Apalutamide – Uses, Dosage, Side Effects, Interactions

Indications

  • Indicated for the treatment of patients with non-metastatic, castration-resistant prostate cancer (NM-CRPC).
  • Erleada is indicated in adult men for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease and in adult men for the treatment of metastatic hormone-sensitive prostate cancer (HSBC) in combination with androgen deprivation therapy (ADT). Apalutamide is a nonsteroidal antiandrogen used to treat nonmetastatic castration-resistant prostate cancer. Apalutamide is associated with a low rate of serum enzyme elevation during therapy but has not been linked to cases of clinically apparent liver injury with jaundice.
  • For the treatment of metastatic castration-sensitive prostate cancer (mCSPC)
  • For the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC)
  • Metastatic Castration Sensitive Prostate Cancer
  • Non-Metastatic Castration-Resistant Prostate Cancer
You Might Also Read  Durvalumab - Uses, Dosage, Side Effects, Interaction

Use in Cancer

Apalutamide is approved to treat:

Contraindications

The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

  • are allergic to apalutamide or any ingredients of the medication
  • are female and are or may become pregnant
  • a low supply of oxygen-rich blood to the heart
  • abnormal EKG with QT changes from birth
  • a disorder of the blood vessels of the brain
  • pregnancy

Dosage

Strengths: 60 mg

 Prostate Cancer

  • 240 mg orally once a day
Oral
  • 240 mg once daily. In the principal efficacy study, therapy was continued until disease progression or unacceptable toxicity occurred.
Dosage Modification for Toxicity
Oral
  • If an intolerable adverse effect or grade 3 or greater toxicity occurs, interrupt therapy until symptoms improve to grade 1 or less or return to baseline; then may resume therapy with or without dosage reduction. If dosage reduction is necessary, reduce dosage to 180 or 120 mg daily.

Dose Adjustments

  • If a patient experiences a Grade 3 or greater toxicity or an intolerable side effect, hold dosing until symptoms improve to G

Side Effects

The Most Common

  • weakness
  • tiredness
  • joint pain
  • muscle weakness or stiffness
  • diarrhea
  • nausea
  • loss of appetite
  • weight loss
  • hot flashes
  • seizures
  • loss of consciousness
  • swelling of the arms, legs, hands, or feet
  • falling
  • chest pain
  • shortness of breath
  • numbness or weakness of face, arm, or leg, especially on one side of the body; difficulty talking or understanding; difficulty seeing in one or both eyes; dizziness; loss of balance or coordination; or difficulty walking
  • rash
  • skin blistering, peeling, or redness with or without a fever

More Common

  • changed sense of taste
  • decreased appetite
  • diarrhea
  • hot flushes
  • itching
  • joint pain
  • muscle spasms
  • nausea
  • skin rash
  • tiredness
  • weight loss
  • broken bones
  • falls
  • high blood pressure

Rare

  • signs of heart problems (e.g., fast, irregular heartbeat or pulse; chest pain; sudden weight gain; difficulty breathing; leg swelling)
  • swelling of hands, ankles, or feet
  • symptoms of irregular heartbeat (e.g., chest pain, dizziness, rapid, pounding heartbeat, shortness of breath)
  • symptoms of scarring of the lungs (e.g., shortness of breath at rest, shortness of breath increased with activity, dry cough)
  • symptoms of underactive thyroid gland (e.g., dry skin, constipation, weight gain, fatigue, aches, pains and stiffness, intolerance to cold, depression, memory problems)
  • seizures
  • signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
  • signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
  • signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; dizziness, sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)

Drug Interactions

There may be an interaction between apalutamide and any of the following:

