Votrient 200mg Novartis drug treatment for renal cell carcinoma (RCC) and software cancer (STS) (30 tablets)

Dosage form Box of 30 tablets
Specifications Pazopanib

Ingredient

Composition information	Content
Pazopanib	200mg

Uses

indications

Votrient 200mg drug indicated in the following cases:

RCE cell carcinoma (RCC)

Votrient is indicated for treatment of progressive and/or metastatic renal cell carcinoma.

Software Cancer (STS)

Votrient is indicated for treating adult patients with a number of selective subgroups of progressive software (STS) that has been used chemotherapy for previous metastatic treatment or for patients who still progress to the disease within 12 months after supplementary treatment.

Efficiency and safety of the drug is only set on certain types of software cancer tissue groups.

Pharmacology

Pharmacy group: Anti -cancer agents - Protein Kinase inhibiting agents, ATC code: L01xe11.

Pazopanib is used by oral, an effective inhibiting agent of Tyrosine Kinase (TKI) at many destinations of receptors of endocardium growth factors (VEGFR) -1, -2, and -3, platelet -derived growth factors (PDGFR) -α and -β, and stem cell receptors (C -KIT), with IIC50 values are the equivalent IC50 values are 10, equivalent 30, 47, 71, 84 and 74Nm.

In preclinical trials, Pazopanib inhibits the dosage on the dosage on the automation phosphorylation automated by the roots combined on the Vegfr-2, C-KIT and PDGFR-β receptors in cells. In Vivo, Pazopanib inhibits the phosphorylation of VEGFR-2 induction by VEGF in the lungs, the pulse formation in many test models on different animals, and the growth of the tumor from the micro-transplanted people in the mouse.

Dynamic pharmacokinetics

In a genetic analysis-general pharmacology from 31 clinical studies on Votrient used alone or in combination with other drugs, ALT> 5 times ULN (NCI CTC level 3) occurs in 19% patients with Allel HLA-B*57: 01 and 10% for patients who do not carry this Allel. In this data, 133/2235 (6%) patients carrying allel HLA-B*57: 01 (see warning).

Absorption: After oral orally, the single dose of Votrient 800mg for patients with solid tumors, the median time reaches the peak concentration in plasma (CMAX) about 19 ± 13 µg/ml of 3.5 hours (about 1.0-11.9 hours) and achieved AUC0 -∞ about 650 ± 500 ± 500 µg. Daily dose increases AUC0-T from 1.23 to 4 times.

AUC and CMAX do not increase consistently when increasing the dose Votrient above 800mg.

Exposure to the body for Votrient increases when taking medicine with food. Using Votrient with a lot of meals or low in fat leads to an increase in AUC and CMAX value about 2 times. Therefore, Votrient must be used at least 2 hours after meals or 1 hour before meals.

Take a dose of crushed Votrient 400mg tablets that has been increased by AUC (0-72) by 46% and increased by cmax by 2 times and reduces TMAX by about 2 hours compared to drinking whole tablets. This result shows that the bioavailability and the ratio of votrient absorption by orally increased when taking tablets has been ground compared to drinking whole tablets.

Distribution: In Vivo, Votrient associated with plasma proteins of people over 99% regardless of concentration in the range of 10-100 μg/ml. In vitro studies suggest that Votrient is the substrate of P-GP and BCRP.

Metabolism: The results from In vitro studies show that Votrient's metabolism is mainly through CYP3A4 intermediaries, and a small part through CYP1A2 and CYP2C8. The four Votrient's original metabolites only account for 6% of plasma exposure. One of these metabolites inhibits the growth of umbilical intravenous endothelial cells that VEGF activated with the same effect as Votrient, other metabolites with less active activity 10-20 times. Therefore, the effect of Votrient depends mainly on exposure to the original Votrient.

