2.5mg herabiopharm hemetrex medicine to treat severe rheumatoid arthritis (10 blisters x 10 tablets)

Dosage form Box of 10 blisters x 10 tablets
Specifications Methotrexate

Ingredient

Composition information	Content
Methotrexate	2.5mg

Uses

indications

Hemetrex drugs are indicated in the following cases:

methotrexate is a folic acid antagonist and is classified as anti -metabolic cytotoxic.

Methotrexate is indicated in the treatment of adults with severe rheumatoid arthritis, active, non -response or intolerant with conventional therapy.

Methotrexate is also indicated for treatment of severe, uncontrolled psoriasis, and non -response to other treatments.

Methotrexate has been designated to treat a variety of cancer including: acute leukemia, hodgkin non -lymphoma, soft tissue sarcoma and bone sarcoma and solid tumors, especially breast, lungs, head and neck, bladder, cervical, ovarian and testicular cancer.

Pharmacological

Pharmacological group: immunosuppressive drugs.

ATC code: L04AX03.

Active mechanism

methotrexate is a folic acid antagonist and its main position is the enzyme dihydrofolate reductase. In addition to the main effect of inhibiting DNA synthesis, methotrexate also directly affects both RNA and protein synthesis. The main impact of methotrexate is to inhibit the phase S phase S of the cell division process.

Inhibition of enzyme dihydrofolate reductase is prevented by using leucovorin (folinic acid, citrovorum element) and can protect normal tissues using Leucovorin calcium at the right time.

Dynamic pharmacokinetics

The absorption of methotrexate when taken orally seems to depend on the dosage. The peak concentration of serum is reached within 1 to 2 hours. In general, at a dose of 30 mg/m2 or less, methotrexate is absorbed quickly and completely. The bioavailability of methotrexate when taken orally (80 - 100%) at a dose of 30 mg/m2 or lower. The saturation is absorbed at the dose of over 30 mg/m2 and is not fully absorbed at a dose exceeding 80 mg/m2. After the injection, the concentration of methotrexate peaks in the serum is about half of this time. After intramuscular injection, the peak concentration of serum is reached within 30 to 60 minutes.

About 50% of methotrexate is absorbed in conjunction with serum protein but easily distributed into tissues. The process of excretion is mainly through the kidneys. About 41% of the dose is eliminated in the form of unchanged urine within the first six hours, 90% within 24 hours. A small part is excreted through bile - has a marked circulation.

Selling time is about 3-10 hours after low doses and 8-15 hours after high doses. If the renal function is impaired, the concentration of methotrexate in serum and tissue can increase rapidly.

methotrexate does not go into cerebrospinal fluid at oral or injection dose. However, cytotoxic concentration (> 10-7m) can be achieved in cerebrospinal fluid with high doses (> 500 mg/m2). When indicating the drug with high concentrations, should be injected directly into the endocardium.

Before taking 2.5mg herabiopharm hemetrex medicine to treat severe rheumatoid arthritis (10 blisters x 10 tablets)

How to use

oral tablets.

Anyone who comes into contact with methotrexate must behing hands after finishing the job. To reduce the risk of exposure, parents and caregivers should wear one -time gloves when exposed to the drug.

Dosage

methotrexate should only be prescribed by experienced doctors using methotrexate and fully understanding about the risks of methotrexate therapy.

Doctors prescribing must make sure that patients or caregivers will follow the treatment regime once a week.

Dosage indications for cancer treatment

Warning: Caution must be carefully adjusted methotrexate based on the body surface area if methotrexate is used to treat tumor diseases.

Cases of death poisoning have been reported after using methotrexate doses that are not calculated accurately. Health care experts and patients should be fully informed about the toxicity of the drug.

Used by oral:

Recommended the test dose of 5 - 10 mg in the gastrointestinal tract, a week before treatment to detect specific adverse effects. Low doses do not exceed 30 mg/m2 for 5 consecutive days.

After that, it takes at least two weeks to rest for the bone marrow to recover normally.

The dose exceeds 100 mg is often used on the gastrointestinal tract, so the injection is indicated. The dose should not exceed 70 mg/m2 without combining with Leucovorin (rescue folinic acid) or testing methotrexate concentration in serum 24 - 48 hours after the drug.

If using methotrexate combined with chemotherapy regimens, methotrexate dose should be reduced, pay attention to any overlapping toxicity of other drug ingredients.

Dosage for psoriasis and rheumatoid arthritis

Important warning about methotrexate dose: In the treatment of psoriasis and rheumatoid arthritis, only methotrexate only once a week. Error in dosage when using methotrexate can lead to serious side effects, including death. Please read the user manual carefully.

