Composition, form of production and packaging
Tablets are dispersible almost white, round, flat-cylindrical, with bevelled edge and impression "J 125 / NVR".
1 tab.
deferazirox 125 mg
Auxiliary substances: silicon dioxide colloidal anhydrous - 900 mcg, crospovidone - 85 mg, lactose monohydrate (200 bases) - 72.6 mg, lactose monohydrate (dry aerosol) - 63.3 mg, magnesium stearate, sodium lauryl sulfate - 2.1 mg, povidone K30 - 12.8 mg , microcrystalline cellulose - 63.3 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
Tablets are dispersible almost white, round, flat-cylindrical, with bevelled edge and impression "J 250 / NVR".
1 tab.
deferazirox 250 mg
Auxiliary substances: silicon dioxide colloidal anhydrous 1.8 mg, crospovidone 170 mg lactose monohydrate 145.2 mg lactose monohydrate 126.6 mg magnesium stearate sodium lauryl sulfate 4.2 mg povidone K30 25.6 mg , cellulose microcrystalline - 126.6 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
Tablets are dispersible almost white, round, flat-cylindrical, with bevelled edge and impression "J 500 / NVR".
1 tab.
deferazirox 500 mg
Auxiliary substances: silicon dioxide colloidal anhydrous - 3.6 mg, crospovidone - 340 mg, lactose monohydrate (200 bases) - 290.4 mg, lactose monohydrate (dry aerosol) - 253.2 mg, magnesium stearate, sodium lauryl sulfate - 8.4 mg, povidone K30 - 51.2 mg , microcrystalline cellulose - 253.2 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Complexing agent. It is a triple ligand, which has a high affinity for iron (III) and binds it in a ratio of 2: 1.
The drug enhances the excretion of iron, mainly with feces. Deferazirox has a low affinity for zinc and copper and does not cause a persistent decrease in the content of these metals in the serum.
In the study of iron metabolism in adult patients with О±-thalassemia with post-transfusion iron overload with the use of deferazirox at daily doses of 10 mg / kg, 20 mg / kg and 40 mg / kg, the average effective iron excretion averaged 0.0119 mg Fe / kg, 0.329 mg Fe / kg and 0.445 mg Fe / kg body weight per day, respectively.
The use of deferazirox was studied in adult patients and children aged 2 years and older with chronic post-transfusion overload with iron. The main diseases requiring regular transfusions include? -talassemia, sickle-cell anemia and other congenital and acquired anemia (myelodysplastic syndromes, congenital hypo-plastic anemia of Diamond-Blackfen, acquired aplastic anemia and other rare forms of anemia).
Daily use of deferazirox in doses of 20 mg / kg and 30 mg / kg for 1 year in adults and children with? -talassemia on the background of ongoing blood transfusions led to a decrease in the total iron stores in the body; the iron content in the liver decreased on the average by approximately 0.4 mg Fe / g and 0.9 mg Fe / g of dry liver substance, respectively, the concentration of serum ferritin decreased by an average of almost 36 Ојg / l and 926 Ојg / l, respectively.
When using the drug in the same doses, the ratio of excretion of iron to iron intake in the body was 1.02 (which is an indicator of the normal iron balance) and 1.67 (which corresponds to increased excretion of iron from the body). A similar therapeutic response was observed with the use of deferasirox in patients with iron overload and with other types of anemia. The use of the drug at a daily dose of 10 mg / kg for 1 year allowed to maintain the normal iron content in the liver, the concentration of serum ferritin and contributed to the balance of iron (the balance between iron intake and excretion) in patients who rarely receive blood transfusion or exchange blood transfusions . Since the level of serum ferritin, determined monthly, reflected changes in the iron content in the liver, the dynamics of serum ferritin concentration may be a criterion for evaluating the effectiveness of therapy.
