Afinitor

Name: Afinitor

Afinitor Drug Class

Afinitor is part of the drug class:

  • Protein kinase inhibitors

Afinitor Food Interactions

You should not drink grapefruit juice or eat grapefruit during your treatment with Afinitor. It may make the amount of Afinitor in your blood increase to a harmful level.

Inform MD

Before taking Afinitor, tell your healthcare provider about all of your medical conditions, including if you:

  • Have or have had kidney problems
  • Have or have had liver problems
  • Have diabetes or high blood sugar
  • Have high blood cholesterol levels
  • Have any infections
  • Previously had hepatitis B
  • Are scheduled to receive any vaccinations. You should not receive a “live vaccine” or be around people who have recently received a “live vaccine” during your treatment with Afinitor. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. 
  • Are pregnant, or could become pregnant. Afinitor can cause harm to your unborn baby. You should use effective birth control while using Afinitor and for 8 weeks after stopping treatment. Talk to your healthcare provider about birth control options while taking Afinitor.
  • Are breastfeeding or plan to breastfeed. It is not known if Afinitor passes into your breast milk. You and your healthcare provider should decide if you will take Afinitor, or breastfeed. You should not do both.

Tell your healthcare provider about all of the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

What is the most important information I should know about Afinitor?

Afinitor can cause serious and sometimes fatal side effects. Call your doctor right away if you have symptoms such as: fever, chills, joint pain, cough, chest pain, wheezing, trouble breathing, swelling, little or no urinating, loss of appetite, dark urine, yellowing of your skin or eyes, or upper stomach pain.

Afinitor side effects

Get emergency medical help if you have signs of an allergic reaction: hives; chest pain, difficult breathing; swelling of your face, lips, tongue, or throat. You may be more likely to have some of these symptoms if you also take an "ACE inhibitor" heart or blood pressure medication.

Stop using Afinitor and call your doctor at once if you have:

  • new or worsening cough, chest pain, wheezing, feeling short of breath;

  • signs of infection--fever, chills, joint pain, red or swollen gums, painful mouth sores, skin sores, rapid heart rate, pale skin, easy bruising, unusual bleeding, feeling light-headed;

  • kidney problems--little or no urination; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath;

  • liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  • any wound that will not heal; or

  • a surgical incision that is red, warm, swollen, painful, bleeding, or oozing pus.

Common side effects may include:

  • infections, cough, nosebleeds;

  • mouth sores, taste problems, dry mouth;

  • nausea, vomiting, diarrhea, constipation;

  • weight loss, feeling weak or tired;

  • pain or swelling anywhere in your body;

  • dry skin, rash, acne;

  • missed menstrual periods;

  • unusual changes in mood or behavior;

  • sleep problems (insomnia);

  • dizziness, headache; or

  • high blood sugar--increased thirst or urination, hunger, fruity breath odor, blurred vision.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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 Afinitor. 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.

Afinitor Pharmacokinetics

Absorption

Bioavailability

Peak everolimus concentrations attained within 1–2 hours following oral administration of doses ranging from 5–70 mg in patients with advanced solid tumors.1 13

Increases in peak plasma concentrations dose-proportional following single doses of 5–10 mg.1 4 10 Peak plasma concentrations and AUC also dose-proportional at steady state following oral dosages of 0.5–2 mg twice daily in renal allograft patients.13 Increases in peak plasma concentrations less than dose-proportional following single doses of ≥20 mg;1 4 10 considered unlikely to be clinically important.10 Increases in AUC dose-proportional over dosage range of 5–70 mg.1

AUC of everolimus tablets for oral suspension (Afinitor Disperz) was equivalent to that of everolimus tablets (Afinitor); peak concentrations were 20–36% lower for everolimus tablets for oral suspension.1 Predicted trough concentrations at steady state were similar between these dosage forms following daily administration.1

In patients with advanced solid tumors, steady-state concentrations achieved within 2 weeks of once-daily dosing.1 In renal allograft patients, steady-state concentrations achieved by day 4 with an accumulation in blood concentrations of twofold to threefold compared with exposure following the first dose.13

In patients with SEGA and TSC, everolimus trough concentrations were dose-proportional at daily dosages of 1.35–14.4 mg/m2.1