Elimination: Votrient is slowly eliminated with an average selling time of 30.9 hours after the recommended dose of 800mg. The drug excreted mainly in feces with excretion through the kidneys accounts for

Before taking Votrient 200mg Novartis drug treatment for renal cell carcinoma (RCC) and software cancer (STS) (30 tablets)

How to use

votrient should not be taken with food (at least 1 hour ago or 2 hours after meals).

Should swallow the votrient tablet with water and do not break or crush the pill.

Dosage

Dosage recommended by Votrient to treat kidney cell carcinoma (RCC) or software cancer (ST) is 800mg orally once daily.

In case of forgetting to take medicine, do not drink if there is less than 12 hours until the next dose.

Dose adjustment

The adjustment of the dose, or increasing or decreasing dose, must follow the ladder model with each step 200mg based on the level of tolerance of each patient to limit the unwanted effects of the drug. Votrient's dose must not exceed 800mg.

Special target groups

Patients with renal failure

Renal failure is said to have no clinical effects on pharmacokinetics of votrient by votrient and less metabolites are eliminated through the kidneys. Therefore, do not need to adjust the dose in patients with creatinine clearance above 30ml/min. Be careful for patients with creatinine clearance under 30ml/min because there is no experience using votrient in this patient group.

Patients with liver failure

recommended doses for patients with liver failure are based on Votrient's pharmacokinetic studies in patients with different levels of liver dysfunction. Should be cautious when using Votrient for patients with mild or medium liver failure and need to strictly control the intake of the drug. The dose of 800mg Votrient once daily is recommended for patients with mild abnormalities in serum tests to assess liver function (defined as or normal bilirubin and increase ALT at any level or increase bilirubin (> 35% directly) to 1.5 times the upper limit of normal levels (ULN) regardless of ALT values). Recommendation to reduce the dose of votrient to 200mg once daily for medium liver failure patients (defined as increased bilirubin> 1.5 to 3 times ULN regardless of ALT values).

It is not recommended to use votrient for patients with severe liver failure (defined as a total bilirubin> 3 times limited above normal [x ULN] regardless of any ALT values).

Children

Do not use Votrient for children under 2 years of age due to safety concerns for the development of the organ and the maturity of children.

The safety and effectiveness of Votrient in children from 2 to 18 years old has not been set. There is currently no data.

Elderly

Data on the use of Votrient in patients aged 65 and over is limited. In studies with Votrient in RCC patients, it is generally not observed that there is a significant difference in clinical differences in safety when taking Votrient between patients aged 65 and older and younger patients. Clinical experiences do not indicate the difference in response to drugs between elderly patients and younger patients but cannot exclude drug sensitivity in some elderly patients.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose? Fatigue level 3 (toxicity causes dose limit) and hypertension of degree 3, each expression has been recorded in 1 of 3 patients using the dose of 2000mg and 1000mg daily in the corresponding self.

Symptoms and signs: Currently only limited experience of Votrient's overdose.

Treatment: The next treatment must follow the clinical indications or the recommendations of the National Poison Control Center, if any. Hemorrhage is not thought to increase Votrient's excretion because Votrient excreted through the kidneys negligible and due to high -connected drugs with plasma proteins.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Side Effects

Data after circulation:

The following unwanted effects have been recorded during the use of Votrient after approval. These effects include spontaneous reports as well as serious unwanted effects from the conducted studies, clinical pharmacological studies and exploration studies for unpopular indications.

Infections and parasites

Not common: infection (with or without neutropenia).

Blood disorders and lymphatic systems

Rare: capillary thrombosis (including thrombocytopenic hemorrhage and hemolytic hyperur syndrome).

Not common: The rear brain damage syndrome is capable of recovering (see warning).

Digestive disorders

Popular: flatulence.

Popular: Increase gamma-glutamyl transpeptidase.

Very common: joint pain.

common: muscle spasm.

Unsatibly: peeling/peeling of the retina.

