Afinitor Information
Afinitor (Everolimus) indications And Usage
Afinitor (Everolimus) is indicated for the treatment of progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease.
The safety and effectiveness of Afinitor (Everolimus) in the treatment of patients with carcinoid tumors have not been established.
Afinitor (Everolimus) is indicated for the treatment of patients with SEGA associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection.
The effectiveness of Afinitor (Everolimus) is based on an analysis of change in SEGA volume . Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been demonstrated.
Afinitor (Everolimus) dosage Forms And Strengths
2.5 mg tablet
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “LCL” on one side and “NVR” on the other.
5 mg tablet
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “5” on one side and “NVR” on the other.
7.5 mg tablet
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “7P5” on one side and “NVR” on the other.
10 mg tablet
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “UHE” on one side and “NVR” on the other.
Afinitor (Everolimus) contraindications
Hypersensitivity to the active substance, to other rapamycin derivatives, or to any of the excipients. Hypersensitivity reactions manifested by symptoms including, but not limited to, anaphylaxis, dyspnea, flushing, chest pain, or angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment) have been observed with everolimus and other rapamycin derivatives.
Afinitor (Everolimus) warnings And Precautions
Non-infectious pneumonitis is a class effect of rapamycin derivatives, including Afinitor (Everolimus) . Non-infectious pneumonitis was reported in 11-14% of patients treated with Afinitor (Everolimus) . The incidence of Common Terminology Criteria (CTC) grade 3 and 4 non-infectious pneumonitis was 1.6-4.0% and 0.1%, respectively Fatal outcomes have been observed.
Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough, or dyspnea, and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations. Advise patients to report promptly any new or worsening respiratory symptoms.
Patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms may continue Afinitor (Everolimus) therapy without dose alteration. Imaging appears to overestimate the incidence of clinical pneumonitis.
If symptoms are moderate, consider interrupting therapy until symptoms improve. The use of corticosteroids may be indicated.
For cases where symptoms of non-infectious pneumonitis are severe, discontinue Afinitor (Everolimus) therapy. Corticosteroids may be indicated until clinical symptoms resolve.
Afinitor (Everolimus) has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections, including infections with opportunistic pathogens . Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections, such as aspergillosis or candidiasis, and viral infections including reactivation of hepatitis B virus have occurred in patients taking Afinitor (Everolimus) . Some of these infections have been severe (e.g., leading to respiratory or hepatic failure) or fatal. Physicians and patients should be aware of the increased risk of infection with Afinitor (Everolimus) . Complete treatment of pre-existing invasive fungal infections prior to starting treatment with Afinitor (Everolimus) . While taking Afinitor (Everolimus) , be vigilant for signs and symptoms of infection; if a diagnosis of an infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of Afinitor (Everolimus) . If a diagnosis of invasive systemic fungal infection is made, discontinue Afinitor (Everolimus) and treat with appropriate antifungal therapy.
Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with Afinitor (Everolimus) . Approximately 44%-64% of Afinitor (Everolimus) -treated patients developed mouth ulcers, stomatitis, or oral mucositis, which were mostly CTC grade 1 or 2 . Grade 3 or 4 stomatitis was reported in 6% of patients with neuroendocrine tumors. In the SEGA study, 86% of Afinitor (Everolimus) -treated patients developed stomatitis which was mostly CTCAE grade 1 or 2 . In such cases, topical treatments are recommended, but alcohol- or peroxide-containing mouthwashes should be avoided as they may exacerbate the condition. Antifungal agents should not be used unless fungal infection has been diagnosed .
[see Laboratory Tests and Monitoring (5.5)]
Due to significant increases in exposure of everolimus, co-administration with strong CYP3A4 inhibitors should be avoided .
A reduction of the Afinitor (Everolimus) dose is recommended when co-administered with a moderate CYP3A4 and/or PgP inhibitor
An increase in the Afinitor (Everolimus) dose is recommended when co-administered with a strong CYP3A4 inducer .
Exposure of everolimus was increased in patients with moderate hepatic impairment .
