Afinitor 10mg Novartis treat breast cancer, kidney cancer, brain tumor, stomach tumor, intestines, pancreatic (3 blisters x 10 tablets)
Dosage form Box of 3 blisters x 10 tablets
Specifications Everolimus
Ingredient Novartis
Ingredient
| Composition information | Content |
| Everolimus | 10mg |
Uses
Indications
Afinitor tablets are designated for treatment for:
Everolimus is a signal transmission inhibitor targeting Mtor (Rapamycin's destination in mammals) or more specific than Mtorc1 ("Rapamycin" in mammals- complex 1). Mtor is a key Serine-Threonine Kinase, playing a central role in regulating the growth, proliferation and survival of cells. The complicated MTorC1 signal regulation, regulating by diverse substances, growth factors, energy and nutrients. Mtorc1 is the main regulatory substance that the general protein synthesis is in the direction of the PI3K/AKT path is the path of disordered disorder in most types of cancer in humans.
The activation of the MTor path is the main adaptive change that leads to resistance to endocrine therapy in breast cancer. Many different signal transmission paths have been activated to escape the impact of endocrine therapy. One path is PI3K/AKT/MTOR is activated mainly in long -term estrogen deficiency cells and AROMATASE (AI) inhibitors. In vitro studies show that breast cancer cells depend on Estrogen and Her2+ sensitive to the inhibitory effects of Everolimus, and show the treatment of Everolimus combining with AKT, Her2, or Aromatase inhibitors enhances Everolimus tumor activity in the same way. In breast cancer cells, the resistance of aromatase inhibitors due to the activation of AKT can be overcome by the use in combination with Everolimus.
Two MTORC1 signal air conditioners are oncogen suppressed tuberin-sclerosis complexes 1 & 2 (TSC1, TSC2). Inactive or inactivated TSC1 or TSC2 leads to an increase in RHEB -GTP - a GTPase enamel of RAS family - interacting with the MTORC1 complex to activate this complex. The activation of Mtorc1 led to a stream of Kinase signal waterfall, including the activation of S6K1. S6K1 is a substrate of the Mtor 1 complex (Mtorc1) will phosphorylation of region 1 with the activation function of the estrogen receptor is the substance responsible for activating the receptor independent of the death.
Pharmacological properties (PD)
Everolimus is a selective inhibitor MTor (the target of Rapamycin in mammals), especially targeting the Mtor-Raptor signal transmission complex (MTorc1). Mtor is a main Serine-Threonine Kinase in PI3K/AKT signal waterfall that is known to be known to be disordered in most types of cancer in humans. Everolimus has an impact through a highly affinity interaction with the intracellular protein is FKBP12. FKBP12/Everolimus complex is connected to MTORC1, inhibiting the signal transmission capacity of MTORC1. MTORC1's signal transmission is affected by the phosphorylation regulation of the impact substances that are the most typical of the regulating substances that regulate the Ribosome protein S6 Kinase (S6K1) and Eukaryote 4E-Protein onset (4E-BP). The disruption of the function of S6K1 and 4E-BP1 as a result of the MTORC1 inhibition, hindering the translation of the key proteins encoding the mRNA that plays a role in regulating cell cycle, sugar decomposition and adaptation to oxygen deficiency (reducing tissue oxygen). This inhibits the growth of tumors and inhibits the expression of the induction elements of the lack of oxygen (for example, the HIF-1 transcription factor); The following process leads to a decrease in the expression of factors related to increased vascular creation process of the tumor (for example, blood vascular endothelial growth factors - VEGF). Everolimus is a strong inhibitor of the growth and proliferation of tumor cells, endothelial cells, fiber cells and smooth muscle cells associated with blood vessels. Suitable for the central regulating role of Mtorc1, Everolimus shows reducing tumor cell proliferation, sugar decomposition and vascular formation in vivo solid tumors, thus leading to two independent mechanisms inhibiting tumor growth: tumor anti -tumor activity on tumor cells and inhibiting tumor tissue cavity.
