Afinitor

Name: Afinitor

Side Effects of Afinitor

Afinitor can cause serious side effects. See “Drug Precautions”.

Common side effects of Afinitor in people with advanced hormone receptor-positive, HER 2-negative breast cancer, advanced pancreatic neuroendocrine tumors, and advanced kidney cancer include:

  • Mouth ulcers. Afinitor can cause mouth ulcers and sores. Tell your healthcare provider if you have pain, discomfort, or open sores in your mouth. Your healthcare provider may tell you to use a special mouthwash or mouth gel that does not contain alcohol, peroxide, iodine, or thyme.
  • Infections
  • Feeling weak or tired
  • Cough, shortness of breath
  • Diarrhea and constipation
  • Rash, dry skin, and itching
  • Nausea and vomiting
  • Fever
  • Loss of appetite, weight loss
  • Swelling of arms, hands, feet, ankles, face or other parts of the body 
  • Abnormal taste
  • Dry mouth
  • Inflammation of lining of the digestive system
  • Headache
  • Nose bleeds
  • Pain in arms and legs, mouth and throat, back or joints 
  • High blood glucose
  • High blood pressure
  • Difficulty sleeping
  • Hair loss
  • Muscle spasms
  • Feeling dizzy
  • Nail disorders

Common side effects of Afinitor in people with SEGA or renal angiomyolipoma with TSC include:

  • Mouth ulcers. Afinitor can cause mouth ulcers and sores. Tell your healthcare provider if you have pain, discomfort, or open sores in your mouth. Your healthcare provider may tell you to use a special mouthwash or mouth gel that does not contain alcohol, peroxide, iodine, or thyme.
  • Infections
  • Nausea and vomiting
  • Diarrhea and constipation
  • Swelling of your hands, arms, legs, and feet
  • Joint pain
  • Cough
  • Skin problems (such as rash, acne, or dry skin)
  • Fever
  • Feeling tired
  • Anxiety, aggression, and other abnormal behaviors
  • Absence of menstrual periods (menstruation). You may miss 1 or more menstrual periods. Tell your healthcare provider if this happens.
  • Low red blood cells, white blood cells or platelets
  • Increased blood cholesterol level and certain other blood tests
  • Increased blood sugar levels
  • Decreased blood phosphate levels

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of Afinitor. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. 

Afinitor and Lactation

It is not known if Afinitor crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Afinitor.

 

Afinitor Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your liver function
  • your weight
  • your height

The recommended dose of Afinitor for advanced hormone receptor-positive, HER2-negative breast cancer, advanced PNET, advanced RCC, and renal angiomyolipoma with TSC is 10 mg by mouth once daily.

The recommended dose of Afinitor in SEGA with TSC is 4.5 mg/m2 once daily. 

 

Afinitor FDA Warning

WARNING: MALIGNANCIES AND SERIOUS INFECTIONS, KIDNEY GRAFT THROMBOSIS; NEPHROTOXICITY; AND MORTALITY IN HEART TRANSPLANTATION

Malignancies and Serious Infections

  • Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe Afinitor. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. 
  • Increased susceptibility to infection and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression. 

Kidney Graft Thrombosis

  • An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, was reported, mostly within the first 30 days post-transplantation. 

Nephrotoxicity

  • Increased nephrotoxicity can occur with use of standard doses of cyclosporine in combination with Afinitor. Therefore reduced doses of cyclosporine should be used in combination with Afinitor in order to reduce renal dysfunction. It is important to monitor the cyclosporine and Afinitor whole blood trough concentrations.

Mortality in Heart Transplantation

  • Increased mortality, often associated with serious infections, within the first three months post-transplantation was observed in a clinical trial of de novoheart transplant patients receiving immunosuppressive regimens with or without induction therapy. Use in heart transplantation is not recommended.

How should I take Afinitor?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Everolimus should be taken at the same time each day. You may take everolimus with or without food, but take it the same way each time.

Do not take an Afinitor regular tablet together with an Afinitor dispersible tablet. Use only one form of this medicine.

Take the Afinitor regular tablet with a full glass of water. Do not crush, chew, or break the tablet. Swallow the pill whole.

Do not swallow the dispersible tablet (Afinitor Disperz) whole. Place it into about 2 tablespoons of water and allow the tablet to disperse in the liquid for at least 3 minutes. Stir gently and drink this mixture right away. The dispersed tablet may also be taken with an oral syringe. Wear latex gloves while handling the Afinitor Disperz tablet.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Afinitor can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often.

If you have ever had hepatitis B, Afinitor can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

If you need surgery, tell the surgeon ahead of time that you are using Afinitor. Your surgical incisions or other wounds may take longer to heal while you are taking this medicine.

Store at room temperature in the original container, away from moisture, heat, and light. Keep each tablet in its blister pack until you are ready to take it.

Uses for Afinitor

Breast Cancer

Treatment (in combination with exemestane) of advanced hormone receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative breast cancer in postmenopausal women following failure of letrozole or anastrozole therapy.1 22 32 33

Improves progression-free survival; effects on overall survival remain to be established.1 22

Neuroendocrine Tumors of Pancreatic Origin (PNET)

Treatment of PNET in adults with unresectable, locally advanced, or metastatic disease1 25 26 (designated an orphan drug by FDA for this use).36

Safety and efficacy not established in patients with carcinoid tumors†.1

Improves progression-free survival;1 25 effects on overall survival remain to be established.1

Renal Cell Carcinoma

Treatment of advanced renal cell carcinoma in adults following failure of sunitinib and/or sorafenib therapy.1 2 3 16

Improves median progression-free survival;1 3 16 no substantial difference in overall survival between everolimus and placebo has been demonstrated.1

Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC)

Treatment of renal angiomyolipoma with TSC, not requiring immediate surgery, in adults1 29 (designated an orphan drug by FDA for this use).36

Improved renal angiomyolipoma response rate and skin lesion response rate in patients treated for a median of 8.3 months.1 29

Subependymal Giant Cell Astrocytoma (SEGA) with TSC

Treatment of SEGA with TSC in patients ≥1 year of age when SEGA requires therapeutic intervention but cannot be curatively resected1 17 27 28 (designated an orphan drug by FDA for this use).36