The prescription should specify the date of taking the drug on the prescription.

Psoriasis

Before starting treatment, the patient should try the dose of 2.5 - 5.0 mg to eliminate unwanted toxic effects. If a week later, the related subclinical tests have normal value, it can start treatment.

The usual dose is 7.5 - 15 mg once a week. To treat severe psoriasis, when necessary, the total weekly dose can be raised to 20-25 mg by oral. Dosage should be adjusted according to the patient's response and hematology.

Rheumatoid arthritis

In adults of severe rheumatoid arthritis, inactive, non -response or intolerance with other common treatments, methotrexate should be used at a dose of 7.5 - 15 mg once a week. Total weekly dose can be up to 20 - 25 mg by oral if necessary.

Should adjust the dose according to the patient's response and hypnosis.

Pediatric patients

Should follow the existing treatment regimens for children. The safety and effectiveness of drugs in children has not been established, except in cancer chemotherapy.

Elderly

Methotrexate should be used very carefully in elderly patients, so the dose should be considered in the elderly due to reduced liver and kidney function as well as lower folate reserves when age is higher.

Patients with renal failure - Dosage adjustment

Methotrexate is significantly eliminated through the kidneys, so it should be cautious when used for patients with impaired renal function. Doctors may need to adjust the dose to prevent the accumulation of drugs. The table below provides the recommended starting dose in patients with renal failure, may need to adjust the dosage due to the variation of PK between subjects.

Table 1A: Adjust the dose of methotrexate 59 50 (ml/minute)

% of the designated dose Methotrexate Should use methotrexate very carefully in all patients with severe liver disease or a history of severe liver disease, especially if due to alcohol.

Patients with the third cavity retention of the body (pleural effusion, ascites).

Because the sale time of methotrexate may last 4 times higher than normal in patients with epidemic disease in the third compartment.

Therefore, the dose may be reduced, in some cases, stop treatment with methotrexate.

Special note

If changing the line used from oral to injection, the dose may be reduced due to the bioavailability of methotrexate after drinking.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose? In these cases, symptoms are often reported as reactions on the digestive and hematological system.

toxicity of methotrexate mainly affects hematopoietic organs.

Calcium folinate has an immediate neutralization effect of the toxicity of methotrexate. Calcium folinate intravenous infusion should start within an hour after using methotrexate. The dose of calcium folinate must be at least with methotrexate doses that patients take.

Symptoms of overdose are mainly like unwanted effects, but worse.

Leucovorin is a specific antidote for methotrexate. Leucovorin should be used within an hour when an overdose of methotrexate with the dose is equal to or higher than the dose of methotrexate used. Leucovorin can be quickly intravenous or intravenous.

Higher doses may be specified. Patients need to be carefully monitored and blood transfusion, renal separation may be necessary.

Experienced, methotrexate overdose often occurs when taken and injected in the skin, although overdose when intravenous and intramuscularly have been reported.

Cases of overdose, sometimes death has been reported, due to daily drinking instead of drinking weekly. In these cases, symptoms are often reported as side effects on the digestive system and hematology. Such as leukemia, thrombocytopenia, anemia, hypoglycemia, bone marrow inhibition, mucosal inflammation, stomatitis, mouth ulcers, nausea, vomiting, gastrointestinal ulcers, gastrointestinal bleeding. In some cases, no symptoms are also reported. There has been a report on death after chronic overdose due to the patient self -adjusting the dose of rheumatoid arthritis and psoriasis. In these cases, signs of infections or infections, kidney failure and anemia are also reported.

In case of overdose, water can be rehydrated and alkaline urine to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Hemodialy and peritoneal dialysis are not shown to improve methotrexate elimination. The effective clearance of methotrexate has been reported when the hemorrhage is interrupted and positive with a high flow dialysis. Monitoring serum methotrexate concentration is associated with the correct identification of calcium folinate and treatment time.

Can stop treatments for methotrexate overdose when the serum methotrexate concentration decreases below 5 x 10-8 m (10).

In case of emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Side Effects

When using hemetrex you can experience unwanted effects (ADR):

In general, the proportion and severity of unwanted effects related to the dose, frequency of drugs, sugar and treatment time.

Most unwanted reactions can recover if detected early. When side effects occur, the dose should be reduced or stop using the drug and at the same time take appropriate remedies, including using calcium folinate. Methotrexate therapy should only be carefully carefully careful, after careful consideration of the benefits of treatment with the ability to recur toxicity.

The most serious undesirable reactions of methotrexate include bone marrow inhibition, lung poisoning, liver poisoning, kidney toxicity, neurotoxicity, tolerance, anaphylaxis and Stevens - Johnson syndrome.