Food

Administration of 10-mg tablet with a high-fat meal in healthy individuals reduced peak plasma concentrations and AUC of everolimus by 54 and 22%, respectively; light fat meals reduced peak plasma concentrations and AUC of everolimus by 42 and 32%, respectively.1 However, food had no apparent effect on the postabsorption phase concentration-time profile.1

Special Populations

Mild, moderate, and severe hepatic impairment increased AUC by 1.6-, 3.2-, and 3.6-fold, respectively, in a single-dose study.1 13 40 In another study, average AUC in individuals with moderate hepatic impairment was twice that found in those with normal hepatic function.1 13

Distribution

Extent

Crosses the placenta.1 13 Everolimus and/or its metabolites readily distributed into milk in rats at a concentration 3.5 times higher than in maternal serum.1 13

Plasma Protein Binding

Approximately 74%.1 13

Special Populations

Moderate hepatic impairment does not alter plasma protein binding.1 13

Elimination

Metabolism

Metabolized by CYP3A4 to inactive metabolites;1 10 12 13 also a substrate for P-glycoprotein.1 13

Elimination Route

Excreted in feces (80%) and urine (5%) as inactive metabolites.1 12 13

Half-life

Approximately 30 hours.1 4 13

Special Populations

No significant correlation between Clcr (range: 25–178 mL/minute) and everolimus clearance; renal impairment not expected to influence drug exposure.1

In patients with SEGA, everolimus clearance normalized to body surface area may be higher in pediatric patients compared with adults.1

Higher exposure to everolimus among Japanese patients compared with non-Japanese patients; relevance to safety and efficacy not established.1

Clearance is 20% higher in black patients than in Caucasian patients; relevance to safety and efficacy not established.1

Commonly used brand name(s)

In the U.S.

  • Afinitor
  • Afinitor Disperz
  • Zortress

Available Dosage Forms:

  • Tablet for Suspension
  • Tablet

Therapeutic Class: Antineoplastic Agent

What do I need to tell my doctor BEFORE I take Afinitor?

  • If you have an allergy to everolimus, temsirolimus, sirolimus, or any other part of Afinitor (everolimus tablets (afinitor)).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have an infection.
  • If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with Afinitor. Your doctor or pharmacist can tell you if you are taking a drug that must not be taken with this medicine.
  • If you are taking another drug that has the same drug in it.
  • If you are taking St. John's wort. Do not take St. John's wort with Afinitor. This medicine may not work as well.
  • If you are breast-feeding. Do not breast-feed while you take this medicine and for 2 weeks after your last dose.

This is not a list of all drugs or health problems that interact with Afinitor.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Description

Afinitor (everolimus), an inhibitor of mammalian target of rapamycin (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[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone.

The molecular formula is C53H83NO14 and the molecular weight is 958.2. The structural formula is:

Afinitor Tablets are supplied for oral administration and contain 2.5 mg, 5 mg, 7.5 mg, or 10 mg of everolimus. The tablets also contain anhydrous lactose, butylated hydroxytoluene, crospovidone, hypromellose, lactose monohydrate, and magnesium stearate as inactive ingredients.

Afinitor DISPERZ (everolimus tablets for oral suspension) is supplied for oral administration and contains 2 mg, 3 mg, or 5 mg of everolimus. The tablets for oral suspension also contain butylated hydroxytoluene, colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, mannitol, and microcrystalline cellulose as inactive ingredients.

How supplied/storage and handling

Afinitor (everolimus) Tablets

2.5 mg tablets

White to slightly yellow, elongated tablets with a bevelled edge and 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

5 mg tablets

White to slightly yellow, elongated tablets with a bevelled edge and 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

7.5 mg tablets

White to slightly yellow, elongated tablets with a bevelled edge and 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

10 mg tablets

White to slightly yellow, elongated tablets with a bevelled edge and 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

Afinitor DISPERZ (everolimus tablets for oral suspension)

2 mg tablets 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; available in:

Blisters of 28 tablets………………………………………………………………………………NDC 0078-0626-51

Each carton contains 4 blister cards of 7 tablets each

3 mg tablets 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; available in:

Blisters of 28 tablets………………………………………………………………………………NDC 0078-0627-51

Each carton contains 4 blister cards of 7 tablets each

5 mg tablets 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; available in:

Blisters of 28 tablets………………………………………………………………………………NDC 0078-0628-51

Each carton contains 4 blister cards of 7 tablets each

Store Afinitor (everolimus) Tablets and Afinitor DISPERZ (everolimus tablets for oral suspension) 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.