Reduces SEGA tumor volume; improvement in disease-related symptoms and overall survival has not been demonstrated.1 17 27 28

Renal Allotransplantation

Prevention of rejection of renal allografts in adults with low to moderate immunologic risk.13 18 Used with basiliximab induction therapy and concurrent corticosteroids and reduced dosages of cyclosporine.13 18

Therapeutic drug monitoring of everolimus and cyclosporine recommended for all patients.13

Safety and efficacy not established in renal transplant recipients with high immunologic risk or in recipients of transplanted organs other than kidney and liver.13

Hepatic Allotransplantation

Prevention of rejection of hepatic allografts in adults.13 30 Used ≥30 days posttransplant concurrently with tacrolimus (in reduced dosages) and corticosteroids.13 30

Therapeutic drug monitoring of everolimus and tacrolimus recommended for all patients.13

Safety and efficacy not established in recipients of transplanted organs other than kidney and liver.13

Cautions for Afinitor

Contraindications

  • Known hypersensitivity to everolimus, other rapamycin derivatives (e.g., sirolimus, temsirolimus), or any ingredient in the formulations.1 13

Warnings/Precautions

Warnings

Malignancies and Serious Infections

Immunosuppressants, including everolimus, can increase susceptibility to infection (bacterial, fungal, viral, or protozoal infections, including opportunistic infections).1 13 Severe or fatal localized and systemic infections (e.g., pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections [e.g., aspergillosis, candidiasis], viral infections including HBV reactivation) reported.1 13

Antimicrobial prophylaxis for Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia and cytomegalovirus (CMV) is recommended in transplant recipients.13

Monitor vigilantly for signs and symptoms of infection and institute appropriate treatment if infection develops; consider interruption or discontinuance of everolimus therapy.1

If invasive systemic fungal infection occurs, discontinue everolimus and initiate appropriate antifungal therapy.1 Complete treatment of a preexisting invasive fungal infection prior to initiating everolimus therapy.1

The manufacturer of everolimus (Zortress) states that the drug should be used only by clinicians experienced in immunosuppressive therapy and the management of transplant patients.13 (See Boxed Warning.)

Immunosuppressants, including everolimus, may increase risk of development of lymphomas or other malignancies, particularly of the skin.13 Risk appears to be related to intensity and duration of immunosuppression rather than to the use of any specific drug.13 (See Advice to Patients.)

Kidney Graft Thrombosis

Increased risk of kidney arterial and venous thrombosis, resulting in kidney graft loss; occurs primarily within the first 30 days after renal transplantation.13

Nephrotoxicity

Increased risk of nephrotoxicity when used concurrently with standard cyclosporine dosages; use reduced cyclosporine dosages.13 (See Specific Drugs and Foods under Interactions.)

Increases in Scr and proteinuria reported in patients receiving everolimus (Afinitor).1 2 Cases of renal failure (including acute renal failure), some with fatal outcome, also observed.1 Monitor renal function (including BUN, urinary proteins, and/or Scr) prior to and periodically during therapy.1

Not studied with standard tacrolimus dosages in hepatic transplant recipients;13 use in combination with reduced-dosage tacrolimus to minimize potential risk of nephrotoxicity.13

Monitor renal function in all transplant patients.13 Consider switching to other immunosuppressive therapies if renal function does not improve after dosage adjustments or if renal dysfunction is thought to be drug related.13

Increased risk of proteinuria reported in transplant patients receiving everolimus (Zortress); higher risk observed in patients with higher whole blood trough concentrations of the drug.13 Monitor transplant patients for proteinuria.13

Increased Mortality in Cardiac Transplantation

Increased mortality within the first 3 months posttransplantation observed in de novo cardiac transplant patients receiving everolimus (Zortress) in an immunosuppressive regimen with or without induction therapy in a clinical trial;13 39 use not recommended in cardiac transplantation.13

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, dyspnea, flushing, chest pain, and/or angioedema, reported with everolimus and other rapamycin derivatives.1 13 37 (See Angioedema under Cautions.)

Other Warnings/Precautions

Interstitial Lung Disease/Noninfectious Pneumonitis

Potentially severe or fatal noninfectious pneumonitis reported.1 13

Consider diagnosis of noninfectious pneumonitis in patients presenting with nonspecific respiratory signs and symptoms (e.g., hypoxia, pleural effusion, cough, dyspnea) and in whom other causes (e.g., infection, cancer) have been excluded.1

If moderate or severe symptoms of noninfectious pneumonitis develop, interruption or discontinuance of therapy and subsequent dosage reduction may be required.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

In renal transplant patients, noninfectious pneumonitis may respond to interruption of everolimus therapy with or without glucocorticoid therapy.13

Consider diagnosis of interstitial lung disease in patients presenting with symptoms consistent with infectious pneumonia but not responding to antibiotic therapy and in whom other causes (e.g., infection, cancer, other non-drug causes) have been excluded.13 In renal or hepatic transplant patients, interstitial lung disease generally resolves following interruption of everolimus therapy with or without glucocorticoid therapy; however, fatal cases reported.13

Oral Ulceration

Mouth ulcers, stomatitis, and oral mucositis, mostly grade 1 and 2, reported.1

Topical therapy recommended if oral ulceration occurs.1 Manage grade 1 stomatitis with non-alcoholic or salt water (0.9%) mouthwash several times daily.1 Manage grade 2 and 3 stomatitis with topical analgesic mouth treatments with or without topical corticosteroids.1

Avoid alcohol-, peroxide-, iodine-, or thyme-containing mouthwashes because they may exacerbate the condition.1

Do not use antifungal agents unless fungal infection has been diagnosed.1 (See Specific Drugs and Foods under Interactions.)

