Methotrexate(often abbreviated as MTX ) has been on the market since 1954. It is available as tablets and injections. It is available by prescription as generic methotrexate tablets and methotrexate injection solution. Various ready-made prefilled syringes are also available under the brand names Ebetrex, Emthexate, Injexate, and Metoject.
In dermatology, methotrexate is primarily used for psoriasis , particularly in severe forms where local treatments such as ointments and light therapy are no longer sufficient. Several systemic therapies (tablets, injections, infusions) are available for the treatment of severe psoriasis, but methotrexate is the drug of first choice. Methotrexate is preferred because it is effective and, when used sensibly as described in this leaflet, also safe. The drug can be used for extended periods, for years if necessary.MECHANISM OF ACTION OF METHOTREXATEIn low doses, methotrexate suppresses the immune system and inhibits inflammation. In higher doses, it inhibits the growth of some tumors and has an inhibitory effect on cell division. With psoriasis, the skin is inflamed (red, flaky, itchy), and in response to the inflammation, the cells in the upper skin layer grow too quickly. Methotrexate interferes with both processes.
A low dose is defined as 7.5 to 25 mg per week. For psoriasis, a dose between 10 and 15 mg per week is usually sufficient. However, some patients require more; this varies from person to person and also depends on body weight. The effect of methotrexate does not occur immediately; sometimes it is only visible after several weeks. The optimal effect is achieved after two to three months.DOSAGE FORMSMethotrexate is available as 2.5 mg tablets and as injections (prefilled syringes containing the correct dose). 10 mg tablets are also available, but it's best to avoid these to avoid errors with the correct dosage.
The advantage of tablets is that you can easily take them yourself. A disadvantage is that the effect decreases if you consume milk or dairy products, such as cheese, simultaneously with or shortly afterward. Injections are painful but do not have this disadvantage and are also slightly less likely to cause gastrointestinal complaints. In some cases, if there are doubts about the drug's absorption in tablet form, injections are chosen. These are administered in the hospital, at an outpatient clinic, or at home by a community nurse. Patients can also learn to inject themselves. In most cases, however, tablets are the preferred option.HOW SHOULD METHOTREXATE BE TAKEN?Methotrexate is used only once a weekIt's best to choose a fixed day of the week to take the tablets (or receive an injection) and stick to it. Your doctor will tell you how many tablets you should take per week. If you need to take 15 mg per week, that means six 2.5 mg tablets. You can take all six tablets at once. The weekly dosage varies from patient to patient. The doctor will regularly adjust the dosage, depending on the condition of your skin and the occurrence of side effects. Never change the dosage on your own!
It's best to take the tablets with meals, but not with milk. Milk and foods containing dairy products reduce the absorption of methotrexate. Therefore, do not consume milk or dairy products, such as cheese and yogurt, from two hours before to one hour after taking the tablets. This warning does not apply if you are receiving methotrexate by injection.
It is common practice to always take folic acid tablets in addition to methotrexate. Folic acid is a vitamin that can reduce the side effects of methotrexate. Methotrexate use can lead to a folic acid deficiency; folic acid tablets can be used to replenish this.
If you take less than 15 mg of methotrexate per week, take one 5 mg folic acid tablet per week, taken 24 hours after the methotrexate. If you take 15 mg or more of methotrexate per week, take two 5 mg (i.e., 10 mg) folic acid tablets per week, taken 24 hours after the methotrexate. Folic acid has no side effects.WHAT ARE THE POSSIBLE SIDE EFFECTS?MTX is a powerful drug; excellent results are achieved in 70 to 90% of patients. Unfortunately, side effects can also occur. The most common side effect is nausea on the day of administration. Side effects that go unnoticed by the patient can also occur, such as damage to the liver or to red and white blood cells. To prevent this from happening, it is necessary to check your blood occasionally. Most hospitals perform blood tests before starting MTX. They usually start with a low dose, 10-15 mg. After this, the blood is checked again. If no abnormalities are found, treatment is continued. If the treatment is insufficient, the dosage is increased. If a good effect is achieved, the dosage is reduced to the lowest dose at which the patient is still able to function. If side effects occur, the dosage is reduced. Blood tests must also be performed during treatment, at least after one month, and then every two to three months. If the patient is doing very well, blood tests are required less frequently.
Methotrexate interferes with the production of folic acid in cells. Folic acid is necessary for cell division. Side effects therefore primarily occur in areas with rapidly dividing cells, such as the stomach and intestines, skin, hair, and blood. Methotrexate also inhibits the cells of the immune system.SIDE EFFECTS:Regularly:
- Nausea, stomach and abdominal complaints, diarrhea, especially during the days that you are taking MTX
- Listlessness, tiredness.
If nausea leads to vomiting, the tablets may not be properly absorbed. If you have vomited within two hours of taking MTX, consult your doctor. He or she can tell you whether you should still take further tablets or whether this is not necessary.
Sometimes:
- Mouth ulcers
- Increased susceptibility to all kinds of infections
- Decrease in the number of red blood cells in the blood, which can cause anaemia
- Decrease in the number of white blood cells in the blood, which can lead to an increased risk of infections
Sometimes, after prolonged use:
- Liver damage
- Kidney damage
- Suppression of sperm production (temporary, recovers after stopping treatment)
Regular blood tests are performed to prevent damage to the liver or kidneys. If there are indications in the blood of liver or kidney damage, the dose of MTX must be reduced or stopped. If you have severe liver or kidney problems, you should not use methotrexate. Your blood will also be checked for liver or kidney problems before starting MTX. Tell your doctor if you experience severe nausea, severe diarrhea with blood in the stool, shortness of breath, and yellowing of the skin and gums (the latter indicates liver disease).
