Universal reference book for medicines
Name of the preparation: ICEMPRA (IXEMPRA)

Active substance: ixabepilone

Type: Antitumor antibiotic

Manufacturer: BRISTOL-MYERS SQUIBB (United States) manufactured by BRISTOL-MYERS SQUIBB Company (United States)
Composition, form of production and packaging
Lyophilizate for solution for infusion
1 fl.

Ixabepilone 15 mg

bottles (2) - cardboard trays.

Lyophilizate for solution for infusion 1 fl.

Ixabepilone 45 mg

bottles (2) - cardboard trays.


Description of the drug approved by the manufacturer for the printed edition of 2011.


Ikzempra (Iksabepilon) is a representative of a new class of antitumor drugs - epothilones and their analogues.
Natural epothilones are isolated from the Myxobacterium Sorangium cellulosum. Epothilones have the ability to stabilize the dynamics of microtubules, which leads to blockade of mitosis of tumor cells, and, ultimately, to their apoptosis and death. The mechanism of binding of natural epothilones and their analogues with tubulin differs from that of other substances that stabilize microtubules. Ixabepilone is a semisynthetic analogue of epothilone B, a 16-membered polypeptide macrolide in which the lactone is replaced by a chemically modified lactam, which allows to increase its stability, the degree of binding to proteins and the antitumor effect.
Iksabepilon has low sensitivity to many factors of tumor resistance, including vectors such as multidrug resistance protein (MRP-1) and P-glycoprotein (P-gp), which are involved in the formation of congenital and acquired resistance to antitumor agents.
Linking tubulin, Iksabepilon actively inhibits the dynamics of microtubules of various isoforms of? -tubulin, including? Ill-isoforms of tubulin, the excessive expression of which is associated with the development of resistance to dachas.
In vivo, Ixabepilone is active in various human tumor models, including tumor-resistant tumor types that induce excessive expression of P-gp, MRP-1, tubulin isoforms, or induced tubulin mutations.
Iksabepilon shows activity on tumor models resistant to the action of various drugs, including taxanes, anthracyclines and vinca alkaloids. In combination with capecitabine in vivo, synergism of the antitumor activity of both drugs is observed. In addition to the direct antitumor effect, Ixabepilone has an anti-angiogenic effect.


When administering Ikzempra in the form of ionotherapy in a dosage of 40 mg / m 2 , the C max value was 252 ng / ml (coefficient of CV variation 56%) and the AUC value (area under the concentration-time curve) was 2143 ng h / ml CV 48%).
Usually, this value of C max was achieved after the end of the 3-hour intravenous infusion. When intravenously administered in a dose range of 15 to 57 mg / m 2, the pharmacokinetics of Ixabepilone is linear.

The volume of distribution exceeds 1 000 liters, which indicates the active absorption and binding of Ixabepilone tissues.
In vitro binding of Ixabepilone to human serum proteins is 67-77%; the ratio of blood / plasma concentrations is 0.65 / 0.85 in the blood concentration range from 50 to 5000 ng / ml.

Intensively metabolized in the liver, in vitro - using the isoenzyme CYP3A4 with the formation of more than 30 metabolites, excreted in urine and feces.


T 1/2 of Ixabepilone when administered at a dose of 40 mg / m 2 as a 3-hour intravenous infusion is about 52 hours.
It is excreted mainly in the form of metabolites.Approximately 86% of the administered dose is excreted within 7 days through the intestine (65% of the dose) and kidneys (21% of the dose), including unchanged approximately 1.6% and 5.6%, respectively. With the recommended dosing regimen (intravenous infusion every 3 weeks) no accumulation in the plasma is expected.
Pharmacokinetics in specific patient groups

Elderly patients: differences in pharmacokinetic parameters in elderly and younger patients have not been identified.

Children and adolescents: pharmacokinetics in patients younger than 18 years of age have not been studied.

Patients with impaired hepatic function: the area under the concentration-time curve increased by 22% in patients with serum bilirubin concentration exceeding the upper limit of the norm by no more than 1.5 times, by 30% in patients with serum bilirubin concentration exceeding the upper limit of the norm from 1.5 to 3 times, and 81% - with serum bilirubin concentration three times higher than the upper limit of the norm.

