Voltaren

Active material: Diclofenac
When ATH: M01AB05
CCF: NSAIDs
ICD-10 codes (testimony): G43, K80, M05, M08, M10, M15, M42, M45, M46, M54.1, M54.3, M54.4, M65, M79, N23, N70, N94.4, N94.5, R07, R52.0, R52.2
At KFU: 05.01.01.03.01
Manufacturer: NOVARTIS PHARMA AG (Switzerland)

Pharmaceutical form, composition and packaging

Pills, enteric coated yellow color, round, lenticular, with beveled edges, labeled “CG” on one side and “BZ” – another.

Excipients: Colloidal anhydrous silica, microcrystalline cellulose, lactose, magnesium stearate, corn starch, povidone K30, sodium carboxymethyl, gipromelloza, glyceryl polyethylene glycol oksistearat, iron oxide yellow, talc, Titanium dioxide, Copolymer of methacrylic acid/POLYACRYLIC esters, macrogol 8000, protivovspenivaûŝaâ silicone emulsion SE2.

10 PC. – blisters (3) – packs cardboard.

Pills, enteric coated light brown, round, lenticular, with beveled edges, labeled “CG” on one side and “GT” – another.

Excipients: Colloidal anhydrous silica, microcrystalline cellulose, lactose, magnesium stearate, corn starch, povidone K30, sodium carboxymethyl, gipromelloza, glyceryl polyethylene glycol oksistearat, iron oxide yellow, talc, Titanium dioxide, Copolymer of methacrylic acid/POLYACRYLIC esters, macrogol 8000, protivovspenivaûŝaâ silicone emulsion SE2, iron oxide red.

10 PC. – blisters (2) – packs cardboard.

Excipients: Colloidal anhydrous silica, cetyl alcohol, magnesium stearate, povidone K30, sucrose, gipromelloza, iron oxide red, polysorbate 80, talc, Titanium dioxide, macrogol 8000, sucrose kristallicheskaя, ink black 8015 (for marking).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Excipients: solid fats.

5 PC. – blisters (2) – packs cardboard.

Excipients: solid fats.

5 PC. – blisters (1) – packs cardboard.

The solution for the / m colorless or light yellow.

Excipients: mannyt, sodium bisulfite, benzyl alcohol, propylene glycol, water d / and, Sodium hydroxide.

3 ml – ampoule (5) – packs cardboard.

Pharmacological action

NSAIDs. Voltaren^® contains diclofenac sodium, substance nesteroidna structures, has expressed Antiinflammatory, analgesic and antipyretic effect.

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

Diclofenac sodium in vitro at concentrations, equivalent to those, achieved in treating patients, does not suppress the biosynthesis of proteoglycans of cartilage tissue.

For rheumatic diseases anti-inflammatory and analgesic properties Vol′tarena^® provide clinical effect, characterized by a significant reduction of symptoms of diseases like pain at rest and during movement, morning stiffness and swelling of joints, as well as improving functional status.

Post-traumatic and postoperative inflammatory phenomena of Voltaren Emulgel^® quickly eliminates pain (emerging as alone, and when driving), reduces inflammatory swelling and swelling of the wound.

When applying Vol′tarena^® in tablets and suppositories marked by pronounced analgeziruty effect drug for moderate to severe pain nerevmatičeskogo origin. In applying the drug in the form of solution for the on/m introduction, the product is through 1-15 m. It was also found, that Voltaren Emulgel^® is capable of lowering the pain and reduce blood loss during primary dismenoree.

Besides, Voltaren^® eases migraine attacks (When used in suppositories).

Pharmacokinetics

Absorption

Once inside tablets, covered with kishechnorastvorima liner, diclofenac completely absorbed from the intestine. Although induction is fast, It may be postponed due to the availability of the pill kishechnorastvorima sheath. After a single dose 50 mg C_max Notes on average 2 h and is 1.5 ug / ml (5 mmol / l). Absorption is directly related to the size of the dose.

