Universal reference book for medicines
Product name: CAPRELSA

Active substance: vandetanib

Type: Antitumor drug.
Protein tyrosine kinase inhibitor
Manufacturer: ASTRAZENECA UK (UK) manufactured by IPR PHARMACEUTICALS (Puerto Rico) packed by ASTRAZENECA UK (UK)
Composition, form of production and packaging
The tablets covered with a film cover of
white color, round, biconcave, with engraving Z100 on one side.

1 tab.

vandetanib 100 mg

Excipients: calcium hydrophosphate dihydrate 105 mg, microcrystalline cellulose 25 mg, crospovidone 12.5 mg, povidone K29-32 5 mg, magnesium stearate 2.5 mg.

Composition of the film membrane: hypromellose 2910 4.9 mg, macrogol 300 1 mg, titanium dioxide 1.6 mg.

10 pieces.
- blisters from PVC / PVDC / aluminum foil (3) - packs of cardboard.
The tablets covered with a film shell of white color, oval, biconcave, with engraving Z300 on one side.

1 tab.

vandetanib 300 mg

Excipients: calcium hydrophosphate dihydrate 315 mg, microcrystalline cellulose 75 mg, crospovidone 37.5 mg, povidone K29-32 15 mg, magnesium stearate 7.5 mg.

Composition of the film membrane: hypromellose 2910 14.7 mg, macrogol 300 3 mg, titanium dioxide 4.8 mg.

10 pieces.
- blisters from PVC / PVDC / aluminum foil (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2014.

PHARMACHOLOGIC EFFECT

Vandetanib, as a selective tyrosine kinase inhibitor, suppresses the vascular endothelial growth factor receptor (VEGF) receptor tyrosine kinase, stimulated by the vascular endothelial growth factor (VEGF) in endothelial cells.
Vandetanib inhibits migration, proliferation, endothelial cell survival, and the formation of new blood vessels stimulated with VEGF on in vitro models of aigiogenesis. In vivo, vandetanib reduced angiogenesis induced by tumor cells, tumor vascular permeability and the density of the microvascular tumor network, suppressed tumor growth and metastases on models of human lung cancer heterograft in athymic mice.
In addition, in tumor cells and endothelial cells, vandetanib inhibits the tyrosine kinase of the epidermal growth factor (EGF) receptor stimulated by EGF.
Vandetanib inhibits EGFR-dependent proliferation and cell survival in vitro. In vitro studies have shown that vandetanib also inhibits the activity of other tyrosine kinases, including those rearranged during transfection (RET) and receptor-3 VEGF receptor (Flt-4) tyrosine kinases.
In a clinical trial involving 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer, a statistically significant improvement in progression-free survival as well as an advantage in response rates, disease control, biochemical response, and time to worsening pain syndrome in patients with admission vandetanib compared with placebo.

The dependence of the efficacy of vandetanib therapy on the status of RET mutation has not been proved.

PHARMACOKINETICS

The pharmacokinetics of vandetanib in a dose of 300 mg in patients with medullary thyroid cancer is characterized by a clearance of approximately 13.2 l / h, a distribution volume of approximately 7450 liters and a plasma half-life of approximately 19 days.

Suction

After oral intake of vandetanib absorption is slow, the maximum concentration in the plasma is usually achieved on average after 6 hours (range 4-10 hours) after administration.
With repeated use, an 8-fold cumulation of vandetanib was observed, with the attainment of an equilibrium state after about 2 months.
Distribution

Vandetanib binds to albumin and alpha-1-acid glycoprotein of human serum, while in vitro binding to proteins is approximately 90%.
In ex vivo plasma samples of patients with colorectal cancer at an equilibrium exposure after taking the drug at a dose of 300 mg / day, the binding of the drug to proteins averaged 93.7% (range 92.2% -95.7%).
Metabolism

After ingestion of 14 C-vandetanib, unchanged vandetanib and metabolites of vandetanib-N-oxide and N-desmethyl-vandetanib are found in plasma, urine and feces.The glucuronic acid conjugate was an insignificant metabolite only in the excreta.
N-desmethyl-vandetanib is mainly formed by the action of the CYP3A4 isoenzyme, and the vandetanib-N-oxide is produced by flavipcontaining monooxygenases FM01 and FM03. N-desmethyl-vandetanib and vandetanib-M-oxide circulate in the blood at concentrations of approximately 11% and 1.4%, respectively, of the concentration of vandetanib.
Excretion