When using deferaziroxa at a dose of 20-30 mg / kg / day for 1 year in patients aged? 2 years with О±-thalassemia and chronic post-transfusion overload with iron and initial iron content in the liver? 7 mg Fe / g of dry liver substance, the decrease in iron content in the liver was 5.3 В± 8.0 mg Fe / g of dry matter of liver and was similar to that for deferoxamine (4.3 В± 5.8). Reducing the iron content in the liver to a value of 7 mg Fe / g of dry liver substance was observed in 58.6% of patients receiving Exidzhad (with the initial iron content in the liver? 7 mg Fe / g of dry matter liver).
With the use of deferazirox in a dose of 20-30 mg / kg / day in patients with ОІ-thalassemia and chronic posttransfusion overload with iron with an initial iron content in the liver, 7 mg of dry liver substance that could not receive deferoxamine treatment, a decrease in iron in the liver was 5.5 В± 7.4 mg Fe / g of dry substance of the liver. Reducing the iron content in the liver to a value of? 7 mg Fe / g of dry liver substance was noted in 58.5% of patients receiving Exidjad (with the initial iron content in the liver? 7 mg Fe / g dry substance of the liver).
The effect of the drug on serum ferritin levels and the ratio of iron excretion to its entry into the body was dose-dependent in the dose range of 5-30 mg / kg / day.
In patients with sickle-cell anemia and chronic post-transfusion iron overload, the mean decrease in iron in the liver was 1.3 and 0.7 mg Fe / g of dry liver for Exidzhad and deferoxamine, respectively.
56% of the time of transverse relaxation (T2 *), determined during a magnetic resonance imaging of the myocardium, left 5-20 ms), there was an improvement in myocardial function (an increase in T2 * by 16% of the initial).
The use of deferazirox in a dose of 20 to 40 mg / kg / day for 1 year in patients with? -talassemia, with post-transfusion overload with iron without myocardial damage (LVEF? 56%, T2 *? 20 ms) contributed to the maintenance of normal myocardial function (T2 * 32.0-32.5 ms).
In patients with iron overload and myocardial damage (T2 * <20 ms), treatment with Eksidzhad led to a decrease in iron content in the myocardium and a progressive improvement in T2 * values ​​over 3 years of follow-up. In patients with iron overload without myocardial damage, the use of Excigad prevented the accumulation of iron in the heart (the value of T2 * was maintained at a level of more than 20 ms) for more than a year of observation despite continued transfusion therapy.
In patients with thalassemia and chronic nontransfusion overload with iron, Eksidzhad therapy at a dose of 10 mg / kg of body weight for 1 year leads to a decrease in the iron content in the liver from the initial, on average, 3.80 mg Fe / r dry matter of the liver, while as in patients receiving placebo, the iron content in the liver is increased by 0.38 mg Fe / r dry matter of the liver. In addition, Eksidzhad therapy at a dose of 10 mg / kg body weight for 1 year leads to a decrease in serum ferritin level by 222 Ојg / l from the baseline values, and in patients receiving placebo, the concentration of serum ferritin increases by 114.5 Ојg / l .
PHARMACOKINETICS
Suction
Deferazirox is well absorbed after ingestion, the average Tmax in blood plasma is about 1.5-4 hours. Absolute bioavailability (according to AUC) of deferasirox with oral intake is about 70% compared with the intravenous administration. AUC increased approximately 2-fold when taken at breakfast with a high fat content (fat content accounts for> 50% of energy value) and almost 50% when taken during a standard breakfast. Bioavailability (according to AUC) deferaziroksa moderately (approximately 13-25%) increased with admission 30 minutes before meals with normal or high fat.
The total exposure (AUC) of deferasirox when administered as a suspension with orange or apple juice was equivalent to the drug exposure when applied as an aqueous suspension (relative values ​​of AUC of 103% and 90%, respectively).
In the equilibrium state, Cmax and AUC 0-24 h of deferasirox increase almost linearly with the dose. Deferazirox accumulates in the body, the cumulation factor is 1.3-2.3.