Rare: interstitial lung disease/pneumonia

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

Votrient drugs contraindicated in the following cases:

Votrient is contraindicated in patients sensitive to any ingredients of the drug.

Be cautious when using

The effects on the liver: There are reports on cases of liver failure (including death) when using Votrient. Precautions when using Votrient for patients with mild or medium liver failure and need strict control. The dose of 800mg Votrient once daily is recommended for patients with mild abnormalities in serum tests to assess liver function (or normal bilirubin and increase ALT at any extent or increase bilirubin by 1.5 times ULN regardless of ALT values). The Votrient dose dropped to 200mg once daily is recommended for medium liver failure patients (increasing bilirubin> 1.5 to 3 times ULN regardless of ALT values). It is not recommended to use votrient for patients with severe liver failure (total bilirubin> 3 times ULN regardless of ALT values). Drug exposure at 200mg is significantly reduced in these patients, although there are many changes, these values are not enough to see if it has a clinical impact.

In clinical trials with Votrient, observed the increase of transaminase enzymes (ALT, Aspartat Aminotransferase [AST]) and bilirubin in serum. In most cases, there has been an individually increased ALT and AST increase without increasing alkaline phosphatase or bilirubin. Patients over 60 years of age are at high risk of increasing ALT.

Patients with allel HLA-B*57: 01 may also increase the risk of increasing ALT related to Votrient. Should monitor tight liver function in all patients using Votrient, regardless of genotype and age. The increase in transaminase enamel at the majority (> 90%) occurred in the first 18 weeks. The level of transaminase enamel increases based on the general term standards of adverse events of the National Cancer Institute, version 3 (NCI CTCAE).

should closely monitor serum tests to assess liver function before treatment with Votrient, and in weeks 3, 5, 7 and 9. It is necessary to continue monitoring periodically after the 4th month. The following instructions are provided to patients with the initial value of the total bilirubin ≤1.5 x The upper limit of the normal level (ULN) and AST and ALT ≤2 x ULN.

Patients with individual ALT increases from 3 to 8 times the upper limit of normal levels (ULN) can continue to use votrient along with weekly monitoring liver function until the transaminase returns to level 1 (NCI CTCAE) or before treatment.

Patients with ALT increases> 8 times ULN should suspend votrient until transaminase returns to level 1 (NCI CTCAE) or before treatment. If considering the potential benefits of reusing Votrient is more prominent than the risk of toxicity in the liver, Votrient can be reused at a reduced dose level and conduct liver function assessment tests per week for 8 weeks (see dosage and usage). After reuse Votrient, if ALT rises again> 3 times ULN, it must stop Votrient.

If Alt increases> 3 times ULN simultaneously with bilirubin increases> 2 times ULN, should stop using long -term votrient. Patients should be monitored until the transaminase returns to level 1 (NCI CTCAE) or the level before treatment. Votrient is a UGT1A1 inhibitor. Increasing mild, non -direct blood bilirubin can occur in patients with Gilbert syndrome. Patients who only suffer from mild blood bilirubin, have known or suspect gilbert syndrome, and increase ALT> 3 Uln should be monitored according to the recommendations for an increase in ALT.

Simultaneous use of votrient and simvastatin increases the risk of increasing ALT and should be used carefully and closely monitor.

Except for patients with mild liver failure treated with Votrient 800mg once a day and reducing the starting dose to 200mg daily for patients with average liver failure, no other dose adjustment instructions based on blood test results assessing liver function during treatment for patients who have had liver failure earlier.

Hypertension: In clinical studies with Votrient, there have been events of hypertension including newly diagnosed hypertension (hypertension). Need to control blood pressure well before starting to use Votrient. Patients should be monitored early and strictly hypertension immediately after starting treatment (no more than 1 week after starting Votrient) and regularly then to ensure blood pressure control. Hypertension levels (systolic blood pressure ≥150 or diastolic blood pressure ≥100 mmHg) appeared early in the treatment (approximately 40% of cases appear before the 9th day and approximately 90% of cases appearing within the first 18 weeks). Blood pressure should be closely monitored and immediately controlled by using hypotension combination therapy and adjusting the dose of Votrient (suspension or re -use with a low dose of clinical decreases based on clinical assessment). Votrient must be stopped if there is evidence of persistent hypertension (140/90 mmHg) or if hypertension is serious and persistent despite using anti -hypertension therapy and reducing votrient dose.

