Voltaren candles 50mg №10

Voltaren candles

Clinico-pharmacological group

NSAIDs

Mechanism of action

NSAIDs. Voltaren ^® contains Diclofenac sodium, a nonsteroidal substance that has a pronounced anti-inflammatory, analgesic and antipyretic effect.

The main mechanism of action of diclofenac, established in the experimental conditions, is the inhibition of the biosynthesis of prostaglandins. Prostaglandins play an important role in the genesis of inflammation, pain and fever.

In vitro, diclofenac sodium at concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilage proteoglycans.

In rheumatic diseases, the anti-inflammatory and analgesic properties of Voltaren provide a clinical effect characterized by a significant decrease in the severity of such manifestations of diseases as pain at rest and on movement, morning stiffness and swelling of the joints, as well as an improvement in functional status.

In post-traumatic and postoperative inflammatory phenomena Voltaren^® quickly relieves pain (arising both at rest and when moving), reduces inflammatory swelling and swelling of a postoperative wound.

With the use of Voltaren in pills and suppositories, a pronounced analgesic effect of the drug was noted with moderate and severe non-rheumatic pain.origin. When using the drug in the form of a solution for i / m administration, the effect of the drug occurs in 1-15 minutes. It was also found that Voltaren^® able to reduce pain and reduce blood loss in primary dysmenorrhea.

In addition, Voltaren^® relieves migraine attacks (when used in suppositories).

Pharmacokinetics

Suction

After ingestion enteric-coated tablets Diclofenac is completely absorbed from the intestines. Although absorption is fast, its onset may be delayed due to the enteric coating of the tablet. After a single dose of 50 mg of the drug C_max it is noted on average in 2 hours and is 1.5 μg / ml (5 μmol / l). The degree of absorption is directly dependent on the magnitude of the dose.

In the case of taking Voltaren's pill during or after a meal, its passage through the stomach slows down (as compared with fasting), but the amount of absorbed diclofenac does not change.

Since about half of the dose of diclofenac is metabolized during the "first pass" through the liver (the effect of "first pass"), AUC in the case of Voltaren taking orally or rectal administration is almost 2 times less than in the case of parenteral administration of the drug in an equivalent dose.

After repeated doses of the drug, pharmacokinetic indicators do not change. At observance of the recommended dosage regimen of the drug cumulation is not observed.

Judging by the amount of unchanged diclofenac and its hydroxylated metabolites excreted in urine, after taking tablets of the prolonged action, coated the same amount of active substance is released and absorbed from it as from an ordinary enteric-coated tablet. However, the systemic bioavailability of diclofenac, released from long-acting tablets, averages 82% of the value of the same indicator after taking the coated tablets, in the same dose. This is due, perhaps, to another manifestation of the “first pass” effect through the liver for dosage forms with a slow release of the active substance. Since the active substance is released from the sustained release pill slower then C_max Plasma Diclofenac is less than in the case of taking an enteric-coated tablet.

After taking the prolonged action pill 100 mg C_max Diclofenac in plasma is reached on average after 4 hours; its average value is 0.5 μg / ml (1.6 μmol / l). Eating does not have a clinically significant effect on the absorption of the active substance from the pills of prolonged action and its systemic bioavailability.

Within 24 hours of observation after taking a sustained-release tablet, 100 mg of plasma diclofenac averages 13 ng / ml (40 nmol / l). The degree of absorption is directly dependent on the dose of the drug.

Sinceabout half the amount of diclofenac is metabolized in the “first pass” through the liver; the AUC after taking the prolonged-action pills is about 2 times less than in the case of parenteral administration of an equivalent dose of the drug.

After repeated administration of the drug, the pharmacokinetic parameters do not change. Subject to the recommended dosing regimen of the drug cumulation is not observed. The basal concentration of diclofenac, determined in the morning before taking the next dose, is about 22 ng / ml (70 nmol / l) during Voltaren treatment in the form of long-acting pills at a dose of 100 mg 1 time / day.

Diclofenac suction from rectal suppositories begins quickly, although the rate of its absorption is lower compared with the same indicator for the ingestion of pills enteric-coated. After using a rectal suppository containing 50 mg of the active substance, C_max plasma diclofenac is reached on average within 1 hour, but C value_maxcalculated per unit of the applied dose is approximately 2/3 of the corresponding indicator recorded after ingestion of the enteric tablet. The degree of absorption is directly dependent on the dose of the drug.

With repeated injections of the drug in the form of suppositories, the pharmacokinetic parameters do not change. Subject to the recommended dosing regimen of the drug cumulation is not observed.