Distribution
Deferazirox binds to a high degree with blood plasma proteins (99%), almost exclusively with albumin; has a small apparent V d - about 14 L in adults.
Metabolism
The main way of metabolism of deferasirox is glucuronization followed by excretion with bile. Deferazirox undergoes enterohepatic recirculation. Deconjugation of glucuronates in the intestine and their subsequent reabsorption occurs. In healthy patients who received colestyramine after a single dose of deferazirox, AUC deferaziroxa decreased by 45%. Deferazirox undergoes glucuronization mainly with UGT1A1 (uridine diphosphate glucuronyltransferase / UGT / family 1, polypeptide A1) and to a lesser extent UGT1A3 (family UGT1, polypeptide A3).
Oxidative metabolism of deferasirox, mediated by CYP450, is expressed to a small extent (about 8%).
In vitro, there was no inhibition of metabolism of deferasirox with hydroxycarbamide.
Excretion
Deferazirox and its metabolites are excreted mainly with feces (84% of the dose). Renal excretion of deferazirox and its metabolites is minimal (8% of the dose). The average T 1/2 varies from 8 to 16 hours.
Pharmacokinetics in special clinical cases.
The general bioavailability of deferasirox in adolescents (12 to 17 years) and children (2 to 12 years) after single and multiple doses was lower than in adult patients.In children younger than 6 years, bioavailability is lower by 50% than in adults. However, this has no clinical significance, since the dosage regimen is set individually.
The pharmacokinetics of deferasirox in elderly patients (over 65 years) have not been studied.
In patients with impaired hepatic function or renal function, the pharmacokinetics of deferazirox have not been studied. The mean AUC of deferasirox in patients with impaired liver function of Class A and B on the Child-Pugh scale was higher than in patients with normal liver function by 16% and 76%, respectively. The mean Cmax in patients with impaired liver function of mild and moderate severity exceeded by 22% the value of this parameter in patients with normal liver function.
An increase in the activity of hepatic transaminases up to 5 times in comparison with VGN does not affect the pharmacokinetics of deferasirox.
INDICATIONS
- chronic post-transfusion overload with iron in adults and children 2 years and older;
- chronic nontransfusion overload with iron in patients with thalassemia aged 10 years and older.
DOSING MODE
Chronic posttransfusion overload with iron
Eksidzhad therapy is recommended to begin after transfusion of more than 20 units (about 100 ml / kg) of erythrocyte mass or in the presence of clinical data indicative of the development of chronic iron overload (for example, at a serum ferricin concentration of more than 1000 Ојg / l).
Doses (in mg / kg) should be calculated and rounded as close as possible to the dose of the whole tablet (125 mg, 250 mg, 500 mg).
Eksidzhad preparation should be taken orally 1 time / day on an empty stomach, at least 30 minutes before meals, preferably at the same time of the day every day.
Initial dose
The recommended initial daily dose of Eksidzhad is 20 mg / kg body weight.
For patients receiving transfusions of erythrocyte mass more than 14 ml / kg / month (approximately more than 4 blood transfusions per month for adults) in order to reduce the amount of iron in the body, an initial daily dose of 30 mg / kg can be considered.
In patients receiving less than 7 ml / kg / month of erythrocyte mass (approximately more than 2 blood transfusions per month for adults), an initial 10 mg / kg dose may be considered to maintain normal iron levels in the body.
In patients with a good clinical effect with deferoxamine treatment, the initial dose of Exidzhad should be half of the previously used dose of deferoxamine (for example, in a patient who received 40 mg / kg / day of deferoxamine 5 days a week or an equivalent amount, start with a dose of 20 mg / kg / day).
Maintenance dose
It is recommended to monitor the serum ferritin concentration on a monthly basis and, if necessary, to correct the dose of the Eksidzhad preparation every 3-6 months, based on changes in serum ferritin levels. Correction of the dose should be carried out in "steps"; "step" is 5-10 mg / kg. The direction of dose adjustment is determined by individual effectiveness of treatment and therapeutic tasks (maintenance or reduction of iron content).