The most common undesirable reactions of methotrexate include digestive disorders (stomatitis, indigestion, abdominal pain, nausea, anorexia) and abnormal liver function tests (increased alanineeaminotransferase (alat), aspartate (alat), aspartate aminotransferase (asat), bilirubin, alkali phosphatase). Other frequent side effects are leukopenia, anemia, thrombocytopenia, headache, fatigue, drowsiness, pneumonia, alveolar inflammation, interstitial pneumonia are often associated with eosinophilia, mouth ulcers, diarrhea, foreign rash, erythema and itching.

Most of the harmful reactions are inhibiting the hematopoietic system and gastrointestinal disorders.

In the treatment of anti -cancer, myeloma and mucous inflammation are toxic effects that limit the treatment dose of methotrexate. The severity of these reactions depends on the dose, method and time of using methotrexate. Mucinitis usually appears about 3 to 7 days after using methotrexate, leukopenia and thrombocytopenia usually appear a few days later. In patients with non -affected elimination mechanisms, marrow failure and mucositis are usually recovered within 14 to 28 days.

Unwanted reactions on different agencies are as follows:

Skin disorders and subcutaneously:

Outdoor, Stevens - Johnson syndrome, poisoned epidermal necrosis, erythema, itching, urticaria, light sensitivity, pigmentation changes, diverse roses, peeling nails, hyperpigmentation, hemorrhagic spots, allergic vasculitis, sweat gland inflammation, hair loss, pigmentation, bruising, capillary, acne, pink sense of psoria Calculate.

Skin peeling and scales (unknown frequency).

Recovery has been recorded when skin damage caused by radiation and sunlight. The lesions of psoriasis can become worse when combining UV therapy. Radiation and sunburn can recover.

Blood disorders and lymphatic systems:

Giant red blood cell anemia, hematopoietic disorders, eosinophilia, lymphatic hyperactical disorders (partially recovered), lymph nodes, bone marrow failure (especially when using high -dose methotrexate) is often manifested by platelet reduction (usually recovery), neutropenia, leukopenia, reduced blood cell compressions, immunoclavia, hyperkemis, lymphocytes (very rare) or any combination may occur. Infections or hypotension of blood gamma, hemorrhage in many positions. Bone marrow failure can lead to decreased resistance to infections and infections.

Gastrointestinal disorders:

Mucinitis, stomatitis, gingivitis, vomiting, black stools, pancreatitis, bowelitis, gastrointestinal ulcers (including mouth ulcers) and bleeding, malabsorption, colon poisoning, indigestion, abdominal pain, anorexia, nausea, vomiting, diarrhea.

Needs to adjust the dose when gastric disorders appear. Disrupt treatment if the patient manifests the ulcerative of the mouth and diarrhea, otherwise it can cause bowel inflammation and death due to perforation.

Liver disorders:

Liver poisoning leads to increased transaminase (asat, alat), alkaline phosphatase and bilirubin, reducing serum albumin, acute hepatitis, fibrosis of the door vein, cirrhosis, liver failure, degeneration in the liver, re -activating chronic hepatitis or death.

Kidney and urinary disorders:

Renal failure, hyper urea, bladder ulcers, urination disorders, urinary disorders, hematuria, difficulty urinating, urinary, proteinuria, electrolyte disorders, kidney disease.

Respiratory disorders, chest and mediastinum:

Pneumonia, interstitial or acute or chronic interstitial pneumonia may be fatal and often associated with eosinophilia, acute pulmonary edema, lung/lung fibrosis, chronic obstructive pulmonary disease, sore throat, pleural inflammation, dry cough, chest pain, shortness of breath, pleural effusion, bronchial asthma, respiratory paralysis.

In the treatment of rheumatoid arthritis, methotrexate lung diseases are a serious side effect that can occur at any time during treatment. These manifestations are not always completely recovered.

Nosebleeds (unknown frequency) have been reported. There is a report on lung hemorrhage (unknown frequency) when using methotrexate to treat rheumatoid arthritis and related indications.

Nervous system disorders:

Headache, fatigue, drowsiness, dizziness, dizziness, coma, loss of language, uncomfortable, light paralysis, mild paralysis, seizures, brain white brain disease.

Special brain whites have been reported after using high -dose or low -dose methotrexate or low doses after irradiation of the skull - spine.

Brain edema, exquisite cognitive dysfunction, chaos, abnormal skull. Pain, muscle weakness, change of taste (metal taste), meningitis, acute sterile meningitis, polio.

Perception, tactile reduction (very rare).

Mental disorders:

depression, confusion, mood change, insomnia, mental disorders.