After v / m introduction Diclofenac at a dose of 75 mg; its absorption begins immediately. WITH_max Diclofenac in plasma is reached in 20 minutes and is 2.5 μg / ml (8 μmol / l). The degree of absorption is directly dependent on the magnitude of the dose. AUC after i / m administration is about 2 times more than after its oral or rectal administration, since in the latter cases about half the amount of diclofenac is metabolized during the "first pass" through the liver. Subsequent injections of the drug pharmacokinetic parameters do not change. Subject to the recommended intervals between injections of the drug cumulation is not observed.

Distribution

Binding to serum proteins - 99.7%, mainly with albumin (99.4%). Seeming v_d is 0.12-0.17 l / kg.

Diclofenac penetrates the synovial fluid, where its C_max reached 2-4 hours later than in the blood plasma. Seeming t_1/2 from synovial fluid is 3-6 hours. 2 hours after reaching C_max in plasma, the concentration of diclofenac in synovial fluid is higher than in plasma, and its values ​​remain higher over a period of time up to 12 hours.

Metabolism

Diclofenac is metabolized partially by glucuronization of the unchanged molecule, but mainly through single and multiple hydroxylation and methoxylation, which leads to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5'-hydroxy-, 4 ', 5-dihydroxy and 3'-hydroxy-4'-methoxydiclofenac), most of which are converted into glucuronide conjugates.Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.

Removal

The total systemic plasma clearance of diclofenac is 263 ± 56 ml / min. Final t_1/2 is 1-2 h. T_1/2 4 metabolites, including two pharmacologically active ones, are also short and last for 1-3 hours. One of the metabolites, 3'-hydroxy-4'-methoxydiclofenac, has a longer T_1/2however, this metabolite is completely inactive.

About 60% of the drug dose is excreted in the urine in the form of glucuronic conjugates of the unchanged active substance, as well as in the form of metabolites, most of which are also glucuronic conjugates. Unchanged, less than 1% of diclofenac. The remaining dose of the drug is excreted in the form of metabolites with bile.

Pharmacokinetics in special clinical situations

After taking the drug inside, there are no differences in absorption, metabolism or elimination of the drug, related to the age of the patients.

In children, plasma concentrations of diclofenac when taking equivalent doses of the drug (mg / kg body weight) are similar to those in adults.

In patients with impaired renal function, if the recommended dosing regimen is observed, there is no cumulation of the unchanged active substance. When QA is less than 10 ml / min, the calculated equilibrium concentrations of diclofenac hydroxymetabolites are about 4 times higher than in healthy volunteers, and the metabolites are excreted exclusively with bile.

In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients with intact liver function.

Indications for use of the drug

- inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid arthritis, ankylosing spondyloarthritis, spondyloarthritis, osteoarthritis, juvenile rheumatoid arthritis (for enteric-coated tablets, 25 mg and 50 mg or suppositories of rectal 25 mg);

- inflammatory and degenerative forms of rheumatic diseases: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis (for solution for intramuscular administration);

- diseases of the spine, accompanied by pain;

- rheumatic diseases of extra-articular soft tissues;

- acute gout attack (for enteric-coated pills and solution for i / m administration);

- renal colic (for solution for i / m administration);

- biliary colic (for solution for i / m administration);

- post-traumatic and postoperative pain syndromes, accompanied by inflammation and swelling;

- gynecological diseases, accompanied by pain and inflammation (for example, primary algomenorrhea, adnexitis);

- as an additional tool in severe infectious and inflammatory diseases of the ear, throat and nose, occurring with severe pain, for example, pharyngitis, tonsillitis, otitis (with the exception of long-acting tablets). The main treatment of the disease is carried out in accordance with generally accepted principles, incl. with the use of etiotropic therapy. Isolated fever is not an indication for the use of the drug;

- migraine attacks (for suppositories);

- severe migraine attacks (for solution for i / m administration).

V / m administration of the drug is particularly preferable at the onset of exacerbations of inflammatory and degenerative diseases with a high activity of inflammation and in painful conditions caused by inflammation of non-rheumatic genesis.

Dosing regimen

Enteric-Coated Tablets

Tablets should be swallowed whole with a liquid, preferably before meals.

For adults The recommended initial dose is 100-150 mg / day. In relatively mild cases of the disease, as well as for long-term therapy, 75-100 mg / day is sufficient. The daily dose should be divided into several doses. If necessary, to influence night pain or morning stiffness in addition to taking the drug during the day, Voltaren is prescribed.^® in the form of suppositories at bedtime; at the same time, the total daily dose should not exceed 150 mg.

