Alenthal, 100 mg 20 pcs.

Pharmacotherapeutic group

Non-steroidal anti-inflammatory drug (NSAID).

ATC code

M01AB16

Pharmacological properties

Pharmacodynamics

Aceclofenac has anti-inflammatory, analgesic and antipyretic effects. It inhibits the synthesis of prostaglandins and thus affects the pathogenesis of inflammation, pain and fever. Anti-inflammatory and analgesic effect of acheclofenac in rheumatic diseases significantly reduces the severity of pain, morning stiffness, joint swelling which improves the functional state of the patient.

Pharmacokinetics
Absorption
After oral administration aceclofenac is rapidly absorbed, its bioavailability is close to 100%. Maximum concentration (C_max) in blood plasma is reached 1.25-3 hours after oral administration. Food intake slows absorption, but does not affect its degree.

Distribution
Aceclofenac is highly bound to plasma proteins (> 99.7%). Aceclofenac penetrates into the synovial fluid, where its concentration reaches 60% of its concentration in blood plasma. The volume of distribution is 30 liters.

Metabolism
It is believed that aceclofenac is metabolized by CYP2C9 isoenzyme to form the metabolite 4-ON-aceclofenac, whose contribution to the clinical effects of the drug is likely to be minimal. Diclofenac and 4-ONE-acetylophenac are among the numerous metabolites of acetylophenac.

Elimination
The average elimination half-life (T1/2) is 4-4.3 hours. Clearance is 5 L/hour. Approximately 2/3 of the dose taken is excreted by the kidneys, mainly as conjugated hydroxymetabolites. Only 1% of the dose after oral administration is excreted unchanged.

Indications

Cure inflammation and pain syndrome in lumbago, toothache, scapular periarthritis, rheumatic soft tissue lesions. Symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis.

The drug is intended for symptomatic therapy, reduction of pain and inflammation at the time of use, does not affect the progression of the disease.

Dysmenorrhea.

Active ingredient

Composition

One film-coated tablet contains:

active ingredient: aceclofenac – 100.0 mg;

excipients: Microcrystalline cellulose, 82.6 mg; croscarmellose sodium, 8.0 mg; povidone K-30, 6.4 mg; sodium stearyl fumarate, 3.0 mg;

film coating: [hypromellose, 3.6 mg; talc, 1.2 mg; titanium dioxide, 0.66 mg; macrogol 4000 (polyethylene glycol 4000), 0.54 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] – 6.0 mg.

How to take, the dosage

Interaction

With the exception of warfarin, no studies of drug interactions have been conducted.

Aceclofenac is metabolized by the CYP2C9 isoenzyme; data in vitro indicate that aceclofenac may be an inhibitor of this enzyme. Thus, the risk of pharmacokinetic interaction is possible when aceclofenac is taken concomitantly with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfafenazole.

As with other NSAIDs, there is an increased risk of pharmacokinetic interactions with other drugs that are excreted by active renal secretion, such as methotrexate and lithium preparations.

Aceclofenac is highly bound to plasma albumin and therefore there is the possibility of displacement interactions with other drugs that bind to proteins.

The following is class-specific information for NSAIDs.

Methotrexate: NSAIDs inhibit the tubular secretion of methotrexate; moreover, there may be a slight metabolic interaction, resulting in decreased clearance of methotrexate. Therefore, administration of NSAIDs should be avoided when using high doses of methotrexate.

Lithium and digoxin preparations: some NSAIDs inhibit renal clearance of lithium and digoxin, which leads to increased plasma concentrations of both substances. Co-administration should be avoided unless the plasma concentrations of lithium and digoxin are monitored frequently.

Anticoagulants: NSAIDs inhibit platelet aggregation and damage gastrointestinal mucosa, which may increase the effect of anticoagulants and increase the risk of gastrointestinal bleeding during anticoagulant administration. Concomitant use of acyclofenac and oral anticoagulants of coumarin group, ticlopidine and thrombolytics should be avoided if the patient is not closely monitored.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) when used together with NSAIDs may increase the risk
of gastrointestinal bleeding.