Pharmacokinetics
absorption
In patients with a concentrated tumor after taking Afintior tablets, Everolimus's peak concentration reached 1-2 hours after taking a dose of 5-70 mg of Everolimus when hungry or after mild food. CMAX is proportional to the dose from 5-10 mg according to daily medication mode. At the single dose of 20 mg/week or more, the increase in cmax in a ratio is less than the dose, but AUC shows an increase in the dosage from 5-70 mg.
Effect of food
In healthy people, fat -rich meals reduce the body's 22% concentration with 10 mg Afinitor tablets (based on AUC measurement) and 54% of the concentration of CMAX peak in the blood. Low -fat snacks reduced 32% AUC and 42% cmax.
However, food does not have a significant impact on the drug concentration line over time of the phase after 24 hours of absorption.
Distribution
The ratio of blood concentration compared to the plasma of Everolimus, depends on the concentration range from 5-5000 ng/ml, is 17% to 73%. Observed the amount of Everolimus in plasma approximately 20% of blood concentration in cancer patients using Afinitor 10 mg/ day. The cohesion with plasma proteins is about 74% in both healthy people and medium liver failure patients. For patients with solid tumors, VD in the apparent central compartments of 191 liters and 517 liters in the outpost compartments.
After intravenous injection on the mouse model, Everolimus passes through the brain blood barrier in a non -linear dosage, indicating the saturation of the pump to push the drug in the brain blood barrier. The penetration of Everolimus into the brain has also been shown in the rats using the doses of oral Everolimus.
Biological / metabolic transformation
Everolimus is a substrate of CYP3A4 and PGP. After drinking, Everolimus is an administrative component in the blood in humans. 6 main metabolites of Everolimus have been detected in human blood, including 3 metabolites Monohydroxylation, 2 opening hydrolysis products and an Everolimus phosphatidylcholine complex. These metabolites are also determined in animals used in toxicity research and shows about 100 times inferior to Everolimus. Therefore, the mother substance is considered to contribute greatly to the pharmacological activity of Everolimus.
Elimination
There are no specific elimination studies of Everolimus conducted in cancer patients; However, there are data from organ transplantation. After using the single dose Everolimus, radioactive associated with ciclosporin, 80% of radioactive activity is detected in the feces while 5% are eliminated in the urine. Do not detect mother substance in urine or feces.
Pharmacokinetics in a stable state
After using Afinitor tablets for patients with a solid tumor, AUC0-T in a stable state proportional to the dose between 5-10 mg according to daily medication mode. Stable state is achieved within 2 weeks. CMAX is proportional to the dose from 5-10 mg according to daily medication mode. TMAX reached 1-2 hours after the dose. There is a significant correlation between AUC0-T and the bottom-dose concentration in a stable state according to the daily medication mode. Everolimus average sale time is about 30 hours.
Patients with liver failure
Afinitor's safety, tolerance and pharmacokinetics are assessed in two studies using the only dose Afinitor tablet in people with liver function impairment compared to those with normal liver function. In one study, Everolimus's average AUC in 8 patients with average liver function (Child-Pugh B) was twice as high as 8 patients with normal liver function. In the second study in 34 patients with different liver function impairment, compared to normal people, there is a 1.6 times an increase for mild-pug-a-year-old people, 3.3 times for people with average liver failure (Child-Pugh B) and 3.6 times for people with severe liver (Child-Pugh c) about concentration (ie AUC). Multi -dose pharmacokinetic simulation supports the recommendations of dosage in people with liver failure based on their Child Pugh. Based on the gross analysis data of the two studies, the recommended dose adjustment for patients with liver failure (see the warning and cautious and dosage and usage).
Patients with renal failure
In a pharmacokinetic analysis in groups of researchers in 170 patients with cancer far, no significant effect on creatinine clearance (25-178 ml/min) on Everolimus's oral clearance (Cl/F) of Everolimus. Renal failure after transplantation (creatinine clearance from 11-107 ml/minute) does not affect the pharmacokinetics of Everolimus in patients with organ transplants.
Children's patients
There is no indicator using afinitor in a group of children with cancer (see the dose and how to use).
Elderly patients
In a pharmacokinetic assessment in groups of researchers in cancer patients, there is no significant impact of age (27-85 years old) on the oral clearance of Everolimus (Cl/F: from 4.8 - 54.5 liters/hour).