Posterior reversible encephalopathy syndrome syndrome (preses)/ white brain whitening syndrome can recover (Reversible Posterior Leukiencephalopathy Syndrome (RPLS): Pres/ RPLS has been reported related to Votrient. Pres/Rpls may have a headache, hypertension, convulsions, sleep, confusion, blindness and other neurological and visual disorders and may die. Stop Votrient in patients with Pres/Rpls.

Interstitial lung disease (ILD)/pneumonia: interstitial lung disease, which can be fatal, has been reported to be related to votrient (see adverse effects). Patients with pulmonary symptoms are required to suggest interstitial/pneumonia. Stop using Votrient in patients with interstitial pneumonia or progressive pneumonia.

Heart dysfunction: In clinical trials with Votrient, there have been events of heart dysfunction such as congestive heart failure and reduced left ventricular blood emulsion (LVEF). In a random trial of renal cell carcinoma (RCC), Votrient's control with Sunitinib, in those who are measured in the initial LVEF and monitor, the heart dysfunction has been observed at 13% (47/362) groups of Votrient subjects compared to 11% (42/369) in the group of subjects using Sunitinib. Sound blood failure has been observed in 0.5% of the objects in each treatment group. In phase clinical trial III on software cancer (STS), congestion heart failure has been reported at 3 out of 240 subjects (1%). In this trial, it is found that the reduction of left ventricular blood in the subjects conducted this index after treatment was 11% (16/142) in the Votrient group compared to 5% (2/40) in the placebo group. There are 14/16 subjects in the Votrient group with hypertension and may increase heart dysfunction in patients at risk (for example, the previous patient with anthracyclin treatment) by increasing the heart burden.

Should monitor blood pressure and immediately control by coordinating the treatment regimen of hypertension and adjusting the dose of Votrient (stopping or starting at lower dose based on clinical assessment). Patients should be carefully monitored the clinical signs or symptoms of congestive heart failure. It is recommended to evaluate LVEF before treatment and periodic treatment in patients at risk of heart dysfunction.

extends the QT and torsion interval: In clinical studies with Votrient, there has been a event that extends the distance of QT or torsion. Votrient should be used carefully in patients with a history of extension of QT, patients who use anti -arrhythmic drugs or other drugs may extend the QT range, or patients with previous heart disease. When using Votrient, electrocardiograms need to be monitored before treatment and periodically and maintain the concentration of electrolytes (calcium, magnesium, potassium) in normal range.

Aortic thrombosis: In clinical studies with Votrient, there have been events of myocardial infarction, angina, cerebral infarction stroke and transient brain anemia (ray). Also observed the death events. Votrient should be used in patients with high risk of thrombosis or those who had occurred in the previous 6 months. It is necessary to make treatment decisions based on benefits/risk assessments in each patient.

Varicomatic thrombosis events: In clinical studies with Votrient, there have been events of venous thromboembolism including venous thrombosis and fatal artery embolism. The incidence is higher in STS objects (5%) compared to the RCC group (2%).

capillary thrombosis: capillary thrombosis (TMA) has been reported in Votrient's clinical trials used for monomers, in combination with Bevacizumab, and in combination with Topotecan. Stop completely Votrient in patients with capillary thrombosis. Observing the reversal of capillary thrombosis after stopping treatment. Votrient is not indicated in combination with other substances.

