apalutamide

Absorption: Completely absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: Apalutamide: 96%; N-desmethyl apalutamide: 95%.

Metabolism/Excretion: Metabolized by the CYP2C8 and CYP3A4 isoenzymes in the liver to an active metabolite (N-desmethyl apalutamide). Primarily excreted in urine (65%) and 24% excreted in feces, with only minimal amounts being excreted as unchanged drug.

Half-Life: 3 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

None.

Use Cautiously in:

History of seizures, underlying brain pathology, cerebrovascular accident, TIA, brain metastases, or brain arteriovenous malformation (may ↑ risk of seizures);
Ischemic heart disease, HF, stroke, or TIA;
Rep: Men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema, MI, unstable angina

Derm: hot flushing, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

Endo: hyperglycemia, hypothyroidism

F and E: hyperkalemia

GI: diarrhea, nausea

GU: ↓fertility (males)

Hemat: anemia, leukopenia, lymphopenia

Metab: ↓appetite, hypercholesterolemia, hypertriglyceridemia, weight loss

MS: arthralgia, fracture

Neuro: falls, fatigue, SEIZURES

Resp: INTERSTITIAL LUNG DISEASE/PNEUMONITIS

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2C8 and CYP3A4 inhibitors, including gemfibrozil, may ↑ levels and risk of toxicity; may need to ↓ apalutamide dose.
May ↓ levels and effectiveness of CYP3A4, CYP2C9, and CYP2C19 substrates; avoid concurrent use when possible.
May ↓ levels and effectiveness of fexofenadine and rosuvastatin.
Drugs that seizure threshold may ↑ risk of seizures.

Route/Dosage ⬆ ⬇

PO (Adults ): 240 mg once daily.

Availability ⬆ ⬇

Tablets: 60 mg; 240 mg

Assessment ⬆ ⬇

Monitor for seizures. Implement seizure precautions. If a seizure occurs during therapy, permanently discontinue apalutamide therapy.
Monitor for signs of ILD/pneumonitis (dyspnea, cough, hypoxia, fever). CT scan or chest x-ray should be done prior to and periodically during therapy to monitor lung status. If clinically significant symptoms occur, discontinuation of therapy and/or treatment with corticosteroids and/or antibiotics may be required.
Assess for falls risk. Institute prevention if indicated. Monitor and manage patients at risk for fractures.
Monitor patients for development of severe cutaneous adverse reactions, including DRESS, SJS, and TEN. Advise patients of signs and symptoms of these reactions (prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, lymphadenopathy). If a severe cutaneous adverse reaction is suspected, interrupt therapy until etiology of reaction is determined. Consultation with a dermatologist is recommended. If a severe cutaneous adverse reaction is confirmed or for other Grade 4 skin reactions, permanently discontinue therapy.

Lab Test Considerations:

May cause ↑ TSH levels.

Implementation ⬆ ⬇

Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had a bilateral orchiectomy.
PO: Administer four of the 60-mg tablets or one of the 240-mg tablets once daily without regard to food.DNC: Swallow tablets whole; do not crush, break, dissolve, or chew.
- For patients with difficulty swallowing: Tablets can be dispersed in noncarbonated water and then administered with orange juice, applesauce, or additional water. Place tablets in cup. Do not crush or split tablets. Add about 2 teaspoons (10 mL) (for 240-mg tablet) or 4 teaspoons (20 mL) (for 60-mg tablets) of noncarbonated water to make sure tablets are completely immersed in water. Wait 2 min until tablets are broken up and spread out; then stir mixture. Add 2 tablespoons (30 mL) of orange juice, applesauce, or additional water and stir mixture. Swallow mixture immediately. Rinse cup with enough water to make sure whole dose is taken and drink it immediately; do not save for later. To administer via feeding tube: Place one 240-mg tablet in the barrel of syringe (use at least a 20-mL syringe) and draw up 10 mL of noncarbonated water into the syringe. For 60-mg tablets, place all the needed tablets in the barrel of syringe (use at least a 50-mL syringe) and draw up 20 mL of noncarbonated water into the syringe. For the 240-mg or 60-mg tablets, wait 10 min and then shake vigorously to disperse contents completely. Administer immediately through feeding tube. Refill syringe with noncarbonated water and administer. Repeat until no tablet residue is left in syringe or feeding tube.
- If ≥Grade 3 toxicity or intolerable side effects occur, withhold dose until symptoms improve to ≤Grade 1; then resume at same or ↓ dose (180 mg or 120 mg). For Grade 3 or 4 cerebrovascular and ischemic cardiovascular events, consider permanent discontinuation. For confirmed severe cutaneous adverse reactions or other Grade 4 skin reactions, permanently discontinue therapy.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of apalutamide to patient. Instruct patient to take apalutamide as directed at the same time each day. Take missed doses as soon as remembered within the same day. If a whole day is missed, omit dose and take next day's scheduled dose; do not double doses. Advise patient not to interrupt, modify dose, or stop taking apalutamide without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
May cause seizures, falls, and fractures. Caution patient to avoid driving and other activities requiring alertness until response to medication is known. Notify health care professional immediately if seizure occurs.
Advise patient to notify health care professional immediately of symptoms of lung problems (e.g., shortness of breath, cough, fever).
Advise patient to notify health care professional if rash occurs.
Advise patient to notify health care professional and go to nearest emergency room if signs and symptoms of cardiac problems (chest pain or discomfort at rest or with activity, shortness of breath) occur.
Rep: May cause fetal harm. Caution patients that apalutamide is not approved for use by females. Advise male patients with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose of therapy. May impair fertility in males of reproductive potential.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased growth and spread of prostate cancer.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

59676- Janssen Products, LP
- 59676-600- ERLEADA
  - 59676-600-12- 120 TABLET, FILM COATED in 1 BOTTLE (59676-600-12)

59676- Janssen Products, LP
- 59676-600- ERLEADA
  - 59676-600-56- 2 BLISTER PACK in 1 CARTON (59676-600-56) > 28 TABLET, FILM COATED in 1 BLISTER PACK

59676- Janssen Products, LP
- 59676-600- ERLEADA
  - 59676-600-99- 120 TABLET, FILM COATED in 1 BOTTLE (59676-600-99)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