DR. DOPING

Instructions

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Instructions / Instruction for use: Mimparaa

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Active substance: Cinacalcet

ņ“’ Code: H05BX01 Cinacalcet /3711/

Pharmacological groups

Anti-parathyroid agent [Other hormones, their analogs and antagonists]

Nosological classification (ICD-10)

C75.0 Malignant neoplasm of parathyroid [parathyroid] gland

E21.1 Secondary hyperparathyroidism not elsewhere classified

Secondary Hyperparathyroidism

E21.2 Other forms of hyperparathyroidism

Hyperparathyroidism with bone damage

E83.5.0 * Hypercalcemia

Hypercalcemic crisis, Idiopathic hypercalcemia of newborns, Milk-alkaline syndrome

N18.0 Terminal stage of kidney damage

Terminal stage of renal failure

Composition

Tablets covered with a film membrane 1 tab.

active substance:

cyanacetcet hydrochloride 33.06 mg

(in terms of cinacalcet - 30 mg)

auxiliary substances: corn starch pregelatinized starch - 12.02 mg; MCC - 121.82 mg; povidone - 3.68 mg; crospovidone - 7.62 mg; magnesium stearate - 0.9 mg; silicon dioxide colloidal - 0,9 mg; wax Carnauba - 0.018 mg; (the lactose monohydrate is 40%, the hypromellose 15cP is 28%, the titanium dioxide is 19.38%, the triacetin is 8%, the indigo carmine aluminum varnish is 2.78%, the iron oxide is yellow 1.84%) - 7, 2 mg; opadray transparent (hypromellose 6sR - 90,9%, macrogol 400 - 9,1%) - 2,7 mg

Tablets covered with a film membrane 1 tab.

active substance:

tinacetcet hydrochloride 66.12 mg

(in terms of tsinakaltset - 60 mg)

auxiliary substances: corn starch pregelatinized starch - 24.04 mg; MCC - 243.64 mg; povidone - 7.36 mg; crospovidone - 15,24 mg; magnesium stearate - 1.8 mg; silicon dioxide colloidal - 1,8 mg; wax Carnauba - 0.036 mg; opedrai II green (lactose monohydrate 40%, hypromellose 15cR 28%, titanium dioxide 19.38%, triacetin 8%, indigo carmine aluminum varnish 2.78%, iron oxide yellow 1.84%) 14, 4 mg; opadray transparent (hypromellose 6sP - 90.9%, macrogol 400 - 9.1%) - 5.4 mg

Tablets covered with a film membrane 1 tab.

active substance:

cyanaccalcete hydrochloride 99.18 mg

(in terms of cinacalcet - 90 mg)

auxiliary substances: corn starch pregelatinized starch - 36.06 mg; MCC - 365.46 mg; povidone - 11.04 mg; crospovidone - 22.86 mg; magnesium stearate - 2.7 mg; silicon dioxide colloid - 2,7 mg; wax Carnauba - 0.054 mg; opedrai II green (lactose monohydrate 40%, hypromellose 15cP 28%, titanium dioxide 19.38%, triacetin 8%, indigo carmine aluminum varnish 2.78%, iron oxide yellow 1.84%) 21, 6 mg; opadray transparent (hypromellose 6sP - 90.9%, macrogol 400 - 9.1%) - 8.1 mg

Description of dosage form

Oval tablets covered with a filmy coating of light green color with the marking "AMG" on one side and "30", "60" or "90" on the other side.

pharmachologic effect

Pharmacological action - calcium-mimetic, reducing the level of parathyroid hormone.

Pharmacodynamics

Calcium-sensitive receptors on the surface of the main cells of the parathyroid gland are the main regulators of the secretion of parathyroid hormone (PTH). Tsinakaltset has a calcimimetic effect, directly reducing the concentration of PTH, increasing the sensitivity of this receptor to extracellular calcium. Reduction in the concentration of PTH is accompanied by a decrease in the serum calcium level.