Race
Similar oral clearance (Cl/F) in Japanese cancer patients and white people have similar liver function.
Based on the pharmacokinetic analysis by the group of researchers, the oral clearance (Cl/F) of Everolimus is 20% higher than the average of black skin patients with organ transplantation.
The relationship between concentration and response
There is an average correlation between the decrease of the phosphorylation of 4e-BP1 (P4E-BP1) in the tumor and the average cmin of Everolimus in the blood in a stable state after daily use of 5 or 10 mg Everolimus. Additional data shows the phosphorylation inhibition of S6 Kinase is very sensitive to the MTor inhibition by Everolimus. The phosphorylation inhibition of ELF-4G is entirely in all cmin values after daily doses of 10 mg.
A trend of suggesting a survival time does not progress to the disease longer with Everolimus's cmin standardized over time (defined as the area under the cmin curve over time from the beginning of the study until the time of events/time from the beginning of the study to the time of events) is clearly shown in patients with pancreatic nerves with pancreatic ratios (PETN. 95%: 0.50 - 1.08) and in patients with carcinoid tumors far away (hazardous ratio 0.66; reliability range (CI) 95%: 0.40 - 1.08). Everolimus's cmin affects the probability of reducing tumor size (P
Before taking Afinitor 10mg Novartis treat breast cancer, kidney cancer, brain tumor, stomach tumor, intestines, pancreatic (3 blisters x 10 tablets)
How to useafinitor is taken once a day at the same time, along with food or no (see clinical pharmacological part).
Should swallow the Afinitor tablet with a glass of water. Do not chew or crush.
For the disease that cannot be swallowed the whole pill, it is possible to completely dissolve the Afinitor tablet in a glass of water (containing about 30 ml) by stirring slightly until the pills dissolve (about 7 minutes), just before drinking. Should be coated with the same amount of water and completely swallow this coated water to ensure the entire medicine (see clinical pharmacological part).
Dosage
Afinitor treatment should be started by an experienced doctor in the use of anti -cancer therapy.
Should be continuous treatment when it is still recorded in clinical benefits or until unacceptable toxicity occurs.
Overall target patient group:
Dosage in remote breast cancer has a positive hormone receptor, nerve-nerve tumors that are derived from the pancreatic origin and carbon cells from far away
The recommended dose of Afinitor is 10 mg, taken 1 time/day (see the usage).
dose changes
Defined reaction
The handling of adverse drug reactions (ADR) is severe or intolerant may require suspension (with or without a dose reduction) or stop the treatment with Afinitor. If the dose is needed, the proposal is about 50% lower than the daily dose (see the warning and caution). For reducing the dose below the lowest tablet content, it is advisable to consider using Japanese drugs.
Table 1 Summary of recommendations on suspension, dose reduction or stopping the treatment with Afinitor in handling adverse drug reactions, including general treatment recommendations when appropriate. The clinical assessment of the treating doctor will guide the treatment plan for each patient based on the benefit assessment compared to the risk in each patient. The adverse reaction of the drug asymptomatic, signs on X-rays. No dose adjustment. Start the appropriate monitoring. symptoms, do not interfere with ADL3. Consider suspension of treatment, eliminate infections and consider corticosteroid treatment until improved symptoms of ≤ level 1. Start using Afinitor at a lower dose. Stop treatment if not recovered within 4 weeks. Symptoms, obstructing ADL3 to appoint breathing O2 Afinitor stops, eliminating infections and considering corticosteroid treatment until the symptoms are reduced to ≤ level 1. Review and start taking Afinitor at a lower dose. If the recurrent toxicity is at level 3, it is necessary to stop treating. Life threats for respiratory support. Minimum symptoms, normal diet. No dose adjustment. Treatment with non -alcoholic oral mouthwash (0.9%) several times a day. symptoms but can eat and swallow adjustment diet. temporarily suspend the dose until recovery to ≤ level 1. If recurrent stomatitis level 2, suspend the dose until recovery to ≤ level 1. Start using Afinitor at a lower dose. Handling with local oral pain treatment (e.g. Benzocaine, Butyl Aminobenzoate, Tetracaine