obstructive pulmonary disease and alveolitis have occasionally occurred.
Manifestations of methotrexate-induced pulmonary toxicity commonly include fever, cough (especially dry and non-productive), dyspnoea, chest pain, hypoxaemia and/or radiological evidence of pulmonary infiltrates (usually diffuse and/or alveolar).
Ophthalmic: Conjunctivitis, serious visual changes of unknown aetiology including transient blindness.
Carcinogenicity: Cytotoxic drugs have been reported to be associated with an increased risk of development of secondary tumours in humans. Reports of lymphoma, including reversible lymphomas and tumour lysis syndrome have been documented in patients treated with methotrexate. Evidence of chromosomal damage to animal somatic cells and human bone marrow cells has been reported with methotrexate.
Infections: There have been case reports of sometimes fatal opportunistic infections in patients receiving methotrexate therapy for neoplastic and non-neoplastic diseases. Pneumocystis carinii pneumonia was the most common infection. Other reported infections included pneumonia, sepsis, nocardiosis, histoplasmosis, cryptococcosis, Herpes zoster, H. simplex hepatitis, disseminated H. simplex, fatal sepsis and cytomegalovirus, including cytomegaloviral pneumonia.
Others: Other reactions related to, or attributed to, the use of methotrexate are metabolic changes, precipitation of diabetes, osteoporotic effects (including aseptic necrosis of the femoral head), abnormal tissue cell changes, arthralgia/myalgia, proteinuria, nodulosis, stress fracture, loss of libido, impotence and even sudden death have been reported.
Drug Interactions
Methotrexate is bound in part to serum albumin after absorption and toxicity may be increased because of displacement by certain drugs eg, salicylates, sulphonamides, sulphonylureas, phenylbutazone and phenytoin. Renal tubular transport is also diminished by probenecid; use of methotrexate with this drug should be carefully monitored. Hypolipidemic compounds eg, cholestyramine proved preferential binding substrates compared to serum proteins when given in combination with methotrexate.
Penicillins and sulphonamides may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant haematologic and gastrointestinal toxicity have been observed with methotrexate. Use of methotrexate with penicillins and sulphonamides should be carefully monitored.
Nonsteroidal anti-inflammatory drugs (NSAIDs) should not be administered prior to or concomitantly with the high-dose methotrexate used in the treatment of osteosarcoma. Concomitant administration of NSAIDs with high-dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe haematological and gastrointestinal toxicity.
Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate. These drugs have been reported to reduce tubular secretion of methotrexate in an animal model and may enhance its toxicity.
Unexpectedly severe (sometimes fatal) marrow suppression and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high doses) with some NSAIDs including aspirin and other salicylates, asapropazone, diclofenac, indomethacin and ketoprofen. Naproxen has been reported not to affect the pharmacokinetics of methotrexate but a fatal interaction has been reported.
Folate deficiency states may increase methotrexate toxicity. Trimethoprim alone or in combination with sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by decreased tubular secretion and/or an additive antifolate effect. Increased bone marrow suppression has also been reported in patients receiving methotrexate and pyrimethamine. Conversely, multivitamin preparations including folic acid or its derivatives may alter responses to methotrexate and should not be given concomitantly.
Methotrexate is often used in combination with other cytotoxic drugs. Additive toxicity may be expected in chemotherapy regimens which combine drugs with similar pharmacologic effects and special monitoring should be made with regard to bone marrow depression, renal, gastrointestinal and pulmonary toxicity. The dosage of methotrexate should be adjusted if it is used in combination with other chemotherapeutic agents with overlapping toxicities.
In the treatment of patients with osteosarcoma, caution must be exercised if high-dose methotrexate is administered in combination with a potentially nephrotoxic chemotherapeutic agent (eg, cisplatin). Oral antibiotics eg, tetracycline, chloramphenicol and non-absorbable broad-spectrum antibiotics, may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.
The administration of asparaginase has been reported to antagonise the effect of methotrexate. An increased risk of hepatotoxicity has been reported when etretinate and other potential hepatotoxins eg, leflunomide, azathioprine, retinoids and sulfasalazine are given concurrently with methotrexate. The use of nitrous oxide anaesthesia potentiates the effect of methotrexate on folate metabolism, yielding severe unpredictable myelosuppression and stomatitis. This effect can be reduced by the use of calcium folinate.
Methotrexate in combination with leflunomide may also increase the risk of pancytopenia. Amiodarone administration to patients receiving methotrexate treatment for psoriasis has induced ulcerative skin lesions.
Methotrexate increases the plasma levels of mercaptopurine. Combination of methotrexate and mercaptopurine may therefore require dose adjustment.
Skin cancer has been reported in a few patients with psoriasis or mycosis fungoides (a cutaneous T-cell lymphoma) receiving concomitant treatment with methotrexate plus PUVA therapy (methoxalen and ultraviolet light).
Care should be exercised whenever packed red blood cells and methotrexate are given concurrently. Patients receiving 24-hr methotrexate infusion and subsequent transfusions have showed enhanced toxicity probably resulting from prolonged serum-methotrexate concentrations.
Methotrexate is an immunosuppressant and may reduce immunological response to concurrent vaccination. Severe antigenic reactions may occur if a live vaccine is given concurrently.
Methotrexate may decrease the clearance of theophylline; theophylline levels should be monitored when used concurrently with methotrexate.
Incompatibilities: Methotrexate has been reported to be incompatible with cytarabine, fluorouracil and prednisolone.
Pregnancy Category (FDA)