The decrease in the concentration of PTH correlates with the concentration of cyanacetts. Shortly after the administration of cinnacalt, the concentration of PTH begins to decrease; with the maximum decrease occurring approximately 2-6 hours after the dose, which corresponds to the maximum concentration of cinacaltset (Cmax). After that, the concentration of cyanacett begins to decrease, and the concentration of PTH increases within 12 hours after the dose, and then PTH suppression remains approximately at the same level until the end of the daily interval with the dosing regimen once a day. The concentration of PTH in clinical studies of the Mimpara preparation was measured at the end of the dosing interval.

After reaching equilibrium, the concentration of calcium in the serum remains constant throughout the interval between doses of the drug.

Secondary Hyperparathyroidism

Three clinical trials of 6 months (double-blind, placebo-controlled) included patients with end-stage renal failure on dialysis with an uncontrolled form of secondary hyperparathyroidism (1,136 patients). The mean initial concentrations of intact parathyroid hormone (ipTG) in the three clinical trials were 733 and 683 pg / ml (77.8 and 72.4 pmol / L) in the zinc-calset and placebo groups, respectively, 66% of the patients took vitamin D before enrollment , and> 90% took phosphate binding drugs. In patients taking cinacalcet, there was a significant reduction in the concentration of ipPH, calcium and phosphorus in the serum, calcium phosphorus product (Ca × P) compared to patients in the placebo group who received standard therapy. Reduction in the concentration of IPPG and Ca × P was maintained for 12 months of therapy. Tsinakaltset reduced the concentrations of IPPH, calcium and phosphorus and Ca × P, regardless of the initial concentrations of ipHP or Ca × P, the dialysis regime (peritoneal dialysis compared to hemodialysis), the duration of dialysis, and whether or not vitamin D. was used.

The decrease in PTH concentration was associated with an insignificant decrease in the concentrations of bone metabolism markers (specific bone alkaline phosphatase, N-telopeptides, bone tissue renewal and bone fibrosis). In a retrospective analysis of the pool of data collected from 6 and 12-month clinical trials using the Kaplan-Meier method, the bone fracture and parathyroidectomy rates were lower in the cynocalcet group compared to the control group.

Preliminary studies for patients with chronic kidney disease (CKD) and secondary hyperparathyroidism who are not on dialysis indicate that cinacalcet reduced PTH concentrations in a similar manner as in patients diagnosed with end-stage renal failure (TSHD) and secondary hyperparathyroidism, who are on dialysis. However, for patients with renal insufficiency in the pre-dialysis stage, efficacy, safety, optimal dosages and target values of therapy were not established. These studies showed that in patients with CKD not on dialysis and receiving cinacalcet, there is a greater risk of developing hypocalcemia compared to dialysis patients with end-stage renal failure receiving cinacalcet, which may be due to a lower initial concentration of calcium and / or residual function of the kidneys.

Parathyroid carcinoma and primary hyperparathyroidism (GPT)

In the main study, 46 patients (29 patients diagnosed with parathyroid gland carcinoma and 17 with primary GPT (who had no results or were contraindicated for parathyroidectomy) received cinacalcet for up to 3 years (an average of 328 days for patients with parathyroid cancer and 347 days for patients with primary GPT).

Tsinakaltset was used in doses from 30 mg twice a day to 90 mg 4 times a day. The main goal of the therapy was to decrease the serum calcium concentration by ≥1 mg / dl (≥0.25 mmol / l). In patients with parathyroid carcinoma, the mean concentration of calcium decreased from 14.1 to 12.4 mg / dL (3.5-3.1 mmol / L), while in patients with primary GPT the serum calcium concentration decreased from 12.7 to 10.4 mg / dL (3.2 to 2.6 mmol / L). In 18 patients out of 29 (62%) with parathyroid carcinoma and 15 of 17 patients (88%) with primary GPT, a decrease in serum calcium concentration of ≥1 mg / dL (≥0.25 mmol / L) was achieved.

