Salofalk

General characteristics. Structure:

Active agent: месалазин (5-aminosalicylic acid) - 500 mg.

Excipients:

kernel: MKTs — 200/400 mg; a gipromelloza — 18/36 mg; silicon dioxide colloid anhydrous — 0,25/0,5 mg; Eudradzhit NE 40D (40% dispersion of copolymer of methylmethacrylate and ethyl acrylate (2:1) and 2 of % of a nonoksinol) in terms of dry matter — 45/90 mg; magnesium stearate — 7,75/15,5 mg; dry matter of 33% of an emulsion of a simetikon (0,3% of sorbic acid consist of 92% of a simetikon of 7,7% of methyl cellulose) — 0,5/1 mg;

internal cover: gipromelloza of 2/4 mg; copolymer of methacrylic acid and methylmethacrylate (1:1) (Eudradzhit of L100) — 75/150 mg; triethyl citrate — 7,5/15 mg; talc — 20/40 mg — magnesium stearate — 5/10 mg; titanium dioxide — 12,5/25 mg;

external cover: a karmelloza of sodium — 15/30 mg; titanium dioxide — 5/10 mg; aspartame — 1/2 mg; citric acid anhydrous — 3/6 mg; fragrance vanilla — 2/4 mg; talc — 5,5/11 mg; K-25 povidone — 5/10 mg.

Pharmacological properties:

Pharmacodynamics. Possesses the local antiinflammatory action caused by inhibition of cyclooxygenase and synthesis of PG and leukotrienes. Slows down migration, degranulation, phagocytosis of neutrophils, and also secretion of immunoglobulins lymphocytes. Has antioxidant effect (due to ability to contact free oxygen radicals and to destroy them). Mesalazin can also catch the radicals which are formed of reactive compounds of oxygen. The results received in the researches in vitro indicate a possible role of inhibition of a lipoxygenase. Also influence on the maintenance of PG in a mucous membrane of intestines is shown. At oral administration месалазин renders preferential local effect in a mucous membrane of intestines and a submucosal layer, working from an intestines gleam. Therefore it is important that месалазин it is available to area of an inflammation. The ratio of system bioavailability and concentration of a mesalazin in plasma is not significant in respect of a therapeutic effectiveness, and serves more likely as the factor influencing safety. Ensuring release of active ingredient with the right place is helped by the fact that Salofalk's granules differ in stability in relation to a gastric juice and are characterized rn-dependent (thanks to a covering in the form of Eudradzhit of L) and slowed down (thanks to matriksny structure of granules) release of a mesalazin.

Pharmacokinetics.

Biotransformation.

Mesalazin is metabolized as a presistemny way in a mucous membrane of intestines, and a system way in a liver, turning into pharmacological inactive N-acetyl-5-aminosalicylic acid (N-Ats-5-ASK). The nature of acetylation does not depend on acetylating patient's phenotype. In small degree acetylation can be carried out due to action of bacterial microflora of a large intestine. Communication with proteins of plasma of a mesalazin and N-Ats-5-ASK makes respectively 43 and 78%.

Distribution.

Thanks to the size of granules (about 1 mm), transit to a small bowel comes from a stomach quickly. The combined pharmakostsintigrafichesky and pharmacokinetic research showed that drug reaches ileocecal department approximately in 3 h, and the ascending department of a large intestine — approximately in 4 h. The general time of transit on a large intestine makes about 20 h. About 80% of the accepted peroral dose reach thick, sigmoid and a rectum.

Absorption.

Release of a mesalazin from Salofalk begins with delay in 2–3 h, Cmax in plasma is reached approximately in 4–5 h. System bioavailability of a mesalazin after oral administration makes about 15-25%. Meal slows down absorption on 1–2 h, but does not change the speed and extent of absorption.

Meal can slow down transit of drug on 1–2 h, at the same time Tlag values (an interval of time after which the maintenance of a mesalazin for the first time is defined in blood) and Tmax increase, however in connection with the small size of granules it does not change the speed and extent of absorption. Meal causes small increase in Cmax and AUC values (the area under a concentration curve in blood).

Pharmacokinetic data of granules and tablets Salofalk are summed up in the following table (granules: 3 x 500 mg of a mesalazin a day, tablets: 3 x 2 (250 mg) a mesalazina in days; equilibrium state; 24 healthy volunteers).