Depending on severity, interruption of therapy, dosage reduction, and/or drug discontinuance may be required.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Hepatic Artery Thrombosis (HAT)

mTOR inhibitors are associated with an increased risk of HAT.13 Most cases occurred within the first 30 days posttransplant and most resulted in graft loss or death.1 Do not administer everolimus earlier than 30 days after liver transplantation.13

Polyoma Virus Infections

Increased risk of reactivation of latent viral infections, including polyoma virus infections.13 Polyoma virus infections in transplant recipients may be serious or fatal; these include polyoma virus-associated neuropathy (PVAN), mostly due to BK virus infection, and JC virus-associated progressive multiple leukoencephalopathy (PML).13 PVAN may result in deteriorating renal function and renal graft loss.13

Monitoring transplant patients may help detect patients at risk of PVAN.13 Consider reduction in total immunosuppression in patients who develop evidence of PVAN or PML.13 Also consider risk that reduced immunosuppression represents to the functioning allograft.13

Immunization

Avoid use of live vaccines and close contact with individuals who have received live vaccines.1 13

Consider the timing of routine vaccinations in pediatric patients with SEGA who do not require immediate treatment before initiating everolimus therapy.1 Prior to initiation of everolimus therapy, complete the recommended childhood series of live virus vaccinations according to the US Public Health Service Advisory Committee on Immunization Practices (ACIP) guidelines.1 An accelerated vaccination schedule may be appropriate.1

Angioedema

Angioedema reported with everolimus and other mTOR inhibitors.13 37 Concomitant use of other drugs known to cause angioedema (e.g., ACE inhibitors) may increase this risk.13 37 Monitor patients for possible symptoms; if angioedema occurs, treat promptly.13 (See Specific Drugs and Foods under Interactions.)

Delayed Wound Healing and Fluid Accumulation

Increased risk of delayed wound healing and increased incidence of wound-related complications, including wound dehiscence, wound infection, incisional hernia, lymphocele, and seroma, reported; wound-related complications may require surgical treatment.13

Generalized fluid accumulation, including peripheral edema (e.g., lymphedema), and other types of localized fluid accumulation (e.g., pericardial and pleural effusions, ascites) also reported.13

Monitor patients for delayed wound healing and fluid accumulation; if present, treat promptly to minimize potential complications.13 (See Advice to Patients.)

Hyperglycemia and Diabetes Mellitus

Hyperglycemia reported.1 2 6 Monitor fasting glucose concentrations prior to and periodically during everolimus (Afinitor) therapy; when possible, achieve optimal glycemic control prior to initiation of everolimus.1

Following transplantation, increased risk of developing new-onset diabetes mellitus reported.13 Closely monitor glucose concentrations in patients receiving everolimus (Zortress) following renal and hepatic allotransplantation.13

Hyperlipidemia

Hyperlipidemia (e.g., hypercholesterolemia, hypertriglyceridemia), possibly requiring treatment, reported;1 2 6 13 increased risk in patients with higher whole blood trough everolimus concentrations.13

Monitor fasting serum lipids prior to and periodically during everolimus (Afinitor, Zortress) therapy.1 When possible, achieve optimal lipid control prior to initiation of therapy.1 Treat patients who develop hyperlipidemia while receiving everolimus according to current standards of care.13

Normalization of serum lipids with antihyperlipidemic agents may not be possible in patients receiving everolimus (Zortress).13 Consider the risk/benefit of everolimus therapy prior to initiating therapy in patients with baseline hyperlipidemia and of continued therapy in patients who develop severe refractory hyperlipidemia while receiving the drug.13 Safety and efficacy of everolimus in patients with baseline cholesterol concentrations >350 mg/dL not established.13

Patients with Hereditary Disorders

Everolimus may cause diarrhea and malabsorption in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption; avoid use in such patients.13

Hematologic Effects

Anemia, lymphopenia, neutropenia, and thrombocytopenia reported.1 2 6 Monitor CBC prior to and periodically during therapy.1

Increased Risk of Thrombotic Microangiopathy (TMA)/Thrombotic Thrombocytopenic Purpura (TTP)/Hemolytic Uremic Syndrome (HUS)

Concurrent use of everolimus and cyclosporine may increase the risk of TMA/TTP/HUS.13 Monitor hematologic parameters in patients concurrently receiving everolimus and cyclosporine.13

CYP3A4- and P-glycoprotein-mediated Interactions

Concomitant use of everolimus with certain drugs (e.g., moderate or potent inhibitors of CYP3A4, potent inducers of CYP3A4, moderate inhibitors of P-glycoprotein) or foods (e.g., grapefruit juice) is not recommended or requires close monitoring of whole blood trough everolimus concentrations and/or adjustment of everolimus dosage.1 13 (See Interactions.)

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm; teratogenicity and embryolethality demonstrated in animals.1 No adequate and well-controlled studies in humans.1 12 13

Women of childbearing potential should use a highly effective method of contraception during and for up to 8 weeks following discontinuance of everolimus.1 13

If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Impairment of Male Fertility

Possible impairment of male fertility (decreased fertility observed in male rats); azoospermia or oligospermia may be observed.1 13

Adequate Patient Evaluation and Monitoring

Monitor fasting glucose and lipid profiles, CBC, and renal function tests prior to and periodically during therapy.1 13

Specific Populations

Pregnancy

Afinitor and Afinitor Disperz: Category D.1 Women of childbearing potential should use highly effective contraception during and for up to 8 weeks after discontinuance of therapy.1

Zortress: Category C.13 Women of childbearing potential should use effective contraception during and for up to 8 weeks after discontinuance of therapy.13 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

National Transplantation Pregnancy Registry (NTPR) at 877-955-6877 or .34

Lactation

Everolimus and/or its metabolites distribute into milk in rats; not known whether distributed into human milk.1 13

Patients with breast cancer, PNET, renal angiomyolipoma, renal cell carcinoma, or SEGA: Discontinue nursing or the drug.1

Renal and hepatic transplant patients: Avoid breast-feeding.13

Pediatric Use

Safety and efficacy for treatment of SEGA with TSC have been evaluated in pediatric patients ≥1 year of age.1 Safety and efficacy not established in children <1 year of age with SEGA and TSC.1 Safety and efficacy for treatment of renal angiomyolipoma with TSC in the absence of SEGA not established in pediatric patients.1

Safety and efficacy for prevention of renal or hepatic allograft rejection not established in pediatric patients <18 years of age.13

In pediatric patients with SEGA not requiring immediate therapy, complete recommended childhood series of live virus vaccinations prior to initiating everolimus therapy; accelerated vaccination schedule may be appropriate.1 (See Immunization under Cautions.)