Hydrochloride, Methol or Phenol), with or without topical corticosteroids (ie triamcinolon oral medication) .4 Symptoms and not so or drinking by oral. temporarily suspend the dose until recovery to level 1. Start using Afinitor at a lower dose. Treatment by mouth analgesic treatments (ie benzocaine, butyl aminobenzoate, tetracainehydrocholoride, methol or phenol) or non -local corticosteroids (ie triamcinolone oral medication) .4 There are symptoms related to life -threatening consequences. Start appropriate medical treatment and monitor. If toxicity becomes unable to tolerate, suspend the drug until recovery is ≤ level 1. If recurrent toxicity is at level 2, suspend Afinitor until recovery to ≤ level 1. Start using Afinitor at a lower dose. temporarily suspend the dose until recovery to ≤ level 1. Start appropriate medical treatment and monitor. Considering the start of using Afinitor at a lower dosage. If the recurrent toxicity is at level 3, it is necessary to stop treating. degrees 4 Start appropriate medical treatment and monitor. Treatment with appropriate medical treatment and monitoring. Start using Afinitor at a lower dose. Treatment with appropriate medical treatment and monitoring. degrees 4. 2 = Average symptoms; 3 = severe symptoms; 4 = Symptoms of life threatening. 2 If the dose is needed, the suggestion is about 50% compared to the daily dose before. 3 daily activities. 4 Avoid using substances containing alcohol, hydrogen peroxide, iodine and dehydrated western trees in handling stomatitis because these can make mouth ulcers worse. Be careful when used in combination with average inhibitor CYP3A4 or PGP. If the patient needs to be used in combination with an average CYP3A4 or PGP inhibitor, reduce the dose of afinitor to about 50% compared to the daily dose before. More dose can be reduced to control the adverse reactions of the drug. For reducing the dose below the lowest Afinitor content, it is advisable to consider using Japanese drugs. An additional dose may be required to handle the adverse reactions of the drug (see the warning and caution and drug interaction). Aide breast cancer has a positive hormone receptor, a distant hormonal nerve tumor originating in the pancreatic origin, carbon cell cargoma moves away: If you stop using the average inhibitor CYP3A4/PGP, it is advisable to consider the stage of discharging drugs at least 2 to 3 days (the average time for the most medium -sized drug inhibitors) before increasing the dose of Afinitor. The Afinitor dose can return to the previous dose when starting to use the average inhibitor CYP3A4/PGP (see the warning and caution and drug interaction). strong CYP3A4 induction substance Avoid using simultaneously with strong induction substances CYP3A4. Aide breast cancer has a positive hormone receptor, a distant hormonal nerve tumor originating in the pancreatic origin, the carbinoma caret cells go far: If the patient needs to be used in combination with a powerful CYP3A4 induction, considering double the daily Afinitor (based on dynamic dynamic data) by no more than 5 mg each time the dose increases. Predicting this Afinitor dose will adjust the area under the curve (AUC) to the range without induction substances. However, there is no clinical data on the adjustment of the dose in patients who are using strong CYP3A4 induction agents. If the CYP3A4 is stopped by a strong induction substance, then consider the elimination phase of at least 3 to 5 days (a reasonable time for the process of eliminating an important enzyme induction) before reducing the dosage of Afinitor back to the dose used before starting to use a strong CYP3A4 induction substance (see warning and cautious and drug interactions). Dosage in special patients Group of children's patients There is no recommendation to use Afinitor for children with cancer. Elderly patients (≥ 65 years old) No dose adjustment (see clinical pharmacological part). kidney failure No dose adjustment (see clinical pharmacological part). liver failure Aara breast cancer has a positive hormone receptor, hormonal nerve tumor that is from pancreatic origin, carbinoma caret cells go far: Do not observe death toxicity or severe toxicity in mice or rats given a single dose of 2,000 mg/kg (limit test). Experience reported on overdose in humans is still very limited. Single doses of up to 70 mg have been used with acceptable tolerances. Need to take general support measures in all cases of overdose. What to do when you forget 1 dose?