The total quantity of a mesalazin and N-ATs-5-ASK removed by kidneys during 24 h is equivalent to about 25-32% according to the appointed dose of granules and tablets Salofalk. About 30% of this quantity are soaked up in an ileocecal zone, and about 90% in general — in an ileocecal zone and the ascending large intestine. Thus, about 80-90% 5-ACK the appointed doses are present at the descending large intestine, sigmoid and direct guts where the speed of their absorption is low.

Values of serumal Cmax 5-ACK and Ats-5-ASK in an equilibrium state were approximately in 1,4 and 1,2 times is higher at reception in comparison with the values observed at administration of drug 3 times a day in the same daily dose once a day. Equilibrium serumal contents at the time of the end of the period of dosing at reception was a little bit lower once a day, than at reception 3 times a day (in 0,3 and 0,4 times for 5-ACK and N-Ats-5-ASK respectively). At administration of drug once a day signs of system accumulation are noted.

At single peroral purpose of granules Salofalk in a dose of 20 mg/kg to 13 children (age from 5,9 to 15,8 years) with an active inflammatory disease of a large intestine indicators of system exposure of drug corresponded to that at adults. Salofalk was safe and was well had.

Data on Salofalk's pharmacokinetics at elderly at its use, both in tablets, and in granules are absent.

Elimination.

At reception of a mesalazin in a dose of 500 mg 3 times a day the general elimination by kidneys of a mesalazin and N-Ats-5-ASK in the conditions of the sating concentration made about 25%. Excretion of a nemetabolizirovanny part of a mesalazin made less than 1% of orally accepted dose. T1/2 is 4,4 h.

Indications to use:

- exacerbation of ulcer colitis of average and easy weight;

- maintenance of remission and/or long therapy of ulcer colitis.

Route of administration and doses:

Inside. Salofalk's granules should not be chewed. The ordered Salofalk's dose in granules needs to be accepted in the morning, in lunch time and in the evening or all dose once in the morning. Salofalk's granules should be put on language and to swallow, without chewing, washing down with a large amount of liquid.

For treatment of an exacerbation of ulcer colitis.

3 times a day or 3 bags depend on the clinical need for each individual case, on 1 bag of 500-1000 mg of a mesalazin once a day (there correspond 1,5–3,0 g of a mesalazin a day).

For maintenance of remission of ulcer colitis.

On 500 mg of a mesalazin 3 times a day or 3 bags once a day (there correspond 1,5 g of a mesalazin a day).

Children up to 6 years.

Salofalk in granules should not children be appointed younger than 6 years as experience of use of drug for patients of this age group is very limited.

Children are more senior than 6 years and teenagers.

At an exacerbation of a disease, depending on its weight, месалазин it is appointed in a dose of 30-50 mg/kg/days with distribution of a daily dose to 3 receptions or in 1 reception. For remission maintenance месалазин it is appointed in a dose of 15-30 mg/kg/days, at the same time the daily dose can be distributed on 2 receptions. To children with body weight to 40 kg usually recommend to appoint a half of a dose for adults, to children with body weight more than 40 kg — a dose for adults.

Both at treatment of aggravations of inflammatory process, and at prolonged use for the purpose of maintenance of remission of a granule have to be accepted regularly and consistently that allows to reach required therapeutic effect. The exacerbation of ulcer colitis usually abates in 8–12 weeks then the dose of a mesalazin at most of patients can be reduced to 1,5 g a day.

Features of use:

Before an initiation of treatment and in the course of its carrying out at the discretion of the attending physician it is necessary to determine parameters of a functional condition of a liver (such as activity of ALT or ACT) and to control analyses of urine (by means of test strips). Monitoring procedure is recommended usually in 14 days after an initiation of treatment, then 2-3 more times at an interval of 4 weeks. If results of analyses are normal, it is necessary to conduct control researches each 3 months. If emergence of additional symptoms is noted, control researches need to be carried out immediately.

It is necessary to be careful at patients with an abnormal liver function. Salofalk's appointment in granules is not recommended to patients with an impaired renal function.

If the renal failure developed in treatment time, it is necessary to think of nephrotoxic action of a mesalazin.

At Salofalk's appointment in granules the patient with diseases of lungs, in particular bronchial asthma, it is necessary to exercise careful control in the course of treatment.

Patients at whom anamnestic instructions on side reactions at purpose of the drugs containing Sulfasalazinum were noted are subject to careful observation during an initial stage of treatment by Salofalk in granules. If against the background of treatment by Salofalk there are reactions of acute intolerance, such as spasms, acute abdominal pains, fever, the expressed headache and rash, use of drug it is necessary to stop immediately.