Long-term effects on growth and pubertal development not known.1

Geriatric Use

Patients with advanced hormone receptor-positive, HER2-negative breast cancer, advanced renal cell carcinoma, or advanced PNET: No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 (See Geriatric Patients under Dosage and Administration.)

Transplant recipients: Limited clinical experience with use of everolimus following transplantation in patients ≥65 years of age.13

Hepatic Impairment

Patients with breast cancer, PNET, advanced renal carcinoma, or renal angiomyolipoma, or renal or hepatic allograft recipients: Dosage adjustment recommended in those with mild, moderate, or severe (Child-Pugh class A, B, or C) hepatic impairment.1 13 (See Hepatic Impairment under Dosage and Administration.)

Patients with SEGA: Adjustment of initial dosage may not be required in those with mild or moderate (Child-Pugh class A or B) hepatic impairment; however, individualize subsequent dosage based on therapeutic drug monitoring.1 Initial dosage adjustment recommended for those with severe (Child-Pugh class C) hepatic impairment; individualize subsequent dosage based on therapeutic drug monitoring.1 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Safety and efficacy in patients with renal impairment not studied specifically to date.1 (See Renal Impairment under Dosage and Administration and also see Elimination: Special Populations under Pharmacokinetics.)

Common Adverse Effects

In patients with advanced HER2-negative breast cancer: Stomatitis (e.g., mouth ulceration, aphthous stomatitis, glossodynia, gingival pain, glossitis, lip ulceration),1 22 infections,1 rash,1 22 fatigue or asthenia,1 22 diarrhea,1 22 decreased appetite,1 22 nausea,1 weight loss,1 22 cough,1 22 dysgeusia,1 22 headache,1 22 dyspnea,1 22 arthralgia,1 peripheral edema,1 22 pneumonitis (e.g., interstitial lung disease, lung infiltration, pulmonary fibrosis),1 22 epistaxis,1 22 vomiting,1 22 pyrexia,1 22 back pain,1 22 constipation,1 22 pruritus,1 22 insomnia,1 22 dry mouth,1 alopecia,1 hypercholesterolemia,1 hyperglycemia,1 22 increased AST,1 anemia,1 22 leukopenia,1 thrombocytopenia,1 22 lymphopenia,1 increased ALT,1 hypertriglyceridemia,1 decreased albumin,1 neutropenia,1 hypokalemia,1 increased Scr.1

In patients with advanced PNET: Stomatitis,1 25 rash,1 25 diarrhea,1 25 fatigue/malaise,1 25 edema (peripheral or generalized),1 25 abdominal pain,1 fever,1 25 headache/migraine,1 25 decreased appetite,1 25 vomiting,1 25 weight loss,1 25 nasopharyngitis/rhinitis/upper respiratory tract infection,1 cough,1 25 nail disorders,1 25 epistaxis,1 25 pruritus,1 25 dyspnea,1 dysgeusia,1 25 pneumonitis,1 25 urinary tract infection,1 arthralgia,1 back pain,1 pain in extremity,1 insomnia,1 constipation,1 dry skin,1 25 hypertension,1 dizziness,1 dry mouth,1 oropharyngeal pain,1 diabetes mellitus,1 muscle spasms,1 anemia,1 increased alkaline phosphatase,1 hyperglycemia,1 hypercholesterolemia,1 decreased bicarbonate,1 increased AST,1 increased ALT,1 lymphopenia,1 thrombocytopenia,1 leukopenia,1 hypophosphatemia,1 hypertriglyceridemia,1 hypocalcemia,1 neutropenia,1 hypokalemia,1 increased Scr,1 hypoalbuminemia.1

In patients with renal cell carcinoma: Stomatitis,1 2 3 infections,1 2 asthenia,1 2 3 fatigue,1 2 3 diarrhea,1 2 3 cough,1 2 rash,1 2 3 6 anemia,1 hypercholesterolemia,1 increased Scr,1 hypertriglyceridemia,1 hyperglycemia,1 lymphopenia.1

In patients with renal angiomyolipoma with TSC: Stomatitis,1 29 hypercholesterolemia,1 29 acne,1 29 cough,1 29 vomiting,1 29 diarrhea,1 29 arthralgia,1 29 amenorrhea,1 29 peripheral edema,1 upper respiratory tract infection,1 29 anemia,1 hypertriglyceridemia.1

In patients with SEGA with TSC: Stomatitis (e.g., mouth and lip ulceration),1 27 respiratory tract infection,1 27 elevated cholesterol,1 increased ALT and AST,1 elevated PTT,1 neutropenia,1 reduced hemoglobin,1 pyrexia,1 27 fatigue,1 vomiting,1 27 diarrhea,1 27 constipation,1 gastroenteritis,1 psychiatric disorders (e.g., anxiety, aggression, other behavioral disturbances),1 hyperglycemia,1 cellulitis,1 rash,1 27 acne,1 increased Scr,1 hypertriglyceridemia,1 pharyngitis.1 27

In renal transplant patients: Infections,13 peripheral edema,13 constipation,13 hypertension,13 nausea,13 anemia,13 urinary tract infection,13 hyperlipidemia,13 diarrhea,13 pyrexia,13 headache,13 hyperkalemia,13 increased Scr,13 hypercholesterolemia,13 insomnia,13 incision site pain,13 upper respiratory tract infection,13 dyslipidemia,13 procedural pain,13 vomiting,13 abdominal pain,13 hypomagnesemia,13 hypophosphatemia,13 extremity pain,13 hematuria,13 hyperglycemia,13 hypokalemia,13 back pain,13 dysuria.13

In hepatic transplant patients: Infections,13 30 diarrhea,13 headache,13 peripheral edema,13 hypertension,13 nausea,13 leukopenia,13 30 abdominal pain,13 pyrexia.13

Interactions for Afinitor

Metabolized principally by CYP3A4; competitive inhibitor of CYP3A4 and mixed inhibitor of CYP2D6 in vitro.1 13 Also a substrate and moderate inhibitor of the efflux transporter P-glycoprotein (P-gp).1 13

