Instruction for use: Velphoro 500

Dosage form: Chewing tablets

Active substance: Ferri (III) oxyhydroxidum saccharosum-dextranum complexum

ATX

V03AE05 Iron hydroxide (III) metahydroxide, sucrose complex

Pharmacological group

Drugs for the treatment of hyperkalemia and hyperphosphatemia [Other metabolites in combinations]

The nosological classification (ICD-10)

N18.0 Terminal stage of kidney damage: Terminal stage of renal failure

N25.0 Renal osteodystrophy: Nephrocalcinosis; Osteodystrophy of renal genesis; Renal osteodystrophy in chronic renal failure; Osteodystrophy in chronic renal failure

Description of dosage form

Round, flat-cylindrical tablets of red-brown color with a facet and engraving "PA500" on one side, with the presence of a berry smell.

Pharmachologic effect

Mode action - hypophosphatemic.

Pharmacodynamics

The active ingredient of the preparation VelphoroŽ 500 is a complex of β-iron (III) oxyhydroxide (pn-FeOOH), sucrose and starch.

Binding to phosphate occurs by the exchange of ligands between hydroxyl groups and / or water and phosphate ions in the interval of physiological pH values in the digestive tract.

The concentration of phosphorus in the blood serum, as well as the concentration of calcium / phosphorus-containing substance, decreases due to a decrease in the absorption of the phosphate obtained from food.

Pharmacokinetics

The mechanism of action of the drug VelphoroŽ 500 is the binding of phosphate in the gastrointestinal tract, therefore, the concentration of this drug in the blood serum is not related to its effectiveness. Due to the insolubility and peculiarities of the splitting of the preparation of VelphoroŽ 500, it is not possible to carry out classical pharmacokinetic studies, for example, determination of Vd, AUC, mean retention time.

Suction

The active substance of the preparation of VelphoroŽ 500 is practically insoluble and, therefore, is not absorbed in the digestive tract.

However, cleavage products, monocyclic iron-containing compounds, can be released from the surface of pn-FeOOH and absorbed.

Distribution

Due to the insolubility and peculiarities of the splitting of the preparation of VelphoroŽ 500, there is no possibility of carrying out classical pharmacokinetic studies of this preparation. Thus, there is no data to evaluate the distribution of this drug.

Biotransformation

The active substance of the preparation VelphoroŽ 500 is not subjected to metabolic transformations. However, the cleavage products of the β-iron (III) complex of oxyhydroxide, sucrose and starch (mononuclear iron-containing substances) can be released from the surface of said polynucleotide complex and absorbed into the gastrointestinal tract. The results of clinical studies indicate a low systemic absorption of iron contained in the preparation of VelphoroŽ 500.

Data from in vitro studies suggest that sucrose and starch that are part of this drug can decompose into glucose and fructose during digestion. These substances can be absorbed into the blood.

Excretion

The data were obtained from studies in animals with oral administration to rats and dogs of the labeled 59Fe complex of β-iron (III) complex oxyhydroxide, sucrose and starch. Radioactively labeled iron was found in feces, but not in urine.

Indication of the drug Velphoro 500

Control of serum phosphorus concentration in patients with terminal stage of chronic renal failure who are on hemodialysis or peritoneal dialysis. The drug VelphoroŽ 500 should be used in complex therapy aimed at preventing the development of renal osteodystrophy, in combination with calcium preparations, 1,25-dihydroxycholecalciferol (vitamin D3) or its analog, or with calcimimetics.

Contraindications

Hypersensitivity to the active substance or any of the excipients;

Hemochromatosis and any other impairment of iron accumulation;

Hereditary intolerance to fructose, glucose-galactose malabsorption or sugar-isomaltase deficiency

Due to the fact that the safety and effectiveness of the preparation of VelphoroŽ 500 is not established in patients under 18 years of age, it is not recommended to use Velphorî 500 in this category of patients.