Heart disorders:

pericardial effusion, pericarditis, pericardial compression.

vascular disorders:

thrombosis (arterial thrombosis, brain thrombosis, deep vein thrombosis, retinal venous thrombosis, intravenous inflammation, pulmonary embolism), vasculitis, hypotension.

Eye disorders:

Conjunctivitis, blurring/vision impairment, retinopathy.

benign, evil and unknown tumors (including cysts and polyps):

recovery lymphoma, methotrexate can cause tumor solving syndrome in patients with fast growing tumors.

Breeding and breast disorders:

Milk in men, decreased libido/helplessness, sperm or egg birth defect, fleeting sperm, infertility, menstrual disorders, vaginal bleeding, vaginal ulcer, vaginitis, vaginal discharge.

Infections and parasites:

Respiratory or skin infections, herpes infections, opportunistic infections, pneumocystis carinii/jiroveci pneumonia and other lung infections, triggered chronic physical infections.

Connection and musculoskeletal disorders:

Osteoporosis, fractures due to stress, joint pain/muscle pain, rheumatism.

jaw bone tumor (unknown frequency) (secondary after lymphatic proliferation).

Endocrine disorders:

diabetes.

immune system disorders:

allergies, anaphylactic reactions, anaphylactic shock.

Disorders of ears and mesmerizing:

tinnitus.

Body and on -site:

Fever, chills, slow wound healing, weakness. Edema (unknown frequency).

Other:

Increased risk of toxic reactions in radiation therapy (soft tissue necrosis, bone necrosis).

Instructions on how to handle ADR:

Notify the physician the unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

anti -contraindications in the following cases:

Significant impaired liver function. Significant bridge or anemia.

Alcoholism. Methotrexate, must not be vaccinated simultaneously with live vaccines.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Methotrexate must be indicated by doctors with experience in anti -metabolic chemotherapy.

Patients must be monitored appropriately during treatment so that they can detect and evaluate the early signs of toxicity or unwanted reaction.

Special monitoring of patients with previous radiation therapy (especially pelvic area), impaired hematopoietic function (for example, after radiation or previous chemotherapy), general physical impairment as well as high -age patients and young children.

Due to the possibility of serious or even fatal toxic reactions, patients need to be fully notified by the doctor about the risks (including early signs and toxic symptoms) and recommended safety measures. Patients need to be informed that they must notify the doctor immediately if there is any symptom of an overdose and need to monitor the symptoms of overdose (including regular subclinical tests).

Dose exceeding 20 mg per week may increase significant toxicity, especially bone marrow inhibition.

Due to the slow excretion of methotrexate in patients with renal impairment, careful treatment of these patients and only with low doses of methotrexate.

Use methotrexate carefully on all patients with severe liver disease, especially if related to Rugu.

Avoid skin contact and mucosa with methotrexate injection solution.

Do not encourage the use of dmard toxic to toxic liver or blood (anti -rheumatoid drugs slowly acting, such as leflunomide).

Acute or chronic interstitial pneumonia, often associated with eosinophilia in the blood, may occur and the death of death has been reported. The typical symptoms include shortness of breath, cough (especially dry cough) and fever that patients need to be monitored each re -examination.

Patients should be notified of the risk of pneumonia and should be recommended to contact the doctor immediately if the cough is prolonged or shortness of breath. Methotrexate should be stopped in patients with thorough lung symptoms and examinations (including X-ray) to eliminate infections and tumors. If methotrexate is suspected, corticosteroid treatment should be started and should not be re -treated with methotrexate.

Methotrexate lung diseases such as pneumonia can occur at any time during the treatment process, not always completely recovered and have been recorded at all doses (including low doses of 7.5 mg/week).

For psoriasis, methotrexate should be restricted for severe psoriasis, anti -psoriasis psoriasis does not fully respond to other treatments, but only when diagnosis is determined by biopsy and/or after a dermatological examination.

Death cases have been reported related to methotrexate in the treatment of psoriasis.

Methotrexate should be used very carefully in patients who are or have a history of infection, peptic ulcer, ulcerative colitis, weakness, very young and elderly patients. Contraindicated in patients with gastrointestinal ulcers. If serious leukopenia occurs during treatment, infection may occur or become a threat. Typically, these cases should be stopped and treated with appropriate antibiotics. In case of severe bone marrow failure, it is necessary to need blood transfusion or platelet.

Diarrhea and mouth ulcers are toxic effects often encountered and need to stop treatment, otherwise it can cause bowel inflammation and death from perforation.

If vomiting blood, black stools or bloody diarrhea must stop treatment.