Drugs and Foods Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased peak plasma concentrations and AUC of everolimus).1 13 Avoid concomitant use with potent CYP3A4 inhibitors.1 13 Reduced everolimus dosage may be required in patients who require coadministration of a moderate CYP3A4 inhibitor.1 13

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased peak plasma concentrations and AUC of everolimus).1 13 Avoid concomitant use with potent CYP3A4 inducers; if concomitant use cannot be avoided, consider an increase in everolimus dosage.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4 and CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations).13 Use with caution in patients receiving CYP3A4 or CYP2D6 substrates.13

Drugs Affecting the P-Glycoprotein Transport System

Inhibitors of P-gp: Potential pharmacokinetic interaction (increased peak plasma concentrations and AUC of everolimus).1 13 Use with caution.1 Reduced everolimus dosage may be required.1 13

Nephrotoxic Agents

Potential for increased risk of nephrotoxicity with concomitant cyclosporine therapy in renal transplant patients.13 Use other drugs known to impair renal function concomitantly with caution.13

Specific Drugs and Foods

Drug or Food

Interaction

Comments

ACE inhibitors

Possible increased risk of angioedema13 37

Consider use of alternative antihypertensive agents if necessary37

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Decreased plasma everolimus concentrations1

Breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Avoid concomitant use; if cannot avoid, increase everolimus dosage from 10 to 20 mg daily (titrated in 5-mg increments), based on pharmacokinetic data; if the anticonvulsant is discontinued, reduce everolimus dosage to previous level1 12

SEGA: Avoid concomitant use if alternative therapy is available; if cannot avoid, increase everolimus dosage twofold, assess trough concentrations in 2 weeks, and adjust dosage to maintain trough concentrations of 5–15 ng/mL; if the anticonvulsant is discontinued, reduce everolimus dosage to previous level and reassess trough everolimus concentrations in approximately 2 weeks1

Antifungals, azole (fluconazole, itraconazole, ketoconazole, voriconazole)

Increased plasma everolimus concentrations1 13

Itraconazole, ketoconazole, voriconazole: Avoid concomitant use1 13

Fluconazole: Use concomitantly with caution1 13

Fluconazole in patients with breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Reduce everolimus dosage to 2.5 mg daily; may increase dosage to 5 mg daily based on patient tolerance.1 If fluconazole is discontinued, allow interval of 2–3 days before increasing everolimus dosage to the previous level1

Fluconazole in patients with SEGA: Reduce everolimus dosage by approximately 50%; administer every other day in patients receiving the lowest available strength.1 Assess trough everolimus concentrations approximately 2 weeks after dosage reduction.1 If fluconazole is discontinued, increase everolimus dosage to previous level and reassess trough everolimus concentration in approximately 2 weeks1

Antilipemic agents (HMG-CoA reductase inhibitors [statins], fibric acid derivatives)

Pharmacokinetic interaction with atorvastatin, pravastatin, or simvastatin unlikely1

Renal or hepatic transplant patients: Monitor for rhabdomyolysis and other adverse effects associated with antilipemic therapy13

Antimycobacterials, rifamycins (rifabutin, rifampin, rifapentine)

Decreased plasma everolimus concentrations1 13

Breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Avoid concomitant use, if cannot avoid, increase everolimus dosage from 10 to 20 mg daily (titrated in 5-mg increments) based on pharmacokinetic data; if the rifamycin is discontinued, reduce everolimus dosage to previous level1 12

SEGA: Avoid concomitant use if alternative therapy is available; if cannot avoid, increase everolimus dosage twofold, assess trough concentrations in 2 weeks, and adjust dosage to maintain trough concentrations of 5–15 ng/mL; if the rifamycin is discontinued, reduce everolimus dosage to previous level and reassess trough everolimus concentrations in approximately 2 weeks1

Renal or hepatic transplant patients: Concomitant use with rifampin or rifabutin not recommended13

Aprepitant

Increased plasma everolimus concentrations1

Use concomitantly with caution1

Breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Reduce everolimus dosage to 2.5 mg daily; may increase dosage to 5 mg daily based on patient tolerance.1 If aprepitant is discontinued, allow interval of 2–3 days before increasing everolimus dosage to previous level and reassess trough everolimus concentrations in approximately 2 weeks1

SEGA: Reduce everolimus dosage by approximately 50%; administer every other day in patients receiving the lowest available strength.1 Assess trough everolimus concentrations approximately 2 weeks after dosage reduction.1 If aprepitant is discontinued, increase everolimus dosage to the previous level and reassess trough everolimus concentration in approximately 2 weeks1

Calcium-channel blocking agents (diltiazem, verapamil)

Increased plasma everolimus concentrations1 13

Use concomitantly with caution; if concomitant use required, reduced everolimus dosage may be necessary1

Breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Reduce everolimus dosage to 2.5 mg daily; may increase dosage to 5 mg daily based on patient tolerance.1 If moderate CYP3A4 inhibitor (e.g., diltiazem, verapamil) is discontinued, allow interval of 2–3 days before increasing everolimus dosage to previous level1

SEGA: Reduce everolimus dosage by approximately 50%; administer every other day in patients receiving the lowest available strength.1 Assess trough everolimus concentrations approximately 2 weeks after dosage reduction.1 If moderate CYP3A4 inhibitor is discontinued, increase everolimus dosage to previous level and reassess trough everolimus concentration in approximately 2 weeks1

Cyclosporine

Increased plasma concentrations of everolimus13 19 20

Increased risk of nephrotoxicity with concomitant use of everolimus and standard-dose cyclosporine13

Increased risk of proteinuria13

Possible increased risk of thrombotic microangiopathy/thrombotic thrombocytopenic purpura/hemolytic uremic syndrome13

Renal transplant patients: Use reduced-dose cyclosporine therapy to minimize risk of nephrotoxicity; monitor cyclosporine and everolimus concentrations in all patients13 19 20

Monitor renal function; consider alternative immunosuppressive therapies if renal function does not improve after dosage adjustments or if renal dysfunction is thought to be drug related13