For advanced PNET and advanced RCC patients with moderate hepatic impairment (Child-Pugh class B), a dose reduction is recommended .
For SEGA patients with moderate hepatic impairment (Child-Pugh class B), adjustment to the starting dose may not be needed. However, subsequent dosing should be individualized based on therapeutic drug monitoring .
Afinitor (Everolimus) has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should not be used in this population
The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with Afinitor (Everolimus) Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.
The timing of routine vaccinations in pediatric patients with SEGA should be considered prior to the start of everolimus therapy.
There are no adequate and well-controlled studies of Afinitor (Everolimus) in pregnant women. However, based on the mechanism of action, Afinitor (Everolimus) may cause fetal harm when administered to a pregnant woman. Everolimus caused embryo-fetal toxicities in animals at maternal exposures that were lower than human exposures for advanced PNET, advanced RCC, and SEGA patients. If this drug is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to use an effective method of contraception while using Afinitor (Everolimus) and for up to 8 weeks after ending treatment
Afinitor (Everolimus) adverse Reactions
The following serious adverse reactions are discussed in greater detail in another section of the label:
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
Afinitor (Everolimus) drug Interactions
Everolimus is a substrate of CYP3A4, and also a substrate and moderate inhibitor of the multidrug efflux pump PgP, everolimus is a competitive inhibitor of CYP3A4 and a mixed inhibitor of CYP2D6.
In healthy subjects, compared to Afinitor (Everolimus) treatment alone there were significant increases in everolimus exposure when Afinitor (Everolimus) was coadministered with:
Concomitant strong inhibitors of CYP3A4 should not be used .
Use caution when Afinitor (Everolimus) is used in combination with moderate CYP3A4 and/or PgP inhibitors. If alternative treatment cannot be administered reduce the Afinitor (Everolimus) dose
In healthy subjects, co-administration of Afinitor (Everolimus) with rifampin, a strong inducer of CYP3A4, decreased everolimus AUC and C by 63% and 58% respectively, compared to everolimus treatment alone. Consider a dose increase of Afinitor (Everolimus) when co-administered with strong CYP3A4 inducers if alternative treatment cannot be administered. St. John’s Wort may decrease everolimus exposure unpredictably and should be avoided .
Studies in healthy subjects indicate that there are no clinically significant pharmacokinetic interactions between Afinitor (Everolimus) and the HMG-CoA reductase inhibitors atorvastatin (a CYP3A4 substrate) and pravastatin (a non-CYP3A4 substrate) and population pharmacokinetic analyses also detected no influence of simvastatin (a CYP3A4 substrate) on the clearance of Afinitor (Everolimus) .
Coadministration of everolimus and depot octreotide increased octreotide Cmin by approximately 50%.
Afinitor (Everolimus) use In Specific Populations
Pregnancy Category D
There are no adequate and well-controlled studies of Afinitor (Everolimus) in pregnant women. However, based on the mechanism of action, Afinitor (Everolimus) may cause fetal harm when administered to a pregnant woman. Everolimus caused embryo-fetal toxicities in animals at maternal exposures that were lower than human exposures for advanced PNET, advanced RCC, and SEGA patients. If this drug is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to use an effective method of contraception while receiving Afinitor (Everolimus) and for up to 8 weeks after ending treatment.
In animal reproductive studies, oral administration of everolimus to female rats before mating and through organogenesis induced embryo-fetal toxicities, including increased resorption, pre-implantation and post-implantation loss, decreased numbers of live fetuses, malformation (e.g., sternal cleft), and retarded skeletal development. These effects occurred in the absence of maternal toxicities. Embryo-fetal toxicities occurred at approximately 4% the exposure (AUC) in patients receiving the recommended dose of 10 mg daily in advanced PNET and advanced RCC patients. In rabbits, embryotoxicity evident as an increase in resorptions occurred at an oral dose approximately 1.6 times the recommended human dose for advanced PNET and advanced RCC patients, and 0.7 times the maximum dose administered to SEGA patients on a body surface area basis. The effect in rabbits occurred in the presence of maternal toxicities.