In addition, conditions that lead to dehydration such as vomiting can increase the toxicity of methotrexate due to the high active ingredient level. In these cases, methotrexate should be stopped until the symptoms are terminated. It is important to monitor to detect an increase in methotrexate levels within 48 hours after treatment, if no methotrexate poisoning may not occur.

Due to serious toxicity and even life -threatening reactions, the treating doctor should notify the patient fully about related risks before starting treatment with methotrexate.

Patients should be closely monitored during treatment.

Patients need to be notified of the signs and symptoms of toxicity, need to see a doctor immediately if these symptoms appear and closely monitor, including regular tests for toxic monitoring.

Psoriasis treatment patients should be notified only once a week. The prescription should specify the date of taking the drug on the prescription.

Patients should be explained the importance of adhering to medication once a week and the wrong daily recommended dosage leads to death toxicity.

Most side effects can recover if detected early.

When the reactions are harmful, reduce the dose or stop the drug and apply appropriate remedies. If necessary, you can add calcium folinate and/or interrupt, positive blood separator with dialysis with high flow.

Use methotrexate very carefully for patients with mental disorders. Patients with pleural and ascites should be drainage before starting treatment with methotrexate or stopping treatment.

Before starting methotrexate or re-treatment after a period of stopping the drug, lung x-ray should be taken, kidney function assessment, liver function and blood component by exploiting prehistoric, clinical examination and testing. This will include periodic examination of lymph nodes and patients should notify the treating doctor if any abnormal swelling is detected.

Patients using low -dose methotrexate:

Check the adequate blood formula and check the liver function before starting treatment. Should check weekly until the treatment is stable. After that, regular monitoring every 2-3 months during the treatment process. Any infection must be noted before starting treatment with methotrexate.

Hemorrhage inhibitor by methotrexate can occur suddenly and with a safe dose. Should closely monitor the full blood formula before, during and after treatment. If the number of leukemia or platelets is significantly reduced clinically, methotrexate should be stopped immediately and offer appropriate supportive treatment. Patients should notify the doctor all the symptoms or signs of suspected infection. Any infection should be noted before starting treatment with methotrexate.

methotrexate can be toxic to the liver, especially at high doses or during prolonged treatment. Hepatic atrophy, necrosis, cirrhosis, fat changes and fibrosis around the portal vein have been reported. Risk factors for serious liver damage such as patients with a history of liver disease, many abnormal liver function tests and alcoholism. Do not coordinate liver toxic drugs with methotrexate during treatment, unless it is really necessary. Should avoid or reduce drinking during treatment with methotrexate.

Patients with diabetes under treatment with insulin will increase the risk of liver toxicity.

Liver function test

Pay special attention to the manifestations of liver toxicity. When developing or developing abnormalities in liver function test or liver biopsy, do not start treatment or stop treatment with methotrexate.

These abnormalities will return to normal within the next two weeks. Treatment may be considered according to the doctor's decision.

Check the liver enzyme in serum

There have been reports on 13-20% of patients temporarily increasing transaminase levels doubled or three times the upper limit of normal levels. In the case of continuous increase in liver enzymes, consider reducing dose or stopping treatment. More closely monitoring of liver enzymes is necessary, especially in patients who are taking in combination with toxic drugs for the liver or other hematopoietic systems (such as leflunomide). More research is needed to determine whether a series of liver function tests or determining the Propeptide of Collagen Typ III are suitable to detect toxicity to the liver or not.

Patients with risk factors

These factors mainly include:

There is a history of alcoholic abuse.

Secondary (the level of relevance may be lower):

diabetes.

obesity. The necessity of the liver biopsy should be evaluated in each case and comply with the national recommendations.

Kidney

Methotrexate treatment in patients with renal function should be done very carefully because the impaired renal function will reduce methotrexate excretion. Improving renal function can lead to methotrexate accumulation in toxic amounts or even worsen kidney damage. In patients with renal failure, methotrexate dose should be reduced.

Monitor kidney function by kidney function tests and urine analysis. If the serum creatinine levels increase, the dose should be reduced.

If creatinine clearance is below 30 ml/min, methotrexate should not be treated. If creatinine clearance is below 60 ml/min, do not use methotrexate doses> 100 mg/m2.

Do not start treatment with methotrexate doses> 100 mg/m2 when the urine pH is below 7.0. Urine alkalization must be checked by monitoring regular urine pH (greater value or equal to 6.8) for at least the first 24 hours after starting using methotrexate.

Kidney damage may appear if the urine is hindered and low urine pH, especially if the patient has high doses.

methotrexate can cause kidney damage leading to acute renal failure. Strictly monitoring renal function includes adequate water compensation, alkalizing urine by drinking or intravenously sodium bicarbonate (5 sodium bicarbonate 625 mg, every three hours) or acetazolamide (500 mg orally four times a day), recommended checking blood methotrexate concentration and renal function.