Follow special handling and disposal procedures for anticancer pharmaceuticals.2

Afinitor Tablets and Afinitor DISPERZ should not be crushed. Do not take tablets which are crushed or broken.

Pharmacology

Mechanism of Action

Afintior: mTOR kinase inhibitor (mammalian target of rapamycin, a serine-threonine kinase, downstream of the PI3K/AKT pathway, which is dysregulated in several human cancers); binds to intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) which inhibits mTOR kinase activity; reduces activity of S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4E-BP1); inhibits expression of hypoxia-inducible factor (eg, HIF-1) and reduces expression of vascular endothelial growth factor (VEGF); inhibits of mTOR reduces cell proliferation, angiogenesis, and glucose uptake; constitutive activation of PI3K/Akt/mTOR pathway contributes to endocrine resistance in breast cancer; in vitro studies show sensitivity of estrogen-dependent and HER2+ breast cancer cells to therapy and combination treatment enhances anti-tumor activity of everolimus in a synergistic manner

Zortress: Inhibits antigenic and interleukin (IL-2 and IL-15) stimulated activation and proliferation of T and B lymphocytes; binds to cellular cytoplasmic protein, the FK506 Binding Protein-12 (FKBP-12), to form an immunosuppressive complex (everolimus: FKBP-12) that binds to and inhibits the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase; in the presence of everolimus phosphorylation of p70 S6 ribosomal protein kinase (p70S6K), a substrate of mTOR, is inhibited; consequently, phosphorylation of the ribosomal S6 protein and subsequent protein synthesis and cell proliferation are inhibited

Absorption

Peak Plasma Time: 1-2 hr

Distribution

Protein Bound: 74%

Metabolism

CYP3A4 substrate

PgP substrate and moderate inhibitor

Competitive inhibitor of CYP3A4 and mixed inhibitor of CYP2D6

Elimination

Half Life: 30 hr

Excretion: 80% feces; 5% urine

Pharmacogenomics

Rapamycins form complexes with an intracellular immunophillin (FKBP), which bind to a kinase called the mammalian target of rapamycin (mTOR)

Intrinsic rapamycin resistance may be caused by genetic mutations identified for FKBP and mTOR genes

Afinitor May Interact with Other Medications

Afinitor can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Food interactions

You shouldn’t drink grapefruit juice or eat grapefruit while you’re taking Afinitor. Grapefruit may increase the amount of Afinitor in your blood to a harmful level.

Alcohol interaction

Afinitor can make you feel tired. Drinking alcohol may also cause drowsiness or dizziness. You should limit the amount of alcohol you drink while taking this medication. Don’t drive, use machinery, or perform similar tasks that require alertness if you drink alcohol while taking Afinitor.

Medications that might interact with Afinitor

Antifungal drugs

These drugs may increase the amount of Afinitor in your body. Examples of these drugs include:

  • fluconazole
  • itraconazole
  • ketoconazole
  • posaconazole
Antibiotics

These drugs may decrease the amount of Afinitor in your body. Examples of these drugs include:

  • rifampin
  • rifabutin
  • rifapentine
  • rifaximin

These drugs may increase the amount of Afinitor in your body. Examples of these drugs include:

  • clarithromycin
  • erythromycin
  • telithromycin
High blood pressure or heart drugs

These drugs may increase the amount of Afinitor in your body. Examples of these drugs include:

  • verapamil
  • diltiazem

Drugs called angiotensin-converting enzyme (ACE) inhibitors raise your risk of a severe allergic reaction when taken with Afinitor. Examples of these drugs include:

  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • lisinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril
Antidepressant

This drug may increase the amount of Afinitor in your body:

  • nefazodone
HIV drugs

These drugs may increase the amount of Afinitor in your body. Examples of these drugs include:

  • atazanavir
  • indinavir
  • lopinavir/ritonavir
  • nelfinavir
  • ritonavir
  • saquinavir
Herbal supplement

This drug may decrease the amount of Afinitor in your body:

  • St. John's wort
Seizure drugs

These drugs may decrease the amount of Afinitor in your body. Get medical help right away if you have trouble breathing or develop swelling of your tongue, mouth, or throat during treatment with Afinitor and any of these drugs. Examples of these drugs include:

  • carbamazepine
  • phenobarbital
  • phenytoin
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking. Afinitor warnings

People with kidney disease

This drug may cause kidney failure. Your doctor will likely do tests to check your kidney function before and during your treatment to make sure this drug isn’t harming your kidneys.

