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*For medical professionals only
So come to flunomide, are you using it all right?
Leflunomide has strong immunosuppressive, anti-inflammatory and other effects, and is a very commonly used anti-rheumatic drug (DMARD)
to improve the condition.
It belongs to the isoxazole derivative, the chemical structure is different from the previous immunosuppressants, and can be rapidly and completely converted to the active metabolite teriflunomide (A771726).
Clinically, flunomide has been widely used in the treatment
of rheumatic immune diseases, organ transplantation and other diseases.
Since the vast majority of rheumatic immune diseases are chronic diseases, and many patients need to take drugs for a long time or even for life, this article organizes the drug experience of leflunomide in rheumatic immune diseases, and analyzes the four most common medication misunderstandings to improve the safety
of patients.
Medication misunderstanding 1: Only for the treatment of rheumatoid arthritis (RA)?
A trial of RA
in the United States set up three groups: the leflunomide group, which was maintained at 20 mg/day after loading dose; Methotrexate (MTX) group, 7.
5-15 mg/w, and placebo group
.
The trial demonstrated that both drugs were superior to placebo
.
Compared with placebo, both leflunomide and MTX delay the radiological progression of
RA disease.
Another clinical trial compared the efficacy of leflunomide and MTX (20 mg/day and 10-15 mg/w after loading dose, respectively) for one year, and a 1-year extended trial
.
It was found that after 2 years of observation, the clinical effect and delayed radiological progression of the MTX group were statistically superior to those in the leflunomide group
.
SLE has been shown to be effective against LLE
by flunomide.
In one randomized controlled trial, leflunomide improved disease activity over placebo and had a good safety profile and tolerability
.
In subsequent small prospective open trials of patients with lupus nephritis who did not respond well to conventional therapies, leflunomide continued to show efficacy and good tolerability
.
PsA compared to placebo, leflunomide showed its effectiveness in the treatment of PsA
.
In
an open-label trial, leflunomide showed efficacy for peripheral arthritis in patients with AS, but not
for axial arthritis.
Granulomatous polyangiitis
: An open-ended trial and a randomized controlled trial have shown that leflunomide maintains remission
after cyclophosphamide induces remission.
Subsequent trials also found that leflunomide was superior to MTX
in preventing recurrence of granulomatous vasculitis.
Leflunomide has also been shown to be safe and effective
in patients with JIA who do not respond well to MTX or cannot tolerate MTX.
Medication misunderstanding two: regardless of adults and children, take the same dose?
.
Oral tablets of leflunomide are available in 3 doses
: 10 mg, 20 mg and 100 mg.
Leflunomide can be rapidly metabolized to teriflunomide after oral administration, and the half-life of the latter is quite long; Therefore, the recommended standard dosing method is to start with a loading dose of 100 mg/day for 3 days, followed by a standard maintenance dose of 20 mg/day
.
However, despite this recommendation, most clinicians do not give patients a loading dose because they believe that such administration increases gastrointestinal toxicity
.
In addition, when toxic side effects occur or disease control is good, it is common practice to reduce the dose of leflunomide to 10 mg/day
.
Some physicians also believe that leflunomide has a long half-life, so the frequency of administration should be reduced (3~5 times a week).
There are currently no pharmacokinetic studies
specifically targeting leflunomide in elderly patients.
The recommended dose for elderly patients is the same as for the
general population.
At present, there is no clinical experience with the use of this drug in patients with renal insufficiency, so this type of patients should be closely monitored
when taking the drug.
Although leflunomide is not approved for the treatment of JIA in the United States, leflunomide is still used off-label for the treatment of JIA, and the general dose is 10~20mg/d, which is usually based on the patient's weight
。 Studies have suggested that the dose of patients weighing less than 20kg is 10mg every other day, the dose of patients weighing 20~40kg is 10mg/d, and the dose of patients weighing more than 40kg is 20mg/d
.
Medication misunderstanding three: female patients start to stop taking drugs when they are pregnant?
Leflunomide is grade X in FDA pregnancy
.
Grade X drugs in pregnancy have been shown to cause fetal malformations in animal or human studies, or are known to be dangerous to the fetus based on human experience, and the risks of the drug in pregnant women significantly outweigh any possible benefits
.
The drug is contraindicated in women
who are pregnant or about to become pregnant.
Low-dose leflunomide in animal experiments has shown significant teratogenic and embryo-death effects
.
Therefore, it is strongly recommended that women with childbearing potential should have specialist counseling about this issue before taking medication, and women of childbearing age should only start taking leflunomide
after using reliable contraception.
A pregnancy test
should be considered before administration.
Leflunomide is contraindicated in lactating women (see Table 1).
Table 1: Special notes on leflumide It is worth noting that the active metabolite of leflunomide, A771726, may remain in vivo for several years, mainly because it is involved in enterohepatic circulation
.
Therefore, if a woman taking leflunomide is planning to have a family plan, her A771726 level
should be measured.
It is generally believed that when it exceeds 0.
02mg/L, it should be actively removed from the body, and oral cholestyramine for 11 days (8g 3 times a day) can achieve the elimination effect
.
The A771726 level of the patient before pregnancy must be below 0.
02 mg/L on both tests, and the interval between the two tests should be greater than 14 days; After confirming the concentration, the patient should also wait another 3 menstrual cycles to ensure a safe
pregnancy.
Sometimes patients may need to take more than one course of cholestyramine to achieve this goal
.
Although data are lacking, men with family planning should undergo the same elution procedure as women and wait another 3 months to reconfirm that plasma concentrations are below 0.
02 mg/L
.
Medication misunderstanding four: As long as you take medicine on time, you don't need to draw blood from laboratory tests?
.
Like MTX, the American College of Rheumatology (ACR) has published a series of guidelines
on the timing and monitoring of leflunomide.
Patients taking leflunomide should have a basic complete blood count and liver enzymes, including AST, ALT, and albumin
.
Serum creatinine is also important because leflunomide is partially excreted
by the kidneys.
The frequency of testing depends on the duration of administration (see Table 2).
If the patient is also taking other immunosuppressants, such as MTX, more intensive follow-up
is indicated.
If the patient has serious adverse effects, drug elution should be performed to accelerate its clearance
.
It is important to be vigilant that live vaccines
should be avoided when using leflunomide.
Table 2: Leuflunomide medication monitoring and contraindications Note: HBV: hepatitis B; HCV: Hepatitis C
References:
[1] Pinto P,Dougados M.
Leflunomide in clinical practice.
Acta Reumatol Port.
2006 Jul-Sep; 31(3):215-24.
[2] Kiely PD.
The broadening use of leflunomide in clinical practice.
Hosp Med.
2004 Dec; 65(12):735-9.
[3] Mayer DF,Kushwaha SS.
Transplant immunosuppressant agents and their role in
autoimmune rheumatic diseases.
Curr Opin Rheumatol.
2003 May; 15(3):219-25.
[4] SaagK,Geng G.
American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease modifying antirheumatic drugs in rheumatoid arthritis.
Arthritis Rheum 59:762-784,2008.
[5] Fox R:Mechanism of action of letlunomide in rheumatoid arthritis.
J Rheumatol 25(Suppl 53):20-26,1998.
[6] YUAN Xingdong,ZHOU Juan,LIU Zhijun,ZHANG Wei,XU Yuming.
Risk analysis of adverse reactions of leflunomide[J].
Straits Pharmacy,2021,33(02):202-205.
)
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