Use in pregnancy: Pregnancy Category D.

Methotrexate has caused fetal death and/or congenital abnormalities; therefore, it is not recommended in women of childbearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant psoriatic women should not receive methotrexate (see Contraindications). Women of childbearing potential should not be started on methotrexate until pregnancy is excluded and should be fully counselled on the serious risk to the fetus should they become pregnant while undergoing treatment.
Pregnancy should be avoided if either partner is receiving methotrexate, during and for a minimum of 3 months after therapy has ceased, although the optimal time interval between the cessation of methotrexate treatment of either partner and pregnancy, has not been clearly established.

Use in lactation: Methotrexate passes into breast milk and is contraindicated during breastfeeding. The highest breast milk to plasma concentration ratio reached was 0.08:1. Because of the potential for serious adverse reactions from methotrexate in breastfed infants, it is contraindicated in nursing mothers.

Caution For Usage
Handling Precautions: As with all antineoplastic agents, trained personnel should prepare Methotrexate Pfizer. This should be performed in designated area (preferably a cytotoxic laminar flow cabinet). Protective gown, mask, gloves and appropriate eye protection should be worn while handling methotrexate. Where solution accidentally contacts skin or mucosa, the affected area should be immediately washed thoroughly with soap and water. It is recommended that pregnant personnel not handle cytotoxic agents eg, methotrexate.
Luer-lock fitting syringes are recommended. Large bore needles are recommended to minimise pressure and possible formation of aerosols. Aerosols may also be reduced by using a venting needle during preparation.
Items used to prepare Methotrexate or articles associated with body waste, should be disposed of by placing in a double-sealed polythene bag and incinerating at 1100°C.
Spills and Disposal: If spills occur, restrict access to the affected area. Wear 2 pairs of gloves (latex rubber), a respirator mask, a protective gown and safety glasses. Limit the spread of the spill by covering with absorbent material eg, absorbent towel or adsorbent granules. Collect up absorbent/adsorbent material and other debris from spill and place in a leak-proof plastic container and label accordingly. Cytotoxic waste should be regarded as hazardous or toxic and clearly labeled 'Cytotoxic Waste For Incineration at 1100°C'. Waste material should be incinerated at 1100°C for at least 1 sec. Cleanse the remaining spill area with copious amounts of water.
Storage
Store below 25°C. Protect from light. Single use only. Discard unused portion.
Pharmacology
Methotrexate has as its principal mechanism of action the competitive inhibition of the enzyme folic acid reductase. Folic acid must be reduced to tetrahydrofolic acid by this enzyme in the process of DNA synthesis and cellular replication.
Methotrexate inhibits the reduction of folic acid and interferes with tissue cell reproduction. It is a phase-specific substance. Its main effect is directed to the S-phase of cell division. Actively proliferating tissues eg, malignant cells, bone marrow, fetal cells, dermal epithelium, buccal and intestinal mucosa and cells of the urinary bladder are in general more sensitive to the effects of methotrexate. Cellular proliferation in malignant tissue is greater than in most normal tissue and thus methotrexate may impair malignant growth without irreversible damage to normal tissues.
In psoriasis, the rate of production of epithelial cells in the skin is greatly increased over that in normal skin. This differential in reproduction rates is the basis for the use of methotrexate to control the psoriatic process.
Pharmacokinetics: After parenteral injection, peak serum levels are seen in about 0.52 hrs. Approximately ½ the absorbed methotrexate is reversibly bound to serum protein, but exchanges with body fluids easily and diffuses into the body tissue cells. Elimination is triphasic. The 1st phase probably describes distribution into organs; the 2nd, renal excretion; and the 3rd, passing of methotrexate into the enterohepatic circulation. Excretion occurs mainly through the kidneys. Approximately 41% of the dose is excreted unchanged in the urine during the first 6 hrs; 90% within 24 hrs. Repeated daily doses result in more sustained serum levels and some retention of methotrexate over each 24-hr period which may result in accumulation of the drug within the tissues. The liver cells appear to retain certain amounts of methotrexate for prolonged periods even after a single therapeutic dose. Methotrexate is retained in the presence of impaired renal function and may increase rapidly in the serum and in the tissue cells under such conditions. Methotrexate does not penetrate the blood cerebrospinal fluid barrier in therapeutic amounts when given orally or parenterally. High concentrations of methotrexate when needed may be attained by direct intrathecal administration.
ATC Classification
L01BA01 - methotrexate; Belongs to the class of antimetabolites, folic acid analogues. Used in the treatment of cancer.