Bleeding events: In clinical studies with Votrient, there have been hemorrhagic events. There have been deadly hemorrhage events. Votrient has not been studied in patients with a history of hematuria, cerebral hemorrhage, or serious gastrointestinal bleeding in the previous 6 months. Be cautious to use Votrient in patients at high risk of bleeding.

Perforation and gastrointestinal leaks: In clinical studies with Votrient, there have been puncture events or gastrointestinal leaks. The death of death has occurred. Caution should be used for Votrient in patients at risk of puncture or gastrointestinal leak.

Heal wounds: There is no official research on the influence of Votrient on the healing process. Because the factors inhibiting blood vessel growth factors (VEGF) can slow down the healing of wounds, it is necessary to stop treating Votrient at least 7 days before the surgical schedule. The decision to reuse Votrient after surgery must be based on clinical evaluation, showing the wound healing process stable. Votrient must be stopped in patients with open wounds.

Reduce thyroid function: In clinical studies with Votrient, there has been a thyroid function incident. Should proactively supervise thyroid function tests.

proteinuria: In clinical studies with Votrient, proteinuria cases have been noted. Urine analysis should be conducted before treatment and periodically during treatment and should monitor patients about proteinuria development worse. Votrient must be stopped if the patient progresses into a kidney syndrome.

Pneumothorax: In clinical studies with Votrient in progressive software cancer, pneumothoraxes have occurred. Patients being treated with Votrient should be closely monitored with signs and symptoms of pneumothorax.

Infections: Severe infections (with or without neutropenia) in some cases of death have been reported.

Collaborate with other anti -cancer therapies using systemic tract: Clinical trials using Votrient in combination with Pemetrexed (non -small cell lung cancer (NSCLC)) and Lapatinib (Cervical cancer) have to end early due to concerns about increased toxicity and/death, and have not yet set up safe and effective coordination with these regimen. Votrient is not indicated in combination with other substances.

Toxicity on adult animals: Due to the mechanism of action of Votrient can seriously affect the growth and maturity of the agency during the early development of postpartum development. Do not use votrient for children under 2 years old.

Pregnancy: Pre -clinical studies in animals have shown reproductive toxicity.

If Votrient is used during pregnancy, or if the patient is pregnant when using Votrient, it is necessary to explain to the patient about potential dangers to the fetus. It is necessary to advise women of reproductive age to perform contraception when treated with Votrient.

Interactive: avoid simultaneous treatment with strong inhibitors CYP3A4, P-Glycoprotein (P-GP) or breast cancer-resistant protein (BCRP) due to the risk of increased exposure to Votrient. It is advisable to consider choosing alternative drugs that are not available at the same time or have the ability to inhibit at least CYP3A4, P-GP or BCRP.

Should avoid simultaneously with CYP3A4 induction drugs due to the risk of exposure to Votrient.

Observed cases of hyperglycemia when used simultaneously with ketoconazole.

Be cautious when using simultaneously votrient with Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) (for example Irinotecan) because Votrient is UGT1A inhibitor.

Should avoid using grapefruit juice during treatment with Votrient.

The effect of the drug on the ability to drive and operate machinery

The ability to perform tasks requires judgment, cognitive or exercise skills: No research has determined the effect of Votrient on driving or operating machinery. Harmful effects on such activities cannot be predicted based on the pharmacological properties of Votrient. The patient's clinical condition and the adverse incident records of Votrient when considering the patient's ability to perform tasks require judgment, motor skills or perception.

Using drugs for women during pregnancy and lactation

Pregnancy:

There is no enough data from using Votrient in pregnant women. Animal studies show that drugs are toxic to reproduction. Potential risks on people have not been determined. Do not use Votrient during pregnancy unless the patient's clinical condition requires Votrient to treat. If Votrient is used during pregnancy, or if the patient is pregnant while using Votrient, it is necessary to explain to the patient about the potential danger to the fetus.

Women who are likely to be pregnant should be advised to use appropriate contraception during treatment and 2 weeks after stopping treatment with Votrient and must be avoided pregnancy while being treated with Votrient.