Dosage adjustment of everolimus may be required if cyclosporine dosage is altered13

Monitor hematologic parameters and for proteinuria13

Exemestane

Increased plasma exemestane concentrations; however, steady-state estradiol concentrations not altered and no increase in exemestane-related adverse effects observed1

Grapefruit or grapefruit juice

Increased plasma everolimus concentrations1 13

Avoid concomitant use1 13

HCV protease inhibitors (boceprevir, telaprevir)

Increased plasma everolimus concentrations1

Avoid concomitant use13

HIV protease inhibitors (atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir)

Increased plasma everolimus concentrations1

Atazanavir, indinavir, nelfinavir, ritonavir, saquinavir: Avoid concomitant use1 13

Fosamprenavir: Use concomitantly with caution1 13

Fosamprenavir in patients with breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Reduce everolimus dosage to 2.5 mg daily; may increase dosage to 5 mg daily based on patient tolerance.1 If fosamprenavir is discontinued, allow interval of 2–3 days before increasing everolimus dosage to previous level1

Fosamprenavir in patients with SEGA: Reduce everolimus dosage by approximately 50%; administer every other day in patients receiving the lowest available strength.1 Assess trough everolimus concentrations approximately 2 weeks after dosage reduction.1 If fosamprenavir is discontinued, increase everolimus dosage to previous level and reassess trough everolimus concentration in approximately 2 weeks1

HMG CoA reductase inhibitors (statins) (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin)

Clinically important pharmacokinetic interactions with atorvastatin, pravastatin, or simvastatin unlikely; however, cannot extrapolate these results to other statins1 13

Use of statins such as lovastatin or simvastatin was strongly discouraged in clinical trials of everolimus with cyclosporine in renal transplant patients because of an adverse interaction with cyclosporine13

Atorvastatin or pravastatin: Dosage adjustments not necessary13

Monitor patients receiving everolimus, cyclosporine, and a statin for possible development of rhabdomyolysis and other adverse effects13

Immunosuppressive agents

Increased risk of lymphoma and other malignancies and susceptibility to infection1 13

Use with caution13

Macrolide antibiotics (clarithromycin, erythromycin, telithromycin)

Increased plasma everolimus concentrations1 13

Clarithromycin or telithromycin: Avoid concomitant use1 13

Erythromycin: Use concomitantly with caution1 13

Erythromycin in patients with breast cancer, PNET, renal cell carcinoma, or renal angiomyolipoma: Reduce everolimus dosage to 2.5 mg daily; may increase dosage to 5 mg daily based on patient tolerance.1 If erythromycin is discontinued, allow interval of 2–3 days before increasing everolimus dosage to previous level1

Erythromycin in patients with SEGA: Reduce everolimus dosage by approximately 50%; administer every other day in patients receiving the lowest available strength.1 Assess trough everolimus concentrations approximately 2 weeks after dose reduction.1 If erythromycin is discontinued, increase everolimus dosage to previous level and reassess trough everolimus concentration in approximately 2 weeks1

Erythromycin in transplant patients: Monitor everolimus concentration and adjust everolimus dosage as necessary13

Midazolam

Increased peak plasma concentrations and AUC of midazolam; elimination half-life of midazolam and metabolic AUC ratio not affected1 13 38

Dosage adjustment of midazolam not necessary13

Nefazodone

Increased plasma everolimus concentrations1

Avoid concomitant use1

Octreotide

Long-acting parenteral formulation of octreotide acetate: trough plasma concentrations of octreotide increased by approximately 50%1

St. John’s wort (Hypericum perforatum)

Unpredictable decreases in everolimus exposure1

Avoid concomitant use1

Tacrolimus

Hepatic transplants: Everolimus not studied with standard-dosage tacrolimus13

Increased risk of nephrotoxicity with concomitant use of standard-dosage tacrolimus13

Hepatic transplant patients: Use reduced-dosage tacrolimus and reduce target therapeutic range for tacrolimus to minimize risk of nephrotoxicity; monitor tacrolimus and everolimus concentrations in all patients13

Everolimus dosage adjustment generally not necessary13

Monitor renal function; consider alternative immunosuppressive therapies if renal function does not improve after dosage adjustments or if renal dysfunction is thought to be drug related13

Vaccines

Possible decreased immune response to vaccination1

Avoid use of live vaccines1 13

Stability

Storage

Oral

Tablets

Original container at 25°C (may be exposed to 15–30°C); protect from light and moisture.1 13

Tablets for Oral Suspension

Original container at 25°C (may be exposed to 15–30°C); protect from light and moisture.1

Advice to Patients

  • Importance of providing patient a copy of manufacturer’s patient information (Afinitor and Afinitor Disperz) or medication guide (Zortress).1 13

  • Importance of taking everolimus tablets as directed either consistently with food or consistently without food; take at the same time each day (or twice daily approximately 12 hours apart), swallowing the tablets whole with a glass of water.1 13

  • Everolimus tablets for oral suspension (Afinitor Disperz) should be taken as a suspension only and should not be swallowed.1 Importance of reviewing procedures for preparation of everolimus tablets for oral suspension with patients.1

  • Importance of storing everolimus (Afinitor or Afinitor Disperz) tablets in the original package and keeping the blister package and tablets dry and protected from light.1 Importance of opening the blister package (scissors may be used to avoid spillage) immediately prior to taking everolimus.1 Importance of keeping everolimus (Zortress) tablets dry and protected from light.13

  • If a dose of everolimus (Afinitor or Afinitor Disperz) is missed by ≤6 hours, take dose as soon as it is remembered, and take the next dose at the regularly scheduled time; if a dose is missed by >6 hours, omit the dose and take the next dose at the regularly scheduled time.1 Do not take a double dose to make up for a missed dose.1

  • Importance of informing patients about risks, including serious allergic reactions (e.g., anaphylaxis), noninfectious pneumonitis, and increased susceptibility to infection.1 13 Importance of patients promptly reporting any facial swelling,12 new or worsening respiratory symptoms (e.g., cough, shortness of breath, difficulty breathing, wheezing), or any signs or symptoms of infection (e.g., fever, chills).1 13