Within 21 days after a single intake of C-vandetanib, approximately 69% of the drug was excreted: 44% with feces and 25% with urine.
Removal of the drug was slow, and it should be expected that further excretion after 21 days is based on the half-life of plasma.
Vandetanib was not a substrate for hOCT2 expressed in HEK293 cells.
Vandetanib inhibits the uptake of the selective substratum OCT2 of the 14 C-creatinine marker HEK-OST2 cells, with an average IC 50 value of approximately 2.1 Ојg / ml. This is higher than the plasma concentrations of vandetanib (approximately 0.81 and 0.32 Ојg / ml) achieved after repeated administration of the drug at doses of 300 mg and 100 mg, respectively. Vandetanib inhibits renal excretion of creatinine, as a result of which the concentration of creatinine in the blood plasma of patients taking vandetanib increases.
INDICATIONS

- Unresectable, locally advanced or metastatic medullary thyroid cancer.

DOSING MODE

Inside, 300 mg once a day (1 tablet 300 mg or 3 tablets 100 mg), regardless of food intake.

The tablet can also be dispersed in 50 ml of non-carbonated drinking water.
Other liquids can not be used. The tablet should be lowered into water without crushing, stirring until complete destruction (for about 10 minutes) and immediately drink the resulting suspension. After washing the walls of the glass, pour another 50 ml of water, and drink the resulting suspension. A suspension of the Capresa preparation can also be administered via a nasogastric tube or gastrostomy.
Therapy with Capresa should be continued until patients with medullary thyroid cancer continue to benefit from the treatment.

In case the patient missed the next dose, the next daily dose should be taken according to the prescribed treatment regimen.

Correction of dose

With the development of toxicity of the 3rd degree of STAAE (General terminology criteria for assessing adverse events) or higher, or the prolongation of the QT interval on the ECG, it is necessary to temporarily suspend therapy until the toxicity is resolved or its severity is reduced to SCAE degree 1 (see section "Special instructions"), then resuming treatment with a lower dose.
The daily dose of 300 mg can be reduced to 200 mg (2 tablets of 100 mg), and then, if necessary, up to 100 mg.
Special populations of patients

Children or teenagers

The drug Kaprulsa is not intended for use in children, since safety and efficacy have not been established.

Elderly patients (over 65 years of age)

It is not necessary to adjust the initial dose in elderly patients.
Clinical data on the use of the drug in patients over the age of 75 years are limited.
Patients with renal insufficiency

Data on the use of the drug in patients with moderate renal insufficiency are limited.
According to available data, the safety profile in patients with mild renal insufficiency is similar to the safety profile in patients with normal renal function. Correction of the initial dose in patients with mild renal failure is not required. In patients with moderate renal failure (CK> 30 and <50 ml / min), the initial dose should be reduced to 200 mg. Vandetanib is contraindicated in patients with severe renal insufficiency (CC <30 mL / min), since the experience of using the drug in this population is limited, safety and efficacy not established.
A study of the pharmacokinetics of vandetanib in volunteers with severe renal insufficiency showed that the exposure of vandetanib can be increased up to 2-fold.

Patients with hepatic insufficiency

According to the results of pharmacokinetics studies, volunteers do not need to change the initial dose of the drug in patients with mild, moderate or severe hepatic insufficiency.
Experience with the use of the drug Capresa in patients with hepatic insufficiency (serum bilirubin concentration above the upper limit of the norm is more than 1.5 times) is limited. The use of the drug Cairelsa in patients with hepatic insufficiency is contraindicated due to inadequate data on the safety and efficacy of the drug in this group of patients.
SIDE EFFECT

The most frequent undesirable side reactions with the use of the drug Kaprulsa were diarrhea, rash, nausea, hypertension and headache.
The undesirable reactions observed in the completed clinical trials involving patients with medullary thyroid cancer who received the Cairella drug are described below.
The frequency of unwanted reactions is presented in the following gradation: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000 , <1/1000), very rarely (<1/10000), including individual messages.

