Trexol Special Precautions

Warnings: Methotrexate must be used only by physicians experienced in antimetabolite chemotherapy.
Because of the possibility of fatal or severe toxic reactions, the patient should be fully informed by the physician of the risks involved and be under his constant supervision.
The prescriber should specify the day of intake on the prescription. The prescriber should make sure patients understand that methotrexate should only be taken once a week. Patients should be instructed on the importance of adhering to the once-weekly intakes.
Acute or chronic interstitial pneumonitis, often associated with blood eosinophilia, may occur and deaths have been reported. Symptoms typically include dyspnoea, cough (especially a dry non-productive cough), thoracic pain, and fever for which patients should be monitored at each follow-up visit. Patients should be informed of the risk of pneumonitis and advised to contact their doctor immediately should they develop persistent cough or dyspnoea.
In addition, pulmonary alveolar haemorrhage has been reported with methotrexate used in rheumatologic and related indications. This event may also be associated with vasculitis and other comorbidities. Prompt investigations should be considered when pulmonary alveolar haemorrhage is suspected to confirm the diagnosis.
Methotrexate should be withdrawn from patients with pulmonary symptoms and a thorough investigation should be made to exclude infection. If methotrexate induced lung disease is suspected treatment with corticosteroids should be initiated and treatment with methotrexate should not be restarted.
When a patient presents with pulmonary symptoms, the possibility of Pneumocystis carinii pneumonia should be considered.
Methotrexate has the potential for serious, sometimes fatal toxicity. The toxic effects may be related in frequency and severity to the dose or frequency of administration but have been seen at all doses. Because the toxic reactions can occur at any time during therapy, the patients have to be observed closely and must be informed of early signs and symptoms of toxicity.
Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitor (PPI) therapy. Case reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs, such as omeprazole, esomeprazole, and pantoprazole, with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was coadministered with PPIs, but was not observed when methotrexate was coadministered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted.
Precautions: Methotrexate has a high potential toxicity, usually dose related, and should be used only by physicians experienced in antimetabolite chemotherapy, in patients under their constant supervision. The physician should be familiar with the various characteristics of the drug and its established clinical usage. Before beginning methotrexate therapy or reinstituting methotrexate after a rest period, assessment of renal function, liver function and blood elements should be made by history, physical examination and laboratory tests.
It should be noted that intrathecal doses are transported into the cardiovascular system and may give rise to systemic toxicity. Systemic toxicity of methotrexate may also be enhanced in patients with renal dysfunction, ascites, or other effusions due to prolongation of serum half-life. In rare cases, following intrathecal administration, a tumour lysis syndrome has been observed.
Fertility and reproduction: Fertility: Methotrexate has been reported to cause impairment of fertility, oligospermia, menstrual dysfunction and amenorrhoea in humans, during and for a short period after cessation of therapy, affecting spermatogenesis and oogenesis during the period of its administration - effects that appear to be reversible on discontinuing therapy. In addition, methotrexate causes embryotoxicity, abortion and foetal defects in humans.
For contraception advice for men, see Use in Pregnancy & Lactation: Patients undergoing therapy should be subject to appropriate supervision so that signs or symptoms of possible toxic effects or adverse reactions may be detected and evaluated with minimal delay. This may occur abruptly and on apparent safe dosage, and any profound drop in blood cell count indicates immediate stopping of the drug and appropriate therapy. In patients with malignant disease who have pre-existing bone marrow aplasia, leukopenia, thrombocytopenia or anaemia, methotrexate should be used with caution, if at all.
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: complete haemogram; haematocrit; urinalysis; renal function tests; liver function tests and chest X-ray.
Methotrexate is bound in part to serum albumin after absorption, and toxicity may be increased because of displacement by certain drugs such as salicylates, sulphonamides, phenytoin, and some antibacterials such as tetracycline, chloramphenicol and para-aminobenzoic acid. These drugs, especially salicylates and sulphonamides, whether antibacterial, hypoglycaemic or diuretic, should not be given concurrently until the significance of these findings is established.
Vitamin preparations containing folic acid or its derivatives may alter response to methotrexate.
Since it is reported that methotrexate may have an immunosuppressive action, this factor must be taken into consideration in evaluating the use of the drug where immune responses in a patient may be important or essential.
Effects on Ability to Drive and Use Machine: Central nervous system symptoms, such as fatigue and dizziness can occur during treatment with methotrexate which may have minor or moderate influence on the ability to drive and use machines.