  • Risk of reactivation of HBV infection.1 Importance of promptly reporting any signs and symptoms of possible HBV infection (e.g., loss of appetite, pale stool or dark urine, yellowing of the skin, pain in upper right side of the stomach).1

  • Risk of malignancy, including lymphoma and skin cancer.13 Importance of limiting exposure to sunlight and ultraviolet light by wearing protective clothing and using sunscreen with a high protection factor.13

  • Risk of new-onset diabetes mellitus; importance of reporting any signs or symptoms of diabetes mellitus (e.g., frequent urination, increased thirst or hunger).13

  • Risk of mouth ulcers, stomatitis, and oral mucositis.1 35 Importance of reporting any signs or symptoms of oral ulceration (e.g., pain, discomfort, open sores in mouth).1 Use of mouthwashes and/or topical treatments is recommended; however, avoid alcohol-, peroxide-, iodine-, or thyme-containing preparations.1

  • Risk of kidney arterial and venous thrombosis leading to graft loss in renal transplant recipients; usually occurs within first 30 days after transplantation.13 Importance of promptly reporting any signs and symptoms of possible kidney thrombosis (e.g., pain in groin, lower back, side, or stomach, decreased urination, blood in urine or dark colored urine, fever, nausea, or vomiting).13

  • Risk of PVAN, which may result in deteriorating renal function and renal graft loss.13

  • Risk of proteinuria in patients receiving everolimus following transplantation.13

  • Risk of angioedema; risk may be increased by other drugs known to cause angioedema (e.g., ACE inhibitors).13 37 Importance of seeking prompt medical attention if symptoms (e.g., sudden swelling of face, mouth, throat, tongue, or hands; hives or welts; itchy or painful swollen skin; trouble breathing) develop.13

  • Risk of impaired wound healing and fluid accumulation.13 Importance of careful observation of incision site in patients who have undergone renal or hepatic allotransplantation; promptly inform healthcare provider if incision is red, warm, or painful; if there is blood, fluid, or pus in incision; if incision opens up; or in case of swelling of incision.13

  • Risk of increased blood glucose, triglyceride, and/or cholesterol concentrations; risk of adverse renal and hematologic effects.1 13 Fasting glucose and lipid profiles, CBC, and renal and liver function tests are required; importance of adherence to laboratory appointment schedules.1 13

  • Need for therapeutic drug monitoring in patients receiving everolimus for the treatment of SEGA or for the prevention of rejection of renal or hepatic allografts; importance of adherence to laboratory appointment schedules.1 13

  • Importance of avoiding use of live vaccines and close contact with those who have received live vaccines.1 13

  • Importance of avoiding grapefruit and grapefruit juice during everolimus therapy.1 13

  • Importance of informing clinicians of hereditary disorders of galactose intolerance (Lapp lactase deficiency or glucose-galactose malabsorption); avoid Zortress therapy in patients with these conditions.13

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., antifungals, antivirals, anticonvulsants [carbamazepine, phenytoin, barbiturates]) and herbal products (e.g., St. John’s wort), as well as any concomitant illnesses (e.g., hepatic impairment, diabetes mellitus or hyperglycemia, hyperlipidemia, infection, history of HBV infection, personal or family history of skin cancer).1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women of childbearing potential to avoid pregnancy and to use a highly effective contraceptive method during therapy and for 8 weeks following discontinuance of therapy.1 13 Necessity of advising women to avoid breastfeeding while receiving everolimus therapy.1 13 Risk of male infertility (low or no sperm count).13 Everolimus tablets for oral suspension (Afinitor Disperz) can cause harm to an unborn baby; the suspension should be prepared by an adult who is not pregnant or planning to become pregnant.1 Anyone who prepares everolimus tablets for suspension (Afinitor Disperz) for another person should wear gloves to avoid possible contact with the medicine.1

  • Importance of informing patients of other important precautionary information.1 13 (See Cautions.)

How is this medicine (Afinitor) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food. Always take with food or always take on an empty stomach.
  • To gain the most benefit, do not miss doses.
  • Keep taking Afinitor (everolimus tablets (afinitor)) as you have been told by your doctor or other health care provider, even if you feel well.
  • Take this medicine at the same time of day.
  • Do not switch between different forms of Afinitor without first talking with the doctor.
  • Take with a full glass of water.
  • Swallow whole. Do not chew, break, or crush.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it has been 6 hours or more since the missed dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Dosage forms and strengths

     Afinitor Tablets

2.5 mg tablet

White to slightly yellow, elongated tablets with a bevelled edge and 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 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 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 engraved with “UHE” on one side and “NVR” on the other.

     Afinitor DISPERZ

2 mg tablet for oral suspension

White to slightly yellowish, round, flat tablets with a bevelled edge and engraved with “D2” on one side and “NVR” on the other.

3 mg tablet for oral suspension

White to slightly yellowish, round, flat tablets with a bevelled edge and engraved with “D3” on one side and “NVR” on the other.

5 mg tablet for oral suspension

White to slightly yellowish, round, flat tablets with a bevelled edge and engraved with “D5” on one side and “NVR” on the other.

Contraindications

Afinitor is contraindicated in patients with 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.

What other drugs will affect Afinitor?

Many drugs can interact with Afinitor. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • an antibiotic;

  • antifungal medicine;

  • heart or blood pressure medication;

  • medicine to treat hepatitis C, or HIV/AIDS;

  • seizure medicine;

  • St. John's wort;

  • tuberculosis medication; or

  • drugs that weaken the immune system, such as cancer medicine, steroids, and medicines to prevent organ transplant rejection.