From the side of the heart and blood vessels:

Very often: prolongation of QTc interval on ECG 1,2 , arterial hypertension

Often: ischemic cerebrovascular events, hypertensive crisis

Infrequent: heart failure, acute heart failure, rhythm disturbances, cardiac conduction disorder, ventricular arrhythmia and cardiac arrest

From the gastrointestinal tract:

Very often: diarrhea, nausea, vomiting, abdominal pain, indigestion

Often: stomatitis, dry mouth, colitis, dysphagia.
constipation, gastritis, gastrointestinal bleeding
Infrequently: pancreatitis, peritonitis, intestinal obstruction, intestinal perforation, fecal incontinence

General disorders:

Very often: fatigue, asthenia, pain, swelling

Often: fever

Infrequent: wound healing disorder

Laboratory and instrumental data:

Very often: prolongation of the QTc interval on the ECG

Often: weight loss, increased activity of ALT and ACT, an increase in the concentration of creatinine in the blood

Infrequent: increased hemoglobin concentration, increased activity of amylase in serum

From the side of metabolism and nutrition:

Very often: decreased appetite, hypocalcemia.

Often: hypokalemia, hypercalcemia, hyperglycemia, dehydration, hyponatremia

Infrequent: eating disorder (exhaustion)

From the endocrine system:

Often: hypothyroidism

Disorders of the psyche:

Very often: insomnia

Often: depression, anxiety

From the side of the kidneys and urinary tract:

Often: proteinuria, nephrolithiasis, hematuria, dysuria, renal insufficiency, frequent urination, mandatory urges to urinate

Infrequently: chromaturia, anuria

From the respiratory system:

Often: epistaxis, hemoptysis, pneumonitis

Infrequent: respiratory failure, pneumonia

From the skin and subcutaneous tissues:

Very often: rashes and other skin reactions (including acne, dry skin, dermatitis, pruritus), photosensitivity reactions, nail damage.

Often: palmar-plantar erythrodysesthesia, alopecia

Infrequent: bullous dermatitis

From the side of the organ of vision:

Very often: structural changes in the cornea (including corneal precipitate and corneal opacification)

Often: blurred vision, conjunctivitis, dry eyes, blurred vision, photopsy, iridescent circles around the light source, glaucoma, keratopathy

Infrequently: cataract, violation of accommodation

From the nervous system:

Very often: headache, paresthesia, dysesthesia, dizziness

Often: tremor, lethargy, loss of consciousness, imbalance, taste disorders

Infrequent: seizures, clonus, cerebral edema

Infectious and parasitic diseases:

Very often: pasopharyngitis, bronchitis, upper respiratory tract infections, urinary tract infections

Often: pneumonia, sepsis, influenza, cystitis, sinusitis, laryngitis, folliculitis, furuncle, fungal infections, pyelonephritis

Infrequently: appendicitis, staphylococcal infections, diverticulitis, cellulitis, abscess of the abdominal wall

Disorders from the liver and bile ducts:

Often: cholelithiasis

1 In 13.4% of patients in the vandetanib group, the QTc interval (according to Bazett) was?
500 ms compared with 1.0% in the placebo group. The prolongation of the QTcF interval at> 20 ms was noted in more than 91% of patients,> 60 ms in 35% of patients,> 100 ms in 1.7% of patients. In connection with the prolongation of the QTc interval, in 8% of patients the dose of the drug was reduced.
2 Including 2 fatalities (one due to sepsis and one due to heart failure) in patients with a QTc interval greater than 550 ms.

On the background of monotherapy with vandetanib, there were cases of arrhythmia of the ventricular tachysystolic type "pirouette", Stiveis-Johnson syndrome, erythema multiforme, interstitial lung disease (in some cases fatal) and reversible leukoencephalopathy syndrome.
It is expected that in patients with medullary thyroid cancer receiving vandetanib. these undesirable phenomena will be noted infrequently.
Visual impairment, for example, blurred vision, was often observed in patients with medullary thyroid cancer who received the drug Kaprels.
A routine examination with a slit lamp revealed corneal opacity (vorticose keratopathy) in patients, however, regular slit-lamp ophthalmologic examination is not required.
In a randomized trial, the following changes in laboratory parameters were very often observed in patients with medullary thyroid cancer: protein and blood in the urine (rapid test strip assay), increased serum levels of thyrotropic hormone, hemoglobin and creatinine, increased amylase activity, increased lipase activity.
There was an increase in the concentration of creatinine 1-2 degrees of CACAE, which may be due to inhibition of OCT2 (see the section "Pharmacokinetics").
In patients taking vandetanib, the hemoglobin concentration was raised by an average of 0.5-1.5 g / dl compared to the baseline value.