Side Effects
Notify the doctor with unwanted effects when using the drug.
Use in cancer - Summary of safety data
The adverse reaction information of the drug (ADR) is based on the synthetic safety data in patients using Afinitor (n = 2470) in clinical trials including random, double blindness, control with placebo or active comparative substances and Il phase research related to indications in the approved cancer.
The most common side effects of the drug (the rate of ≥ 10% and the doubt is related to the research by the researcher) from the safety data (in order of decreasing) is stomatitis, rash, diarrhea, infection, nausea, decreased appetite, anemia, taste, pneumonia, hyperglycemia, weight loss, itching, weakness, hematuria, blood, orange hyperkemen.
The side effects of the drug level 3-4 are most common (the ratio of ≥ 1/100 to
Summary of the side effects of the drug from clinical trials in cancer
Table 2 presents the type of frequency of side effects of the drug that has been reported in the gross analysis of safety.
The side effects of the drug are listed according to the classification group of Medrra system. In each system group, side effects are arranged by frequency, first the most common side effects. In addition, there is also the corresponding frequency for each side effect, using the following convention (Cioms III): Very common (≥1/10); Common (≥ 1/100 to rarely B includes different cases of bleeding not listed separately. C includes common side effects: pulmonary tissue; interstitial lung disease; and rare: alveolar inflammation, lung hemorrhage and lung poisoning. D includes very common side effects: stomatitis; Common: throgum stomatitis, mouth ulcer and tongue; Uncommon: tongue inflammation, tongue pain. E is reported in the form of hands-foot-legged hand syndrome. F frequency is assessed based on the number of women at about 10-55 years old in general analysis of safety.
Warnings
Before using the drug you need to read the instructions carefully and refer to the information below.
Contraindicated
Afinitor contraindicent for patients with hypersensitivity to active ingredients, with other Rapamycin derivatives or any ingredients of excipients (see warning and caution).
Be cautious when using
Read the instructions carefully before use. If you need more information, please ask for the idea of Uncle Si.
This drug is only used as prescribed by a doctor.
Non -infectious pneumonia
Non -infection pneumonia is a type of effect of rapamycin derivatives. Cases of non -bacterial pneumonia (including interstitial lung disease) have also been described in patients using Afinitor (see the auxiliary use of the drug). Some of these cases are severe and in very rare cases, the death of death. It is necessary to consider diagnosing non -bacterial pneumonia in patients with nonspecific respiratory signs and symptoms such as tissue oxygen, pleural effusion, cough or shortness of breath and in people where bacterial infections, neo -born tumors and other causes are not due to the appropriate drug. Distinguished diagnosis should be diagnosed to eliminate opportunistic infections such as pneumocystis jirovecii (pneumocystis jirovecii pneumonia) when diagnosing non -bacterial pneumonia (see infection).
Advise patients to immediately report any new respiratory symptoms or worsening.
For patients with changes on X-rays suggesting non-bacterial pneumonia and with little symptoms or asymptomatic, can continue to treat with afinitor without changing the dose (see the dose and usage, Table 1).
If symptoms are average (degree 2), consider suspension of treatment until symptoms improve. Corticosteroid can be appointed. Afinitor can be reused with a daily dosage to about 50% compared to the previous dose.
For cases of pneumonia 3 -infected pneumonia, it is necessary to stop treating with afinitor until symptoms are reduced to level 1 or less. Afinitor can be reused with a reduction of about 50% compared to the previous dose depending on the clinical condition of each patient. If the recurrent toxicity is at degree 3, then consider stopping Afinitor. For cases of pneumonia 4 -infected pneumonia, Afinitor should be stopped completely. Corticosteroids may be indicated until clinical symptoms retreat.
Consider pneumocystis jirovecii (PJP) pneumonia for patients who must treat non -infectious pneumonia with corticosteroids.
The appearance of pneumonia has also been reported at a decreased dose level (see the dose and usage, table 1).