Patients with renal insufficiency: in patients with moderate renal insufficiency (creatinine clearance not less than 28.6 ml / min) no changes in the pharmacokinetics of Ixabepilone have been detected.


Locally advanced or metastatic breast cancer with ineffectiveness of previous therapy:

- in combination with capecitabine in the ineffectiveness of previous therapy with taxanes and anthracyclines, with resistance to taxanes or in the absence of indications for further therapy with anthracyclines;

- in the form of monotherapy with ineffectiveness of previously conducted therapy with taxanes, capecitabine and anthracyclines.


To minimize the risk of developing hypersensitivity reactions, all patients approximately 1 hour before the infusion of Ikzempra should undergo adequate premedication using:

- blocker of H 1 -gistamine receptors (eg, diphenhydramine 50 mg or its equivalent) and

- blocker of H 2 -gistamine receptors (for example, ranitidine 150-300 mg or 50 mg intravenously, or its equivalent).

If there is an increased sensitivity to Ixabepilone in addition to premedication with H 1 - and H 2 - histamine receptors blockers, premedication with glucocorticosteroids (for example, dexamethasone 20 mg intravenously 30 minutes before the infusion of Ikzempra or inside 12 and 6 hours before infusion of Ikzempra preparation) .

The recommended dose of Ikzempra, when combined with capecitabine, is 40 mg / m 2 intravenously, as a 3-hour infusion every 3 weeks;
Capecitabine is taken at 1000 mg / m 2 2 times a day (30 minutes after eating) for 2 weeks, followed by a 7-day break.
In monotherapy, the recommended dose of Ikzempra is 40 mg / m 2 intravenously, as a 3-hour infusion every 3 weeks.

The dose of Ikzempra preparation with a body surface area exceeding 2.2 m 2 is calculated based on the body surface area of ​​2.2 m 2 .

Recommendations for adjusting the dose of the drug.

To assess possible toxic reactions, periodic examination of patients and laboratory tests, including an extensive clinical blood test and determination of liver function parameters, should be carried out periodically.
When detecting significant toxic reactions, treatment should be postponed until they are reduced or docked. Dose adjustment should be performed at the beginning of each treatment course for non-hematologic signs of toxicity or for the number of blood elements (see Table 1). A new course of treatment should begin with an absolute neutrophil count of not less than 1,500 cells / μl, a platelet count of not less than 100,000 cells / μl, while non -hematological signs of toxicity should decrease. If the toxic reactions after the initial dose reduction recur, it is recommended to reduce the dose by another 20%.
Table 1: Correction of the dose of Ikzempra during toxic reactions

Non-hematological: Suggested dose adjustment

Neuropathy 2 degrees (moderate) duration?
7 days Reduce the dose by 20%
Neuropathy 3 degrees (severe) lasting less than 7 days Reduce the dose by 20%

Neuropathy 3 degrees (severe) duration?
7 days, or disabling neuropathy Discontinue therapy
Any toxic reaction of 3 degrees (severe), in addition to neuropathy, or transient arthralgia / myalgia and fatigue Reduce the dose by 20%

Any toxic reaction of 4 degrees (disabling) Discontinue therapy


Neutropenia <500 cells / μl for> 7 days Reduce the dose by 20%

Febrile neutropenia Reduce the dose by 20%

The number of platelets <25 000 / μL or the number of platelets <50 000 / μL with bleeding Reduce the dose by 20%

Renal impairment

Correction of the dose with a decrease in kidney function is not required.

Liver disorders

At signs of a lesion of a liver the risk of development of toxic reactions raises.
The dose in the first course of treatment should be adjusted in accordance with the degree of impaired liver function (Tables 2 and 3). Caution should be exercised in the activity of serum ACT or ALT, which is 5 times higher than the upper limit of the norm (UGN), since there is insufficient data on therapy in such patients.
Table 2: Recommended doses of Ikzempra in combination with capecitabine against a background of liver dysfunction

The recommended dose of Ikzempra (mg / m 2 ) a

Serum bilirubin concentration?
1 ? VLN and • Serum ACT and ALT? 2.5 x VGN 40
Serum bilirubin concentration b > 1?
VLN and • Serum ACT and ALT> 2.5 x VGN Contraindicated
a Dose recommendations are for the first course of treatment;
Further dose reduction in subsequent courses should be carried out depending on individual tolerability.
b Except for patients in whom the serum concentration of total bilirubin is increased in Gilbert's disease.