Because methotrexate is excreted mainly through the kidneys, the concentration will increase when there is renal failure, which can lead to serious harmful reactions.

If there is a risk of kidney failure (for example, in the elderly), it should be monitored more often in shorter periods of time. Especially important when coordinated with drugs that affect the excretion of methotrexate, or cause kidney damage (NSAID) or those that can lead to impaired hematopoietic ability.

If there is risk factors such as renal dysfunction, including mild kidney failure, not in combination with NSAID drugs. Dehydration can also increase the toxicity of methotrexate.

Should avoid simultaneous use of Proton pump inhibitors (PPI) and high doses of methotrexate, especially in patients with renal failure.

immune system

Methotrexate has some immunosuppressive and immune response activities for immunization and may be reduced. Contraindicated vaccination by live vaccine during treatment.

Methotrexate immunosuppressive effects should be noted when responding to the patient's immune response is important or necessary. Pay special attention in cases of non -active physical infections (such as herpes zoster, tuberculosis, hepatitis B or C) because of the ability to activate.

Methotrexate can cause tumor syndrome in patients with rapid growth tumors.

Malignant lymphoma can occur in patients using low -dose methotrexate, in that case, it is necessary to stop treatment. If lymphoma does not show signs of self -regression, it is necessary to start treatment with cytotoxic therapy.

Because cases of brain white brain diseases occur in cancer patients treated with methotrexate, it is impossible to exclude this case in non -cancer patients.

Need to monitor the disappearance of methotrexate from plasma, if possible. Special recommendations when using high or very high doses to allow adequate calculation of antidote to rescue leucovorin (folinic acid).

Concomitance methotrexate with radiation can increase the risk of soft tissue necrosis and bone necrosis.

In the treatment of rheumatoid arthritis, acetylsalicylic acid can be continued, nonsteroidal anti -inflammatory (NSAID) and or low -dose steroids, although combining NSAID and methotrexate may increase the risk of toxicity. Steroids can be gradually reduced in patients responding to methotrexate.

The interaction of methotrexate and other anti -joint drugs such as penicillamine, hydroxychloroquine, sulfasalazine or non -comprehensive cytotoxic drugs, simultaneous use may increase unwanted effect rate.

Concomitance of folate antagonistic drugs such as Trimethoprim/Sulfamethoxazole has been reported to cause a lack of hemorrhage, huge primary red blood cell anemia in some rare cases.

In addition, alveolar hemorrhage has been reported when using methotrexate to treat rheumatoid arthritis and related indications.

This manifestation may be related to vasculitis and other accompanying diseases. Timely examination when there is suspicion of lung bleeding to determine diagnosis.

If acute methotrexate poisoning occurs, patients may need to be treated with folinic acid. In patients with rheumatoid arthritis or psoriasis, supplementing folic acid or folinic acid can reduce the toxicity of methotrexate, such as symptoms on the digestive system, stomatitis, hair loss and liver enzyme.

Proceed to check the concentration of vitamin B12 before supplementing folic acid, especially in adults over 50 years old, as the amount of folic acid can hide the deficiency of vitamin B12. Methotrexate can cause harmful reactions to the urinary tract such as cystitis and hematitis.

Methotrexate has been shown to cause teratogenicity - the risk of reproduction, embryo poisoning drugs, miscarriage and fetal defects in humans.

Therefore, the effects that can occur on the reproductive system, miscarriage and birth defects should be discussed with female patients of reproductive age.

In indications that are not treated with cancer, it is necessary to determine the non -pregnant condition before treatment with methotrexate. If women of reproductive age are treated with methotrexate, they must use effective contraception during treatment and at least six months later.

If this drug is used during pregnancy with indications for cancer treatment, or if the patient is pregnant while using methotrexate, it is advisable to assess the potential risk for the fetus.

Methotrexate has been reported to reduce fertility, sperm reduction, menstrual disorders and menstruation in people during and after stopping treatment for a short time, affecting the process of sperm and eggs during the use of drugs - these unwanted effects can be lost when stopped treatment.

Radiation and sunburn dermatitis may reappear when treated with methotrexate (memorization reaction). Psoriasis lesions can be worse when UV rays combine treatment with methotrexate.

Serious skin reactions, sometimes fatal, including poisoned epidermal necrosis (Lyell syndrome) or Stevens - Johnson syndrome has been reported after one or more methotrexate doses.