Infections
Afinitor has immunosuppressive properties and can cause patients to be susceptible to infection, fungal infection, viral infection or unicellular infection, including infections due to opportunistic causes (see the side effects of the drug). Local and body infections include pneumonia, other bacterial infections, invasive fungal infections such as Aspergillus fungus, candidiasis, or pneumocystis jirovecii (PJP) and virus infection, including the hepatitis B virus that has been described in patients using Afinitor. Some of these infections are severe (for example, leading to infections, respiratory failure or liver failure) and sometimes death.
Doctors and patients need to be aware of the increased risk of infection when taking Afinitor. Before starting treatment with Afinitor, it is necessary to handle the infection before. While treating with Afinitor, there must be signs and symptoms of infection; If the infection has been diagnosed, appropriate treatment must be conducted immediately and consider suspension of treatment or stop therapeutic with Afinitor.
If the fungal infection has been diagnosed with the whole body, afinitor must be stopped and treated with appropriate antifungal therapy.
Cases of patients treated with Everolimus died of pneumocystis jirovecii pneumonia have been reported. Pneumocystis jirovecii pneumonia may be related to simultaneous use of Everolimus with corticosteroids or immunodeficiency drugs. Consider the prevention of pneumocystis jirovecii pneumonia when having to simultaneously use Everolimus with corticosteroids or other immunodeficiency drugs.
Hypersensitivity reaction
Hypersensitivity reactions are manifested by symptoms including, but not only limited to anaphylaxis, shortness of breath, blushing, chest pain or angioedema (for example: religion or tongue, with or no respiratory failure) have been observed with Everolimus (see the contraindication section).
Eventy fleet is simultaneously used Everolimus and enzyme inhibitors
angiotensin (Ace: Angiotensin-Converting Enzyme)
Patients treated simultaneously with Everolimus with enzyme inhibitors that may increase the risk of angioedema (for example, respiratory edema or tongue may be accompanied by or without respiratory failure.
mouth ulcer
mouth ulcer, stomatitis and oral mucosa have been recorded in patients treated with afinitor (see the side effects of the drug). In these cases, it is recommended to use local treatments but avoid alcoholic mouthwash, hydrogen peroxide, iodine, or basil because these can worsen. Antivopedic drugs should not be used unless the fungal infection is diagnosed (see the drug interaction).
Cases of renal failure
Cases of renal failure (including acute renal failure), some deaths have been observed in patients treated with Afinitor. Need to monitor special kidney function in patients with more risk factors that can lead to renal function (see the test and monitor and side effects of the drug).
Testing and monitoring
Kidney function
Increase serum, usually mild and proteinuria has been reported in patients using Afinitor (see the side effects of the drug). Recommendation for monitoring of kidney function, including blood urea nitrogen measurement (bun), proteinuria or serum creatinine before starting treatment with afinitor and periodic monitoring.
Blood sugar
Hyperglycemia has been reported in patients using Afinitor (see the side effects of the drug). Recommendations to monitor blood sugar at hunger before starting treatment with Afinitor and periodic monitoring later. It is more frequent to monitor when Afinitor is used simultaneously with other drugs that can increase blood sugar. It is necessary to achieve optimal blood sugar control before starting treatment with Afinitor for patients.
Blood lipidabnormal blood lipids (including hypercholesterolytic hyperkemen and hyper triglycerides) have been reported in patients using Afinitor. It is recommended to monitor blood cholesterol and blood triglycerides before starting treatment with afinitor and periodically as well as appropriate medical control.
Hematology parameters
There have been a report on hemoglobin, lymphocytes, platelets and neutrophils in patients using Afinitor (see the side effects of the drug). Recommendations to monitor total blood formula before starting treatment with Afinitor and periodic monitoring.
Drug-interaction
Avoid using in combination with strong CYP3A4 or PGP inhibitors (see drug interactions).
Be cautious when used in combination with CYP3A4 inhibitors or medium PGP inhibitors. If you have to use a combination of Afinitor with CYP3A4 inhibitors or medium PGP inhibitors, careful monitoring of patients should be careful about unwanted effects and reduce the dose of afinitor if necessary (see the dose and usage and drug interactions).
Avoid using in combination with CYP3A4 or PGP induction agents (see drug interactions). If a combination of Afinitor with a strong CYP3A4 or PGP induction is a strong clinical response. Consider increasing the afinitor dose when used in conjunction with a strong CYP3A4 or PGP induction substance if it is not possible to replace (see the dose and how to use and the drug interaction).