If the drug is ineffective at a dose of 30 mg / kg (serum ferritin concentration remains at? 2500 Ојg / l), the dose should be increased to 40 mg / kg. It is not recommended to use a dose of more than 40 mg / kg, since the experience of using the drug in higher doses is limited.
Patients should achieve a gradual reduction (with a "step" of 5-10 mg / kg) of the dose of the drug in order to maintain serum ferritin concentration in patients with a target serum ferritin concentration (usually from 500 Ојg / L to 1000 Ојg / L) this target range.
If serum ferritin concentration is well below 500 Ојg / L, consideration should be given to interrupting treatment with Exidjad.
In patients with a low degree of iron overload or a slightly elevated serum ferritin concentration, the risk of toxic effects of the Eksidzhad preparation, as well as of other iron chelators, may increase with an unreasonably high dose of the drug.
Chronic nontransfusion overload with iron
Helicopter therapy with Eksidzhad in this category of patients is only possible with proven iron overload (iron content in the liver> 5 mg Fe / g of dry matter liver or serum ferritin concentration> 800 Ојg / l). If patients did not assess the iron content in the liver, then chelation therapy should be carried out with caution in order to minimize the risk of excessive chelation.
Initial dose
The recommended initial daily dose of Eksidzhad is 10 mg / kg body weight.
Dose selection
It is recommended to monitor the concentration of serum ferritin every month. Every 3-6 months, a step-by-step increase in the dose of the drug by 5-10 mg / kg is possible. Correction of the dose is possible while maintaining the iron content in the liver at the level of? 7 mg Fe / g of dry liver substance or persisting (without a downward trend) serum ferritin level> 2000 Ојg / l and with good tolerability of therapy. The use of the drug Eksidzhad in patients with thalassemia in a dose of more than 20 mg / kg body weight is not recommended (due to a lack of data on the efficacy and safety of use in this dose).
If the evaluation of iron in the liver is not carried out and the serum ferritin concentration? 2000 Ојg / l, then the dose of the drug Eksidzhad should not exceed 10 mg / kg of body weight.
In patients receiving therapy at a dose of more than 10 mg / kg body weight, it is recommended to reduce the dose of the drug Eksidzhad when the iron content in the liver is <7 mg Fe / g dry matter liver or ferritin concentration? 2000 Ојg / l.
The therapy with Eksidzhad should be completed when the iron content in the liver reaches 3 mg Fe / g of dry liver substance or ferritin concentration <300 Ојg / l. In the future, it is possible to resume therapy if there is a therapeutic need.
For patients of advanced age (over 65 years), there is no need for correction of the dosing regimen. Since clinical trials in elderly patients showed an increase in the incidence of adverse events compared with patients less than 65 years of age, this category of patients should carefully monitor adverse events and, if necessary, reduce the dose of the drug.
For children and adolescents aged from 2 to 17 years, correction of the dosing regimen is not required. When calculating the dose for this category of patients, you should consider the change in body weight over time.
For patients with impaired renal function with a QC greater than 60 ml / min , the Eksidzhad preparation should be administered with caution, especially if there are additional risk factors, such as simultaneous use of drugs capable of causing renal dysfunction, dehydration or severe infections. Treatment with Eksidzhadom should be conducted with caution in patients with a serum creatinine level above the age norm. There is no need for correction of the initial dose for patients with impaired renal function. The level of serum creatinine should be monitored once a month; If necessary, the daily dose should be reduced by 10 mg / kg.
The use of the drug Eksidzhad in patients with impaired liver function has not been studied; in patients with impaired liver function of an average degree (class B on the Child-Pugh scale), the initial dose should be reduced by approximately 50%. The drug should not be used in patients with hepatic impairment, severe (class C Child-Pugh).
Monitoring of liver function should be performed before the initiation of treatment, every 2 weeks during the first month voremya treatment and monthly thereafter.