This list is not complete and many other drugs can interact with everolimus. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

For Healthcare Professionals

Applies to everolimus: oral tablet, oral tablet dispersible

General

The most common side effects included stomatitis, infection, rash, fatigue, diarrhea, edema, peripheral edema, anemia, nausea, hyperlipidemia, headache, abdominal pain, fever, asthenia, cough, constipation, hypertension, urinary tract infection, leukopenia, and decreased appetite.[Ref]

Metabolic

Very common (10% or more): Hypercholesterolemia (up to 85%), cholesterol increased (up to 77%), glucose increased (up to 75%), alkaline phosphatase increased (up to 74%), triglycerides increased (up to 73%), bicarbonate decreased (56%), hypertriglyceridemia (up to 52%), creatinine increased (up to 50%), hypophosphatemia (up to 49%), phosphate decreased (up to 40%), calcium decreased (37%), appetite decreased (up to 30%), potassium decreased (29%), weight decreased (up to 28%), anorexia (25%), hyperlipidemia (up to 21%), hyperkalemia (18%), sodium decreased (16%), dyslipidemia (15%), hyperglycemia (14%), hypomagnesemia (14%), hypokalemia (12%), diabetes mellitus (up to 10%)
Common (1% to 10%): Dehydration, blood urea increased, acidosis, gout, hypercalcemia, hyperuricemia, hypocalcemia, hypoglycemia, hyponatremia, iron deficiency, vitamin B12 deficiency, potassium increased[Ref]

Hematologic

Very common (10% or more): Decreased hemoglobin (up to 92%), elevated partial thromboplastin time (72%), anemia (up to 61%), WBC decreased (up to 58%), lymphocytes decreased (up to 54%), platelets decreased (up to 54%), neutropenia (up to 46%), leukopenia (up to 37%), albumin decreased (up to 33%), neutrophils decreased (up to 31%), lymphopenia (up to 20%), thrombocytopenia (up to 19%)
Common (1% to 10%): Hemorrhage, leukocytosis, lymphadenopathy, pancytopenia
Uncommon (0.1% to 1%): Pure red cell aplasia[Ref]

Gastrointestinal

Very common (10% or more): Stomatitis (up to 78%), diarrhea (Up to 50%), constipation (up to 38%), abdominal pain (up to 36%), nausea (up to 32%), vomiting (up to 29%), dry mouth (up to 11%), gastroenteritis (10%)
Common (1% to 10%): Abdominal distention, dyspepsia, dysphagia, epigastric discomfort, flatulence, gastritis, gastroesophageal reflux disease, gingival hypertrophy, hematemesis, hemorrhoids, ileus, mouth ulceration, oral candidiasis, oral pain, peritonitis[Ref]

Other

Very common (10% or more): Fatigue (up to 45%), peripheral edema (up to 45%), edema (39%), asthenia (up to 33%), pyrexia (up to 31%), mucosal inflammation (19%), incision site pain (16%), procedural pain (15%)
Common (1% to 10%): Mucosal inflammation, irritability, blood lactate dehydrogenase increased, non-cardiac chest pain, chills, incisional hernia, edema[Ref]

Dermatologic

Very common (10% or more): Rash (up to 59%), cellulitis (29%), nail disorders (22%), acne (up to 22%), pruritus (up to 21%), dry skin (13%), alopecia (10%)
Common (1% to 10%): Dermatitis acneiform, erythema, folliculitis, hand-foot syndrome, hirsutism, hyperhidrosis, hypertrichosis, night sweats, onychoclasis, onychomycosis, oral herpes skin exfoliation, skin lesion, tinea pedis
Uncommon (0.1% to 1%): Angioedema, Herpes zoster[Ref]

Respiratory

Very common (10% or more): Respiratory tract infection (up to 31%), cough (up to 30%), dyspnea (up to 24%), epistaxis (up to 22%), pneumonitis (up to 19%), oropharyngeal pain (up to 11%), streptococcal pharyngitis (10%)
Common (1% to 10%): Nasopharyngitis, pharyngitis, pneumonia, pulmonary embolism, bronchitis, sinusitis, pleural effusion, rhinorrhea, atelectasis, nasal congestion, pulmonary edema, sinus congestion, wheezing
Uncommon (0.1% to 1%): Hemoptysis, acute respiratory distress syndrome[Ref]

Genitourinary

Very common (10% or more): Amenorrhea (up to 17%), urinary tract infection (up to 16%), hematuria (12%), dysuria (11%), menorrhagia (up to 10%), menstrual irregularities (up to 10%)
Common (1% to 10%): Urethritis, bladder spasm, micturition urgency, pollakiuria, polyuria, pyuria, urinary retention, erectile dysfunction ovarian cyst, scrotal edema, blood luteinizing hormone increased, vaginal hemorrhage, blood follicle stimulating hormone increased, metrorrhagia, dysmenorrhea, delayed menstruation[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (up to 20%), back pain (up to 15%), extremity pain (up to 14%), muscle spasms (up to 10%)
Common (1% to 10%): Osteomyelitis, jaw pain, joint swelling, muscular weakness, myalgia, osteonecrosis, osteopenia, osteoporosis, spondylitis[Ref]

Hepatic

Very common (10% or more): AST increased (up to 69%), ALT increased (up to 51%), hepatitis C (up to 11%), bilirubin increased (up to 10%)
Common (1% to 10%): Transaminases increased[Ref]

Nervous system

Very common (10% or more): Headache (up to 30%), dysgeusia (22%), dizziness (up to 12%)
Common (1% to 10%): Tremor, paresthesia, hemiparesis, hypoesthesia, lethargy, neuralgia, somnolence, syncope
Uncommon (0.1% to 1%): Ageusia[Ref]

Psychiatric

Very common (10% or more): Behavioral disturbances (up to 21%), insomnia (up to 17%)
Common (1% to 10%): Depression, agitation, anxiety, hallucination[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 30%)
Common (1% to 10%): Angina pectoris, hot flush, atrial fibrillation, congestive cardiac failure, hypotension, palpitations, tachycardia, venous thromboembolism (including deep vein thrombosis)[Ref]

Immunologic

Very common (10% or more): Infections (50%)
Common (1% to 10%): BK virus infection, bacteremia, candidiasis, influenza, otitis media, sepsis[Ref]

Renal

Common (1% to 10%): Renal failure, proteinuria, pyelonephritis, hydronephrosis, interstitial nephritis, renal artery thrombosis

Ocular

Common (1% to 10%): Cataract, conjunctivitis, blurred vision, eyelid edema[Ref]

Endocrine

Common (1% to 10%): Cushingoid, hyperparathyroidism[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity[Ref]

Some side effects of Afinitor may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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