Table 3: Recommended doses of Ikzempra * for monotherapy with liver function disorder

Activity of transaminases Serum bilirubin concentration b Ikzempra (mg / m 2 ) a

Serum ACT and ALT?
2.5? VGN and? 1 х VGN 40
Serum ACT and ALT> 2.5? VGN -? 10? VGN and?
1 х ВГН 32
Serum ACT and ALT> 2.5? VGN -? 10? VGN and?
1.5 х ВГН 32
Serum ACT and ALT?
10? VGN and> 1.5 x VGN -? 3 x VGN 20-30
Serum ACT and ALT> 10? VGN and / or> 3 x VLN Application not recommended

a Dose recommendations are for the first course of treatment;
Further dose reduction in subsequent courses should be carried out depending on individual tolerability.
b Except for patients in whom the serum concentration of total bilirubin is increased in Gilbert's disease.

Elderly patients

Clinically significant differences in pharmacokinetics in elderly patients have not been identified.
A change in the dose of the drug for elderly patients is not required.
Simultaneous therapy

For patients who simultaneously receive potent inhibitors of the CYP3A4 isoenzyme (eg, ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, voriconazole), the initial dose of Ixabepilone is 20 mg / m 2 .

Instructions for preparation and administration of the drug

Dissolution of the preparation:

Vials with lyophilizate and solvent are removed from the refrigerator and kept at room temperature (20-25 ° C) for about 30 minutes.
First, a precipitate can be observed in the solvent vial, which dissolves when room temperature is reached.
As with other antineoplastic agents, caution should be exercised when preparing and administering Ixabepilone Solution!
The specified actions should be carried out by specially trained personnel with the use of protective gloves in a specially designated room for these purposes in aseptic conditions!
In aseptic conditions, using a syringe of the appropriate size, the solvent is slowly introduced into a vial of lyophilizate.

The contents of the 15 mg dose vial are reconstituted with 8 ml of solvent, the contents of the 45 mg dose vial are reconstituted with 23.5 ml of a solvent.
Carefully shake the vial until the contents of the vial are completely dissolved. After dissolution, the concentration of Ixabepilone in the solution is 2 mg / ml. The reconstituted solution is stable for 1 hour when stored in a vial (not in a syringe) at room temperature and room lighting. Preparation of solution for infusion:
Before administration, the reconstituted solution should be diluted with a suitable infusion solution.
For this purpose, the following infusion solutions are allowed, which should have a pH of 6.0 to 9.0:
• Ringer's lactate solution

• Ringer's acetate solution

• 0.9% solution of sodium chloride for injection (If using 0.9% solution of sodium chloride for injection, its pH should be adjusted to pH> 6.0 by adding sodium bicarbonate solution for injection at a rate of 1 ml (range of concentrations from 4.2 % to 8.4%) for 250 ml of 0.9% solution of sodium chloride, and only then add the solution of Ixabepilone).

When preparing the solution for infusion, containers that do not contain DEHP [di- (2-ethylglycyl) phthalate] should be used.

The final concentration of the solution for infusion of the preparation of Ikzempra® should be from 0.2 mg / ml to 0.6 mg / ml.

To calculate the final concentration of the solution for infusion, use the following formulas:

• Total infusion volume = ml reconstituted drug solution + ml infusion solution

• Final concentration of solution for infusion = dose of Ixabepilone (mg) / total infusion volume (ml)

The required amount of reconstituted solution at a concentration of 2 mg / ml is removed from the vial by means of a syringe, transferred to a vial of the appropriate amount of the infusion solution and mixed thoroughly by rotating the container.
For the introduction, infusion systems with a filter having a pore diameter of 0.2 to 1.2 microns should be used.
Unused infusion solution must be disposed of in accordance with the procedure provided for all antitumor drugs.
The infusion solution is stable for 6 hours when stored at room temperature and illumination. Solution for infusion should be administered within 3 hours; The administration of the drug should be completed no later than 6 hours after the preparation of the infusion solution.

The most frequent (in more than 20% of patients) adverse events with monotherapy with Ikzempra were: peripheral sensory neuropathy, fatigue / asthenia, myalgia / arthralgia, alopecia, nausea, vomiting, stomatitis / mucositis, diarrhea.