CONTRAINDICATIONS

- hypersensitivity to vandetanib or any auxiliary substance;

- congenital syndrome of prolongation of the QT interval;

- pregnancy and the period of breastfeeding;

- Patients with a QTc interval of more than 480 ms;

- simultaneous use with other drugs capable of prolonging the QTc interval and / or causing flutter / flicker: arsenic, cisapride, erythromycin (intravenously), toremifene, misolastine, moxifloxacin, antiarrhythmics of Class I and III;

- children's age till 18 years;

- severe renal failure (CK <30 ml / min);

- liver failure.

With caution: moderate renal failure (CK> 30 and <50 mL / min).

PREGNANCY AND LACTATION

Pregnancy

Adequate and well-controlled studies of the drug Kaprels with the participation of pregnant women were not conducted.
According to preclinical research, the administration of Kaprel's drug may harm the fetus, since the risk of developing embryo / fetal pathologies is high. In accordance with the pharmacological action, vandetanib exerted a significant effect on all stages of reproductive function in female rats.
The use of the drug during pregnancy is contraindicated.

Breastfeeding period

There is no data on the use of the drug Capresa in women during breastfeeding.
Vandetanib was excreted in the milk of rats, and was found in the blood plasma of the young after administration of the drug to the latent rats. Breastfeeding is contraindicated in the period of treatment with the drug Capresa.
APPLICATION FOR FUNCTIONS OF THE LIVER

Data on the use of the drug in patients with moderate renal insufficiency are limited.
According to available data, the safety profile in patients with mild renal insufficiency is similar to the safety profile in patients with normal renal function. Correction of the initial dose in patients with mild renal failure is not required. In patients with moderate renal failure (CK> 30 and <50 ml / min), the initial dose should be reduced to 200 mg. Vandetanib is contraindicated in patients with severe renal insufficiency (CC <30 mL / min), since the experience of using the drug in this population is limited, safety and efficacy not established.
A study of the pharmacokinetics of vandetanib in volunteers with severe renal insufficiency showed that the exposure of vandetanib can be increased up to 2-fold.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

According to the results of pharmacokinetics studies, volunteers do not need to change the initial dose of the drug in patients with mild, moderate or severe hepatic insufficiency.
Experience with the use of the drug Capresa in patients with hepatic insufficiency (serum bilirubin concentration above the upper limit of the norm is more than 1.5 times) is limited. The use of the drug Cairelsa in patients with hepatic insufficiency is contraindicated due to inadequate data on the safety and efficacy of the drug in this group of patients.
APPLICATION FOR CHILDREN

The drug Kaprulsa is not intended for use in children, since safety and efficacy have not been established.

APPLICATION IN ELDERLY PATIENTS

It is not necessary to adjust the initial dose in elderly patients.
Clinical data on the use of the drug in patients over the age of 75 years are limited.
SPECIAL INSTRUCTIONS

