4/18. Apalutamide- Anti-cancer-( ERLEADA)-@- (Feb- 2018)
Drug Name:4/18. Apalutamide- Anti-cancer-( ERLEADA)-@- (Feb- 2018)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
• Concomitant use with medications that are sensitive substrates of CYP3A4, CYP2C19, CYP2C9, UGT, P-gp, BCRP, or OATP1B1 may result in loss of activity of these medications.
Indication:
BRIEF SUMMARY
4/18 Apalumide- (Feb 2018)
Indn- To treat a certain type of prostrate cancer using novel clinical trial endpoint
Comp- Tablets: 60 mg 240 mg (four 60 mg tablets) administered orally once daily. Swallow tablets whole. can be taken with or without food.
ADR- The most common adverse reactions (=10%) are fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
CI- Pregnancy
WARNINGS -
• Falls and Fractures occurred in 16% and 12% of patients receiving, respectively. Evaluate patients for fracture and fall risk, and treat patients with bone targeted agents according to established guidelines.
Pat Inform -
Falls and Fractures • Inform patients that the drug is associated with an increased incidence of falls and fractures
Seizures
• Inform patients that has been associated with an increased risk of seizure. Discuss conditions
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U.S. FDA APPROVED DRUGS DURING 2018
Sr.No- 4
Name of the Drug- ERLEADA
Active Ingredient - Apalutamide
Pharmacological Classification-
To treat a certain type of prostrate cancer using novel clinical
trial endpoint
Date of Approval- 2-14-2018
(Ref- FDA approved List 2018)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
ERLEADA safely and effectively. See full prescribing information for ERLEADA. ERLEADATM (apalutamide) tablets, for oral use
Initial U.S. Approval – 2018
INDICATIONS AND USAGE
ERLEADA is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions (=10%) are fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
Contra-Indications:
CONTRAINDICATIONS
Pregnancy
WARNINGS AND PRECAUTIONS
• Falls and Fractures occurred in 16% and 12% of patients receiving ERLEADA, respectively. Evaluate patients for fracture and fall risk, and treat patients with bone targeted agents according to established guidelines.
• Seizure occurred in 0.2% of patients receiving ERLEADA. Permanently discontinue ERLEADA in patients who develop a seizure during treatment.
ADVERSE REACTIONS
The most common adverse reactions (=10%) are fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
DRUG INTERACTIONS
• Concomitant use with medications that are sensitive substrates of CYP3A4, CYP2C19, CYP2C9, UGT, P-gp, BCRP, or OATP1B1 may result in loss of activity of these medications.
USE IN SPECIFIC POPULATIONS
• Females and Males of Reproductive Potential: Advise males with female partners of reproductive potential to use effective contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ERLEADA is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.
DOSAGE AND ADMINISTRATION
ERLEADA 240 mg (four 60 mg tablets) administered orally once daily. Swallow tablets whole. ERLEADA can be taken with or without food.
Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
DOSAGE FORMS AND STRENGTHS
Tablets: 60 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Falls and Fractures
• Inform patients that ERLEADA is associated with an increased incidence of falls and fractures
Seizures
• Inform patients that ERLEADA has been associated with an increased risk of seizure. Discuss conditions that may predispose to seizures and medications that may lower the seizure threshold.
Advise patients of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.
Inform patients to contact their healthcare provider right away if they experience a seizure
Rash
• Inform patients that ERLEADA is associated with rashes and to inform their healthcare provider if they develop a rash.
Dosage and Administration
• Inform patients receiving concomitant gonadotropin-releasing hormone (GnRH) analog therapy that they need to maintain this treatment during the course of treatment with ERLEADA.
• Instruct patients to take their dose at the same time each day (once daily). ERLEADA can be taken with or without food. Each tablet should be swallowed whole.
• Inform patients that in the event of a missed daily dose of ERLEADA, they should take their normal dose as soon as possible on the same day with a return to the normal
schedule on the following day. The patient should not take extra tablets to make up the missed dose
Embryo-Fetal Toxicity
• Inform patients that ERLEADA can be harmful to a developing fetus. Advise patients having sex with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA.
Advise male patients to use a condom if having sex with a pregnant woman
Infertility
• Advise male patients that ERLEADA may impair fertility and not to donate sperm during therapy and for 3 months following the last dose of ERLEADA
Manufactured by: Janssen Ortho LLC Gurabo, PR 00778
Manufactured for: Janssen Products, LP Horsham, PA 19044
© 2018 Janssen Pharmaceutical Companies
Reference ID: 4221951
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Apalutamide is an Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.