In a pre- and post-natal development study in rats, animals were dosed from implantation through lactation. At approximately 10% of the recommended human dose for advanced PNET and advanced RCC patients and 4% of the maximum dose administered to SEGA patients, based on body surface area, there were no adverse effects on delivery and lactation and there were no signs of maternal toxicity. However, there was reduced body weight (up to 9% reduction from the control) and slight reduction in survival in offspring (~5% died or missing). There were no drug-related effects on the developmental parameters (morphological development, motor activity, learning, or fertility assessment) in the offspring.
Doses that resulted in embryo-fetal toxicities in rats and rabbits were ≥0.1 mg/kg (0.6 mg/m) and 0.8 mg/kg (9.6 mg/m), respectively. The dose in the pre- and post-natal development study in rats that caused reduction in body weights and survival of offspring was 0.1 mg/kg (0.6 mg/m).
In the randomized advanced RCC study, 41% of Afinitor (Everolimus) -treated patients were ≥ 65 years in age, while 7% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out .
No dosage adjustment is required in elderly patients .
The safety and pharmacokinetics of Afinitor (Everolimus) were evaluated in a study in eight patients with moderate hepatic impairment (Child-Pugh class B) and eight subjects with normal hepatic function. Exposure was increased in patients with moderate hepatic impairment.
For advanced PNET and advanced RCC patients with moderate hepatic impairment (Child-Pugh class B), a dose reduction is recommended ].
For SEGA patients with moderate hepatic impairment (Child-Pugh class B), adjustment to the starting dose may not be needed. However, subsequent dosing should be individualized based on therapeutic drug monitoring .
The impact of severe hepatic impairment (Child-Pugh class C) has not been assessed and use in this patient population is not recommended.
Afinitor (Everolimus) overdosage
In animal studies, everolimus showed a low acute toxic potential. No lethality or severe toxicity were observed in either mice or rats given single oral doses of 2000 mg/kg (limit test).
Reported experience with overdose in humans is very limited. Single doses of up to 70 mg have been administered. The acute toxicity profile observed with the 70 mg dose was consistent with that for the 10 mg dose.
Afinitor (Everolimus) description
Afinitor (Everolimus) (everolimus), an inhibitor of mTOR, is an antineoplastic agent.
The chemical name of everolimus is (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18- dihydroxy-12-{(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-aza-tricyclo[30.3.1.0]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone.
The molecular formula is CHNOand the molecular weight is 958.2. The structural formula is:
Afinitor (Everolimus) is supplied as tablets for oral administration containing 2.5 mg, 5 mg, 7.5 mg or 10 mg of everolimus together with butylated hydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone, and lactose anhydrous as inactive ingredients.
Afinitor (Everolimus) clinical Pharmacology
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTORC1 and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in and/or studies.
Two regulators of mTORC1 signaling are the oncogene suppressors tuberin-sclerosis complexes 1 and 2 (, ). Loss or inactivation of either or leads to activation of downstream signaling. In tuberous sclerosis (TS), a genetic disorder, inactivating mutations in either the or the gene lead to hamartoma formation throughout the body.
In a randomized, placebo-controlled, crossover study, 59 healthy subjects were administered a single oral dose of Afinitor (Everolimus) (20 mg and 50 mg) and placebo. There is no indication of a QT/QTc prolonging effect of Afinitor (Everolimus) in single doses up to 50 mg.
Markers of protein synthesis show that inhibition of mTOR is complete after a 10 mg daily dose.
In patients with SEGA, higher everolimus trough concentrations appear to be associated with larger reductions in SEGA volume. However, as responses have been observed at trough concentrations as low as 3 ng/mL, once acceptable efficacy has been achieved, additional dose increase may not be necessary.
Absorption
In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, C is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in C is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing.
Food effect: In healthy subjects, high fat meals reduced systemic exposure to Afinitor (Everolimus) 10 mg tablet (as measured by AUC) by 22% and the peak blood concentration C by 54%. Light fat meals reduced AUC by 32% and C by 42%. Food, however, had no apparent effect on the post absorption phase concentration-time profile.