In case of taking the pill Vol′tarena^® during or after eating passing it through the stomach slows (compared with the reception of prandial), but the number of vsasyvaûŝegosâ diclofenac is not changed.

Unnecessarily. about half the dose of diclofenac is metabolised during “first pass” through the liver (effect “first pass”), AUC in case reception Vol′tarena^® inside or rectal almost 2 half, than in the case of injecting the drug equivalent dose.

After repeated receptions drug pharmacokinetics indicators do not change. While respecting the recommended dosage of the drug there was no cumulation.

Judging by the number of output with urine unchanged diclofenac and its metabolites gidroksilirovannyh, after administration sustained-release tablets, coated, from it is released and absorbed the same amount of active substance, as is usual pills, covered with kishechnorastvorima liner. Nonetheless, System bioavailability diclofenac, released from tablets prolonged action, averages 82% the value of this same indicator after taking the pill, coated, in the same dose. This is due to the, perhaps, another manifestation of the effect “first pass” through the liver for dosage forms with a slow release of the active substance. Unnecessarily. active substance released from pills prolonged action slower, then C_max diclofenac in the blood plasma is less than, than in the case of taking the pill, covered with kishechnorastvorima liner.

After taking the Tablet prolonged action 100 mg C_max diclofenac in plasma achieved on average 4 no, the average value of 0.5 ug / ml (1.6 mmol / l). Food intake has no clinically significant effect on the absorption of the active substance tablets prolonged action and its systemic bioavailability.

During 24 h monitoring after taking the Tablet prolonged action 100 mg diclofenac concentration in the plasma is on average 13 ng / ml (40 nmoli /). Absorption is directly related to the size of the dosage.

Unnecessarily. at “first pass” through the liver metabolizes about one half the number of diclofenac, The AUC after administration of tablets prolonged action around 2 half, than in the case of Parenteral drug equivalent dose.

After repeated receptions drug pharmacokinetic indicators do not change. Subject to the recommended dosage of the drug there was no cumulation. Basal concentration of diclofenac, defined in the morning before taking another dose, is about 22 ng / ml (70 nmoli /) during treatment Vol′tarenom^® in the form of tablets prolonged action dose 100 mg 1 time / day.

Intake of diclofenac rectal suppositories It begins quickly, Although his speed suction less compared to ingestion of tablets, covered with kishechnorastvorima liner. After applying the rectal suppositories, contains 50 mg of the active substance, C_max diclofenac in plasma achieved on average within 1 no, but the value of C_max, calculated per unit of the applied dose, is approximately 2/3 from the corresponding figure, logging onto intake of enteric tablets. Absorption is directly related to the size of the dosage.

When re-introductions of the drug in the form of suppositories pharmacokinetic indicators do not change. Subject to the recommended dosage of the drug there was no cumulation.

After the / m diclofenac in a dose 75 mg its absorption begins immediately. FROM_max diclofenac in plasma achieved through 20 and m is 2.5 ug / ml (8 mmol / l). Absorption is directly related to the size of the dose. AUC after the/m of reference around 2 times, than after his oral or rectal use, Since in the latter cases, about half the number of diclofenac is metabolised in “first pass” through the liver. Subsequent introductions drug pharmacokinetic indicators do not change. Subject to the recommended intervals between wvedeniami drug cumulation is not indicated.

Distribution

Serum protein binding – 99.7%, mostly to albumin (99.4%). In Кажущийся_d is 0.12-0.17 l / kg.

Diclofenac penetrates into synovial fluid, where his C_max achieved at 2-4 hours later, than in blood plasma. Seems T_1/2 of the synovial fluid is 3-6 no. Through 2 hours after reaching C_max plasma concentration of diclofenac in synovial fluid above, than in plasma, and its values remain higher throughout the period of time until the 12 no.

Metabolism

Metabolism of diclofenac is exercised partly through glucuronidation unmodified molecules, but, predominantly, through a single and multiple hydroxylation and metoksilirovaniâ, that leads to the formation of several phenolic metabolites (3′-hydroxy-, 4′-hydroxy-, 5′-hydroxy-, 4′,5-dihydroxy- and 3′-hydroxy-4′-metoksidiklofenaka), most of which turns into glûkuronidnye conjugates. Two phenolic metabolites of biologically active, but to a much lesser extent, Cem diclofenac.