Fertility: Votrient can impair fertility on both men and women. In studies on reproductive toxicity on female varieties in rats, fertility has been reduced.

Breastfeeding period:

Safety when using votrient during breastfeeding has not been determined. Do not know if Votrient is excreted through breast milk. Should stop breastfeeding during treatment with Votrient.

Drug interaction

The effect of other drugs on votrient

In vitro studies suggest that Votrient's oxidation metabolism at microsome in the liver is mainly through CYP3A4 intermediaries, with a small part of the CYP1A2 and CYP2C8. Therefore, the inhibiting and touch agents of CYP3A4 can change the metabolism of Votrient.

CYP3A4, P-GP, BCRP inhibitors

Votrient is a substrate for CYP3A4, P-GP and BCRP.

Simultaneous use Votrient (400mg once daily) with strong inhibitors CYP3A4 and P-GP, ketoconazole (400mg once daily) for 5 consecutive days, increasing the corresponding 66% and 45% of the average value of AUC (0-24) and CMAX of Votrient compared to when using single Votrient (400mg once daily in 7 days). Compare the pharmacokinetic parameters of Votrient CMAX (an average value range from 27.5 to 58.1 µg/ml) and AUC (0-24) (The average value is from 48.7 to 1040 µg*hour/ml) after using Votrient 800mg and after using Votrient 400mg combined with ketoconazole 400mg (CMAX average 59.2 µg/ml, AUC (0-24) On average, 1300 µg*hour/ml) shows that with the presence of strong inhibitors CYP3A4 and P-GP, reducing the dose of Votrient 400mg once a day in most patients will lead to the same body exposure as observed after using 800mg Votrient once a day. However, some patients may have more votrient exposure than patients using 800mg of solitary votrient.

Simultaneous use of Votrient with other strong inhibitors of CYP3A4 groups (for example Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole) can increase Votrient levels. Grapefruit juice contains CYP3A4 inhibitors can also increase the level of votrient in plasma.

Use 1500mg Lapatinib (a substrate and a mild inhibitor CYP3A4, P-GP and a strong BCRP inhibitor) along with 800mg Votrient increases about 50% to 60% of the average AUC (0-24) and CMAX of Votrient when compared to the use of 800mg Votrient. The inhibition of P-GP and/or BCRP by Lapatinib probably contributed to the increase in exposure to Votrient.

Simultaneous use Votrient with CYP3A4, P-GP, and BCRP inhibitors, such as Lapatinib, will increase Votrient concentration in plasma. Simultaneously used with strong P-GP or BCRP inhibitors can also change Votrient's exposure and distribution, including distribution to the central nervous system (CNS).

Should avoid simultaneous use of votrient with strong inhibitors CYP3A4. If there is no other acceptable medical option to replace strong CYP3A4 inhibitors, Votrient dose should be reduced to 400mg daily while using a combination. In these cases, you should closely monitor unwanted effects, and may consider reducing additional dose if observations see unwanted effects that are likely to be related to drugs.

Avoid combining with powerful inhibitors P-GP or BCRP, or recommend choosing an alternative to simultaneously without or capable of inhibiting at least P-GP or BCRP.

CYP3A4, P-GP, BCRP induction drugs

CYP3A4 induction drugs like rifampin may reduce the level of votrient in plasma. Simultaneous use of Votrient with strong P-GP or BCRP induction drugs can change Votrient's exposure and distribution, including distribution to the central nervous system (CNS). It is recommended to choose an alternative to the same time without or have the ability to touch at least with the enzyme or transportation.