Cyclosporine, tacrolimus: When concomitant use of NSAIDs with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to reduced renal formation of prostacyclin should be considered. Therefore, renal function parameters should be carefully monitored when concomitant use.

Other NSAIDs: Concomitant use of acetylsalicylic acid or other NSAIDs may increase the incidence of adverse events, so caution should be exercised.

Glucocorticosteroids: There is an increased risk of gastrointestinal ulcers or gastrointestinal bleeding.

Diuretics: Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics and may decrease the diuretic effect of furosemide and bumetanide and the antihypertensive effect of thiazides. Concomitant use with potassium-saving diuretics may lead to an increase in plasma potassium content. Aceclofenac had no effect on blood pressure control when coadministered with bendrofluazide, although interactions with other diuretics cannot be excluded.

Hypotensive drugs: NSAIDs may also reduce the effect of hypotensive drugs. Co-administration of angiotensin-converting enzyme inhibitors (ACE) or angiotensin II receptor antagonists and NSAIDs may lead to impaired renal function. The risk of acute renal failure, which is usually reversible, may increase in some patients with impaired renal function, such as elderly patients, or in dehydration. Therefore, caution should be exercised when using hypotensive drugs together with NSAIDs. Patients should consume adequate amounts of fluid and be appropriately monitored (monitoring of renal function at the beginning of coadministration and periodically during treatment).

Hypoglycemic agents: Clinical studies suggest that diclofenac can be used with oral hypoglycemic agents without affecting their clinical effect. However, there are separate reports on hypoglycemic and hyperglycemic effects of diclofenac. Thus, doses of drugs that may cause hypoglycemia should be adjusted when taking aceclofenac.

Zidovudine: concomitant administration of NSAIDs and zidovudine increases the risk of hematologic toxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive (HIV-human immunodeficiency virus) patients with hemophilia receiving zidovudine and ibuprofen.

Mifepristone: Aceclofenac can be used 8-12 days after mifepristone because NSAIDs reduce the effect of this group of drugs.

Colestyramine: other drugs, including NSAIDs, should be used at least 1 hour before or 4-6 hours after taking colestyramine to reduce its effect on drug absorption.

Special Instructions

Allental® and other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided concomitantly.

Adverse events can be minimized by using the lowest effective dose and reducing the duration of treatment necessary to control symptoms.

Gastrointestinal effects
.Bleeding, ulceration, or fatal GI perforation have been observed with any NSAID during any period of treatment, both in the presence of associated symptoms and with a history of serious GI disease (gastric and duodenal ulcers, Crohn’s disease, ulcerative colitis, etc.) and without.

The risk of bleeding, ulcer formation and gastrointestinal perforation increases with increasing dosage of NSAIDs in patients with a history of peptic ulcer disease, especially if accompanied by bleeding or perforation, as well as in elderly patients. In such patients the minimum effective dose of aceclofenac should be prescribed. Also when treating these groups of patients and patients who require concomitant use of low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal complications, the need for combination therapy with proton pump inhibitors (e.g., misoprostol or proton pump inhibitors) should be considered.

Patients with GI disease, including elderly patients, should report any unusual GI-related symptoms (especially bleeding), including when first taking Alenthal®. Particular caution should be exercised in patients concomitantly taking drugs that may increase the risk of bleeding or ulceration, such as systemic glucocorticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors or antiaggregants (such as acetylsalicylic acid).

If gastrointestinal bleeding or ulcers occur, treatment with Alenthal should be stopped.

Influence on the cardiovascular and central nervous system
.Patients with mild to moderate arterial hypertension and/or congestive heart failure require appropriate monitoring, since administration of NSAIDs (particularly in high doses with long-term use) may not significantly increase the risk of arterial thrombosis (e.g., myocardial infarction or stroke). There are no reliable data on the absence of this risk when taking acyclofenac.