Pharmacokinetics

After oral administration of the Mimpara preparation, the maximum concentration (Cmax) of cyanacalt in the blood plasma is reached after about 2-6 hours. Absolute bioavailability of the cinacalcet at fasting, established on the basis of comparing the results of various studies, was approximately 20-25%. Taking Mimparaa along with food increased the bioavailability of the cinacaltset by about 50-80%. A similar increase in the concentration of cyanacetts in the blood plasma was observed regardless of the fat content in the food. The decrease in the concentration of the cinacaltset occurs in two stages; the initial half-life is approximately 6 hours, the final half-life is between 30 and 40 hours. The equilibrium state is reached within 7 days with minimal cumulation. The increase in the area under the concentration-time curve (AUC) and Cmax of the cinacalcet occurs almost linearly in the dosing range of 30-180 mg once a day. At dosages above 200 mg absorption saturation is observed, probably due to poor solubility. The pharmacokinetic parameters of the cinacaltset do not change with time. There is a high volume of distribution (approximately 1000 liters), which indicates a large distribution. Cyanaccal is approximately 97% bound to plasma proteins and distributed at a minimal level in erythrocytes. Tsinakaltset is metabolized by microsomal enzymes of the liver, mainly CYP3A4 and CYP1A2 (the role of CYP1A2 has not been confirmed by clinical methods). The main circulating metabolites are inactive. According to in vitro studies, cinacalcet is a potent inhibitor of CYP2D6, however, at concentrations attained in the clinical setting, cinacalcet does not inhibit the activity of other CYP enzymes, including. CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4, and is also not an inducer of CYP1A2, CYP2C19 and CYP3A4. After administration of 75 mg of radio-isotope-labeled dose to healthy volunteers, cyanaccalcet was subjected to a rapid and significant oxidative metabolism followed by conjugation. Excretion of radioactivity occurred mainly as a result of excretion of metabolites through the kidneys. Approximately 80% of the administered dose was found in urine and 15% in feces.

Elderly: in the pharmacokinetics of cinacaltset, there are no clinically significant differences associated with the age of the patients.

Renal insufficiency: the pharmacokinetic profile of cyanacet in renal failure of mild, moderate and severe degrees, and in hemodialysis or peritoneal dialysis, is comparable with the pharmacokinetic profile of the drug in healthy volunteers.

Hepatic insufficiency: mild liver failure does not have a significant effect on the pharmacokinetics of cinacaltset. Compared with the group with normal liver function, the average values of AUC of cinacalts were approximately 2 times higher in the group with moderate violations of the liver function, and approximately 4 times higher for hepatic insufficiency of severe degree. The average half-life of cinacalcet in patients with moderate to severe hepatic impairment is prolonged by 33 and 70%, respectively. Hepatic failure does not affect the degree of binding of cinacaltset to proteins. Since the selection of doses is based on the parameters of efficacy and safety, for patients with hepatic insufficiency, additional dose adjustment is not required (see the sections "Dosing and Administration", "Special instructions").

Gender: The zincalcetax clearance may be lower in women than in men. Since the selection of doses is carried out individually, no additional dose adjustment is required, depending on the patient's sex.

Children: the pharmacokinetics of cyanacetts were studied in 12 children (6-17 years) with CKD on dialysis, after a single oral intake of 15 mg. The mean values of AUC and Cmax (23.5 (range 7.22 to 77.2) ng ∑ h / ml and 7.26 (range 1.80 to 17.4) ng / ml, respectively) were within approximately 30% of the average values of AUC and Cmax observed in one study in healthy adults after a single oral intake of 30 mg of the drug (33.6 (range from 4.75 to 66.9) ng ∑ hr / ml and 5.42 (range from 1 , 41 to 12.7) ng / ml, respectively). Due to limited data in children, a potentially more pronounced exposure of a given dose of cyanacette in young children, with a lower body weight, than older children with a higher body weight, is not excluded. The pharmacokinetics of repeated doses in children have not been studied.