In more than 20% of patients who received combination therapy, the following reactions further developed: palmar-plantar erythrodysesthesia, anorexia, abdominal pain, shtei lesions, constipation.

Adverse events with the use of Ikzempra are represented by the frequency of their registration: very frequent (? 1/10), frequent (? 1/100, <1/10), infrequent (? 1/1 000, <1/100), rare ? 1/10 000, <1/1 000), very rare (<1/1 000).

From the laboratory indicators:

frequent: weight loss;

infrequent: increased activity of transaminases;

rare: increased activity of alkaline phosphatase in the blood, increased activity of gamma-glutamyltransferase in the serum.

Disorders from the cardiovascular system:

frequent: "tides" with a feeling of heat;

infrequent: myocardial infarction, ventricular dysfunction, supraventricular arrhythmia, thrombosis, lowering blood pressure;

rare: myocardial ischemia, angina pectoris, cardiomyopathy, atrial fibrillation, hypovolemic shock, pulmonary embolism, bleeding, vasculitis.

Diseases of the blood and lymphatic system:

very frequent: neutropenia, thrombocytopenia, anemia, leukopenia;
frequent: febrile neutropenia;
rare: coagulopathy, lymphopenia.

From the nervous system:

very frequent: peripheral sensory neuropathy, headaches;

frequent: peripheral motor neuropathy, dizziness, change in taste, insomnia;

infrequent: fainting, cramping disorders;

Bacterial and parasitic infections:

frequent: infections of the upper respiratory tract;

infrequent: sepsis, infection against neutropenia, pneumonia, urinary tract infection, infection;

rare: infections of the lower respiratory tract, enterocolitis, bacterial infection, laryngitis.

Common diseases and diseases developing at the site of injection:

very frequent: fatigue / asthenia;

frequent fever, swelling, pain in the sternum, pain, lacrimation;

rare: chills.

Disorders from the liver and biliary tract:

rare: acute liver failure, jaundice.

From the immune system:

frequent: hypersensitivity.

rare: hemorrhagic stroke, impaired coordination of movements, drowsiness.

From the side of the kidneys and urinary tract :

rare: renal failure, nephrolithiasis.

From the skin and subcutaneous tissue:

very frequent: alopecia;

frequent: erythrodysesthesia syndrome of the fingers and toes, skin rashes, skin hypernigmentation, itching, skin peeling, nail damage;

rare: erythema multiforme

From the musculoskeletal system, connective tissue:

very frequent: myalgia / arthralgia, skeletal muscle pains,

infrequent: muscle weakness,

rare: muscle spasms, trismus.

From the respiratory tract, chest and mediastinum:

frequent: shortness of breath, cough;

infrequent: respiratory failure, pneumonitis, hypoxia,

rare: acute pulmonary edema, dysphonia, pain in the larynx and pharynx.

Metabolic and nutritional disorders:

very frequent: anorexia;

frequent: dehydration;

infrequent: hyponatremia, metabolic acidosis;

rare: hypokalemia, hypovolemia.

From the gastrointestinal tract:

very frequent: stomatitis / mucositis, diarrhea, vomiting, constipation, abdominal pain, nausea;

frequent: gastroesophageal reflux disease;

infrequent: intestinal obstruction, colitis, violation of the evacuation of stomach contents esophagitis;

rare: gastrointestinal bleeding, dysphagia, gastritis.


- absolute number of neutrophils less than 1,500 cells / μl or platelets less than 100,000 cells / μl;

- in combination with capecitabine: with serum aspartate aminotransferase (ACT) or alanine aminotransferase (ALT) 2.5 times the upper limit of the norm, or with a serum bilirubin concentration exceeding the upper limit of the norm;

- pregnancy and the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- severe (grade 3-4 according to common toxicity criteria) a history of hypersensitivity to the Cremophor EL or other preparations containing Krsmofor EL or its derivatives (e.g. polyoxyethylated castor oil).

- diabetes;

- neuropathy;
- liver failure;

- dysfunction of the cardiovascular system in history.

Contraindicated during pregnancy and lactation.

Dose adjustment in reducing kidney function is not required.