The effect of votrient on other drugs

In vitro studies on liver liver microsomes have shown that votrient has the effect of inhibiting CYP enzymes 1A2, 3A4, 2B6, 2C8, 2C9, 2C19, and 2E1. The potential induction effect on CYP3A4 in humans has been shown in a test PXR in vitro in humans. Clinical pharmacological studies, using Votrient 800mg once a day, have shown that Votrient has no clinical related effects on pharmacokinetics of caffeine (CYP1A2's polling substrate), Warfarin (CYP2C9's exploration substrate), or Omeprazole (CYP2C19 exploration substrate) in cancer patients. Votrient increases about 30% of the average value of AUC and CMAX of Midazolam (CYP3A4's exploration substrate) and increases 33% to 64% of dextrometrophan concentration ratio on dextrorphan in urine after drinking dextromethorphan (pollutants of CYP2D6). Simultaneous use of Votrient 800mg once daily and Paclitaxel 80mg/m2 (substrate of CYP3A4 and CYP2C8) once a week leads to an average increase of 25% and 31% of the AUC and CMAX values of Paclitaxel.

Based on the values of IC50 in vitro and CMAX in Vivo plasma, the metabolites of Votrient GSK1268992 and GSK1268997 can contribute to Votrient's actual inhibitor effect on BCRP. Moreover, Votrient is not eliminated inhibiting BCRP and P-GP on the digestive tract. Be careful when using Votrient simultaneously with other orally BCRIC and P-GP substrates.

In vitro, Votrient inhibit polypeptide transportation of organic anion in humans (OATP1B1). Votrient is not excluded, which will affect the pharmacokinetics of the substrates of OATP1B1 (e.g. Statin, see the "Effect when using Votrient and Simvastatin" below).

Votrient is an uridine diphosphoronosyl-gansferase 1A1 (UGT1A1) in vitro. The metabolites have the activity of Irinotecan, SN-38, a substrate of OATP1B1 and UGT1A1. Simultaneous use of Votrient 400mg once daily with Cetuximab 250mg/m2 and Irinotecan 150mg/m2 lead to an increase of about 20% of the body exposure with SN-38. Votrient may have more influence on the SN-38 arrangement in objects with UGT1A1*28 polymorphism compared to those with natural Allen. However, the UGT1A1 genotype does not always predict the effect of Votrient on SN-38 arrangement. Be cautious when using Votrient along with the substrates of UGT1A1.

Effects when using simultaneously votrient and simvastatin

Simultaneous use of votrient and simvastatin increases the increase in ALT. The result from a gross analysis using data from clinical trials with Votrient shows that ALT> 3 times ULN has been reported at 126/895 (14%) patients do not use statins, compared to 11/41 (27%) patients use simultaneously with simvastatin (P = 0.038). If the patient takes simultaneously simvastatin, there is an increase in ALT, it is necessary to follow the instructions on how to use votrient and stop using simvastatin. In addition, it is necessary to be cautious when using votrient simultaneously with other statins because there is not enough data to assess the effect of these drugs on ALT levels. Votrient may not affect the pharmacokinetics of other statins (for example, Atorvastatin, Fluvastatin, Pravastatin, Rosuvastatin).

Effect of food on votrient

Use votrient along with high or low -fat meals, which leads to an increase in AUC and CMAX values. Therefore, Votrient must be used at least 1 hour before meals or 2 hours after meals.

Gastroenter pH drugs

Simultaneous use of votrient with Esomeprazole reduces Votrient's bioavailability by about 40% (AUC and CMAX), and should be avoided simultaneously Votrient with gastric pH medications. If the use in combination with proton pump inhibitors (PPI) is medical necessary, recommends using Votrient doses once a day without food and in the evening at the same time with PPI. If concurrent use with H2 receptor drug is necessary in terms of medical, Votrient should not be used with food at least 2 hours ago or at least 10 hours after taking the H2 receptor resistance dose. Votrient should be used for at least 1 hour before and 2 hours after taking the antacids to work short -term. Simultaneous recommendations with PPI drugs and H2 receptor drugs will be based on physiological reviews.

Storage

Leave a cool place, avoid light, temperatures below 30⁰C.

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