Deduction

Total system plasma clearance of diclofenac is 263 ± 56 mL/min. The final T_1/2 is 1-2 no. T_1/2 4-x metabolites, including two pharmacologically active, also short and is 1-3 no. One of the metabolites, 3′-hydroxy-4′-metoksidiklofenak, has a longer T_1/2, However, this metabolite is completely inactive.

About 60% dose presented with urine in the form of glûkuronovyh conjugates of unchanged active substance, as well as in the form of metabolites, most of them are also glûkuronovye conjugates. The unchanged output less 1% diclofenac. The remainder of the dose appears in the form of metabolites with jelchew.

Pharmacokinetics in special clinical situations

After taking the drug inside differences in absorption, metabolism or excretion of the drug, associated with ageing patients, not indicated.

Children of diclofenac concentrations in plasma during reception of equivalent doses of the drug (mg / kg body weight) are similar to those in adults.

In patients with impaired renal dosing regime recommended subject to cumulation of unchanged active substance not celebrated. At least QC 10 mL/min the estimated equilibrium concentrations of diclofenac gidroksimetabolitov about 4 times higher, than in healthy volunteers, When the metabolites are excreted with jelchew exclusively.

In patients with chronic hepatitis or compensated liver cirrhosis the pharmacokinetics are similar to diclofenac such indicators in patients with preserved liver function.

Testimony

is inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid arthritis, ankylosing spondylitis, Spondyloarthropathies, osteoarthritis, juvenile rheumatoid arthritis (Pill, covered with kishechnorastvorima liner, 25 mg 50 mg or rectal suppositories 25 mg);

is inflammatory and degenerative forms of rheumatic diseases: rheumatoid arthritis, ankiloziruyushtiy spondylitis, osteoarthritis, Spondyloarthropathies (for solution for the on/m introduction);

-spinal diseases, accompanied by pain syndrome;

-rheumatic diseases of abarticular soft tissues;

— acute gout attack (Pill, covered with kishechnorastvorima liner and solution for the on/m introduction);

— renal colic (for solution for the on/m introduction);

-Biliary colic (for solution for the on/m introduction);

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

-Gynecologic diseases, accompanied by pain syndrome and inflammation (eg, Primary algomenorrhea, adnexitis);

as an additional tool in heavy infectious-inflammatory diseases of the ear, nose and throat, occur with the expressed pain syndrome, eg, When pharyngitis, tonsillitis, otite (with the exception of tablets prolonged action). The main treatment is carried out in accordance with generally accepted principles of, incl. with the use of antiviral therapy. Isolated fever is not an indication for use of drug;

is migraine attacks (suppository);

-severe migraine attacks (for solution for the on/m introduction).

In/m introduction of the drug particularly preferably at the beginning of the complications of inflammatory and degenerative diseases with high activity of inflammation and pain conditions, caused by inflammation nerevmatičeskogo Genesis.

Dosage regimen

Pills, enteric coated

The tablets should be swallowed whole, with some liquid, preferably before meals.

To Adult The recommended starting dose – 100-150 mg / day. In a relatively mild cases of the disease, as well as for long-term therapy is enough 75-100 mg / day. Daily dose should be divided into several receptions. If necessary, the influence of night pain or morning stiffness in addition to receive medication during the day prescribed Voltaren Emulgel^® in the form of suppository at bedtime; If the total daily dose should not exceed 150 mg.

At primary dismenoree daily dose picked individually; usually it is 50-150 mg. The initial dose should be 50-100 mg; When you need within a few menstrual cycles can be increased up to 150 mg / day. Admission drug should begin when the first symptoms. Depending on the dynamics of clinical symptoms treatment can continue for a few days.