Taking into account possible risks, it is very important to prescribe vandetanib therapy only to patients to whom it is objectively shown, namely to patients with symptomatically-aggressive course of the disease.
Only the presence of symptoms or progression of the disease is not only a sufficient basis for assigning vandetaniba.
The indicator concentration change biomarkers such as calcitonin and / or cancer embryonic antigen (CEA), and the tumor growth rate observations during dynamic help identify patients in need of this therapy, as well as the optimal time of its start.
Elongation QTc interval
In patients receiving the drug Kaprelsa observed lengthening the ECG QTc interval (see. The section "Side effect"). In 8% of patients with medullary thyroid carcinoma treated with drug dose of 300 mg / day, in Phase III study confirmed observed lengthening QTc interval on the electrocardiogram. Elongation QTc interval on the ECG is dose-dependent, and can be treated by an appropriate monitoring, halting therapy and dose reduction, if required.
Infrequently reported cases of ventricular arrhythmias tachysystolic type "pirouette" (torsades de pointes) and ventricular tachycardia when using the drug Kaprelsa 300 mg.
Do not start Kaprelsa drug therapy in patients with the corrected QT interval on the ECG value of more than 480 ms. It should appoint a drug Kaprelsa patients with ventricular fibrillation tahisistolicheskoy type "pirouette" in history, except when her risk factors contributing to its development, adjusted.
Research Kaprelsa application of the drug in patients with ventricular arrhythmias or recent myocardial infarction were not carried out.
ECG and the results of measurements of serum concentrations of potassium, calcium, magnesium and TSH (thyroid stimulating hormone) must be received prior to, after 2-4 weeks, and 8-12 weeks after initiation of Kaprelsa preparation and then every 3 months for one year. ECG and blood tests are necessary to perform as clinically indicated during this period and afterwards. The concentration of potassium in blood serum must be maintained at a value of 4 meq / l or higher, and the calcium and magnesium concentrations should be within the normal range for reducing the risk QT interval elongation (the ECG). If no alternative therapy Kaprelsa drug can be used with some drugs, prolong the QT interval on the ECG (see. The section "interaction with other drugs and other interactions"). If such drugs are administered to a patient,Kaprelsa already receiving the drug, it is necessary to perform EKG monitoring QT interval in accordance with the pharmacokinetics of the added drug.
If the value QTcna ECG interval longer than 500 ms for a single measurement need to suspend therapy with Kairelsa. QTc interval after the return to the original value of 450 msec or less can be resumed taking the drug at a lower dose.
Skin reactions
during therapy with Kairelsa patients observed the development of rashes and other skin reactions (including photosensitivity reactions and palmar-plantar syndrome eritrodizestezii).
Mild to moderate skin reactions are usually resolved during symptomatic therapy or dose reduction Kairelsa preparation. In case of more severe skin reactions (such as Stevens-Johnson syndrome) may require systemic glucocorticosteroids assignment and termination of drug therapy Kaprelsa.
During therapy with Kaprelsa need to wear clothing that protects against sun exposure, and / or use sunscreen.
Diarrhea
Patients taking the drug Kaprelsa observed development of diarrhea. For the treatment of diarrhea is recommended the use of conventional antidiarrheal agents. Serum concentration of electrolytes is necessary to control carefully. With the development of severe diarrhea (grade 3-4 CTCA) the drug must be suspended until improvement resuming therapy at a lower dose (see. The sections "Dosage and Administration" "Side effect").
Bleeding
have been reported cases of intracranial hemorrhage, and therefore caution should be exercised when using Kaprelsa drug in patients with brain metastases.
Arterial hypertension

While taking the drug Kaprelsa noted the development of hypertension, including hypertensive crisis. In connection with this observation it is recommended patients and appropriate treatment of hypertension. When high blood pressure is uncontrollable drug, the drug Kaprelsa should not reopen until blood pressure normalization (see. The section "Side effect"). You may need to reduce the dose.
Heart failure
patients who took the drug Kaprelsa, pointed out the development of heart failure, in some cases, irreversible and fatal. With the development of heart failure may need a temporary or complete cancellation of drug therapy Kaprelsa.
Increased ALT
While taking the drug Kaprelsa often noted increased ALT. Most cases were allowed to continue treatment as others - after the suspension of treatment for 1-2 weeks. In applying Kaprelsa drug is recommended to periodically evaluate ALT.
Interstitial lung disease
Using drugs Kaprelsa saw the development of interstitial lung disease, in some cases fatal. At occurrence of respiratory symptoms such as breathlessness, cough and fever, application Kaprelsa drug must be suspended and held immediate examination. If confirmed interstitial lung disease, receiving Kaprelsa drug should be discontinued and appropriate treatment.
Reversible posterior leukoencephalopathy syndrome (SLDF)
in patients taking the drug Kaprelsa in combination with chemotherapy, or in children with brain tumors treated with monotherapy Kaprelsa, marked syndrome develop reversible posterior leukoencephalopathy syndrome of subcortical vasogenic edema detectable on brain MRI. SLDF noted in patients treated with vandetanib. This syndrome should be suspected when a patient have seizures, headache, visual disturbances, confusion or disturbance of mental function.
Renal failure
patients with mild renal insufficiency (clearance kreatiniia> 30 and <50 ml / min), the initial dose should be reduced to 200 mg (see. The section "Method of administration and dose").
Liver failure
Experience of using Kaprelsa the drug in patients with hepatic impairment (serum bilirubin levels above the upper limit of normal is more than 1.5 times) is limited safety and efficacy in this patient population has not been established. Kaprelsa The drug is contraindicated in patients with hepatic insufficiency (see. Section "Contraindications").
Isoenzyme CYP3A4 inducers
should be avoided simultaneous application Kaprelsa drug with potent inducers of CYP3A4 isoenzyme, such as rifampicin, Hypericum perforatum preparations, carbamazepine, phenobarbital (see. The section "Interaction with other drugs and other interactions").
Other