Smoking: The clearance of zincalcite is higher in smokers than in non-smokers. Apparently, this is due to the induction of metabolism, which takes place with the participation of CYP1A2. If the patient stops or starts smoking during therapy, the concentration of cyanacalt in the plasma may change and dose adjustment may be required.

Preclinical safety studies

During the preclinical studies, neither genotoxic nor carcinogenic potential of cinacaltset was detected. The safe range, according to toxicology studies, is narrow enough, because in animal experiments the dose-limiting factor was hypocalcemia. The development of cataracts and clouding of the lens were observed during toxicological and carcinogenic studies on rodents with multiple doses. However, such phenomena were not observed in experiments on dogs or monkeys, or in clinical studies, where monitoring was conducted with respect to cataract formation. It is known that cataracts in rodents can occur as a consequence of hypocalcemia.

Indication of Mimpara

secondary hyperparathyroidism in patients with terminal stage of renal failure who are on dialysis. Mimparaa can also be prescribed as part of a combination therapy, including drugs that bind phosphates and / or vitamin D;

hypercalcemia in patients (with the purpose of reducing the severity), caused by the following diseases:

- carcinoma of the parathyroid glands;

- Primary hyperparathyroidism, if, in spite of serum calcium concentrations, parathyroidectomy is clinically unacceptable or contraindicated.

Contraindications

hypersensitivity to the active ingredient or any other components of the drug;

children under 18 years of age (efficacy and safety not studied).

pregnancy and lactation

Clinical data on the use of cinnamyl acetate in pregnancy are absent. As preclinical studies on rabbits have shown, cinacaltset penetrates the placental barrier. In animal experiments, there was no direct adverse effect on pregnancy, childbirth or postnatal development. There was also no embryotoxic or teratogenic effect in experiments on pregnant female rats and rabbits, except for the reduction in embryo body weight in rats with the use of toxic doses in pregnant females. In pregnancy, Mimparaa should be used only if the potential benefit justifies the potential risk to the fetus.

Until now, the possibility of excretion of cyanacet in breast milk has not been studied. Tsinakaltset is excreted into the breast milk of lactating rats, with a high concentration ratio in milk to plasma concentrations. After a thorough assessment of the risk / benefit ratio, a decision should be made whether to stop breastfeeding or take the Mimpara preparation.

Side effects

Secondary Hyperparathyroidism

In controlled clinical trials, data were obtained from 656 patients taking the Mimpara preparation and 470 patients who took a placebo for up to 6 months. The most common adverse events were nausea and vomiting, which were observed in 31% of Mimparaa patients and 19% of patients in the placebo group, as well as in 27% of patients in the Mimparaa group and 15% in the placebo group, respectively. Nausea and vomiting were of mild to moderate severity and, in most cases, were of short duration. The discontinuation of therapy as a result of unwanted reactions was mainly caused by nausea (1% in the placebo group, 5% in the cynocalcet group) and vomiting (<1% in the placebo group, 4% of the cyanacetts).

Undesirable reactions associated with the use of cynacalt and found more often in the Mimparaa group than in the placebo group, in double-blind clinical trials, are given below in the following sequence: very often (> 1/10); often (from> 1/100 to <1/10); sometimes (from> 1/1000 to <1/100); rarely (from> 1/10000 to <1/1000); very rarely (<1/10000).

From the immune system: sometimes - hypersensitivity reactions.

Metabolism and food intake: often - anorexia.

From the nervous system: often - dizziness, paresthesia; sometimes - cramps.

From the digestive tract: very often - nausea, vomiting; sometimes - dyspepsia, diarrhea.

From the skin and subcutaneous tissue: often - a rash.

From the skeletal musculature, connective tissue and bone system: often - myalgia.

Common disorders and reactions to taking the drug: often - asthenia.