Children weighing ≥ 25 kg prescribed medication at a dose rate of 0.5-2 mg / kg body weight / day (in 2-3 admission, depending on the severity of the disease). To treatment of rheumatoid arthritis the maximum daily dose can be increased to 3 mg / kg (in divided doses).

Apply tablets, enteric coated, 50 mg children not recommended.

Sustained-release tablets, coated

The tablets should be swallowed whole, preferably during meals.

To Adult The recommended starting dose – 100 mg (1 tab. long-acting)/d. The same dose used in relatively mild cases of the disease, as well as for long-term therapy. Where, when symptoms are most pronounced at night or in the morning, pills prolonged action preferably taken at night.

Nor should appoint tablets prolonged action children.

Rectal Suppositories

To Adult The recommended starting dose – 100-150 mg / day. In a relatively mild cases of the disease, as well as for long-term therapy is enough 75-100 mg / day. The multiplicity of use – 2-3 times. To facilitate night pain or morning stiffness prescribed Voltaren Emulgel^® in suppositories before bedtime, In addition to the use of the drug in pill form during the day; If the total daily dose should not exceed 150 mg.

At primary dismenoree daily dose picked individually; usually it is 50-150 mg. The initial dose should be 50-100 mg; When you need within a few menstrual cycles can be increased up to 150 mg / day. Treatment should begin when the first symptoms. Depending on the dynamics of clinical symptoms treatment can continue for a few days.

At onset of migraine starting dose is 100 mg. The drug is prescribed at the first sign of an approaching attack. Optionally, on the same day, you can optionally apply Voltaren Emulgel^® in suppositories in the dose to 100 mg. If necessary, further treatment in the following days, the daily dose should not exceed 150 mg (several introductions).

Children weighing ≥ 25 kg drug appointed dose of calculation 0.5-2 mg / kg body weight / day (daily dose, Depending on the severity of symptoms, should be divided into 2-3 single doses). To the treatment of juvenile rheumatoid arthritis the maximum daily dose can be increased to 3 mg / kg (several introductions).

Apply suppositories 50 mg 100 mg children not recommended.

The solution for the / m

Voltaren^® Enter through deep in the gluteus muscle injection. It should not be used Vol′tarena injection^® more 2 days in a row. If necessary, treatment can be continued Vol′tarenom^® in the form of tablets or rectal suppositories.

The/m injections in order, to avoid damaging the nerve or other tissues, We recommend that you enter the drug deep into the/m in the upper outer quadrant of the gluteal region.

Usual dose is 75 mg (contents 1 ampoule) 1 time / day.

IN severe cases (eg, colic) as an exception,, may be held 2 injections of 75 mg, several hours apart (second injection should be opposite the gluteus area). Alternatively, a single injection of the drug per day (75 mg) can be combined with the admission of other dosage forms Vol′tarena^® (tablets, rectal suppositories), While the total daily dose should not exceed 150 mg.

At attacks of migraine the best result is achieved, If injected Voltaren Emulgel^® as soon as possible after the beginning of the attack, the/m in a dose of 75 mg, with subsequent application of suppository in the dose to 100 mg in the same day, if required. The total daily dose should not exceed 175 mg on the first day.

Side effect

When assessing the incidence of various adverse reactions following graduation: often – >10%, sometimes – >1-10%, rarely – >0.001-1%, in some cases – <0.001%.

From the digestive system: sometimes – epigastric pain, nausea, vomiting, diarrhea, stomach cramps, dyspepsia, flatulence, anorexia, the increase in the aminotransferaz in serum; rarely – gastrointestinal bleeding (vomiting blood, ground, diarrhea mixed with blood), ulcers of the stomach and intestines, accompanied or not accompanied by bleeding or perforation, hepatitis, accompanied or not accompanied by jaundice; in some cases – thrush, glossitis, damage to the esophagus, the emergence of diafragmopodobnyh strictures in the gut, disorders of the distal colon, such as non-hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis, fulminant hepatitis.

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

From the senses: in some cases – visual impairment (blurred vision, diplopia), hearing loss, noise in ears, dysgeusia.