Women of childbearing age should use reliable methods of contraception during treatment with Kaprelsa and at least for 3 months after the last dose.
Impact on the ability to drive vehicles and manage mechanisms

No studies on the effect of the drug Kaprelsa on ability to drive vehicles and management mechanisms. However, fatigue and blurred vision can be observed during therapy. In the case of these phenomena, patients should use caution when driving and other mechanisms.
OVERDOSE

No specific treatment for overdose Kairelsa does not exist, are not installed Possible overdose symptoms. Increasing the frequency and severity of certain undesirable reactions such as rash, diarrhea, hypertension, noted when taking the drug in the multiple doses of 300 mg and higher. It is necessary to consider the possible prolongation of the QT interval and ventricular arrhythmia development tahisistolicheskoy type "pirouette".
In case of adverse reactions associated with overdose should provodin, symptomatic treatment, in particular, appropriate treatment of severe diarrhea. In overdose should stop further taking the drug, and to take appropriate measures to prevent the development of undesirable phenomena, for example, perform an electrocardiogram for 24 hours to determine the elongation of QTc interval.
DRUG INTERACTION

Vandetaniba influence on the pharmacokinetics of other drugs
These in vitro indicate that vandetanib is moderate inducer isoenzyme CYP3A4. In this connection should be careful when applying vandetaniba substrates isoenzyme CYP3A4, especially estrogen / progesterone combination therapies, immunosuppressive agents such as cyclosporin or tacrolimus, or antineoplastic drugs like dotsstakselu and bortezomib. Application vandetaniba with drugs excretion which occurs with the participation transporter P-glycoprotein (P-gp) (e.g., dabigatran or digoxin), may lead to increased concentrations of these drugs in plasma and require close clinical and laboratory observations of the patient and even reduce the dose these drugs.
Vandetanib, being organic cation transporter inhibitor (OST2) may slow excretion of metformin and other substrates OST2, thereby increasing their exposure. It may require more careful monitoring of the patient and a reduction in the dose of metformin.
Combined use vandetaniba and proton pump inhibitors (PPIs) can reduce exposure to vandetapibu, so the use of this combination of drugs is not recommended.
The effect of other drugs on the pharmacokinetics vandetaniba
There were no clinically significant interaction vandetaniba and potent inhibitor of isozyme CYP3A4, itraconazole. However, with the concomitant use vandetaniba and itraconazole, and other potent inhibitors of isoenzyme CYP3A4 (e.g., ketoconazole and ritonavir, clarithromycin) caution.
When the joint application vandetaniba and rifampitsiia, a potent inducer isoenzyme CYP3A4 men vandetaniba exposure was decreased by 40%, so avoid concomitant use vandetaniba and powerful inducers isoenzyme CYP3A4 (e.g., rifampicin, carbamazepine, phenobarbital and preparations Hypericum perforatum) (see. The section " Special instructions").
Medications that can prolong the interval QTc
Vandetanib can cause elongation of QTc interval, however it should not be taken simultaneously with other medicines capable lengthened QTc interval and / or causing flutter / flicker:
- Do not use this with arsenic, cisapride, erythromycin (iv) torsmifenom, mizolastine, moxifloxacin, antiarrhythmics means IA and class III (see. the section "Contraindications").
- Not recommended the use of methadone, haloperidol, amisulpride, hlorpromazipom, sulpiride, zuclopenthixol, halofantrine, pentamidine and Lumefantrine.
In the absence of suitable alternative therapy application deprecated drug combination may, if provided on the ECG monitoring QTc interval, controlling the concentration of electrolytes and additional control in case of diarrhea or amplification.
When applied together with ondansetron vandetaniba slight additive effect was observed on the elongation of QTc interval (approximately 10 ms), therefore the concomitant use of these drugs is not recommended. In case the destination together with vandetanibom ondansetron requires careful control of the electrolyte concentration in the serum and electrocardiogram, as well as any breaches intensive therapy. Food intake does not affect the exposure Kaprelsa drug.
In view of possible interaction of vitamin K antagonists and chemotherapeutic drugs recommended more frequent monitoring of international normalized ratio (MNO).
TERMS OF RELEASE FROM PHARMACY

On prescription.

TERMS AND CONDITIONS OF STORAGE

Store at a temperature not higher than 30 В° C. Keep out of the reach of children.
Shelf life - 3 years.
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