Laboratory indicators: often - hypocalcemia (see section "Special instructions"), decrease in testosterone level (see section "Special instructions").

Parathyroid carcinoma and primary hyperparathyroidism

The safety profile of Mimpara in these patient populations is generally consistent with the pattern observed in patients with chronic kidney disease. In these populations, the most common adverse reactions were nausea and vomiting.

Postmarketing observational studies

When using the Mimpara preparation in routine practice, the following adverse reactions were identified, the frequency of which can not be estimated on the basis of the available data:

- In patients with heart failure and receiving cinacaltset, individual idiosyncratic cases of lowering blood pressure (hypotension) and / or worsening of the course of heart failure were recorded;

- allergic reactions, including angioedema and urticaria.

Interaction

The effect of the combined use of other drugs on the pharmacokinetics of cyanacalt

Tsienakaltset is partially metabolized by the enzyme CYP3A4. Simultaneous administration of 200 mg of ketoconazole 2 times a day (a potent inhibitor of CYP3A4) resulted in an increase in the concentrations of cinacalcete by approximately a factor of 2. If simultaneous administration of potent inhibitors (eg, ketoconazole, itraconazole, telithromycin, voriconazole, ritonavir) or inducers (eg rifampicin) CYP3A4 is required, a dose adjustment of the Mimpara preparation may be required (see "Specific guidance").

The data obtained during in vitro experiments indicate that cinacalcet is partially metabolized by the enzyme CYP1A2. Smoking stimulates the activity of CYP1A2. It was noted that the clearance of cinacaltset is 36-38% higher in smokers than in non-smokers. The effect of inhibitors of CYP1A2 (fluvoxamine, ciprofloxacin) on plasma concentrations of zincalcite has not been studied. Dose adjustment may be required if, during treatment with Mimpara, the patient begins or stops smoking or initiates or stops simultaneous administration of potent inhibitors of CYP1A2.

Calcium carbonate: simultaneous application of calcium carbonate (a single dose of 1500 mg) did not change the pharmacokinetics of cyanacetts.

Sevelamer: simultaneous application of sevelamer (2,400 mg 3 times a day) had no effect on the pharmacokinetics of the cinacaltset.

Pantoprazole: simultaneous application of pantoprazole (80 mg once a day) did not change the pharmacokinetics of cyanacetts.

Effect of cinacaltset on the pharmacokinetics of other drugs

Drugs metabolized by the isoenzyme CYP2D6: cinacalcet is a potent inhibitor of CYP2D6. The combined use of cyanacetts and drugs with a narrow therapeutic range and / or variable pharmacokinetics metabolized by the CYP2D6 isoenzyme (eg, flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine) may require adequate dosage adjustment of these drugs (see section "Special instructions"). .

Desipramine: simultaneous dosing of 90 mg tsinakaltseta 1 time per day with 50 mg desipramine, mainly metabolized by CYP2D6, significantly increased the level of exposure to desipramine (3.6 times) (90% confidence interval 3.0, 4.4) in patients with active metabolism of CYP2D6.

Warfarin: repeated oral administration of cinnamyl acetate did not affect the pharmacokinetics or pharmacodynamics of warfarin (measured by MI and factor VII activity).

The absence of the effect of cinacaltset on the pharmacokinetics of R- and S-warfarin and the absence of autoinduced enzymes in patients after repeated administration of the drug indicates that cinacalcet is not an inducer of CYP3A4, CYP1A2 or CYP2C9 in humans.

Midazolam: simultaneous use of cinacaltset (90 mg) and oral midazolam (2 mg), substrate CYP3A4 and CYP3A5, does not affect the pharmacokinetics of midazolam. These data indicate that cinacalcet does not affect the pharmacokinetics of the class of drugs metabolized by CYP3A4 and CYP3A5 isoenzymes, such as certain immunosuppressants, including cyclosporin and tacrolimus.

Incompatibility. Not applicable.