  • abiraterone
  • aliskiren
  • alpha-blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
  • antiarrhythmics (e.g., amiodarone, disopyramide, dronedarone, propafenone, quinidine)
  • anticancer medications (e.g., cabazitaxel, docetaxel, doxorubicin, etoposide, ifosfamide, irinotecan, vincristine)
  • anticoagulants (e.g., apixaban, clopidogrel, dabigatran, edoxaban, rivaroxaban, ticagrelor)
  • antipsychotics (e.g., aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
  • aprepitant
  • “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
  • benzodiazepines (e.g., chlordiazepoxide, clobazam, clonazepam, diazepam, lorazepam)
  • bictegravir
  • bisoprolol
  • bromocriptine
  • buprenorphine
  • buspirone
  • calcium channel blockers (e.g., amlodipine, diltiazem, felodipine, nifedipine, verapamil)
  • cannabis
  • clarithromycin
  • clindamycin
  • clonazepam
  • cobicistat
  • conivaptan
  • corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
  • cyclosporine
  • dapsone
  • digoxin
  • domperidone
  • dronedarone
  • eliglustat
  • elvitegravir
  • enzalutamide
  • estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
  • eszopiclone
  • everolimus
  • exemestane
  • fexofenadine
  • flibanserin
  • gemfibrozil
  • “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
  • guanfacine
  • hepatitis C antivirals (e.g., elbasvir, grazoprevir, ledipasvir, letermovir, paritaprevir, voxilaprevir)
  • HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., doravirine, efavirenz, etravirine, nevirapine, rilpivirine)
  • HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
  • ivabradine
  • ivacaftor
  • lemborexant
  • lidocaine
  • losartan
  • lumacaftor and ivacaftor
  • macitentan
  • maraviroc
  • mefloquine
  • methadone
  • midazolam
  • mirtazapine
  • naloxegol
  • narcotic pain relievers (e.g., codeine, fentanyl, oxycodone, tramadol)
  • ondansetron
  • praziquantel
  • progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
  • protein kinase inhibitors (e.g., bosutinib, dasatinib, imatinib, nilotinib, tofacitinib)
  • proton pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole)
  • quinine
  • ranolazine
  • remdesivir
  • repaglinide
  • rifabutin
  • roflumilast
  • riociguat
  • romidepsin
  • saxagliptin
  • seizure medications (e.g., carbamazepine, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone)
  • selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, escitalopram, fluoxetine, paroxetine, sertraline)
  • sildenafil
  • solifenacin
  • “statin” anticholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
  • stiripentol
  • tacrolimus
  • tadalafil
  • tamoxifen
  • thyroid replacements (e.g., desiccated thyroid, levothyroxine)
  • tolvaptan
  • trazodone
  • triazolam
  • vitamin D analogues (e.g., calcifediol, calcitriol)
  • vortioxetine
  • warfarin
  • zolpidem
  • zopiclone
You Might Also Read  Colchicine Tablet - Uses, Dosage, Side Effects

Pregnancy and Lactation

Pregnancy

May cause fetal harm and potential loss of pregnancy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female. There are no available data on ERLEADA use in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of apalutamide to pregnant rats during and after organogenesis resulted in fetal abnormalities and embryo-fetal lethality at maternal exposures ≥ 2 times the human clinical exposure (AUC) at the recommended dose

Lactation

Not known whether apalutamide or its metabolites are distributed into milk, affect milk production, or affect nursing infants; drug not indicated for use in women. The safety and efficacy of ERLEADA have not been established in females. There are no data on the presence of apalutamide or its metabolites in human milk, the effect on the breastfed child, or the effect on milk production

What special precautions should I follow?