With caution: Patients with peritonitis on a background of peritoneal dialysis, expressed violations of the gastrointestinal tract or liver, and patients after extensive surgical interventions on the gastrointestinal tract were not included in the clinical studies of the drug VelphoroŽ 500. The preparation of VelphoroŽ 500 in these patient groups should be used Only after a thorough assessment of the benefit / risk ratio.

Application of pregnancy and breastfeeding

Data on the use of the drug VelphoroŽ 500 in women during pregnancy are absent. According to the results of studies of toxic effects on reproductive function and fetal development in animals, no undesirable effects of this drug on the course of pregnancy and childbirth, embryo / fetus development, or postnatal development have been identified. Prescribe this drug to pregnant women with caution.

Data on the use of Velphorî 500 in women during breastfeeding are not available. Since the absorption of iron contained in the preparation of VelphoroŽ 500 is minimal, its excretion into breast milk is unlikely. The decision to continue breastfeeding or treatment with VelphoroŽ 500 should be taken in consideration of the benefits of breastfeeding for the baby and the benefits of treatment with the Velphorî 500 for the mother.

Side effects

The classification of adverse reactions is given by the frequency of their development (number of reported cases / number of patients).

* Fecal matter color changes were observed very often in accordance with expectations from the use of oral iron-containing preparations.

** There have been several cases of transient discoloration of tooth enamel and tongue.

Laboratory Tests

Significant deviations of the results of laboratory safety tests from the norm are not registered.

Clinically significant changes in the parameters of iron accumulation in the body (ferritin, transferrin saturation and transferrin) and fat-soluble vitamins (A, D, E and K) were not detected during treatment with VelphoroŽ 500.

Interaction

Studies of inter-drug interactions in patients on dialysis have not been conducted.

Investigations of inter-drug interactions with losartan, furosemide, digoxin, warfarin and omeprazole were conducted with the participation of healthy male and female subjects. According to the results of the AUC determination, the concomitant administration of the preparation of VelphoroŽ 500 does not affect the bioavailability of the above drugs.

In vitro studies established inter-drug interactions (the adsorption effect of the drug VelphoroŽ 500) with the following drugs: doxercalciferol, paricalcitol. Nevertheless, according to the results of clinical studies, the absence of influence of the preparation of VelphoroŽ 500 on the effect of oral vitamin D analogues, associated with a decrease in the concentration of intact parathyroid hormone, was established. The concentrations of vitamin D and 1,25-dihydroxy vitamin D in the serum remained unchanged. It is important to take into account the recommendations for use listed below.

In vitro studies established inter-drug interactions (adsorption effect of the drug VelforoŽ 500) with the following medicines: alendronate, cefalexin, doxycycline and levothyroxine.

The results of clinical studies are currently not available. It is important to take into account the recommendations for use listed below.

In vitro studies established inter-drug interaction (adsorption effect of the drug VelphoroŽ 500) with the drug atorvastatin. Nevertheless, clinical studies indicate that the preparation of VelphoroŽ 500 does not affect the lipid-lowering effect of HMG-CoA reductase inhibitors (eg, atorvastatin and simvastatin), and the concentrations of vitamin D and its 1,25-dihydroxy metabolite remained unchanged.

In in vitro studies, the absence of inter-drug interactions with the following drugs has been established: cinacalcet, ciprofloxacin, clopidogrel, enalapril, hydrochlorothiazide, metformin, metoprolol, nifedipine, pioglitazone, simvastatin and quinidine.

With the appointment of any drug that interacts with iron, such a drug should be taken no later than 1 hour before or 2 hours after taking VelphorîŽ 500.

Dosing and Administration

Inside. Tablets must be chewed. Do not swallow the tablets completely. Take with food.

To achieve maximum adsorption of food phosphate, the total daily dose of the drug should be divided between meals during the day. Patients do not need to drink more fluids than their usual drinking rations.

Before use, the tablets can be ground.

If you skip 1 dose of the drug or more, you should take the usual dose of this medication during the next meal.

The initial dose (adult patients, including elderly patients (over 65 years of age)

The recommended initial dose of VelforoŽ 500 is 1500 mg / day (3 tablets). The drug should be taken with food.