At primary dysmenorrhea daily dose picked individually; usually it is 50-150 mg. The initial dose should be 50-100 mg; if necessary, for several menstrual cycles, it can be increased to 150 mg / day.The drug should be started when the first symptoms appear. Depending on the dynamics of the clinical symptoms, treatment can be continued for several days.

Children weighing ≥ 25 kg prescribe the drug in a dose rate of 0.5-2 mg / kg of body weight / day (in 2-3 doses, depending on the severity of the disease). For treatment of rheumatoid arthritis The daily dose can be maximized to 3 mg / kg (in several doses).

Use enteric-coated pills 50 mg u children Not recommended.

Coated Extended Release Tablets

Tablets should be swallowed whole, preferably with meals.

For adults The recommended initial dose is 100 mg (1 tab. prolonged action) / day. The same dose is used in relatively mild cases of the disease, as well as for long-term therapy. In cases where the symptoms of the disease are most pronounced at night or in the morning, it is advisable to take long-acting pills at night.

Do not use prolonged-release tablets. for children.

Rectal suppositories

For adults The recommended initial dose is 100-150 mg / day. In relatively mild cases of the disease, as well as for long-term therapy, 75-100 mg / day is sufficient. Frequency of use - 2-3 times. For relief of night pain or morning stiffness, Voltaren is prescribed.^® in suppositories at bedtime, in addition to the use of the drug in pill form throughout the day; at the same time, the total daily dose should not exceed 150 mg.

At primary dysmenorrhea daily dose picked individually; usually it is 50-150 mg. The initial dose should be 50-100 mg; if necessary, for several menstrual cycles, it can be increased to 150 mg / day. Treatment should begin when the first symptoms appear. Depending on the dynamics of the clinical symptoms, treatment can be continued for several days.

At migraine attack the initial dose is 100 mg. The drug is prescribed at the first symptoms of an approaching attack. If necessary, on the same day, you can additionally apply Voltaren^® in suppositories in a dose of up to 100 mg. If it is necessary to continue treatment in the following days, the daily dose of the drug should not exceed 150 mg (in several injections).

Children weighing ≥ 25 kg the drug is administered at a dose of 0.5–2 mg / kg body weight / day (the daily dose, depending on the severity of the disease, should be divided into 2-3 single doses). For treatment of juvenile rheumatoid arthritis The daily dose may be maximized to 3 mg / kg (in several injections).

Use suppositories 50 mg and 100 mg in children Not recommended.

Solution for i / m administration

Voltaren^® administered by deep injection into the gluteus maximus muscle. Do not use Voltarena injections for more than 2 days in a row. If necessary, treatment can be continued by Voltarenum in the form of pills or rectal suppositories.

When conducting intramuscular injections in order to avoid damage to the nerve or other tissues, it is recommended to inject the drug deeply in intramuscular in the upper outer quadrant of the gluteal region.

The dose is usually 75 mg (contents of 1 ampoule) 1 time / day.

AT severe cases (such as colic) as an exception, 2 injections of 75 mg can be given, with an interval of several hours (the second injection should be carried out in the opposite gluteal region). Alternatively, a single injection of the drug per day (75 mg) can be combined with taking other Voltaren dosage forms (tablets, rectal suppositories), and the total daily dose should not exceed 150 mg.

At migraine attacks the best result is achieved if Voltaren is administered^® as soon as possible after the onset of an attack, i / m at a dose of 75 mg, followed by the use of suppositories at a dose of up to 100 mg on the same day, if required. The total daily dose should not exceed 175 mg on the first day.

Side effect

When assessing the frequency of occurrence of various adverse reactions, the following gradations were used: often (> 10%), sometimes (> 1-10%), rarely (> 0.001-1%), in some cases (<0.001%).

From the digestive system: sometimes - epigastric pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia , flatulence, anorexia, increased serum aminotransferase activity; rarely, Gastrointestinal bleeding (vomiting of blood, melena, diarrhea mixed with blood), stomach and intestinal ulcers, accompanied or not accompanied by bleeding or perforation, hepatitis, accompanied or not accompanied by jaundice; in some cases - aphthous stomatitis, glossitis, damage to the esophagus, the occurrence of diaphragm-like strictures in the intestine,disorders of the distal colon, such as non-specific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis, fulminant hepatitis.

From the side of the central nervous system and peripheral nervous system: sometimes - headache, dizziness; rarely - drowsiness; in some cases, sensitivity disorders, including paresthesias, memory disorders, disorientation, insomnia, irritability, convulsions, depression, anxiety, nightmares, tremor, psychotic reactions, aseptic meningitis .