Dosing and Administration

Inside, with food or soon after a meal, as during the research it was shown that the bioavailability of cinacalcet is increased when the drug is taken with food (see section "Pharmacokinetics"). Tablets should be taken whole, not chewing and not dividing them.

Liver failure

Patients with hepatic insufficiency do not need correction of the initial dose. Mimpra should be given with caution to patients with moderate or severe hepatic impairment. Careful clinical observation of the patient during the period of dose selection (titration) and continuation of therapy is necessary (see sections "Special instructions" and "Pharmacokinetics").

Secondary Hyperparathyroidism

Adults and the elderly (> 65 years of age): the recommended initial dose of Mimpara for adults is 30 mg once a day. Titration of the Mimpara dose should be performed every 2-4 weeks to a maximum dose of 180 mg (1 time per day), in which patients in dialysis achieve a target PTH concentration in the range of 150-300 pg / ml (15.9-31.8 pmol / l), determined by the concentration of IPPH. The determination of PTH concentrations should be carried out no earlier than 12 hours after taking the Mimpara preparation. When assessing the concentration of PTH should adhere to the current recommendations.

Determination of the concentration of PTH should be carried out 1-4 weeks after starting therapy or correcting the dose of Mimpara preparation. When taking a maintenance dose, monitoring of PTH concentration should be performed approximately 1 time in 1-3 months. To determine the concentration of PTH, the content of ipTG or bio-active PTH (biPTG) can be used; therapy with Mimparaa does not change the relationship between ipTG and biPTG.

During the titration of the dose, it is often necessary to monitor the concentration of calcium in the serum, incl. 1 week after starting therapy or correcting the dose of Mimpara. When reaching the target concentration of PTH and switching to a maintenance dose, the concentration of calcium in the blood serum should be evaluated approximately once a month. If the concentration of calcium in the blood serum falls below the normal range, appropriate measures should be taken, including correction of concomitant therapy (see section "Special instructions").

Parathyroid carcinoma and primary hyperparathyroidism

Adults and elderly (> 65 years): the recommended initial dose of Mimpara for adults is 30 mg, the frequency of intake is 2 times a day. Titration of Mimparaa dose should be done in 2-4 weeks increments as follows, increasing the dose of the drug: 30 mg twice a day; 60 mg twice a day; 90 mg 2 times a day and 90 mg 3 or 4 times a day as needed to reduce the serum calcium concentration to the upper limit of the normal range or lower. The maximum dose used in clinical trials was 90 mg with a multiplicity of intake 4 times a day.

The concentration of calcium in the blood serum should be determined 1 week after the initiation of therapy or the dose adjustment step of the Mimpara preparation.

When reaching the target concentration of PTH and switching to a maintenance dose, serum calcium concentrations should be evaluated every 2-3 months. At the end of the titration period to the maximum dose, periodic monitoring of serum calcium concentration should be performed.

If clinically significant decrease in serum calcium concentration is not achieved on a maintenance dose, the issue of discontinuing Mimparaa therapy should be addressed (see the section "Pharmacodynamics").

Overdose

Doses titrated up to 300 mg (1 time per day) are safe for patients on dialysis.

Symptoms: an overdose of Mimparaa can lead to hypocalcemia. In case of an overdose, patients should monitor the calcium concentration for timely detection of hypocalcaemia.

Treatment: symptomatic and supportive therapy should be given. Since the degree of binding of cinacaltset to proteins is high, cinacalcet is not excreted in hemodialysis, i.e. Hemodialysis with an overdose is not effective.

special instructions

Convulsions

In three studies involving patients with chronic kidney disease (CKD) and those on dialysis, 5% of patients in each of the groups receiving Mimparaa or placebo received seizures at the time of initiation of therapy. In these studies, seizures were noted in 1.4% of patients receiving Mimparaa and 0.4% of patients in the placebo group. Although the causes of reported differences in the occurrence of seizures are unclear, the convulsive threshold decreases with a significant decrease in the serum calcium concentration.