The effect of drugs on driving and operating machinery

Symptoms of the central nervous system such as fatigue and dizziness, which can occur when treatment with methotrexate, these manifestations often have a slight impact on the average driving and operating machinery.

Use drugs for women during pregnancy and lactation

fertility

Methotrexate affects the process of sperm and eggs and can reduce fertility. In humans, methotrexate is reported to reduce sperm, menstrual disorders and amenorrhea. These cases seem to recover after stopping treatment in most cases.

In cancer treatment indications, women who are planning to get pregnant should consult a doctor before treatment and men should be advised on sperm preservation before starting treatment because methotrexate can be toxic to genes at higher doses.

contraceptive in women

Women are not pregnant when treated with methotrexate and must use effective contraception during treatment with methotrexate and last for at least 6 months later. Before starting treatment, women of reproductive age must be notified of the risk of malformations related to methotrexate and any existing pregnancy must be firmly eliminated by taking appropriate measures, such as pregnancy tests. During treatment, regular pregnancy tests are required by clinical requirements (after any time of not using contraception). Women's patients of reproductive age must be advised on pregnancy and pregnancy plan.

contraceptive in men

It is still not known whether methotrexate is in semen.

Methotrexate has been shown to be genetic toxicity in animal studies, so it is not possible to completely eliminate the risk of genetic toxicity on sperm cells. Due to limited clinical evidence, the risk of deformities or miscarriage increases after the father is exposed to low -dose methotrexate (less than 30 mg/week). For higher doses, there is no enough data to estimate the risk of deformities or miscarriage after the father is exposed to the drug.

As preventive measures, male patients have sex or their partner is recommended to use effective contraceptive measures during the time the male patient is treated and at least 6 months after stopping using methotrexate. Male patients should not donate sperm during treatment or for 6 months after stopping using methotrexate.

Pregnancy

Methotrexate is contraindicated during pregnancy in non -cancer indications. If pregnant during treatment with methotrexate and within six months after stopping the drug, medical advice for patients on the risk of harmful to the fetus related to treatment and should perform ultrasound to check the normal development of the fetus.

In animal studies, methotrexate has shown toxicity to reproduction, especially in the first three months. Methotrexate has been shown to be teratogenic for humans. Methotrexate is reported to cause pregnancy, miscarriage or birth defects for the fetus (such as face, cardiovascular, central nervous system and related to expenditure).

Methotrexate is a strong teratogenic substance in humans, increasing the risk of natural miscarriage, which slows up the development of the fetus in the uterus and birth defects in the case of medication during pregnancy.

Natural miscarriage has been reported at 42.5% of pregnant women treated with low doses of methotrexate (less than 30 mg/week), compared to the reported rate of 22.5% in patients treated with non -methotrexate drugs.

Severe birth defects occur at 6.6% of babies born in women treated with low doses of methotrexate (less than 30 mg/week) during pregnancy, compared to about 4% of babies born in patients treated with drugs other than methotrexate.

Not enough data on methotrexate treatment during pregnancy with a dose higher than 30 mg/week, but the rate of natural miscarriage and birth defects is expected to be higher, especially at the common doses that are indicated for cancer treatment.

Cases of normal pregnancy when stopping using methotrexate before conception has been reported.

Do not specify methotrexate for patients during pregnancy to treat cancer, especially in the first three months of pregnancy.

In each individual case, the benefits of treatment must be considered with possible risks to the fetus. If the drug is used during pregnancy or if the patient is pregnant during treatment with methotrexate, the patient should be notified of the risks that may occur to the fetus.

Women who are breastfeeding

Patients should not breastfeed while using methotrexate.

Drug interaction

methotrexate is highly linked to plasma proteins and can be replaced, or replaced by other acidic drugs. Simultaneous use of drugs such as diphenylhydantins, acidic anti-inflammatory drugs, salicylate, phenylbutazone, phenytoin, barbiturate, sedative, oral contraceptives, amidepyrine derivatives, p-aminobenzoic acid, thiazide diuretic, oral hemorrhagic drugs, Doxorubicin, DOXORUBICIN, TETROCYCYCYCYCOCK, PROBENICCYCKCYCY SulfinPyrazone will reduce the function of transporting the renal tubules, thus reducing the secretion and increasing the toxicity of methotrexate.

Because Probenecid and cipher acids, such as "strap diuretics" as well as pyrazols reduce the excretion in the renal tubules, so be careful when combining these drugs with methotrexate.

Avoid combining other drugs that canxicate kidneys or liver (such as sulphasalazine, leflunomide and alcohol). It is necessary to be especially cautious when examining patients being treated with methotrexate in combination with azathioprine or retinoid.

methotrexate combined with leflunomide may increase the risk of reducing all bloody hematomas.

