Iguratimod Tablets

Iguratimod Tablet

Generic Name: Iguratimod Tablets
Brand name: IREMOD
Composition:N-[7-methanesulfonamido-4-oxo-6-(phenoxy)chromen-3-yl]formamide
Chemical structure:

 

Molecular formula: C17H14N2O6S 
Molecular weight:374.37
Description:
White or off-white tablets.
Indications:
For treatment of active rheumatoid arthritis symptoms
Strength:25mg
Dosage and Administration:
Orally taken 25mg (1 tablet) twice daily (morning and evening) after meal.

Precautions:
(1)Liver toxicity:Clinical trial results have shown that the product may cause reversible liver enzyme elevations
most of the elevations of aminotransferase are mildly [≤ 2 times ULN (Upper Limit of Normal)], and usually
continues to ease in the course of treatment; remarkable increase (> 3 times ULN) is infrequent, and can be
alleviated by dose reduction or withdrawal. Elevated aminotransferase in most patients usually occur within
3 months during treatment, therefore the blood alanine aminotransferase (ALT) and glutamate aminotransfer
ase (AST) should be regularly examined at the early dosing period, the examination intervals is depending on
the patient's condition.
Patients with liver damage or definite positive hepatitis B or hepatitis C serology indicators should use this
product with cautions and receive ALTexamination monthly both before and after the treatment.The inspection
interval is depending on patients' specific condition.
If ALT level increase occurs during treatment, the following principles should be adopted for dosing adjustment
 or of treatment abortion: 1 ,ALT level is at 2 to 3 times of upper limit of normal value, the patient can continue
to receive Iguratimod under close monitoring, and the dose should be reduced to 25mg/day. 2 if ALT increases
by 2 to 3 times upper limit of normal value, and remains high at 2 to 3 times or more than 3 times upper limit
of normal value after the dose reduction, the dosing should be discontinued, and the patient should receive
strengthened Liver treatment and be closely observed
(2) Active gastrointestinal disease: Caution should be taken in patients with active gastrointestinal disease,
and it's necessary to inform patients should call doctor and go to the hospital as soon as possible in case of
melena, anemia, abnormal stomach/abdominal pain and other symptoms etc., Iguratimod should be
discontinued immediately once the patient was diagnosed as gastric ulcer or duodenal ulcer; and the patient
should take symptomatic treatment.
(3) Living vaccines: There's no clinical data of the efficacy and safety for immunization of living vaccines during
treatment, so the living vaccines should not be administrated during Iguratimod treatment.
(4) Caution should be taken in patients with immune deficiency, uncontrolled infection, renal insufficiency,
bone marrow dysplasia.
(5) There was no systematic carcinogenicity test during development, so the time frame of treatment is
temporarily limited to 24 weeks (including 24 weeks).
Clinical studies:
The multi-center clinical trial period (totally 780 cases) at Phase II, III of this product is completed by the
collaborative group together with S Renji Hospital, Shanghai Jiaotong University School of Medicine as
head unit.

Pharmacology and toxicology:
Pharmacology: Non-clinical studies of this compound revealed that Iguratimod can inhibit rat paw swelling in
collagen-induced arthritis models, and reduce the rat bone and cartilage damage. The mechanism of action
is not fully clear. According to some literature reports, Iguratimod in vitro inhibits the activity of nuclear factor-
κB (NF-κB), thereby inhibit the generation of inflammatory cytokines (interleukin -1, interleukin-6, interleukin-8,
and α tumor necrosis factor). Iguratimod in vitro can also directly interact with mouse or human B cells and
inhibit the generation of immune globulin. In addition, It is also reported that Iguratimod in vitro inhibits the
activity of purified cyclooxygenase -2 (COX-2) (IC50 = 7.7μg/ml), but it has no effect on the activity of
cyclooxygenase -1 (COX-1).

Pharmacokinetics:
24 healthy volunteers were divided in two groups, with 12 cases in each group. Single-dose group: it is further
divided into two sub dosage groups by low dosage 25mg and high dosage 50mg. Multiple dose group: 25mg
per 12h for 6 continuous days. Dosing after diet: subjects in the single high-dosage group received 50mg
once orally.
Iguratimod in vivo complies with one-compartment model of pharmacokinetics. Within the therapeutic dosage
range (25mg - 50mg), the exposure of Iguratimod is in ratio to its dose. The main pharmacokinetic parameters
have no gender differences. The bioavailability of Iguratimod is not affected by food.
After Iguratimod is orally taken at the treatment dose, it will arrive at peak blood concentration in 3.1 to 4.6
hours. Given twice a day, Iguratimod will reach steady-state concentration in 3 days after multiple dosing.
The average steady-state concentration Cav is 0.76 ± 0.19 (μg / ml), mean apparent volume of distribution is
0.20 L/ Kg; the average plasma clearance rate is 0.0133 L/ h/ Kg. Half-life of Iguratimod elimination is 10.5
hours, certain amount of drug accumulation in the plasma can be observed. Urinary excretion test showed
that after Iguratimod is taken orally at 50mg dosage, only 0.0685 ± 0.056%,  and 0.0608 ± 0.033% of the
drug is eliminated from kidney unmetabolized in the fasting group and diet group separately.

Storage:
Protect from light, and keep air-tightly

Packs:
Medicinal composite film for packaging. 7 tablets/ box; 14 tablets/ box; 21 tablets/ box; 28 tablets/ box;
56 tablets / box
Shelf-life:24 months