Brand/Product Info


Total Products : 7       
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
EMTHEXATE Pharmachemie Methotrexate (as sodium salt) 50mg vial Injection 50mg x25's: 3250.00 TP
G-METHOTREXATE Gonoshasthaya Pharmaceuticals Ltd Methotrexate BP 2.5mg Tablet 18's: 72.36 MRP
METHOTRAX Delta Pharma Limited Methotrexate BP 2.5mg & 10mg Tablet 2.5mg x30's, 10mg x20's: 150.00 & 300.00 MRP
METHOX Popular Pharmaceuticals Ltd. Methotrexate BP 2.5mg & 10mg Tablet 2.5mg x30's, 10mg x10's: 165.59 & 451.79 MRP
MTX Choongwae/NTS Methotrexate BP 2.5mg Tablet 100's: 539.00 MRP
MTX Injection Choongwae/NTS Methotrexate BP 50mg vial Injection 50mg/2ml vial: 129.47 MRP
TREXONATE Beacon Pharmaceuticals Limited Methotrexate (as sodium salt) 50mg vial Injection 50mg x1's: 130.00 MRP

Gen. MedInfo

IMPORTANT WARNING:

Methotrexate may cause very serious, life-threatening side effects. You should only take methotrexate to treat cancer or certain other conditions that are very severe and that cannot be treated with other medications. Talk to your doctor about the risks of taking methotrexate for your condition.

inform your doctor if you have or have ever had excess fluid in your stomach area or in the space around your lungs and if you have or have ever had kidney disease. Also inform your doctor if you are taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, choline magnesium trisalicylate, ibuprofen, magnesium salicylate, naproxen or salsalate. These conditions and medications may increase the risk that you will develop serious side effects of methotrexate. Your doctor will monitor you more carefully and may need to give you a lower dose of methotrexate or stop your treatment with methotrexate.

Methotrexate may cause a decrease in the number of blood cells made by your bone marrow. inform your doctor if you have or have ever had a low number of any type of blood cells or any other problem with your blood cells. Call your doctor immediately if you experience any of the following symptoms: sore throat, chills, fever, or other signs of infection; unusual bruising or bleeding; excessive tiredness; pale skin; or shortness of breath.

Methotrexate may cause liver damage, especially when it is taken for a long period of time. If you drink or have ever drunk large amounts of alcohol or if you have or have ever had liver disease, your doctor may inform you not to take methotrexate unless you have a life-threatening form of cancer because there is a higher risk that you will develop liver damage. The risk that you will develop liver damage may also be higher if you are elderly, obese, or have diabetes. inform your doctor if you are taking any of the following medications: acitretin, azathioprine (Imuran), isotretinoin, sulfasalazine or tretinoin. Ask your doctor about the safe use of alcoholic beverages while you are taking methotrexate. Call your doctor immediately if you experience any of the following symptoms: nausea, extreme tiredness, lack of energy, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, or flu-like symptoms. Your doctor may order liver biopsies (removal of a small piece of liver tissue to be examined in a laboratory) before and during your treatment with methotrexate.

Methotrexate may cause lung damage. inform your doctor if you have or have ever had lung disease. Call your doctor immediately if you experience any of the following symptoms: dry cough, fever, or shortness of breath.

Methotrexate may cause damage to the lining of your mouth, stomach, or intestines. inform your doctor if you have or have ever had stomach ulcers or ulcerative colitis (condition in which part or all of the lining of the intestine is swollen or worn away). If you experience any of the following symptoms, stop taking methotrexate and call your doctor right away: mouth sores, diarrhea, black, tarry, or bloody stools, or vomit that is bloody or looks like coffee grounds.

Taking methotrexate may increase the risk that you will develop lymphoma (cancer that begins in the cells of the immune system). If you do develop lymphoma, it might go away without treatment when you stop taking methotrexate, or it might need to be treated with chemotherapy.

If you are taking methotrexate to treat cancer, you may develop certain complications as methotrexate works to destroy the cancer cells. Your doctor will monitor you carefully and treat these complications if they occur.

Methotrexate may cause serious or life-threatening skin reactions. If you experience any of the following symptoms, call your doctor immediately: fever, rash, blisters, or peeling skin.

Methotrexate may decrease the activity of your immune system, and you may develop serious infections. inform your doctor if you have any type of infection and if you have or have ever had any condition that affects your immune system. Your doctor may inform you that you should not take methotrexate unless you have life-threatening cancer. If you experience signs of infection such as a sore throat, cough, fever, or chills, call your doctor immediately.