Cardio-vascular system: in some cases, palpitations, chest pain, increased blood pressure, exacerbation of congestive heart failure.

Dermatological reactions: sometimes – skin rash; rarely – hives; in some cases, Bullous rashes, eczema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (acute toxic Epidermal Necrolysis), erythroderma (exfoliative dermatitis), hair loss, photosensitivity reaction, purpura (incl. allergic).

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

From the hematopoietic system: in some cases – thrombocytopenia, leukopenia, gemoliticheskaya anemia, aplasticheskaya anemia, agranulocytosis.

Hypersensitivity reactions: rarely – bronchospasm, System/anaphylacticskie anaphylactoidnye reaction, including arterial hypotension; in some cases – vasculitis, pneumonitis.

Local reactions: when using suppositories – Local reactions, aggravation of hemorrhoids, When the/m introduction sometimes – packing, pain, in some cases – abscesses, nekrozy.

Listed side effects observed including. When you apply the dose and duration of treatment, differing from the recommended.

Contraindications

— the ulcer of the stomach or intestines;

-ill information about attacks of bronchial asthma, krapivnice, acute rhinitis, associated with the use of acetylsalicylic acid or other NSAIDS, as well as any medications, suppress the production of prostaglandins;

- Proctitis (only for suppositories);

- Childhood and adolescence up 18 years (for a solution for / in);

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

The drug is not recommended for use in the third trimester of pregnancy (possible suppression of uterine contractility and premature closure of the ductus arteriosus in fetuses).

Solution for the on/m introduction is not appointed during pregnancy.

Pregnancy and lactation

The use of Voltaren^® when pregnancy is possible only in cases, the expected benefit to the mother outweighs the potential risk to the fetus. The drug is prescribed in the minimum effective dose. Same, as in the case of use of other inhibitors of prostaglandin-synthetase, These recommendations are particularly important in the third trimester of pregnancy (possible suppression of uterine contractility and premature closure of the ductus arteriosus in fetuses).

The use of Voltaren^® in the form of solution for the on/m introduction during pregnancy is not recommended.

When taking Vol′tarena^® oral dose 50 mg every 8 h diclofenac penetrate breast milk, but in such small quantities, that there is no reason to expect any adverse events in a child, breastfed.

If necessary, the appointment of Vol′tarena^® in the form of solution for the on/m introduction lactation should decide on the termination of breastfeeding.

Cautions

During the application Vol′tarena^® careful medical observation of the sick, have complaints, pointing to gastrointestinal disease; having information in history of ulcerative lesions of stomach or intestines; living with ulcerative colitis or Crohn's disease, as well as having a human liver.

During the application Vol′tarena^®, same, as well as other NSAIDs, may increase levels of one or more liver enzymes. Therefore, when long-term therapy Vol′tarenom^® as a precaution showed monitoring liver function. If a breach of the liver functional parameters are saved or amplified, or if there are clinical manifestations of liver disease or other symptoms (incl. eozinofilija, rash), Voltaren^® should be abolished. It will be appreciated, that hepatitis b with the use Vol′tarena^® can arise without prodromal′nyh phenomena.

Caution is needed in the appointment of Vol′tarena^® patients with hepatic Porphyria, tk. the drug can provoke attacks by porfirii.

Because prostaglandins play an important role in maintaining renal blood flow, particular caution is required when treating patients with impaired heart function or kidney, patients, receiving diureticeskie means, as well as patients, which have a significant decrease in volume of circulating blood plasma of any etiology, eg, in the period before and after the massive surgical interventions. In these cases, while applying Vol′tarena^® It is recommended as a precaution monitoring kidney function. Discontinuation of the drug usually leads to the restoration of the kidney to its original level.

Use caution when applying Vol′tarena^® in elderly patients. This is especially true the weakened or with low body weight of older people; they are encouraged to designate product in the minimum effective dose.

Special caution should be exercised when the/m a Vol′tarena^® patients with bronchial asthma, because of the risk of enhancing disease symptoms.