Distribution
The blood-to-plasma ratio of everolimus, which is concentration-dependent over the range of 5 to 5000 ng/mL, is 17% to 73%. The amount of everolimus confined to the plasma is approximately 20% at blood concentrations observed in cancer patients given Afinitor (Everolimus) 10 mg/day. Plasma protein binding is approximately 74% both in healthy subjects and in patients with moderate hepatic impairment.
Metabolism
Everolimus is a substrate of CYP3A4 and PgP. Following oral administration, everolimus is the main circulating component in human blood. Six main metabolites of everolimus have been detected in human blood, including three monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus. These metabolites were also identified in animal species used in toxicity studies, and showed approximately 100-times less activity than everolimus itself.
Excretion
No specific excretion studies have been undertaken in cancer patients. Following the administration of a 3 mg single dose of radiolabeled everolimus in patients who were receiving cyclosporine, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine. The parent substance was not detected in urine or feces. The mean elimination half-life of everolimus is approximately 30 hours.
Approximately 5% of total radioactivity was excreted in the urine following a 3 mg dose of [C]-labeled everolimus. In a population pharmacokinetic analysis which included 170 patients with advanced cancer, no significant influence of creatinine clearance (25–178 mL/min) was detected on oral clearance (CL/F) of everolimus .
The average AUC of everolimus in eight subjects with moderate hepatic impairment (Child-Pugh class B) was twice that found in eight subjects with normal hepatic function. AUC was positively correlated with serum bilirubin concentration and with prolongation of prothrombin time and negatively correlated with serum albumin concentration.
For advanced PNET and advanced RCC patients with moderate hepatic impairment (Child-Pugh class B), a dose reduction is recommended . For SEGA patients with moderate hepatic impairment (Child-Pugh class B), adjustment to the starting dose may not be needed. However, subsequent dosing should be individualized based on therapeutic drug monitoring .
Afinitor (Everolimus) should not be used in patients with severe hepatic impairment (Child-Pugh class C) as the impact of severe hepatic impairment on everolimus exposure has not been assessed .
In a population pharmacokinetic evaluation in cancer patients, no relationship was apparent between oral clearance and patient age or gender.
Ethnicity
Based on a cross-study comparison, Japanese patients (n=6) had on average exposures that were higher than non-Japanese patients receiving the same dose.
Based on analysis of population pharmacokinetics, oral clearance (CL/F) is on average 20% higher in Black patients than in Caucasians.
The significance of these differences on the safety and efficacy of everolimus in Japanese or Black patients has not been established.
Dose Proportionality in Patients with SEGA
In patients with SEGA, intra-patient steady-state trough concentrations were dose-proportional at daily doses of 1.5 to 14.6 mg/m .
Afinitor (Everolimus) Nonclinical Toxicology
Administration of everolimus for up to 2 years did not indicate oncogenic potential in mice and rats up to the highest doses tested (0.9 mg/kg) corresponding respectively to 3.9 and 0.2 times the estimated clinical exposure (AUC) at the recommended human dose for patients with advanced PNET and advanced RCC.
Everolimus was not genotoxic in a battery of assays (Ames mutation test in mutation test in L5178Y mouse lymphoma cells, and chromosome aberration assay in V79 Chinese hamster cells). Everolimus was not genotoxic in an mouse bone marrow micronucleus test at doses up to 500 mg/kg/day (1500 mg/m/day, approximately 255-fold the recommended human dose for patients with advanced PNET and advanced RCC, and 103-fold the maximum dose administered to patients with SEGA, based on the body surface area), administered as two doses, 24 hours apart.
Based on non-clinical findings, male fertility may be compromised by treatment with Afinitor (Everolimus) . In a 13-week male fertility study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm count, and plasma testosterone levels were diminished at 5 mg/kg, which resulted in infertility at 5 mg/kg. Effects on male fertility occurred at the AUC values below that of therapeutic exposure (approximately 10%-81% of the AUC in patients with advanced PNET and advanced RCC receiving the recommended dose of 10 mg daily). After a 10-13 week non-treatment period, the fertility index increased from zero (infertility) to 60% (12/20 mated females were pregnant).