If you take methotrexate while you are being treated with radiation therapy for cancer, methotrexate may increase the risk that the radiation therapy will cause damage to your skin, bones, or other parts of your body.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before, during, and after your treatment to check your body's response to methotrexate and to treat side effects before they become severe.

inform your doctor if you or your partner is pregnant or plan to become pregnant. If you are female, you will need to take a pregnancy test before you begin taking methotrexate. Use a reliable method of birth control so that you or your partner will not become pregnant during or shortly after your treatment. If you are male, you and your female partner should continue to use birth control for 3 months after you stop taking methotrexate. If you are female, you should continue to use birth control until you have had one menstrual period that began after you stopped taking methotrexate. If you or your partner become pregnant, call your doctor immediately. Methotrexate may cause harm or death to the fetus.

 

Why Methotrexate is prescribed?

Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis(RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.

How to use Methotrexate?

Methotrexate may come as a tablet to take by mouth. Your doctor will inform you how often you should take methotrexate. The schedule depends on the condition you have and on how your body responds to the medication.

Your doctor may inform you to take methotrexate on a rotating schedule that alternates several days when you take methotrexate with several days or weeks when you do not take the medication. Follow these directions carefully and ask your doctor if you do not know when to take your medication.

If you are taking methotrexate to treat psoriasis or rheumatoid arthritis, your doctor may inform you to take the medication once a week. Pay close attention to your doctor's directions. Some people who mistakenly took methotrexate once daily instead of once weekly experienced very severe side effects or died.

Follow the directions on your prescription label carefully, and ask your doctor to explain any part you do not understand. Take methotrexate exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are taking methotrexate to treat psoriasis or rheumatoid arthritis, your doctor may start you on a low dose of the medication and gradually increase your dose. Follow these directions carefully.

If you are taking methotrexate to treat rheumatoid arthritis, it may take 3 to 6 weeks for your symptoms to begin to improve, and 12 weeks or longer for you to feel the full benefit of methotrexate. Continue to take methotrexate even if you feel well. Do not stop taking methotrexate without talking to your doctor.

Other uses

Methotrexate is also sometimes used to treat Crohn's disease (condition in which the immune system attacks the lining of the digestive tract, causing pain, diarrhea, weight loss and fever), multiple sclerosis (MS; condition in which the immune system attacks the nerves, causing weakness, numbness, loss of muscle coordination, and problems with vision, speech, and bladder control), and other autoimmune diseases (conditions that develop when the immune system attacks healthy cells in the body by mistake). Ask your doctor about the risks of using Methotrexate for your condition.

Methotrexate may be prescribed for other uses; ask your doctor for more information.

What special precautions to follow?

Before taking methotrexate,

  • inform your doctor if you are allergic to methotrexate, any other medications, or any of the ingredients in methotrexate tablets. Ask your doctor for a list of the ingredients.
  • inform your doctor what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: certain antibiotics such as chloramphenicol, penicillins, and tetracyclines; folic acid (available alone or as an ingredient in some multivitamins); other medications for rheumatoid arthritis; phenytoin; probenecid; sulfonamides such as co-trimoxazole, sulfadiazine, sulfamethizole and sulfisoxazole and theophylline. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • inform your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or a low level of folate in your blood.
  • do not breast-feed while you are taking methotrexate.
  • if you are having surgery, including dental surgery, inform the doctor or dentist that you are taking methotrexate.
  • plan to avoid unnecessary or prolonged exposure to sunlight or ultraviolet light (tanning beds and sunlamps) and to wear protective clothing, sunglasses, and sunscreen. Methotrexate may make your skin sensitive to sunlight or ultraviolet light. If you have psoriasis, your sores may get worse if you expose your skin to sunlight while you are taking methotrexate.
  • do not have any vaccinations during your treatment with methotrexate without talking to your doctor.

What special dietary instructions to follow?

Unless your doctor informs you otherwise, continue your normal diet.

What to do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can Methotrexate cause?

Methotrexate may cause side effects. inform your doctor if any of these symptoms are severe or do not go away:

  • dizziness

  • drowsiness

  • headache

  • swollen, tender gums

  • decreased appetite

  • reddened eyes

  • hair loss

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:

  • blurred vision or sudden loss of vision

  • seizures

  • confusion

  • weakness or difficulty moving one or both sides of the body

  • loss of consciousness

Methotrexate may cause other side effects. Call your doctor if you have any unusual problems while taking Methotrexate.

What to know about storage and disposal of Methotrexate?

 

Keep Methotrexate in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.

What other information to know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to Methotrexate.

Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Ref:  U.S. National Library of Medicine.


This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.

See FDA approved Prescribing Information for | Methotrexate InjectionMethotrexate Tablet |  Manufacturer's 
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