Before taking apalutamide,

  • tell your doctor and pharmacist if you are allergic to apalutamide, any other medications, or any of the ingredients in apalutamide tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin), fexofenadine (Allegra), gemfibrozil (Lopid), itraconazole (Onmel, Sporanox, Tolsura), ketoconazole (Nizoral), omeprazole (Prilosec, in Yosprala, Zegerid), midazolam (Nayzilam, Seizalam), rifampin (Rifadin, Rimactane, in Rifamate, in Rifater), rosuvastatin (Crestor, Ezallor). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with apalutamide, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • tell your doctor if you have or have ever had heart problems such as a heart attack, angina (chest pain), heart failure, or hypertension or a stroke or ministroke. Also, tell your doctor if you have ever had seizures, a brain injury, a brain tumor, high cholesterol, diabetes, or osteoporosis.
  • you should know that apalutamide is only for use in men. Women should not take this medication, especially if they are or may become pregnant or are breastfeeding. If taken by pregnant women, apalutamide may harm the fetus. If a pregnant woman takes apalutamide, she should call her doctor immediately.
  • if your partner is pregnant, you must use a condom whenever you have sex during your treatment with apalutamide and for three months after your final dose. If your partner is not pregnant but could become pregnant, you must use a condom and another form of birth control whenever you have sex during your treatment and for 3 months after your final dose. Do not donate semen or sperm while you are taking apalutamide and for 3 months after your final dose.
  • you should know that apalutamide may cause seizures. Do not drive a car or operate machinery until you know how this medication affects you.
  • you should know that apalutamide may cause your muscles and bones to get weak, which may increase your risk of falling and breaking a bone.

Warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Abnormal heart rhythm: Apalutamide can cause changes to the normal rhythm of the heart, called QT prolongation. QT prolongation is a serious life-threatening condition. If you are at risk for heart rhythm problems (e.g., have heart failure, angina, low potassium or magnesium levels; have congenital long QT syndrome; or are taking medications that can prolong the QT interval, such as quinidine, procainamide, amiodarone, sotalol, flecainide), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

You Might Also Read  Indications Dosage Side Effects of Botox

Bone health and fractures: Long-term use of anti-androgen medications such as apalutamide has been shown to cause reduced bone strength and may increase the risk of bone fractures. Apalutamide may also increase the risk of falls. If you have osteoporosis or are at increased risk of developing osteoporosis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart disease: The risk of heart attack or heart failure is increased for people taking apalutamide. If you have a high blood pressure or a history of heart disease or risk factors for heart disease (obesity, high blood cholesterol, smoking), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Seizures: There have been rare reports of seizures occurring with apalutamide in studies. The safety of using this medication if you have a seizure disorder has not been determined. If you have a history of epilepsy or medical conditions that increase the risk of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Stroke: Apalutamide may increase the risk of having a stroke or mini-stroke (transient ischemic attack [TIA]) caused by decreased blood flow to parts of the brain. If you have a history of either stroke or TIA, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of a stroke or TIA, such as confusion, difficulty speaking, loss of coordination, sudden headache, or vision changes, contact your doctor as soon as possible.

Thyroid disease: This medication may cause decreased thyroid gland function. If you have problems with your thyroid gland, apalutamide may make these problems worse. If you experience symptoms of underactive thyroid, such as unexpectedly feeling cold, depression, constipation, or fatigue, let your doctor know. If you have a history of thyroid disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Apalutamide
  2. https://pubchem.ncbi.nlm.nih.gov/compound/Apalutamide-COOH
  3. https://pubchem.ncbi.nlm.nih.gov/compound/Apalutamide-D4
  4. https://medlineplus.gov/druginfo/meds/a618018.html
  5. https://go.drugbank.com/drugs/DB11901
  6. https://dailymed.nlmhttps://www.drugs.com/apalutamide.html.nih.gov/dailymed/drugInfo.cfm?setid=d1cda4f7-cb33-46ea-b9ac-431f6452b1a5
  7. https://www.webmd.com/drugs/2/drug-174785/apalutamide-oral/details/list-contraindications
  8. https://www.cancer.gov/about-cancer/treatment/drugs/apalutamide
  9. https://www.medbroadcast.com/drug/getdrug/erleada
  10. ChemIDplus Chemical Information Classification
  11. CompTox Chemicals Dashboard Chemical Lists
  12. 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
    4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
  13. NCI Thesaurus Tree
  14. PubChem
  15. LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
  16. LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    Therapeutic category of drugs in Japan
    Anatomical Therapeutic Chemical (ATC) classification
    Target-based classification of drugs
  17. Guide to Pharmacology Target Classification
  18. LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    NORMAN Suspect List Exchange Classification