Oral doses of everolimus in female rats at ≥0.1 mg/kg (approximately 4% the AUC in patients with advanced PNET and advanced RCC receiving the recommended dose of 10 mg daily) resulted in increases in pre-implantation loss, suggesting that the drug may reduce female fertility. Everolimus crossed the placenta and was toxic to the conceptus .
Afinitor (Everolimus) clinical Studies
A randomized, double-blind, multi-center trial of Afinitor (Everolimus) plus best supportive care (BSC) versus placebo plus BSC was conducted in patients with locally advanced or metastatic advanced pancreatic neuroendocrine tumors (PNET) and disease progression within the prior 12 months. Patients were stratified by prior cytotoxic chemotherapy (yes/no) and by WHO performance status (0 vs. 1 and 2). Treatment with somatostatin analogs was allowed as part of BSC. The primary endpoint for the trial was progression-free survival (PFS) evaluated by RECIST (Response Evaluation Criteria in Solid Tumors). After documented radiological progression, patients could be unblinded by the investigator; those randomized to placebo were then able to receive open-label Afinitor (Everolimus) . Other endpoints included safety, objective response rate [ORR (complete response (CR) or partial response (PR)], response duration, and overall survival.
Patients were randomized 1:1 to receive either Afinitor (Everolimus) 10mg/day (n=207) or placebo (n=203). Demographics were well balanced (median age 58 years, 55% male, 79% Caucasian). Crossover from placebo to open-label Afinitor (Everolimus) occurred in 73% (148/203) of patients.
The trial demonstrated a statistically significant improvement in PFS (median 11.0 months versus 4.6 months), resulting in a 65% risk reduction in investigator-determined PFS (HR 0.35; 95%CI: 0.27 to 0.45; p
Investigator-determined response rate was low (4.8%) in the Afinitor (Everolimus) arm and there were no complete responses. The overall survival results are not yet mature and no statistically significant treatment-related difference in OS was noted [HR=1.05 (95% CI: 0.71 to 1.55)].
In a randomized, double-blind, multi-center trial in 429 patients with carcinoid tumors, Afinitor (Everolimus) plus depot octreotide (Sandostatin LAR) was compared to placebo plus depot octreotide. After documented radiological progression, patients could be unblinded by the investigator: those randomized to placebo were then able to receive open-label Afinitor (Everolimus) plus depot octreotide. The study did not meet the primary efficacy endpoint (PFS) and the OS interim analysis numerically favored the placebo plus depot octreotide arm. Therefore, the use of Afinitor (Everolimus) in patients with carcinoid tumors remains investigational.
An international, multi-center, randomized, double-blind trial comparing Afinitor (Everolimus) 10 mg daily and placebo, both in conjunction with best supportive care, was conducted in patients with metastatic RCC whose disease had progressed despite prior treatment with sunitinib, sorafenib, or both sequentially. Prior therapy with bevacizumab, interleukin 2, or interferon-α was also permitted. Randomization was stratified according to prognostic score and prior anticancer therapy.
Progression-free survival (PFS), documented using Response Evaluation Criteria in Solid Tumors (RECIST) was assessed via a blinded, independent, central radiologic review. After documented radiological progression, patients could be unblinded by the investigator: those randomized to placebo were then able to receive open-label Afinitor (Everolimus) 10 mg daily.
In total, 416 patients were randomized 2:1 to receive Afinitor (Everolimus) (n=277) or placebo (n=139). Demographics were well balanced between the two arms (median age 61 years; 77% male, 88% Caucasian, 74% received prior sunitinib or sorafenib, and 26% received both sequentially).
Afinitor (Everolimus) was superior to placebo for PFS (see Table 8 and Figure 2). The treatment effect was similar across prognostic scores and prior sorafenib and/or sunitinib. The overall survival (OS) results were not mature and 32% of patients had died by the time of cut-off.