Can increase the toxicity on the kidneys if using methotrexate dose suitable for a chemotherapy agent that is potentially toxic to the kidneys (such as cisplatin).

In some cases, antibiotics such as penicillin, glycopeptide, sulfonamide, ciprofloxacin and cefalotin can reduce the clearance of methotrexate through the kidney, so it can increase the concentration of serum methotrexate, and may occur toxicity on blood and gastrointestinal systems.

Oral antibiotics such as tetracycline, chloramphenicol and universal antibiotics can not be absorbed, which can reduce the absorption of methotrexate in the intestine or hinder the intestinal circulation due to inhibition of intestinal bacteria or inhibit the metabolism of bacteria.

Methotrexate dose should be monitored if started in combination with aspirin, ibuprofen or indomethacin (NSAID), because simultaneous use of NSAID is related to death methotrexate poisoning.

Should avoid toxic drugs for the liver, blood and kidneys.

Vitamin products or other products containing folic acid or its derivatives can reduce the effectiveness of methotrexate.

Patients are being treated (previously) with drugs that may have side effects on the bone marrow (such as sulfonamide, trimethoprim/sulfamethoxazole, chloramphenicol, pyrimethamine), should consider the possibility of hematuria disorders.

Simultaneous use of folate deficiencies (such as trimethoprim/sulfamethoxazole, sulfonamide) may increase the toxicity of methotrexate. Therefore, it is also necessary to be particularly cautious when there are signs of folic acid deficiency.

Acitretin (psoriasis treatment) is converted into eretinate.

Methotrexate levels may increase due to Eretinate and severe hepatitis that have been reported after combined use.

Bone marrow inhibitors and folate levels are described when used simultaneously triamterene and methotrexate.

Combining toxic drugs for hematoma (such as Metamizole) makes the toxicity of methotrexate on the hematopoietic system.

There is evidence that simultaneous use of methotrexate and omeprazole extends the time to eliminate methotrexate through the kidney. Concentrated use of proton pump inhibitors such as omeprazole or pantoprazole may cause interaction. One case has been reported when combining methotrexate with pantoprazole, hydroxymethotrexate metabolites are inhibited through the kidneys, causing muscle pain and chills.

methotrexate can reduce theophylline's clearance, so monitor theophylline concentration when used simultaneously with methotrexate. To avoid using too much drinks containing caffeine or theophyllline (coffee, soft drinks with caffeine, black tea) while treatment with methotrexate because the effectiveness of methotrexate may be reduced due to interaction between methotrexate and methylxanthin at Adenosine receptors.

There is a pharmacokinetic interaction between methotrexate, anti -convulsions (reducing blood methotrexate levels), and 5 -fluorouracil (increasing the sale time of 5 - fluorouracil).

Using nitrogen oxide will increase the effect of methotrexate on folate metabolism, increasing toxicity such as stomatitis and severe marrow failure, unpredictable. These unwanted effects can be reduced when using calcium folinate, avoiding simultaneous use of nitrogen and methotrexate oxide.

Colestyramine may increase the excretion of methotrexate outside the kidney by interrupting the intestinal circulation.

Reducing methotrexate clearance should be considered when combined with other cell pliers.

Use processbazine when treated with high doses of methotrexate, increasing the risk of renal function.

Radiation therapy during the use of methotrexate may increase the risk of soft tissue or bone necrosis.

methotrexate increases the concentration of Mercaptopurine in plasma.

Therefore, the dose may be adjusted when combined with methotrexate and mercaptopurine.

Vaccination vaccinated in patients with chemotherapy can cause severe infections and death. Due to the immune system influence, methotrexate may falsify the test results and vaccinations (the process of recording the immune reaction). While treatment with methotrexate, no vaccination with live vaccine.

Spopolized drugs may reduce phenytoin's absorption, which can reduce the effectiveness of phenytoin and increase the severity of seizures. The risk of increased toxicity or loss of effect of cytotoxic drugs due to increased metabolism through the liver because phenytoin may occur.

ciclosporin may increase the effectiveness and toxicity of methotrexate. There is a risk of excessive immunity, accompanied by the risk of lymphatic proliferation when used in combination.

Special in the case of orthopedic surgery, where susceptible to infection, must be cautious when combining methotrexate with immunosuppressive drugs.

Combining levetiracetam and methotrexate are reported to reduce the clearance of methotrexate, resulting in prolonged increase in blood methotrexate levels to toxicity. Should carefully monitor the concentration of methotrexate and levetiracetam in the blood in patients treated simultaneously.

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

To be out of reach of children, read the user manual carefully before use.

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