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, transient ischemic attack, 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 flush, 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

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.
Assess for falls risk. Institute prevention if indicated.
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, 240 mg tablet can be dispersed in noncarbonated water and then administered with orange juice, applesauce, or additional water. Place 240 mg tablet in a cup. Do not crush or split tablet. Add about 2 tsp (10 mL) of noncarbonated water to make sure tablet is completely immersed in water. Wait 2 min until tablet is broken up and spread out; then stir mixture. Add 2 tbsp (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. OR mix 60 mg tablets in 4 oz of applesauce by stirring; do not crush tablets. Wait 15 min; stir again. Wait another 15 min; stir mixture until tablets are well mixed with no chunks remaining. Use a spoon; have patient consume mixture right away (do not store). Rinse container with 2 oz of water and drink immediately; repeat rinse a second time to ensure entire dose is taken. 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. 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 for 1 wk or until symptoms improve to ≤Grade 1; then resume at same or reduced 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 ⬆ ⬇

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.
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 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.
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.
Rep: May cause fetal harm. Caution patients that apalutamide is not approved for use with 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