LEXIB [Celecoxib] 200 mg Tablets
instructions
for the medical use of the medicinal product
LEXIB
Tradename
Lexib, Лексиб
International non-proprietary name or generic name
Celecoxib, Целекоксиб
Dosage form
Tablets.
Composition per 1
tablet:
active
substance: celecoxib 200 mg;
excipients: microcrystalline
cellulose, lactose, povidone, sodium croscarmellose, sodium lauryl sulfate,
poloxamer 407, ethanol, magnesium stearate.
Nonsteroidal anti-inflammatory drugs (NSAIDs).
ATX code: M01AH01
Pharmacodynamics
Celecoxib has
anti-inflammatory, analgesic and antipyretic effects by blocking the formation
of inflammatory prostaglandins (Pg), mainly due to the inhibition of
cyclooxygenase-2 (COX-2). COX-2 induction occurs in response to inflammation
and leads to the synthesis and accumulation of prostaglandins, especially
prostaglandin E2, which increases the manifestations of inflammation (edema and
pain). At therapeutic doses in humans, celecoxib does not significantly inhibit
cyclooxygenase-1 (COX-1) and does not affect the prostaglandins synthesized as
a result of COX-1 activation, and does not affect the normal physiological
processes associated with COX-1 and occurring in tissues, primarily in the
tissues of the stomach, intestines and platelets.
When taken on an empty
stomach, celecoxib is well absorbed, reaching the maximum concentration (Cmax)
in the blood plasma in approximately 2-3 hours. Cmax in blood plasma after
taking 200 mg is 705 ng/ml. Cmax and the area under the pharmacokinetic curve
"concentration-time" (AUC) are approximately proportional to the dose
taken in the dose range up to 200 mg 2 times a day; with the use of celecoxib
in higher doses, the degree of increase in Cmax and AUC occurs less
proportionally. Binding to plasma proteins is independent of concentration and
is about 97%, celecoxib does not bind to red blood cells. Celecoxib penetrates
the blood-brain barrier. It is metabolized in the liver by hydroxylation,
oxidation and partially glucuronidation. It is excreted through the intestines
and kidneys in the form of metabolites (57% and 27%, respectively), less than
1% of the dose taken is unchanged. With repeated use, the half-life (T1/2) is
8-12 hours, and the clearance is about 500 ml/min. With repeated use,
equilibrium concentrations in the blood plasma are achieved by the 5th day. The
variability of the main pharmacokinetic parameters (AUC, Cmax, T1/2) is about 30%.
Indications
for use
• symptomatic therapy of osteoarthritis, rheumatoid arthritis and
ankylosing spondylitis;
• pain syndrome (back pain, musculoskeletal, postoperative and other
types of pain);
• treatment of primary dysmenorrhea.
• hypersensitivity to celecoxib or any of the components of the drug;
• known hypersensitivity to sulfonamides;
• complete or incomplete combination of bronchial asthma, recurrent
nasal polyposis and paranasal sinuses, and intolerance to acetylsalicylic acid
or other NSAIDs, including other COX-2 inhibitors (including history);
• the period after coronary artery bypass grafting;
• active erosive and ulcerative lesions of the gastric or duodenal
mucosa, or gastric ulcer and duodenal ulcer in the acute stage, or
gastrointestinal bleeding;
• inflammatory bowel disease (Crohn's disease, ulcerative colitis) in
the acute stage;
• chronic heart failure (II-IV functional class according to the NYHA
classification);
• confirmed ischemic heart disease, peripheral arterial disease and/or
cerebrovascular disease at an advanced stage;
• hemorrhagic stroke;
• subarachnoid hemorrhage;
• severe liver failure;
• severe renal failure (CC less than 30 ml/min), progressive kidney
disease, confirmed hyperkalemia;
• pregnancy and breastfeeding;
• childhood and adolescence up to 18 years.
Method
of administration and dosage
The
drug is taken orally. The tablets should be swallowed whole with a small amount
of water, regardless of food intake. The drug should be taken in the minimum
effective dose for the shortest possible course. The maximum recommended daily
dose for long-term use is 400 mg.
Symptomatic
treatment of osteoarthritis: the
recommended dose is 200 mg per day in 1 or 2 doses.
Symptomatic
treatment of rheumatoid arthritis: the recommended dose is 100 mg or 200 mg 2 times per day.
Symptomatic
treatment of ankylosing spondylitis: the recommended dose is 200 mg per day in 1 or 2 doses.
Treatment of
pain: the recommended initial dose is 400 mg,
followed by an additional dose of 200 mg on the first day if necessary. On
subsequent days, the recommended dose is 200 mg twice a day, as needed.
Treatment of
primary dysmenorrhea: The
recommended initial dose is 400 mg, followed by an additional dose of 200 mg on
the first day if necessary. On subsequent days, the recommended dose is 200 mg
twice daily, as needed.