People with liver disease

Your body may not process this drug very well. This may increase the levels of the drug in your body and cause more side effects. Your doctor may give you a lower dosage of this drug.

People with weakened immune systems

This drug can make your immune system less able to fight infections. These infections may be severe and may cause death. Tell your doctor right away if you have chills or a temperature of 100.5˚F or greater.

People with a history of hepatitis B virus infection

This drug may make a past hepatitis B virus infection become active again. Your doctor may test you for the hepatitis B virus before you start this drug.

People with diabetes

This drug may increase your blood sugar levels. You and your doctor may need to check your blood sugar levels more often while you take this drug.

People with high blood pressure

This drug may increase your blood pressure. You and your doctor may need to monitor your blood pressure more closely while you take this drug.

Pregnant women

This drug is a category D pregnancy drug. That means two things:

  1. Research in humans has shown adverse effects to the fetus when the mother takes the drug.
  2. This drug should only be used during pregnancy in serious cases where it's needed to treat a dangerous condition in the mother.

Tell your doctor if you’re pregnant or plan to become pregnant. This drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Ask your doctor to tell you about the specific harm that may be done to the fetus.

Use effective birth control while you’re on this medication and for 8 weeks after stopping treatment with this drug. Your doctor can tell you about your birth control options.

Women who are breast-feeding

It isn’t known if this drug passes into breast milk. If it does, it may cause serious effects in a child who is breastfed.

Talk to your doctor about breastfeeding your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

For children

This drug is only approved to treat brain tumors in children aged 1 year or older. This drug isn’t approved for use in children with any other condition.

When to call the doctor

Call your doctor right away if you become pregnant while taking this drug.

Allergies

This drug can cause a severe allergic reaction. Symptoms may include:

  • trouble breathing
  • swelling of your throat or tongue
  • hives

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 9-1-1 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Note: This drug raises your risk of a severe allergic reaction if you take it with a drug that’s an angiotensin-converting enzyme (ACE) inhibitor. Tell your healthcare provider before taking this drug if you’re currently taking an ACE inhibitor.

How to Take Afinitor (Dosage)

All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

  • your age
  • the condition being treated
  • how severe your condition is
  • other medical conditions you have
  • how you react to the first dose

What are you taking this medication for?

Certain cancers and noncancerous tumors

Brand: Afinitor

Form: Oral tablet Strengths: 0.25 mg, 0.50 mg, 0.75 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg Adult dosage (ages 18–64 years)

For treating breast cancer, pancreatic neuroendocrine tumors (PNET), kidney cancer (renal cell carcinoma), and kidney tumors (angiomyolipoma) with tuberous sclerosis complex (TSC):

  • 10 mg taken by mouth once per day with or without food

For treating a brain tumor (subependymal giant cell astrocytoma, SEGA) with tuberous sclerosis complex (TSC):

  • Your doctor will decide your dosage using your body surface area. This is calculated by your height and weight, and it’s measured in squared meters (m2).
  • The typical dose is 4.5 mg/m² taken by mouth once per day. Your doctor will adjust your dosage as needed depending on your blood levels of Afinitor.
Child dosage (ages 1–17 years)

For treating a brain tumor (subependymal giant cell astrocytoma, SEGA) with tuberous sclerosis complex (TSC):

  • Your doctor will decide your child’s dosage using your child’s body surface area. This is calculated by their height and weight, and it’s measured in squared meters (m2).
  • The typical dose is 4.5 mg/m² taken by mouth once per day. Your child’s doctor will adjust your child’s dosage as needed.
Child dosage (ages 0–11 months)

This drug should not be used in children younger than 1 year of age.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always to speak with your doctor or pharmacist about dosages that are right for you. Important considerations for taking Afinitor

You can take this drug with or without food

See Details

Take this drug at the same time every day

Don’t crush, cut, or chew the tablets. Do not take tablets that are crushed or broken

Store this drug carefully

See Details

A prescription for this medication is refillable

See Details

Travel considerations

See Details

Clinical monitoring

See Details

Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead

Insurance

See Details

Are there any alternatives?

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