Very rarely
- Hair loss, usually mild and never permanent (recovers spontaneously once treatment is stopped)
- Pneumonitis, a very rare form of pneumonia
- Eye problems, usually inflammation of the conjunctiva
- Headache, dizziness
- Ulcers in the stomach or intestines
- Menstrual disorders
- Increased blood glucose in people predisposed to diabetes
- Kidney damage
- Bladder infection, blood in the urine
- Allergic reactions, skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Low platelet count
- Swelling of the lymph nodesPRECAUTIONSThere are some conditions where prescribing methotrexate can cause problems. If you have any of the following conditions, you should inform your dermatologist:
Porphyria (a metabolic disorder characterized by attacks of abdominal pain, vomiting, fever, and palpitations): MTX can trigger an attack. People with (or a predisposition to) a stomach ulcer or inflammatory bowel disease should be monitored before and during use to prevent excessive worsening of their stomach or intestinal symptoms. Chronic infectious diseases, such as HIV, hepatitis, and tuberculosis. Kidney disease, liver disease, anemia, or immune disorders.INTERACTIONS WITH OTHER MEDICINESThe following medications can cause problems if used at the same time as MTX:
Ciclosporin (another immunosuppressant) increases the side effects of methotrexate. Only use
this combination if your doctor has explicitly told you to. The antibiotics co-trimoxazole (trimethoprim/sulfamethoxazole) and trimethoprim can increase the side effects of methotrexate. Probenicide (a medication for gout) also increases the side effects of methotrexate. Therefore, do not use this combination.
NSAID painkillers such as ibuprofen, naproxen, diclofenac, and indomethacin can increase the side effects of methotrexate, especially if you take more than 15 mg of methotrexate per week, or six 2.5 mg tablets per week. However, patients with joint problems (rheumatism, psoriatic arthritis) often use this combination, and in practice it is not a problem because the MTX dosage is always adjusted individually and blood tests are performed regularly.
Vaccines sometimes don't work well enough in people taking MTX because immunity doesn't develop due to suppressed immune function.
The effectiveness of some antiepileptic drugs, such as valproic acid, carbamazepine, phenytoin, and phenobarbital, can be reduced by MTX. Your doctor will periodically measure the amount of the antiepileptic drug in your blood and adjust the dosage if necessary.
Acitretin, a drug used for skin conditions including severe psoriasis, can increase methotrexate levels. This increases the risk of methotrexate side effects on the liver.
If you are unsure whether any of the above interactions apply to you, contact your pharmacist or doctor. Also, make sure your doctor knows exactly what other medications you are taking, report any changes, and always bring a list of them with you when you visit a doctor. The pharmacist also monitors interactions. If you have a regular pharmacy, all medications you use are registered in the computer system, and this system automatically alerts you if medications are prescribed that are incompatible. In such cases, the pharmacist contacts the prescribing physician, and in a joint consultation, a decision can then be made to adjust the medication or accept the risk of the interaction.DRIVINGThere are no restrictions for this remedy.ALCOHOLAlcohol consumption is not recommended. Concurrent use of alcohol and methotrexate places a heavy burden on the liver and can cause liver damage. Do not drink alcohol on the days you take MTX, and on the remaining days, do not drink more than one alcoholic drink per day. People with severe psoriasis drink more alcohol on average than people without psoriasis. Some studies even show that liver damage in psoriasis is not caused by MTX, but by alcohol consumption.PREGNANCY AND BREASTFEEDING, PLANS FOR EXPANDING YOUR FAMILYYou should not use MTX during pregnancy. Methotrexate is harmful to the unborn fetus and can cause birth defects. You should also not use this medication if you are trying to conceive. If you are taking this medication and are considering becoming pregnant, discuss with your doctor whether you can use a different medication. This also applies to men whose partners are trying to conceive. Methotrexate is also harmful to sperm cells. Both men and women must therefore use effective contraceptive methods while taking methotrexate. For both men and women, methotrexate should be stopped for three months before considering starting a family.
Do not use MTX if you are breastfeeding, or discontinue breastfeeding. This medication is present in breast milk and can cause side effects in the baby. If you wish to breastfeed, discuss this with your doctor or pharmacist. Your doctor may be able to temporarily prescribe a different medication that is safe for you to use.WHAT SHOULD I DO IF I MISS A DOSE?If you remember the next day, you can still take the tablets (or give the injection). The following week, take the methotrexate on your usual day. However, if more than a day has passed, it's best to adjust the day in the future: for example, if you were used to taking your methotrexate on Thursdays and you only realize you forgot on Saturday, take the tablets or injection on Saturday and note Saturday as your regular day from now on. Be sure to inform your dermatologist about this change at your next checkup.STOPPING METHOTREXATESide effects can be a reason to stop. However, don't just stop immediately; contact your doctor. It may be possible to keep the side effects within reasonable limits by lowering the dose, taking folic acid supplements, or using injections instead of tablets. Also consult your doctor if any of the above side effects bother you too much, or if you experience other side effects that concern you.
If it is absolutely necessary to stop, MTX can be stopped immediately. There is no need to taper off the medication; there are no withdrawal symptoms. However, it is necessary to start another therapy first to prevent your psoriasis from returning in full force.FINALLYDespite the extensive list of side effects that can occur, methotrexate is, in practice, a good and (with precautions) safe treatment for severe psoriasis, with over 35 years of experience in dermatology. Most patients tolerate it well and can control their psoriasis with it for extended periods, sometimes even years. |