Dose selection and maintenance dose. Serum phosphorus concentration should be monitored and the dose of VelphoroŽ 500 should be adjusted, increasing or decreasing the dose by 500 mg / day (Table 1) every 2-4 weeks until an acceptable concentration of phosphorus in the blood is obtained, followed by regular monitoring of phosphorus concentration.

In clinical practice, the treatment is based on the need to control the concentration of phosphorus in the blood serum. The usual maintenance dose at which the optimal therapeutic effect is achieved is 1500-2000 mg / day (3-4 tablets).

The maximum daily dose

The maximum recommended dose is 3000 mg / day (6 tablets).

Special patient groups

Children. The safety and efficacy of VelphoroŽ 500 in children under 18 have not been established to date.

Patients of advanced age. When conducting clinical trials in elderly patients (over 65 years) with an approved dosing regimen, no significant problems were identified.

Violations from the kidneys. The preparation VelphorîŽ 500 is used to control the level of phosphorus in the blood in patients with terminal stage of CRF who are on hemodialysis or peritoneal dialysis. Data on the use of the drug VelphoroŽ 500 in patients with renal insufficiency in the early stages are absent.

Violations of the liver. In the course of clinical studies of this drug, no significant changes in hepatic transaminase activity or the development of violations from the liver have been identified.

Overdose

There are no reports of cases of an overdose of the drug VelphoroŽ 500.

Due to the low level of absorption of iron contained in the preparation of VelphoroŽ 500, the risk of developing systemic toxicity of iron is negligible.

Treatment: correction of the consequences of an overdose of the drug VelphoroŽ 500 (eg hypophosphatemia) should be performed in accordance with standard clinical practice.

Special instructions

The preparation of VelphoroŽ 500 can lead to a change in the color of stool (black). Modified (black) color feces can visually mask bleeding from the digestive tract. However, the preparation of VelphoroŽ 500 does not affect the results of latent blood tests with guaiac resin (Hämocult) or immunological (iColo Rectal and Hexagon Obti).

The drug may be harmful to the teeth due to the presence of sucrose in the composition.

The preparation VelphoroŽ 500 contains starches. When prescribing the drug to patients with allergies to gluten, celiac disease or diabetes mellitus, it should be taken into account that one tablet of the drug VelphoroŽ 500 contains the equivalent of 0.116 XE (corresponding to approximately 1.4 g carbohydrates).

Influence on ability to drive vehicles, mechanisms. Studies of the possible effects of the drug on the ability to drive vehicles and control mechanisms have not been conducted.

Release form

Chewable tablets, 500 mg

By 6 table. Chewing in blisters of aluminum foil.

By 30 or 90 tablets. Chewable in vials of HDPE with a capacity of 150 or 400 ml respectively. The bottle is also packed with a dehumidifier and a cotton swab to minimize physical damage to the tablets. The bottle is sealed with a foil, the integrity of which guarantees the absence of the first opening, and is capped with a lid of polypropylene with a cardboard insert and protection from opening by children. A label is attached to the vial.

At 5 bl. Or 1 fl. Put in a pack of cardboard.

Manufacturer

Catalan Germany Schorndorf GmbH. Steinbeißtrasse, 1 and 2, 73614 Schorndorf, Germany.

Or Vifor SA Rue des Moncors, 10, 1752, Villars-sur-Glains, Switzerland.

Issued quality control: Vifor (International) Inc. Rehenstrasse, 37, 9014 Art. Gallen, Switzerland.

Name of the owner of the registration certificate: Vifor Fresenius Medical Kea Renal Pharma Ltd. Rehenstrasse, 37, 9014 Art. Gallen, Switzerland.

The address of LLC Fresenius Kabi: 125167, Moscow,

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Velphoro 500

At temperatures not higher than 25 ° C, in the original packaging. Keep the bottle tightly closed to provide protection from moisture.

Keep out of the reach of children.

Shelf life of the drug Velphoro 500

3 years.

Do not use after the expiry date printed on the package.