Due to the ability to interact with drugs, it is necessary to be cautious when using Afinitor in combination with the substrate of CYP3A4 to use oral orally with narrow treatment index. If Afinitor is used with the substrate of CYP3A4, oral orally has a narrow treatment index, patients should be monitored to detect unwanted effects described in the product information of the substrate of CYP3A4 oral (see the drug interaction).
liver failure
Increasing Everolimus concentration in patients with mild liver failure (Child-Pugh A), average (Child-Pugh B) and severe (Child-Pugh C) (see clinical pharmacological part).
It is not recommended to use Afinitor in patients with severe liver failure (Child-Pugh c) to treat long-distance breast cancer with positive hormone receptors in postmenopausal women, hormonal nerve tumors that are far from the origin of although, carbon cell cargomy is far away when the estimated benefits are superior to the risk (see the dosage and use of clinical pharmacies).
vaccinated
Avoid using live vaccines and close contact with people who have vaccinated Vaccin to live during treatment with Afinitor (see drug interaction).
lactose
Patients with rare genetic diseases are galactose or lactase enzyme defects or Glucose - Galactose should not use this drug.
Wounding complications
The process of healing wounds is affected by rapamycin derivatives, including afinitor.
Be cautious when using Afinitor during the surgery stage.
Carcinoid tumor
The effectiveness and safety of Afinitor have not been established in patients with carcinoid tumors.
The effect of the drug on driving and operating machinery
Afinitor can slightly affect the average on the ability to drive and operate machinery.
Patients should be carefully warned when driving or operating machinery if there is expression of fatigue when treating with Afinitor.
Using drugs for women during pregnancy and lactation
Women are likely to be pregnant
advise women who are likely to use pregnancy methods that are highly effective while taking Afinitor and up to 8 weeks after the end of treatment.
Reproduction
Unknown the possibility of Everolimus causes infertility in male and female patients. However, observed irregular menstruation, secondary menstrual amenorrhea and imbalance of royal hormone (LH) / Hormone stimulating follicles (FSH).
Based on the results in non -clinical studies, Afinitor treatment can reduce the fertility of men and women. (See the part of non -clinical safety data).
Pregnant women
There is no enough data on the use of Afinitor in pregnant women. Animal studies have shown toxicity to reproduction including toxicity to embryos and toxicity to the fetus (see the part of non -clinical safety data). Unknown risk for people.
Do not use Afinitor for pregnant women unless the potential benefits are superior to the potential risk to the fetus. It is not recommended for banning male patients from using Afintior trying to have children.
breastfeeding women
It is unclear whether Everolimus is excreted in breast milk or not. However, in animal studies, Everolimus and/or the metabolites of the drug easily enter the milk of breastfeeding rats. So women use Afinitor should not breastfeed.
Drug interaction
Everolimus is a substrate of CYP3A4 and also a medium substrate and inhibitor of p-glycoprotein (PGP) is a pump that pushes many drugs. Therefore, Everolimus's later absorption and elimination may be affected by products that affect Cy3A4 and/or PGP.
In vitro, Everolimus is a competitive inhibitor of CYP3A4 and is a mixed inhibitor of CYP2D6.
substances can increase the concentration of Everolimus in the blood
Everolimus concentration in the blood may increase due to active inhibitors of CYP3A4 and thus reduce Everolimus metabolism. Everolimus concentration in the blood may increase as PGP inhibitors can reduce the push of Everolimus from the intestinal cell.
avoid concurrent treatment with strong CYP3A4 or PGP inhibitors (including but not limited to ketoconazole, iTraconazole, Ritonavir, Clarithromycin and Telithromycin).
There is a significant increase in Everolimus concentration (the highest concentration in plasma (CMAX) increased by 3.9 times and the area under the curve (AUC) increased by 15 times) in healthy people when Everolimus is used in combination with ketoconazole (strong inhibitors CYP3A4 and PGP).