At purpose of drug the patients suffering from a fenilketonuriya should remember that Salofalk in granules contains aspartame (as the substance impacting sweet relish) in the doses equivalent to the following amount of phenylalanine: 0,56 mg (Salofalk of a granule of 500 mg) and 1,12 mg (Salofalk of a granule of 1000 mg).

Salofalk in granules should not be applied to treatment of children 6 years are younger.

Influence on ability to drive the car or to perform the works demanding the increased speed of physical and mental reactions. It is necessary to be careful during the driving and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reaction.

Side effects:

Development of allergic reactions is possible though serious allergic reactions are very rare. At emergence of any of the following symptoms after acceptance of drug it is necessary to see a doctor immediately:

- allergic enanthesis;

- fever;

- breath difficulty.

At deterioration in the general state of health in connection with fever and/or emergence of an inflammation of a throat and mouth it is necessary to stop accepting medicine and to see immediately a doctor. Perhaps, these symptoms were shown owing to lowering of the level of leukocytes in blood (agranulocytosis) that can increase risk of a serious infection (blood test is necessary for definition of changes in a gemogramma).

Rare side effects (which are shown less than at 1 of 1000 patients, but more than at 1 of 10000 patients):

- abdominal pain, diarrhea, abdominal distention, nausea and vomiting;

- headache, dizziness.

Very rare side effects (which are shown less than at 1 of 10000 patients):

- changes in renal function, sometimes with hypostasis of extremities or an abdominal pain;

- a stethalgia, short wind or hypostasis of extremities owing to heart troubles;

- severe pain in a stomach owing to an acute inflammation of a pancreas;

- severe short wind owing to allergic pneumonia;

- severe diarrhea and an abdominal pain owing to an allergic inflammation of intestines;

- skin rashes or inflammation;

- muscle and joints pain;

- fever, quinsy, or an indisposition because of changes of uniform elements of blood;

- jaundice or an abdominal pain owing to disorders of a liver and disturbances of biliation;

- loss of hair and development of baldness;

- numbness and a pricking in hands and legs (a peripheral neuropathy);

- reverse reduction of mobility of spermatozoa.

Interaction with other medicines:

During treatment by Salofalk in granules interactions at simultaneous use of the following medicines can be observed (the majority of these possible interactions are based on theoretical premises): 

Anticoagulants of indirect action	Possible strengthening of anticoagulating effect (increase of risk of gastrointestinal bleedings)
Glucocorticoids	Possible strengthening of undesirable reactions from a stomach
Methotrexate	Possible increase in toxic action of a methotrexate
Пробенецид / Sulfinpyrazonum	Possible reduction of removal of uric acid
Spironolactonum/furosemide	Possible easing of diuretic effect
Rimfampitsin	Possible easing of tuberculostatic effect
The lactulose or other similar drugs reducing рН intestinal contents	Possible reduction of release of a mesalazin from granules owing to decrease рН, caused by metabolism of bacteria

At patients who at the same time receive treatment by Azathioprinum or 6 Mercaptopurinum it is necessary to remember possible strengthening of myelosuppressive effect of Azathioprinum and 6 Mercaptopurinums.

Contraindications:

- hypersensitivity to components of drug and other derivatives of salicylic acid;

- blood diseases;

- peptic ulcer of a stomach and duodenum;

- deficit glyukozo-6-fosfatdegidrogenazy;

- hemorrhagic diathesis;

- heavy renal/liver failure;

- children's age (up to 6 years);

- fenilketonuriya.

With care: pregnancy (I trimester), renal/liver failure easy and moderately severe, diseases of lungs (especially bronchial asthma).

Overdose:

Symptoms: nausea, vomiting, gastralgia, weakness, drowsiness.

Treatment: gastric lavage, purpose of laxatives, symptomatic therapy.

In overdose cases if necessary injection of solutions of electrolytes is carried out (artificial diuresis).

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children.

 

Issue conditions:

According to the recipe

Packaging:

The granules covered with a kishechnorastvorimy cover of the prolonged action, 500 and 1000 mg. On 930 or 1860 mg in PE the package laminated by aluminum foil; on 50 packages place in a cardboard pack.

On 930 or 1860 mg in PE the package laminated by aluminum foil; on 50 packages place in a cardboard pack and 2 cardboard packs No. 50 put a cardboard box.