Patients with uncontrolled arterial hypertension, chronic heart failure, established coronary heart disease, atherosclerosis of peripheral arteries and/or cerebrovascular disorders should use caution when taking Alenthal®. Also, patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should be cautious before first taking Alenthal®.

Influence on the liver and kidneys
Penetration of NSAIDs may cause a dose-dependent decrease in prostaglandin formation and acute renal failure. The importance of prostaglandins in renal blood flow should be considered when taking Alenthal® in patients with impaired heart, renal, or hepatic function, in patients receiving diuretics, in patients after surgery, and in older patients.

Patients with mild to moderate hepatic or renal impairment and patients with other conditions predisposing to fluid retention should use Alentral® with caution. In such patients, NSAIDs may lead to impaired renal function and fluid retention. Patients taking diuretics and persons with increased risk of hypovolemia should also use caution when taking Alenthal®. The minimum effective dose should be prescribed and renal function should be monitored regularly by a physician. Adverse renal events usually resolve after discontinuation of aceclofenac.

The use of aceclofenac should be stopped if changes in liver function persist or worsen, clinical signs or symptoms of liver disease develop, or other manifestations (eosinophilia, rash) occur. Hepatitis may develop without prodromal symptoms.

The use of NSAIDs in patients with hepatic porphyria may provoke an attack.

Hypersensitivity and skin reactions
As with other NSAIDs, acetylophenac may cause allergic reactions, including anaphylactic/anaphylactoid reactions, even when taken for the first time. Severe skin reactions (some of which may be fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been observed very rarely after taking NSAIDs. The highest risk of these reactions is observed during the first month of taking acyclofenac. In case of skin rash, lesions of the oral mucosa or other signs of hypersensitivity the drug Alenthal® should be discontinued. Skin and soft tissue infections may occur in individual cases of chickenpox. At present, the role of NSAIDs in worsening the course of these infections cannot be excluded. Therefore, Alenthal® should be avoided in chickenpox.

Hematologic disorders
Aceclofenac may cause reversible inhibition of platelet aggregation.

Respiratory system disorders
Cautious use of Alenthal® should be made in patients with a history of bronchial asthma or with current bronchial asthma, as administration of NSAIDs may provoke sudden bronchospasm in these patients.

Elderly patients
Caution should be exercised when taking Alenthal in elderly patients, as they are more likely to experience adverse events (especially bleeding and GI perforation) when taking NSAIDs. Complications can be fatal. Older patients are also more likely to have kidney, liver or cardiovascular disease.

Long-term use
All patients receiving long-term treatment with NSAIDs should be monitored closely (e.g., total blood count, functional liver and kidney tests).

Influence on driving and operating ability

Patients should refrain from driving and engaging in other potentially dangerous activities that require increased concentration and rapid psychomotor reactions, since the drug may cause dizziness and other side effects that may affect the above abilities.

Synopsis

Contraindications

– erosive and ulcerative lesions of the gastrointestinal tract (GIT) in the acute phase (including.
– gastrointestinal bleeding or suspected bleeding;
– complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including anamnesis);
– hypersensitivity to acetyllofenac or drug components;
– severe hepatic impairment or active liver disease;
– hematopoiesis and coagulation disorders;
– severe renal function disorder (creatinine clearance <30 ml/min), progressive renal disease, confirmed hyperkalemia;
– decompensated heart failure;
– period after coronary artery bypass grafting;
– pregnancy and lactation;
– age less than 18 years.

With caution

Hepatic, renal and gastrointestinal diseases in anamnesis; presence of Helicobacter pylori infection; bronchial asthma; arterial hypertension; decrease of circulating blood volume (including immediately after major surgical interventions); coronary heart disease; chronic renal, hepatic and cardiac insufficiency; creatinine clearance less than 60 ml/min; history of gastrointestinal ulcers; cerebrovascular disease; dyslipidemia/hyperlipidemia; diabetes mellitus; peripheral arterial disease; smoking; old age; alcoholism; severe somatic diseases; in patients with hemostasis defects, with the risk of cardiovascular thrombosis (myocardial infarction, acute cerebrovascular events (ischemic, hemorrhagic stroke)) systemic lupus erythematosus; long-term use of NSAIDs; simultaneous use of glucocorticosteroids, anticoagulants, antiaggregants, serotonin reuptake inhibitors.