A major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of apalutamide in an in vitro transcriptional reporter assay.
Apalutamide administration caused decreased tumor cell proliferation and increased apoptosis leading to decreased tumor volume in mouse xenograft models of prostate cancer.
2.Pharmacodynamics Cardiac Electrophysiology
The effect of apalutamide 240 mg once daily on the QTc interval was assessed in an open-label, uncontrolled, multi-center, single-arm dedicated QT study in 45 patients with CRPC.
The maximum mean QTcF change from baseline was 12.4 ms (2-sided 90% upper CI: 16.0 ms). An exposure-QT analysis suggested a concentration-dependent increase in QTcF for apalutamide and its active metabolite.
3.Pharmacokinetics
Apalutamide pharmacokinetic parameters are presented as the mean [standard deviation (SD)] unless otherwise specified.
Apalutamide Cmax and area under the concentration curve (AUC) increased proportionally following repeated once-daily dosing of 30 to 480 mg (0.125 to 2 times the recommended dosage).
Following administration of the recommended dosage, apalutamide steady-state was achieved after 4 weeks and the mean accumulation ratio was approximately 5fold. Apalutamide Cmax was 6.0 mcg/mL (1.7) and AUC was 100 mcg·h/mL (32) at steady-state.
Effect of Food
Administration of apalutamide to healthy subjects under fasting conditions and with a high-fat meal (approximately 500 to 600 fat calories, 250 carbohydrate calories, and 150 protein calories) resulted in no clinically relevant changes in Cmax and AUC.
Median time to reach tmax was delayed approximately 2 hours with food.
Distribution
The mean apparent volume of distribution at steady-state of apalutamide was approximately 276 L. Apalutamide was 96% and N-desmethyl apalutamide was 95% bound to plasma proteins with no concentration dependency.
Elimination
The CL/F of apalutamide was 1.3 L/h after single dosing and increased to 2.0 L/h at steady-state after once-daily dosing likely due to CYP3A4 auto-induction.
The mean effective half-life for apalutamide in patients was approximately 3 days at steady-state.
Metabolism
Metabolism is the main route of elimination of apalutamide. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 to form active metabolite, N-desmethyl apalutamide.
Excretion
Up to 70 days following a single oral administration of radiolabeled apalutamide, 65% of the dose was recovered in urine (1.2% of dose as unchanged apalutamide and 2.7% as N-desmethyl apalutamide) and 24% was recovered in feces (1.5% of dose as unchanged apalutamide and 2% as N-desmethyl apalutamide).
Specific Populations
No clinically significant differences in the pharmacokinetics of apalutamide or N-desmethyl apalutamide were observed based on age (18-94 years), race (Black, non-Japanese Asian, Japanese), mild to moderate (eGFR 30-89 mL/min/1.73m2, estimated by the modification of diet in renal disease [MDRD] equation) renal impairment, or mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1.Pregnancy Risk Summary
ERLEADA is contraindicated for use in pregnant women because the drug can cause fetal harm and potential loss of pregnancy. ERLEADA is not indicated for use in females, so animal embryo-fetal developmental toxicology studies were not conducted with apalutamide.
There are no human data on the use of ERLEADA in pregnant women. Based on its mechanism of action, ERLEADA may cause fetal harm when administered during pregnancy.
2. Lactation Risk Summary -
ERLEADA is not indicated for use 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.
3. Females and Males of Reproductive Potential
Contraception Males
Based on the mechanism of action and findings in an animal reproduction study, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA.
Infertility Males
Based on animal studies, ERLEADA may impair fertility in males of reproductive potential
4. Pediatric Use
Safety and effectiveness of ERLEADA in pediatric patients have not been established.
5.Geriatric Use
Of the 803 patients who received ERLEADA in SPARTAN, 87% of patients were 65 years and over and 49% were 75 years and over. Grade 3-4 adverse reactions occurred in 46% (323/697) of patients 65 years or older and in 51% (197/391) of patients 75 years or older treated with ERLEADA compared to 35% (124/355) of patients 65 years or older and 37% (70/187) of patients 75 years or older treated with placebo
. No overall differences in effectiveness were observed between these patients and younger patients.
OVERDOSAGE
There is no known specific antidote for apalutamide overdose. In the event of an overdose, stop ERLEADA, undertake general supportive measures until clinical toxicity has been diminished or resolved.