Hypotension and / or worsening of heart failure

In patients with heart failure who took cinacalcet during post-marketing observations, individual idiosyncratic cases of hypotension and / or worsening of the course of heart failure were recorded in which the causal relationship with cinacalcete can not be completely excluded and may be due to a decrease in serum calcium levels. Clinical studies have shown that hypotension occurred in 7% of patients receiving cinacaltset and in 12% of patients receiving placebo and heart failure in 2% of patients receiving cicacaltzet or placebo.

Whey calcium

Therapy with Mimpara should not be performed at a serum calcium concentration (adjusted for albumin) below the minimum limit of the normal range. Since cinnacalt reduces the concentration of calcium in the blood serum, careful monitoring of the development of hypocalcaemia (see section "Method of administration and dose") should be carried out. In patients diagnosed with CKD who are on dialysis, with the Mimpara preparation, the serum calcium concentration in 4% of cases was below 7.5 mg / dl (1.875 mmol / L). In the case of hypocalcemia, calcium-containing phosphate binders, vitamin D and / or correct calcium concentration in dialysis solution can be used to increase serum calcium concentration. With persistent hypocalcemia, you should reduce the dose or stop taking the drug Mimparaa. Potential signs of development of hypocalcemia can be paresthesia, myalgia, convulsions and tetany.

Tsinakaltset is not indicated for patients with a diagnosis of CKD not on dialysis. Preliminary studies have shown that in patients with CKD not dialysis, the risk of developing hypocalcaemia increases (serum calcium concentration <8.4 mg / dl -2.1 mmol / L) compared with patients on dialysis, which may be due to a lower initial concentration of calcium and / or the presence of residual renal function.

Are common

With chronic suppression of PTH concentration below the concentration of approximately 1.5 from the upper limit of the norm, as a result of the analysis of IPPH, adynamic bone disease may develop. If the PTH concentration falls below the recommended range, reduce the dose of Mimparaa and / or vitamin D, or discontinue therapy.

Concentration of testosterone

The concentration of testosterone is often below the norm in patients with terminal stage of renal failure. Data from a clinical trial that included patients with PTCA and those on dialysis showed that the concentration of free testosterone decreased on average by 31.3% in patients taking Mimpara and 16.3% in patients in the placebo group at 6 months after initiation therapy. The open extended phase of this study did not show a further decrease in the concentration of free and total testosterone in patients over a 3-year period of treatment with Mimpara.

The clinical significance of reducing serum testosterone levels has not been established

Liver failure

The drug should be administered with caution to patients with moderate to severe hepatic impairment (Child-Pugh classification), since plasma concentrations of cyanocalt in the blood plasma may be 2-4 times higher, careful monitoring is necessary during treatment (see "Method of administration and dose "," Pharmacokinetics").

Lactose

Mimpara contains lactose as an auxiliary (each 30 mg tablet contains 2.74 mg of lactose, each 60 mg tablet contains 5.47 mg of lactose, each 90 mg tablet contains 8.21 mg of lactose). Patients with rare hereditary intolerance to galactose, deficiency of Lapp lactase or impaired absorption of glucogalactose should not take the drug.

Influence on the ability to drive a car or work with complex machinery. Studies to study the effect of the drug on the ability to drive a car or work with complex mechanisms have not been carried out. However, some unwanted reactions can affect the ability to drive or work with complex mechanisms (see "Side effects").

Form of issue

Film-coated tablets, 30 mg, 60 mg, 90 mg. According to Table 14. in blister Aklar / PVC (polyvinyl chloride) / PVA and aluminum foil. For 1, 2 or 6 blisters are placed in a cardboard box. For each pack, two transparent protective labels-control of the first opening, which have a longitudinal color strip, are glued.

Conditions of leave from pharmacies

On prescription.

storage Conditions

At a temperature not exceeding 30 į C.

Keep out of the reach of children.

Shelf life of Mimpara

5 years.

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

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