Application rules
When taken while eating deferasirox bioavailability increased to varying degrees, and the drug Eksidzhad must be taken on an empty stomach, and no less than 30 minutes prior to receiving piischi, preferably at the same time of day.
Because dispersible tablets are prepared slurry. Tablets were placed into a glass of water or orange or apple juice (100-200 ml) and stirred in a liquid to obtain a homogeneous suspension. The obtained suspension is taken orally, whereupon its residues in the beaker was added small quantity of water or juice, mixed and then also drink the liquid.
Dispersible tablets are not recommended to plant in carbonated drinks or milk.
Dispersible tablets should not be chewed or swallowed whole.
Since in carbonated drinks or milk-dispersible tablet slowly dissolves to form a foam Eksidzhad not recommended diluted in carbonated drinks or milk.
SIDE EFFECT
In patients with chronic post-transfusional iron overload most frequent adverse reactions reported during prolonged therapy Eksidzhadom in adults and children include disorders of the digestive system (26% of patients) - nausea, vomiting, diarrhea, abdominal pain, and dermatological disorders ( 7%) - a skin rash. These reactions are dose-related, mainly mild or moderate, are transient and disappear in most cases even with continued treatment. Easy non-progressive increase in serum creatinine, mostly within the normal range was observed in almost 34% of patients. This undesirable phenomenon is dose-dependent, often resolves spontaneously and can sometimes decrease at lower doses.
In patients with chronic post-transfusional iron overload in 2% of cases there was an increase in liver transaminases, which is independent of dose. In most patients, an increase of transaminases were observed to receive Eksidzhada. Sometimes (0.3%) showed an increase in liver transaminase more than 10 times above ULN, suggesting the development of hepatitis.
In a clinical study in patients with iron overload and thalassemia patients, in which patients received Eksidzhad preparation in a dose of 10 mg / kg of body weight, the most common side effects were diarrhea (9.1%), rash (9.1%), nausea (7.3%). Increasing the level of creatinine in blood serum and QC decrease noted in 5.5% and 1.8% respectively. Increased activity "liver" trasaminaz more than 2-fold compared with baseline and more than 5 times higher than normal was observed in 1.8% of patients.
As well as in the treatment of other iron chelators, patients treated Eksidzhad, there was a high frequency hearing loss and the eye lens opacity (cataract earlier).
Determination of the frequency of adverse reactions: very often (? 1/10); often (? 1/100, <1/10); infrequently (? 1/1000, <1/100), very rare (<1/10 000); Frequency not known: Isolated reports of these adverse events (establish a link between the use of the drug and the development of these adverse events is not always possible).
Immune system: frequency not known - hypersensitivity reactions (including anaphylaxis and angioedema). In most cases, hypersensitivity reactions have been observed in perivye months of drug treatment.
Mental disorder: infrequent - anxiety, sleep disorders.
From the nervous system: often - headache; rarely - dizziness.
From a sight organ: seldom - an early cataract, maculopathy, rarely - optic neuritis.
On the part of the organ of hearing: rare - loss of hearing.
From the side of respiratory system: rarely - pain in the larynx and pharynx.
From the digestive system: often - diarrhea, constipation, vomiting, nausea, abdominal pain, bloating, indigestion, increase in liver transaminases; rarely - gastrointestinal bleeding, gastric ulcer (including multiple) and duodenal ulcers, gastritis, hepatitis, cholelithiasis; rarely - esophagitis.
Of the liver and biliary tract: rarely - hepatitis, cholelithiasis; frequency is unknown - hepatic insufficiency.
Dermatological reactions: often - a rash, itching; infrequently - pigmentation disorders, the frequency is unknown - Stevens-Johnson syndrome, leukocytoclastic vasculitis, urticaria, alopecia.
From the urinary system: the frequency is unknown - acute renal failure (in most cases, there was an increase in serum creatinine in 2 times above ULN, after the cessation of drug therapy is usually observed in serum creatinine normalized?), Tubulointerstitial nephritis.