If there are signs of liver damage risk of toxic reactions increases. The dose in the first course of treatment should Adjusted in accordance with the degree of liver function abnormalities (Table 2 and 3). Care should be taken when the activity of serum ALT or ACT, 5 times the upper limit of normal (ULN), because the data regarding therapy in these patients is not enough.

Contraindicated in children under 18 years.


No clinically significant differences in pharmacokinetics in elderly patients have been identified. Changing dose when assigning elderly patients is not required.

Hypersensitivity reactions
All patients before drug infusions Ikzempra premedication should hold blockers H 1 - and H 2 histamine receptors and carry out surveillance to detect hypersensitivity reactions (eg, dyspnea, bronchospasm, lowering blood pressure). In case of severe hypersensitivity reactions, such as requiring treatment, the drug infusion should be discontinued immediately and start appropriate symptomatic treatment (eg, epinephrine, corticosteroids). With the development of hypersensitivity reactions in a single cycle in subsequent cycles should be conducted premedication besides blockers H 1 - and H 2histamine receptors, corticosteroids, and consider increasing the infusion time.
Myelosuppression is dose-dependent and is manifested mainly neutropenia. To monitor the development of myelosuppression in all patients receiving the drug, blood count is recommended on a regular basis. 11ri development of severe neutropenia or thrombocytopenia dose should be reduced.
Peripheral Neuropathy

Neuropathy, primarily peripheral sensory neuropathy develops frequently and is usually mild to moderate. When treating drug Ikzempra should be monitored for the development of symptoms of neuropathy such as a burning sensation, hyperesthesia, hypoesthesia, paresteziyai, discomfort, neuropathic pain. When new-onset or worsening peripheral neuropathy may require a lower dose, interrupt treatment or stop the drug. In diabetes mellitus or existing neuropathy risk of severe neuropathy increased. In the treatment of these patients should be careful. Previous therapy neurotoxic chemotherapeutic agents is not a risk factor.
liver damage
Studies in breast cancer when the activity of ACT in serum or ALT greater than 2.5 x ULN Ikzempra drug toxicity in a dose of 40 mg / m 2as monotherapy or in combination with capecitabine are more pronounced than in the case of serum ALT or ACT? 2.5 x ULN. Monotherapy often developed grade 4 neutropenia, febrile neutropenia, other serious adverse events (thrombocytopenia, constipation, gastrointestinal pain, impaired gastric emptying, stomatitis, gipergermiya, hyperbilirubinemia, syncope). In combination therapy with capecitabine, the overall incidence of grade 3-4 adverse reactions (anemia, leucopenia, thrombocytopenia, diessminirovannoe intravascular coagulation, neutropenia, respiratory arrest and cardiac, abdominal pain, diarrhea, nausea, esophagitis, vomiting, asthenia, fatigue, inflammation of the mucous membranes , infections caused by neutropenia, pneumonia, respiratory tract infection, sepsis, septic shock, dehydration,anorexia, hypovolemia, metabolic acidosis, impaired renal function, dysfunction of the respiratory system) febrilyyuy neutropenia, serious adverse events (impaired bone marrow function, angina, atrial flutter, cardiomyopathy, myocardial infarction, myocardial ischemia, ventricular dysfunction, colitis, constipation, dyspepsia , gastritis, intestinal obstruction, gastrointestinal bleeding, stomatitis, chest pain, chills, chest pain is not a cardiovascular origin, hyperthermia, severe liver dysfunction, giperch vstvitelnost reaction type IV hypersensitivity, bacterial infection, cystitis, infectious enterocolitis, infections, laryngitis, difficulty of access to the vessels when administered intravenously, reduced number of granulocytes, hemoglobin, neutrophils, erythrocytes, leukocytes in the blood, hypokalemia, hyponatremia,bone pain, muscle spasms, musculoskeletal chest pain, myalgia, trismus, impaired coordination, hypoesthesia, lethargy, neuralgia, peripheral neuropathy, paresthesia, peripheral sensory neuropathy, syncope, confusion, acute pulmonary edema, hoarseness, dyspnea, faringolaringealnye pain, erythema multiforme, hand-foot eritrodizzeteziya, rash, decreased blood pressure, hypovolemic shock, thrombosis, vasculitis), deaths related to toxicity, increased.palmar-plantar eritrodizzeteziya, rash, decreased blood pressure, hypovolemic shock, thrombosis, vasculitis), deaths related to toxicity, increased.palmar-plantar eritrodizzeteziya, rash, decreased blood pressure, hypovolemic shock, thrombosis, vasculitis), deaths related to toxicity, increased.
Ikzempra drug in combination with capecitabine should not be given when ACT activity of serum ALT or above 2.5? ULN or serum bilirubin greater than 1? ULN, because it increases the risk of toxic effects and mortality associated with neutropenia. It should be used with caution Ikzempra formulation as monotherapy in the human liver, and reduce the dosage as recommended.
Cardiac dysfunction
The incidence of cardiac function (e.g., myocardial ischemia and ventricular dysfunction) for joint reception of Ixabepilone and kapetsigabina was higher (1.9%), compared to capecitabine monotherapy (0.3%). Caution should be exercised when taking Ikzempra drug in patients with heart disease in history. With the development of myocardial ischemia or cardiac function should be interrupted the course of drug treatment Ikzempra or cancel product.
The possibility of cognitive impairment due to the action of fillers
Since the drug Ikzempra include ethanol, should consider the possibility of its influence on the central nervous system and other effects.
Elderly patients