Use in
patients of special clinical groups
Elderly patients: usually
no dose adjustment is required. However, in patients weighing less than 50 kg,
it is better to start treatment with the minimum recommended dose. Patients
with impaired liver function: in patients with mild hepatic impairment
(Child-Pugh class A), no dose adjustment is required. In patients with moderate
hepatic impairment (Child-Pugh class B), the initial recommended dose of the
drug should be halved.
Patients with impaired
renal function: in patients with mild to moderate renal impairment, no dose
adjustment is required.
Special
instructions and precautions
Consult your doctor before
using the drug.
Caution should be exercised
when using the drug in the following conditions:
• gastrointestinal diseases
(peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn's disease,
history of bleeding), Helicobacter pylori infection;
• concomitant use with
anticoagulants (warfarin), antiplatelet agents (acetylsalicylic acid,
clopidogrel), oral glucocorticosteroids (prednisolone), diuretics, selective
serotonin reuptake inhibitors (citalopram, fluoxetine, paroxetine, sertraline),
digoxin;
• fluid retention and
edema;
• moderate liver
dysfunction, history of liver disease, hepatic porphyria;
• chronic renal failure (CC
30-60 ml / min);
• significant decrease in
circulating blood volume (including after surgery);
• cardiovascular diseases,
arterial hypertension;
• cerebrovascular diseases;
• peripheral arterial
diseases;
• concomitant use with
CYP2C9 isoenzyme inhibitors;
• long-term use of NSAIDs;
• severe somatic diseases;
• elderly patients (including
those receiving diuretics, weakened patients with low body weight).
Influence on the ability to drive vehicles and mechanisms
Caution should be exercised
when driving vehicles and engaging in other potentially hazardous activities
that require increased concentration and speed of psychomotor reactions, as the
drug may cause dizziness and other side effects that may affect these
abilities.
From the
digestive system: abdominal pain, diarrhea, dyspepsia,
flatulence, vomiting.
From the
cardiovascular system: peripheral edema, increased blood pressure,
including worsening of arterial hypertension.
From the
nervous system: dizziness, insomnia.
From the
urinary system: urinary tract infection.
From the
respiratory system: bronchitis, cough, sinusitis, upper
respiratory tract infections, pharyngitis, rhinitis.
From the
skin: skin itching, skin rash, urticaria.
Others: facial edema.
If any of the
side effects listed in the instructions worsen, or you notice any other side
effects not listed in the instructions, tell your doctor.
Interaction
with other medicinal products
Warfarin and other
anticoagulants: prothrombin time may increase with concomitant administration.
Fluconazole, ketoconazole: concomitant administration of 200 mg fluconazole
once daily resulted in a 2-fold increase in plasma celecoxib concentrations.
This effect is due to inhibition of celecoxib metabolism by fluconazole via the
CYP2C9 isoenzyme. Patients taking fluconazole (a CYP2C9 isoenzyme inhibitor)
should take celecoxib at the lowest recommended dose. Ketoconazole (a CYP3A4
isoenzyme inhibitor) has no clinically significant effect on celecoxib
metabolism. ACE inhibitors/angiotensin II antagonists: inhibition of
prostaglandin synthesis may reduce the antihypertensive effect of ACE
inhibitors and/or angiotensin II antagonists. This interaction should be taken
into account when celecoxib is used concomitantly with ACE inhibitors and/or
angiotensin II antagonists. In elderly patients, those who are dehydrated
(including those receiving diuretic therapy), or those with compromised renal
function, concomitant use of NSAIDs, including selective COX-2 inhibitors, with
ACE inhibitors may result in deterioration of renal function, including
possible acute renal failure. These effects are usually reversible. Diuretics:
Previously known NSAIDs may reduce the natriuretic effect of furosemide and
thiazides in some patients due to decreased renal prostaglandin synthesis; this
should be taken into account when using celecoxib. Lithium: An increase in
plasma lithium concentrations of approximately 17% has been observed with
concomitant administration of lithium and celecoxib. Patients receiving lithium
therapy should be closely monitored when celecoxib is started or discontinued.
Other NSAIDs: Concomitant use of celecoxib and other NSAIDs
(non-acetylsalicylic acid) should be avoided.
Clinical experience with overdose is limited. No clinically significant
side effects were observed with a single dose of up to 1.2 g and multiple doses
of up to 1.2 mg/day in 2 divided doses.
Treatment: if overdose is suspected, induce vomiting, administer activated
charcoal and conduct appropriate supportive therapy.
Store
in a dry place at a temperature not exceeding 30°C. Keep out of reach of
children.
3 years. Do not use after the
expiration date stated on the package.
Dispensed by prescription.
10 tablets in a PVC/aluminium blister. 1 blister together with instructions for use in a cardboard box.