Laboratory findings: very often - an increase in the serum creatinine concentration; often - proteinuria; infrequently - tubulopathy (Fanconi syndrome), glucosuria.
Other: rarely - fever, swelling, fatigue.
In applying Eksidzhada been cases of cytopenias, including neutropenia, thrombocytopenia and worsening of anemia. In most cases cytopenia observed in patients with disorders of bone marrow hematopoiesis source. The causal relationship between these adverse events and the use of the drug was not detected.
In applying the drug in clinical Eksidzhad The practical isolated reports of hepatic failure development have been received (including fatal cases). In most cases, liver failure developed in patients with severe concomitant diseases, including cirrhosis and multiple organ failure.
There are rare reports of the development zhzheludochno-intestinal bleeding with a fatal outcome on background therapy with Eksidzhad in elderly patients with advanced hematological malignancies and / or low platelet counts.
Against the background of drug therapy there have been cases of renal tubulopathy (in most cases in children and adolescents?-Thalassemia and serum ferritin concentration <1500mkg / l).
CONTRAINDICATIONS
- QC <60 ml / min or concentration in serum creatinine of 2 or more times the upper limit of age norm;
- patients with myelodysplastic syndrome, or other high-risk hematological malignancies and hematological malignancies in which chelation therapy is ineffective due to the rapid progression of the disease;
- severe liver function abnormalities (class C Child-Pugh);
- Pregnancy;
- the period of lactation (breastfeeding);
- rare inherited disorders associated with galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption;
- Hypersensitivity to the components of the drug.
With careful use in elderly patients aged> 65 years; patients with a serum creatinine concentration of above age norms or CS 60 ml / min, especially in the presence of additional risk factors, such as the simultaneous use of drugs that may cause renal dysfunction, dehydration, or severe infection; patients with impaired hepatic function (use the drug Eksidzhad in patients with impaired liver function was not studied), when used together with anticoagulants and drugs having ulcerogenic effect (NSAIDs, corticosteroids, bisphosphonates for receiving INT) or with a decrease in the platelet count <50h10 9 / l.
Treatment with Eksidzhad performed only in patients with a serum creatinine level within the boundaries of age norm and the value of liver transaminases exceeding ULN not more than 5 times).
In applying the drug in adult patients and children may develop serious complications from the digestive system, such as gastro-intestinal bleeding, ulcerative lesions of the stomach and duodenum, due to which doctors and patients should be especially alert to siptomy ulceration of the stomach or duodenal ulcers, as well as signs of bleeding from the gastrointestinal tract.
The preparation includes lactose (1.1 mg lactose per mg deferasirox).
Eksidzhad The drug should not be used in patients with rare hereditary disorders associated with galactose intolerance, severe lactase deficiency or glucose-galaktaznoy malabsorption.
In case of severe hypersensitivity reactions to the drug Eksidzhadu should be lifted immediately and start appropriate therapy.
PREGNANCY AND LACTATION
Clinical data for use during pregnancy deferasirox net.V experimental studies have shown some reproductive toxicity in doses that are toxic to the maternal organism.
The potential risk to humans is unknown.
Eksidzhad not recommended in pregnant women except in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
In experimental studies it was found that deferasirox quickly and in large numbers comes into breast milk.
The effect of the drug on the offspring was noted. It is not known if deferasirox is excreted in breast milk in humans.
Women treated Eksidzhadom, it is not recommended to continue breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Application Eksidzhada in patients with impaired renal function has not been studied. Eksidzhadom Treatment should be undertaken with caution in patients with creatinine serum levels above the age norm. Not required correction starting dose for patients with impaired renal function. Creatinine serum levels should be monitored 1 time per month; if necessary, the daily dose should be reduced by 10 mg / kg.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Application Eksidzhada in patients with impaired liver function was not studied; in these patients the drug should be used with caution. Not required correction starting dose for patients with impaired liver function. Monitoring of liver function should be performed 1 time per month.