Against the backdrop of Vol′tarena^® can occur at any time (for the first time or again) gastrointestinal bleeding or perforation of DIGESTIVE TRACT ulceration/develop, accompanied or not accompanied by symptoms-predecessors. The more serious consequences of these complications can be observed in elderly patients. In those rare cases, When patients, receiving Voltaren Emulgel^®, develop these complications, the drug must be cancelled.

The first time you use the Vol′tarena^®, as well as other NSAIDS, in rare cases may develop allergic reactions, including anaphylacticskie and anaphylactoidnye reaction.

Possible reactions of hypersensitivity to metabisulfat sodium, is part of the solution for the on/m introduction.

Voltaren^®, Thanks to its farmakodinamičeskim properties, can mask manifestations of infectious diseases.

Voltaren^®, same, like other NSAIDS, may temporarily inhibit platelet aggregation. Therefore, in patients with impaired hemostasis requires careful monitoring of relevant laboratory values.

With long-term use, Vol′tarena^®, as well as other NSAIDs, shows the systematic monitoring picture peripheral blood.

Effects on ability to drive vehicles and management mechanisms

Patients, with a background of application Vol′tarena^® occurs dizziness or other violations of the central nervous system, including the impairment, You should not drive a car or driving arrangements during the period of application.

Overdose

Typical clinical picture, peculiar overdose Vol′tarena^®, does not exist.

Supportive and symptomatic treatment is indicated when such complications as lower HELL, renal failure, convulsions, violations of the gastrointestinal tract and respiratory depression. Unlikely, that forced diuresis, hemodialysis or gemoperfuzia will prove useful for deducing NSAIDS, tk. the active ingredients of these drugs is largely associated with the plasma protein and subjected to intense metabolism.

In the case of an overdose when taking the drug inside, for the early prevention of intake of diclofenac should undertake a gastric lavage and activated charcoal to appoint.

Drug Interactions

Voltaren^® can increase the concentration of lithium and digoxin in plasma together with the use of these drugs.

Voltaren^®, like other NSAIDS, may reduce the effect of diuretics. Simultaneous application Vol′tarena^® with kalisberegatmi dioretikami may lead to an increase in the level of potassium in the blood (in the case of such a combination of medicines this indicator should be frequently monitored).

Simultaneous application Vol′tarena^® with other NSAIDS may increase the risk of side effects.

Although not found in clinical studies the impact of Vol′tarena^® the anticoagulants, There were isolated reports of increased risk of bleeding in their joint application. It is recommended that careful monitoring of patients, receiving these drugs at the same time.

Voltaren^® can be assigned in conjunction with oral gipoglikemicakimi drugs and the effectiveness of the past does not change. However, the known individual messages on development in such cases as hypoglycemia, and hyperglycemia, necessitating changes in dose gipoglikemicakih drugs against the backdrop of Vol′tarena^®.

Caution should be exercised when using NSAIDS for less than 24 hours before the start of the application or after methotrexate therapy, tk. its concentration in the blood (and, Consequently, toxicity) may increase.

The influence of NSAIDS on the activity of prostaglandins in the kidneys can strengthen nefrotoksicnosti cyclosporin.

There are few reports of the occurrence of seizures in patients, at the same time taking NSAIDS and hinolonovye antibacterials.

Pharmaceutical interaction

You should not mix the solution Vol′tarena^®, contained in the sealed, with solutions of other drugs for injection.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

Pills, enteric coated, 25 mg should be protected from exposure to moisture and keep out of reach of children at a temperature of no higher than 30° c.

Pills, enteric coated, 50 mg should be stored out of the reach of children at a temperature of no higher than 30° c. Shelf life – 5 years.

Sustained-release tablets, coated, It should be kept out of the reach of children at a temperature of no higher than 30° c. Shelf life – 5 years.

Rectal suppositories should be stored out of the reach of children at a temperature of no higher than 30° c. Shelf life – 3 year.

Mortar for on/m introduction should be protected from exposure to light and heat and keep out of reach of children at a temperature of no higher than 30° c. Shelf life – 2 year.

The drug should not be used after the expiration date.