Side effects

Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO):

very often > 1/10;

often from > 1/100 to < 1/10;

infrequent from > 1/1000 to < 1/100;

rarely from > 1/10000 to < 1/1000;

very rarely < 1/10000, including individual reports.

Disorders of the blood and lymphatic system:

Rarely, anemia;

very rarely, suppression of bone marrow activity, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.

Immune system disorders:

seldom – anaphylactic reactions, including shock; hypersensitivity.

Mental disorders:

very rarely – depression, “unusual” (atypical) dreams, insomnia.

Nervous system disorders:

often – dizziness;

very rarely – paresthesia, tremor, somnolence, headache, dysgeusia (perversion of taste).

Visual disorders:

rarely – visual impairment.

Hearing organ and labyrinth disorders:

very rarely – vertigo, tinnitus.

Disorders of the cardiovascular system:

Rarely – heart failure, increased blood pressure;

very rarely – tachycardia, skin hyperemia, “hot flashes” (short-term sensation of heat, accompanied by increased sweating), vasculitis.

Remorbid respiratory system, chest and mediastinum disorders:

seldom – shortness of breath;

very rarely – bronchospasm.

Gastrointestinal tract disorders:

often – dyspepsia, abdominal pain, nausea, diarrhea;

infrequently – flatulence, gastritis, constipation, vomiting, ulceration of the oral mucosa;

rarely – melena, gastrointestinal mucosal ulceration, hemorrhagic diarrhea, gastrointestinal mucosal hemorrhages;

very rarely – stomatitis, vomiting blood, intestinal perforation, worsening the course of Crohn’s disease and ulcerative colitis, pancreatitis.

Disorders of the liver and biliary tract:

often – increased activity of “liver” enzymes;

very rare – liver damage (including hepatitis), increased activity of alkaline phosphatase;

Skin and subcutaneous tissue disorders:

infrequent – itching, rash, dermatitis, urticaria;

rarely – angioedema;

Very rare – purpura, eczema, severe skin and mucous membrane reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis);

In isolated cases, serious skin and soft tissue infections have been observed when NSAIDs are taken during chickenpox.

Renal and urinary tract disorders:

infrequent – increased concentration of urea and creatinine in blood plasma;

very rare – nephrotic syndrome, renal failure, interstitial nephritis.

General disorders:

very rarely – increased fatigue, muscle spasms of the lower extremities.

Disorders of metabolism and nutrition:

very rarely – hyperkalemia, weight gain.

Overdose

Possible symptoms:
Nausea, vomiting, pain in the stomach, dizziness, headache, hyperventilation phenomena with increased seizure alertness.
Treatment:
Gastric lavage, administration of adsorbents (activated charcoal), symptomatic therapy. Forced diuresis, hemodialysis are not sufficiently effective.

Pregnancy use

Pregnancy
The drug Alenthal® is contraindicated in pregnancy. There is no information on the use of aceclofenac in pregnancy. Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or development of the embryo/fetus.

In the third trimester of pregnancy, all prostaglandin synthesis inhibitors, with their cardiopulmonary toxicity, may cause premature closure of the Botall’s duct with development of pulmonary hypertension, as well as fetal renal dysfunction, which may progress to renal failure combined with polyhydramnios.

Women in late pregnancy and newborns: aceclofenac may affect the duration of bleeding due to an antiaggregant effect that may develop even after very low doses: aceclofenac may suppress uterine contractions, leading to delayed labor or prolonged labor.

Breastfeeding
Alenthal® should not be taken while breastfeeding. There are no data on excretion of acheclofenac with breast milk; when radioactive 14C-acheclofenac was administered to lactating rats no appreciable transfer of radioactivity into milk was observed.

Fertility
NSAIDs may affect fertility and are not recommended for women planning a pregnancy.

Similarities