APPLICATION FOR CHILDREN
Experience of using Eksidzhada in children under 2 years are not available.
For children and adolescents aged 2 to 17 years of correct dosing regimen is required. When calculating the dose for this category of patients should take into account the change in body weight over time.
Application Eksidzhada not accompanied by growth retardation in children. However, as a precautionary measure when using the drug regularly (every 12 months) to control body weight and growth of the child.
APPLICATION IN ELDERLY PATIENTS
For elderly patients (over 65 years) does not require a correction mode.
SPECIAL INSTRUCTIONS
Therapy with Eksidzhad should start and carry out physicians with experience in the treatment of chronic post-transfusional iron overload, only after voozmozhnogo risk assessment and benefit from chelation therapy for the patient.
In applying adequately high dose Eksidzhad patients with a low degree of iron overload, or with a slight increase of ferritin concentration in serum of the toxic effect of the drug can increase.
Recommended monthly basis to determine the serum concentration of ferritin to evaluate the effectiveness of therapy.
If ferritin concentration in serum decreases steadily to a level less than 500 mg / l (when overloading
iron caused by blood transfusion), or less than 300 g / L (with thalassemia), then discontinue therapy with Eksidzhad.
In clinical studies, approximately 36% of treated Eksidzhadom, noted non-progressive increases in serum creatinine in serum, usually within normal limits.
Approximately one third of patients remained elevated serum creatinine concentration, despite the reduction in dose or discontinuation of the drug. When the post-marketing use of the drug Eksidzhad were cases of acute renal failure.
In adult patients a daily dosage Eksidzhad preparation can be reduced to 10 mg / kg, if during two visits consecutive non-progressive increases in serum creatinine in the serum was more than 33% compared to the average before the treatment, or calculated creatinine clearance became less than the lower limit of normal ( less than 90 ml / min) and it could not be attributed to other causes. In children, the dose can be reduced to 10 mg / kg if creatinine calculated clearance became less than the lower limit of normal (less than 90 ml / min or over two visits row creatinine level in plasma exceeds the upper limit of the age norm. If there is an increase in creatinine concentration in serum of more than 33% compared to the average pre-treatment and / or calculated creatinine clearance of serum less than the lower limit of normal, therapy should be interrupted drug Eksidzhad. The decision to resume le cheniya drug Eksidzhad taken based on the specific clinical situation.
Given the increased risk of complications when using the drug Eksidzhad in patients with impaired renal function or who receive drugs that have a negative impact on renal function is recommended to determine the level of serum creatinine and / or CK weekly during the first month of treatment and then monthly.
It recommended twice to determine the concentration of creatinine in serum before treatment. It is further recommended to determine the creatinine concentration in blood plasma creatinine clearance (calculated by the Cockcroft-Gault or MDRD formula in adults and Schwartz formula in children) and / or the content of cystatin C in blood plasma weekly after initiating or changing the dose Eksidzhad preparation. And then on a monthly basis.
When applying Eksidzhada be monthly to monitor the level of proteinuria.
In some cases it is necessary regularly to monitor additional parameters tubule kidney function (such as glycosuria patients not suffering from diabetes, and low concentrations of potassium, phosphate, magnesium or uric acid phosphaturia, aminoaciduria). When detecting deviations of said tubular indicators of kidney function from normal values should reduce the dose or temporarily stop the drug Eksidzhad.
Recommended monthly monitoring of liver function (hepatic transaminase activity, the concentration of bilirubin, alkaline phosphatase activity). With the progression of increase in liver transaminases, unrelated to any other factors, drug therapy should be interrupted Eksidzhad. Immediately after the determination of the causes biochemical changes or after the normalization of you might consider cautious resumption of therapy with Eksidzhad at a lower dose followed by gradual increase of her.
When applied post-marketing Eksidzhad preparation have been cases of liver failure (including fatal). Although in most cases developed hepatic failure in patients with underlying