The efficacy and safety of the drug Ikzempra monotherapy in patients older than 65 years old and younger people alike.
Required efficiency achieved in both young and elderly patients who use the drug Ikzempra together with capecitabine, but the likelihood of adverse reactions of grade 3-4 in elderly patients was higher. Therefore, combination therapy should be monitored closely for the development of adverse events in elderly patients.
Impact on the ability to drive vehicles and manage mechanisms

Special studies investigating the effect of the drug on Ikzempra opportunity to drive vehicles and use machines have not been undertaken. Considering the content of ethanol in the solvent attached to the drug Ikzempra and the possibility of side effects of the central nervous system that can affect the ability to drive vehicles and work mechanisms, is not suitable for driving and other mechanisms during drug treatment.

Described isolated cases of drug overdose Ikzempra. Observed thus side reactions include peripheral neuropathy, fatigue, bone myshechiye pain / myalgia and gastrointestinal symptoms (nausea, anorexia, diarrhea, abdominal pain, stomatitis).
An antidote to an overdose of the drug is not. Treatment of an overdose should be to symptomatic drug treatment according to clinical manifestations of, and careful monitoring of the patient.

In cancer patients treated with Ixabepilone in combination with capecitabine, values of C max and AUC Ixabepilone were reduced by 19% and 6%, kapetsigabina - 27% and 5%, fluorouracil - increased by 1% and 14%, respectively, compared with appointment of ixabepilone or kapetsigabina separately. This influence is not considered clinically significant.
Drugs that may increase the concentration of ixabepilone in the plasma
Isoenzyme inducers of P450 (CYP) ZA4, Ixabepilone may slow metabolism and increase its concentration in plasma. When assigning Ikzempra drug with potent inhibitors isoenzyme CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, voriconazole) the dose should be reduced. It should also consider the appointment alternative drugs that are not inhibitors of isoenzyme CYP3A4.
Effect of weak or moderate inhibitors (e.g., erythromycin, fluconazole, verapamil) on the systemic concentration of Ixabepilone not studied. Therefore, caution should be exercised during coadministration of these drugs and drug Ikzempra and also possible to assign alternative drugs are not inhibitors isoenzyme CYP3A4.
When co-therapy isoenzyme CYP3A4 inhibitors and drug Ikzempra should more carefully monitor the development of acute toxic effects (e.g., regular monitoring of blood formula in the intervals between treatments).
Drugs that may reduce the concentration of Ixabepilone plasma
preparations inducing isoenzyme CYP3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital, drugs Hypericum perforatum) may accelerate metabolism of Ixabepilone and, thereby, reduce its plasma concentration to subtherapeutic values. Therefore, it is necessary to consider the possibility of appointing simultaneously with Ixabepilone drugs weakly induce this isoenzyme.
Effect of formulation on other drugs Ikzempra
Ixabepilone in concentrations used in clinical practice, does not inhibit cytochrome P450 isozymes, so its influence on the concentration of other drugs in the plasma is expected.

On prescription.


In the dark place at a temperature of 2 ° C to 8 ° C.
Keep out of the reach of children! Shelf life - 2 years.
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