An open-label, single-arm trial was conducted to evaluate the safety and efficacy of Afinitor (Everolimus) in patients with SEGA associated with TS. Serial radiological evidence of SEGA growth was required for entry. Change in SEGA volume at the end of the core 6-month treatment phase was assessed via an independent central radiology review. In total, 28 patients received treatment with Afinitor (Everolimus) ; median age was 11 years (range 3-34), 61% male, 86% Caucasian. Four patients had surgical resection of their SEGA lesions with subsequent re-growth prior to receiving Afinitor (Everolimus) treatment. After the core treatment phase, patients could continue to receive Afinitor (Everolimus) treatment as part of an extension treatment phase where SEGA volume was assessed every 6 months. The median duration of treatment was 24.4 months (range 4.7-37.3 months).
At 6 months, 9 out of 28 patients (32%, 95% CI: 16% to 52%) had a ≥ 50% reduction in the tumor volume of their largest SEGA lesion. Duration of response for these 9 patients ranged from 97 to 946 days with a median of 266 days. Seven of these 9 patients had an ongoing volumetric reduction of ≥ 50% at the data cutoff.
Three of 4 patients who had prior surgery experienced a ≥ 50% reduction in the tumor volume of their largest SEGA lesion. One of these three patients responded by month 6. No patient developed new lesions.
Afinitor (Everolimus) How Supplied/storage And Handling
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “LCL” on one side and “NVR” on the other; available in:
Blisters of 28 tablets………………………………………………………………………………NDC 0078-0594-51
Each carton contains 4 blister cards of 7 tablets each
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “5” on one side and “NVR” on the other; available in:
Blisters of 28 tablets………………………………………………………………………………NDC 0078-0566-51
Each carton contains 4 blister cards of 7 tablets each
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “7P5” on one side and “NVR” on the other; available in:
Blisters of 28 tablets………………………………………………………………………………NDC 0078-0620-51
Each carton contains 4 blister cards of 7 tablets each
White to slightly yellow, elongated tablets with a bevelled edge and no score, engraved with “UHE” on one side and “NVR” on the other; available in:
Blisters of 28 tablets………………………………………………………………………………NDC 0078-0567-51
Each carton contains 4 blister cards of 7 tablets each
Store Afinitor (Everolimus) tablets at 25°C (77°F); excursions permitted between 15°–30°C (59°–86°F). See USP Controlled Room Temperature. Store in the original container, protect from light and moisture. Keep this and all drugs out of the reach of children.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.
Afinitor (Everolimus) tablets should not be crushed. Do not take tablets which are crushed or broken.
Afinitor (Everolimus) patient Counseling Information
Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications and dietary supplements
Avoid concurrent treatment with CYP3A4 inhibitors. Use caution if Afinitor (Everolimus) must be co-administered with CYP3A4 and/or PgP inhibitors; reduce the dose and carefully monitor the patient for undesirable effects. Avoid concurrent treatment with strong CYP3A4 inducers. If Afinitor (Everolimus) must be co-administered with strong CYP3A4 inducers, consider a dose increase and carefully monitor the patient for clinical response
Inform patients to take Afinitor (Everolimus) orally once daily at the same time every day, either consistently with food or consistently without food. The tablets should not be crushed or chewed. Afinitor (Everolimus) should be swallowed whole with a glass of water. For patients unable to swallow tablets, Afinitor (Everolimus) tablet(s) should be dispersed completely in a glass of water (containing approximately 30 mL) by gently stirring, immediately prior to drinking. The glass should be rinsed with the same volume of water and the rinse should be completely swallowed to ensure that the entire dose is administered.
Instruct patients that if they miss a dose of Afinitor (Everolimus) , they may still take it up to 6 hours after the time they would normally take it. If more than 6 hours have elapsed, they should be instructed to skip the dose for that day. The next day, they should take Afinitor (Everolimus) at the usual time. Warn patients to not take 2 doses to make up for the one that they missed.
T2011-98
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