Be careful when treated simultaneously with the average inhibitor CYP3A4 (including but not limited to Erythromycin, Verapamil, Ciclosporin, Fluconazole, Diltiazem, Amprenavir, Fosamprenavir or APrepitant) and PGP inhibitors. Afinitor dose reduction if used in combination with average inhibitor CYP3A4/PGP (see the dosage and usage and warnings and caution).
There is an increase in contact with Everolimus in healthy people when Everolimus is used in combination with:
Should avoid using grapefruit, grapefruit juice, star fruit, oranges and other foods that have affected the activity of cytochrome P450 and PGP during treatment.
There is no clear difference in the lowest concentration in the plasma (cmin) of Everolimus when used with or not with the substrate of CYP3A4 and/or PGP after treatment at a dose of 10 mg or 5 mg daily.
Simultaneously use CYP3A4 weak or not with PGP inhibitors that do not have a clear effect on the cmin of Everolimus after using the treatment mode at a dose of 10 mg or 5 mg daily.
substances that can reduce Everolimus concentration in blood
substances that cause CYP3A4 or PGP induction substances may reduce the concentration of Everolimus in the blood due to increased metabolism or pushing Everolimus from the intestinal cell.
Should avoid simultaneous treatment with strong induction substances CYP3A4 or PGP. If a combination of Afinitor must be used with a powerful CYP3A4 or PGP (for example, Rifampicin and Rifabutin), the dose of afinitor (see the dosage and usage and cautions).
Pre -healthy treatment for many doses of rifampicin (1 CYP3A4 and PGP) 600 mg/day for 8 days, followed by a single -dose of Everolimus waste of the oral dosage of nearly 3 times, CMAX decreased by 58% and AUC decreased by 63%.
Other strong touch substances of CYP3A4 and/or PGP can increase Everolimus metabolism and reduce Everolimus concentration in blood including St. John's Wort (Hypericum Perforatum), anti -convulsions (for example, carbamazepine, phenobarbital, phenytoin) and anti -HIV drugs (for example: Efavirenz, Nevirapine).
substances whose plasma concentrations may be changed by Everolimus
Studies in healthy people show that there is no clinical pharmacokinetic interaction between Afinitor and Atorvastatin is the HMG-Coa Reductase inhibitor (the substrate of CYP3A4) and Pravastatin (not the substrate of CYP3A4) and the dynamic pharmacokinetic analysis of the patient group also detects Simvastatin (the mechanical of CYP3A4) Afinitor.
In vitro, Everolimus inhibits the competition of the metabolism of ciclosporin which is the substrate of CYP3A4 and is a mixed inhibitor of dextromethorphan which is the substrate of CYP2D6. The average cming of Everolimus is stable with oral 10 mg/day or 70 mg/week lower than 12-36 times the KI value of inhibitors in vitro. Therefore, Everolimus is thought to be hard to affect the metabolism of CYP3A4 and CYP2D6 substrates.
A study on healthy people shows that using a combination of a Midazolam oral dose (the substrate of CYP3A4) with Everolimus leads to Midazolam's CMAX by 25% and Midazolam's AUC (0-inF) increases by 30%, while AUC (0-inF) (1-inf) (1-1-inf) metabolism ratio (1- 1-in-hydroxy-midazolam/Midazolam) Not affected. This shows that the increase in midazolam concentration is due to the effect of Everolimus in the digestive system when both drugs are used simultaneously. Therefore, Everolimus can affect the bioavailability of the medications that is the substrate of CYP3A4 used to combine oral combination. Everolimus is hard to affect the concentration of other drugs that the substrate of CYP3A4 is used by orally such as intravenous sugar, subcutaneous and skin -to -skin injection (see the warning and cautious part).
Use combinations of Everolimus and Octreotide Depot, which increases the cmin of octreotide with an average ratio of multiplication (Everolimus/placebo) is 1.47 (reliable range (CI) 90%: 1.32 - 1.64) can hardly affect clinical significance on effective response to Everolimus in patients with hormonal tumors.
Storage
Store at temperatures below 30 degrees C. Keep the drug in the original packaging. Avoid light. Avoid moisture.
Do not use Afinitor after the "exp" "on the drug box.
Must leave Afinitor out of the reach of children and vision of children.
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