From the senses: in some cases - visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, taste disturbances.

Since the cardiovascular system: in some cases - a feeling of heartbeat, chest pain, increased blood pressure, aggravation of congestive heart failure .

Dermatological reactions: sometimes a skin rash; rarely - urticaria; in some cases - bullous rash, eczema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (acute toxic epidermal necrolysis), erythroderma (exfoliative dermatitis), hair loss, photosensitivity reactions, purpura (including allergic).

From the urinary system: rarely swelling; in some cases, acute renal failure , hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hemopoietic system: in some cases - thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, agranulocytosis.

Hypersensitivity Reactions: rarely, bronchospasm, systemic anaphylactic / anaphylactoid reactions, including arterial hypotension; in some cases - vasculitis, pneumonitis.

Local reactions: when using suppositories - local reactions, exacerbation of hemorrhoids; with intramuscular injection, sometimes - compaction, pain; in some cases - abscesses, necrosis.

The listed side effects were observed including. with the use of doses of the drug and the duration of treatment, different from the recommended.

Contraindications to the use of the drug

- a stomach or intestinal ulcer;

- information in the history of attacks of bronchial asthma, urticaria, acute rhinitis, associated with the use of Acetylsalicylic acid or other NSAIDs , as well as any drugs that suppress the production of prostaglandins;

- proctitis (only for suppositories);

- children's and teenage age up to 18 years (for solution for in / in introductions);

- Hypersensitivity to diclofenac and any other ingredients of the drug.

The drug is not recommended for use in the third trimester of pregnancy (possibly suppression of uterine contractility and premature closure of the arterial duct in the fetus).

Solution for i / m administration is not prescribed during pregnancy.

Use of the drug during pregnancy and lactation

Voltaren use during pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. The drug is prescribed in the minimum effective dose. As in the case of the use of other prostaglandin synthetase inhibitors, these recommendations are especially important in the third trimester of pregnancy (suppression of uterine contractility and premature closure of the arterial duct in the fetus are possible).

The use of Voltaren in the form of a solution for i / m administration during pregnancy is not recommended.

When Voltarena is taken orally at a dose of 50 mg every 8 hours, diclofenac passes into breast milk, but in such a small amount that there is no reason to expect any undesirable effects in a breastfed baby.

If necessary, the appointment of Voltaren in the form of a solution for the / m introduction during lactation should decide on the termination of breastfeeding.

Application for violations of the liver

During the application of Voltaren, careful medical supervision of those patients who have impaired liver function is necessary.

During the use of Voltaren, as well as other NSAIDs, the level of one or more liver enzymes may increase. Therefore, during prolonged therapy with Voltaren, monitoring of liver function is shown as a precautionary measure. If abnormalities in the functional parameters of the liver persist or worsen, or if clinical manifestations of liver disease or other symptoms occur (for example, eosinophilia, rash, etc.), Voltaren should be abolished. It should be borne in mind that hepatitis against the background of the use of Voltaren can occur without prodromal phenomena.

Caution is needed when Voltaren is prescribed to patients with hepatic porphyria, since The drug may provoke attacks of porphyria.

Application for violations of kidney function

Since prostaglandins play an important role in maintaining renal blood flow, special care is required in the treatment of patients with impaired renal function, patients receiving diuretics. In these cases, during the application of Voltaren, monitoring of renal function is recommended as a precautionary measure. Discontinuation of the drug usually leads to the restoration of renal function to the initial level.

special instructions

During the application of Voltaren, careful medical supervision of those patients who have complaints pointing to gastrointestinal diseases is necessary; having a history of ulcerative lesions of the stomach or intestines; suffering from ulcerative colitis or Crohn's disease, as well as having impaired liver function.

During the use of Voltaren, as well as other NSAIDs, the level of one or more liver enzymes may increase. Therefore, during prolonged therapy with Voltaren, monitoring of liver function is shown as a precautionary measure. If abnormalities in the functional parameters of the liver persist or increase, or if clinical manifestations of liver disease or other symptoms occur (including eosinophilia, rash), Voltaren^® should cancel.It should be borne in mind that hepatitis against the background of the use of Voltaren can occur without prodromal phenomena.

Caution is needed when Voltaren is prescribed to patients with hepatic porphyria, since The drug may provoke attacks of porphyria.

