Instructions for Flexerin capsules 50 mg blister No. 30
Composition
active ingredient: diacerein;
1 capsule contains diacerein 50 mg;
excipients: lactose monohydrate, croscarmellose sodium, povidone, colloidal anhydrous silicon dioxide, magnesium stearate;
hard gelatin capsule: gelatin, indigo carmine (indigotine) (E 132), quinoline yellow (E 104), titanium dioxide (E 171).
Dosage form
The capsules are hard.
Main physicochemical properties: hard gelatin capsules with a green cap and body. Capsule contents – yellow granulated powder.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A X21.
Pharmacological properties
Pharmacodynamics.
Flexerin is a drug for the treatment of osteoarthritis and osteoarthritis, which has analgesic, antipyretic and anti-inflammatory properties. Diacerein is classified as a slow-acting agent, the effect of which appears within 2–4 weeks of treatment and reaches clinical significance after 4–6 weeks. It has an original mechanism of action, which differs from the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). Diacerein, like its active rhein metabolite, inhibits the synthesis and activity of interleukin-1 (IL-1), which plays a leading role in the pathogenesis of osteoarthritis and at the same time increases the production of transforming growth factor b (TGF-b), which initiates chondrocyte proliferation and stimulates the production of collagen II, proteoglycans and hyaluronan.
Unlike nonsteroidal anti-inflammatory drugs, diacerein does not inhibit prostaglandin synthesis and, therefore, has no gastroduodenal side effects.
Pharmacokinetics.
The absorption of diacerein is slowed down by simultaneous administration with food. Diacerein is completely converted to the rhein metabolite by deacetylation before entering the central circulation. The bioavailability of the rhein metabolite is 35-56%. The volume of distribution is approximately 13.2 l. The rhein metabolite is almost 99% bound to plasma proteins, but this binding is not stable. The rhein metabolite is either excreted by the kidneys unchanged (20%), or conjugated in the liver to rhein glucuronide (60%) or rhein sulfate (20%), which are also excreted in the urine. The half-life is approximately 7-8 hours.
When using diacerein in elderly patients, no changes in its pharmacokinetic properties were observed.
Indication
Rheumatic diseases of the joints (osteoarthritis, osteoarthrosis).
Contraindication
History of hypersensitivity to the components of the drug or to anthraquinone derivatives.
Liver disease, present or history.
Inflammatory bowel diseases (nonspecific ulcerative colitis, Crohn's disease).
Intestinal obstruction or pseudo-obstruction.
Abdominal pain of unknown origin.
Pregnancy or breastfeeding.
Interaction with other medicinal products and other types of interactions
Taking diacerein can lead to diarrhea and hypokalemia. With simultaneous use of diacerein with diuretics (loop and thiazide) and/or cardiac glycosides (digitoxin, digoxin), the risk of arrhythmia increases.
Concomitant administration with antacids (aluminum, calcium and magnesium salts such as oxides and hydroxides) significantly reduces the absorption of diacerein from the digestive tract. Therefore, there should be an interval of 1–2 hours between taking antacids and diacerein.
No interactions due to plasma protein binding of rhein (the active metabolite of diacerein) were observed with warfarin, paracetamol, salicylic acid, indomethacin, ibuprofen, diclofenac, fenbufen, flurbiprofen, naproxen, phenylbutazone, piroxicam, sulindac, tenoxicam, sodium valproate, phenytoin, tolbutamide, glibenclamide or chlorpropamide.
Simultaneous use of diacerein and a blocker of H2-histamine receptors (cimetidine) does not lead to modification of the pharmacokinetic parameters of rhein in blood plasma and urine.
Application features
Given the late onset of action (after 2-4 weeks), during the first month of treatment with Flexerin, it can be combined with other nonsteroidal anti-inflammatory drugs and analgesics.
During diacerein therapy, a complete blood count, liver enzyme determination, and urinalysis should be performed periodically (once every 2-3 months).
Treatment should be temporarily discontinued in case of antibiotic therapy, as the latter may affect the intestinal flora and the kinetics of the drug. Treatment with diacerein may exacerbate symptoms of enterocolitis in patients taking antibiotics and chemotherapy that affect the intestinal flora. Use with caution in patients with chronic renal failure.
During the studies, there were no pharmacokinetic changes in diacerein in moderate and severe liver cirrhosis.
The medicine contains lactose, so it should not be used in cases of hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Use during pregnancy or breastfeeding
Contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no reports of the effect of diacerein on the ability to drive or operate other mechanisms.
Method of administration and doses
During the first 2-4 weeks of treatment, Flexerin is prescribed to adults 1 capsule (50 mg) after a meal at night. Starting from the 2-4th week of treatment, the dose of the drug is increased to 100 mg per day in 2 doses (1 capsule in the morning and evening after meals).
The drug should be used for a long period (at least 6 months). The duration of the course of treatment is determined by the doctor individually.
Elderly patients.
Diacerein is not recommended for patients over 65 years of age due to the fact that this category is more vulnerable to complications associated with diarrhea.
No significant changes in pharmacokinetic parameters have been observed when diacerein is administered to elderly patients, therefore no changes to the recommended dose are required (see section "Pharmacological properties"). However, caution should be exercised. If diarrhea occurs, treatment with diacerein should be discontinued.
Patients with chronic renal failure.
In renal failure, the pharmacokinetics of diacerein may be altered. In these cases, it is recommended to reduce the dose to 1 capsule per day (creatinine clearance < 30 mg/ml).
Children.
The efficacy and safety of the drug in children have not been established, therefore diacerein is contraindicated in this age group.
Overdose
Diarrhea may occur in case of accidental or intentional ingestion of large doses of diacerein. There is no specific antidote. Emergency treatment consists in restoring electrolyte balance.
Adverse reactions
The drug is generally well tolerated, but sometimes dyspeptic disorders (frequent bowel movements, soft bowel movements, flatulence), diarrhea, abdominal pain are possible, which usually disappear with continued treatment. In some cases, prolonged diarrhea can cause complications such as dehydration and impaired water and electrolyte balance.
A change in urine color, which has no clinical significance, has also been noted. Unlike other nonsteroidal anti-inflammatory drugs, diacerein does not have an ulcerogenic effect on the digestive tract.
Adverse reactions are listed according to MedDRA terminology, presented by system organ class and absolute frequency. The frequency of occurrence is defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000) and very rare (<1/10000), frequency unknown (cannot be estimated from the available data).
On the part of the digestive tract: very often - diarrhea, abdominal pain; often - frequent bowel movements, flatulence; rarely - pigmentation of the intestinal mucosa (pseudomelanosis).
Hepatobiliary system: infrequently - cases of increased levels of liver enzymes in the blood serum.
On the part of the kidneys and urinary tract: very often - change in urine color.
Skin and subcutaneous tissue disorders: often - itching, rashes, eczema.
General disorders: frequency unknown - headache.
Hepatobiliary disorders have been reported.
Cases of acute liver injury, including elevations of serum liver enzymes and hepatitis, have been reported with diacerein. Most of these occurred within the first months of treatment. Patients should be monitored for symptoms of liver injury (see section 4.4).
Reporting of adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 capsules in a blister; 1 or 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "KYIV VITAMIN FACTORY"
Location of the manufacturer and address of its place of business
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua
Address
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua.