Since prostaglandins play an important role in maintaining renal blood flow, special care is required when treating patients with impaired heart or kidney function, patients receiving diuretics, as well as patients who have a significant decrease in circulating blood plasma of any etiology, for example, before and after massive surgical interventions. In these cases, during the application of Voltaren, monitoring of renal function is recommended as a precautionary measure. Discontinuation of the drug usually leads to the restoration of renal function to its original level.

Caution must be exercised when applying Voltaren in elderly patients. This is especially true for weakened or low-weight older people; they are recommended to prescribe the drug in the minimum effective dose.

Particular caution should be exercised when the / m administration of Voltaren to patients with bronchial asthma, because of the risk of increased severity of symptoms of the disease.

Against the background of Voltaren's use, gastrointestinal bleeding may occur (for the first time or again) or develop ulceration / perforation of the gastrointestinal tract, accompanied by or not accompanied by precursor symptoms. More serious consequences of these complications may occur in elderly patients.In those rare cases when patients receiving Voltaren^®, these complications develop, the drug must be canceled.

The first use of Voltaren, as well as other NSAIDs, in rare cases, allergic reactions can develop, including anaphylactic and anaphylactoid reactions.

Perhaps the development of hypersensitivity reactions to sodium metabisulfate, which is part of the solution for the / m introduction.

Voltaren^®due to its pharmacodynamic properties, it can mask manifestations of infectious diseases.

Voltaren^®, as well as other NSAIDs, may temporarily inhibit platelet aggregation. Therefore, in patients with impaired hemostasis, careful monitoring of relevant laboratory parameters is necessary.

With long-term use of Voltaren, like other NSAIDs, systematic monitoring of the pattern of peripheral blood is shown.

Influence on ability to drive motor transport and control mechanisms

Patients who develop dizziness or other disorders of the central nervous system, including visual impairment during the use of Voltaren, should not drive a car or operate machinery during the period of use of the drug.

Overdose

The typical clinical picture, peculiar to an overdose of Voltaren, does not exist.

Supporting and symptomatic treatment is indicated for such complications as lowering blood pressure, renal failure, convulsions, gastrointestinal disturbances and respiratory depression.It is unlikely that forced diuresis, hemodialysis or hemoperfusion will be useful for removing NSAIDs, because The active substances of these drugs are largely associated with plasma proteins and are extensively metabolized.

In the event of an overdose while taking the drug inside, in order to quickly prevent the absorption of diclofenac, it is necessary to wash the stomach and appoint activated charcoal.

Drug interaction

Voltaren^® may increase the concentration of lithium and Digoxin in plasma with simultaneous use with these drugs.

Voltaren^®, like other NSAIDs, may reduce the effect of diuretics. The simultaneous use of Voltaren with potassium-sparing diuretics can lead to an increase in the level of potassium in the blood (in the case of this combination of drugs, this indicator should be often monitored).

Simultaneous use of Voltaren with other NSAIDs may increase the risk of side effects.

Although clinical studies have not established the effect of Voltaren on the effect of anticoagulants, there are some reports of an increased risk of bleeding in cases of their joint use. Careful observation of patients receiving these drugs at the same time is recommended.

Voltaren^® can be prescribed together with oral hypoglycemic drugs and at the same time the effectiveness of the latter does not change.However, there are individual reports of the development in such cases of both hypoglycemia and hyperglycemia, which necessitated a change in the dose of hypoglycemic drugs during the use of Voltaren.

Caution should be exercised when using NSAIDs less than 24 hours before the start of application or after the end of therapy with Methotrexate , because its concentration in the blood (and therefore toxicity) may increase.

The effect of NSAIDs on kidney prostaglandin activity may increase cyclosporine nephrotoxicity.

There are isolated reports of seizures in patients who took both NSAIDs and quinolone antibacterial drugs.

Pharmaceutical Interaction

Do not mix Voltaren solution in ampoules with solutions of other drugs for injection.

Pharmacy sales terms

The drug is available on prescription.

Terms and conditions of storage

Tablets, enteric-coated, 25 mg should be protected from moisture and stored out of reach of children at a temperature not higher than 30 ° C.

Tablets, enteric-coated, 50 mg should be stored out of the reach of children at a temperature not exceeding 30 ° C. Shelf life - 5 years.

Tablets of prolonged action, coated, should be stored out of the reach of children at a temperature not above 30 ° C. Shelf life - 5 years.

Rectal suppositories should be kept out of the reach of children at a temperature not exceeding 30 ° C.Shelf life - 3 years.

The solution for i / m injection should be protected from light and high temperatures and kept out of reach of children at a temperature not exceeding 30 ° C.