Rubraca (rucaparib camsylate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Rucaparib, an inhibitor of poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP), is an antineoplastic agent.
Rucaparib camsylate, an inhibitor of mammalian poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, is an antineoplastic agent. PARP enzymes are involved in normal cellular homeostasis, including DNA transcription, cell cycle regulation, and DNA repair.
In vitro studies have demonstrated that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, which result in DNA damage, apoptosis, and cancer cell death. PARP inhibitors, such as rucaparib, appear to be selective for tumor cells that harbor certain homologous recombination deficiencies, including those harboring BRCA1 and BRCA2 mutations. Rucaparib reduced tumor growth of xenograft models of human cancer (with or without deficiencies in BRCA) in mice.
Following oral administration, the mean absolute bioavailability of rucaparib is 36% (range: 30-45%). Rucaparib exhibits linear, time-independent, dose-proportional pharmacokinetics over the dosage range of 240-840 mg twice daily. Following oral administration at the recommended dosage, the median time to peak plasma concentrations of rucaparib is 1.9 hours.
Repeated twice-daily administration of rucaparib resulted in 3.5- to 6.2-fold mean rucaparib accumulation (based on AUC). Administration of rucaparib (single 600-mg dose) with a high-fat meal (800--1000 kcal with 500--600 kcal from fat)in patients with solid tumors decreased the rate but only modestly increased the extent of absorption; time to peak plasma concentration was delayed by 2.5 hours, and peak plasma concentration and AUC were increased by 20 and 38%, respectively, relative to fasted conditions. Rucaparib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 2D6 and, to a lesser extent, by CYP1A2 and 3A4.
Genetic polymorphisms of CYP2D6 (i.e., poor, intermediate, or ultrarapid metabolizer) or CYP1A2 (i.e., hyperinducers) do not substantially affect systemic exposure to rucaparib at steady state. In vitro, rucaparib is 70% bound to plasma proteins at therapeutic concentrations. Following oral administration of a single radiolabeled dose of rucaparib, unchanged rucaparib accounted for 64% of the radioactivity in plasma.
Oxidation,N-demethylation, N-methylation, and glucuronidation were the major metabolic pathways for rucaparib. Rucaparib accounted for 45and95% of the radioactivity recovered in urine and feces, respectively. The mean terminal half-life of the drug is 26 hours.
Data from population pharmacokinetic analyses indicate that age (20--86 years), race (white, Black, Asian), sex, body weight (41--171 kg), and CYP2D6 or CYP1A2 genetic polymorphismsdo not have clinically important effects on systemic exposure to rucaparib.
USES: This medication is used to treat certain cancers (such as ovarian, fallopian tube, peritoneal, prostate cancer). It works by slowing or stopping the growth of cancer cells.
Generic name: rucaparib camsylate
Pronunciation: (roo-KAP-a-rib)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Rubraca
Indications
The following indications are listed for Rubraca:
- Epithelial Ovarian Cancer With Brca Mutation
- Metastatic Castration-Resistant Prostate Cancer With Brca Mutation
Also known as: Brca Mutation-Associated Ovarian Cancer, Brca-Mutated Mcrpc, Malignant Neoplasm Of Ovary Associated With Germline And/Or Somatic Brca Mutation, Mcr Prostate Cancer With Brca Mutation, Ovarian Cancer With Germline And/Or Somatic Brca Mutation.
Dosing
Dosage of rucaparib camsylate is expressed in terms of rucaparib.
If adverse reactions occur, interruption of therapy or dosage reduction of rucaparib should be considered. If a reduction from 600 mg twice daily is necessary, the recommended dosage is 500 mg twice daily. If a dosage reduction from 500 mg twice daily is necessary, the recommended dosage is 400 mg twice daily. If further dosage reduction is necessary, the dosage should be reduced to 300 mg twice daily.
Rucaparib camsylate is administered orally twice daily. The drug may be given without regard to meals.
If a dose of rucaparib is missed or vomited, the next dose should be taken at the regularly scheduled time. Vomited doses should not be replaced.
Store tablets at 20-25degreesC (excursions permitted between 15-30degreesC).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Rucaparib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 2D6 and, to a lesser extent, by CYP1A2 and 3A4. Drug interaction studies indicate that rucaparib inhibits CYP isoenzymes 1A2, 2C19, 2C9, and 3A. In vitro studies indicate that rucaparib is an inhibitor of CYP isoenzymes 2C8 and 2D6 as well as uridine diphosphate-glucuronosyltransferase (UGT) 1A1. In vitro, rucaparib induces CYP1A2.
In vitro, rucaparib is an inhibitor oforganic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2,multidrug and toxic compound extrusion (MATE) 1, MATE2K, and multidrug resistance protein (MRP) 4. The drug does not inhibit MRP2, MRP3, or bile salt export pump (BSEP).
In vitro studies indicate that rucaparib is a substrate of the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but is not a substrate for OAT1, OAT3, OCT2, OATP1B1, or OATP1B3.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 10% or more of patients receiving rucaparib for ovarian cancer include nausea, fatigue/asthenia, vomiting, anemia, dysgeusia, AST/ALT elevation,decreased appetite, diarrhea, thrombocytopenia, neutropenia, increased bloodcreatinine, dyspnea, dizziness, dyspepsia, photosensitivity reactions, and leukopenia.
Adverse effects reported in 20% or more of patients receiving rucaparib for metastatic castration-resistant prostate cancer include fatigue/asthenia, nausea, anemia, AST/ALT elevation, decreased appetite, rash, constipation, thrombocytopenia, vomiting, and diarrhea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of rucaparib have not been established in pediatric patients.
Rucaparib may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.
Verification of pregnancy status prior to initiation of rucaparib therapy is recommended.
It is not known whether rucaparib is distributed into milk. Because of the potential for serious adverse reactions to rucaparib in breast-fed infants, women should be advised to discontinue breast-feeding during rucaparib therapy. Women may begin breast-feeding 2 weeks after discontinuance of therapy. The effects of the drug on breast-feeding infants or on milk production are unknown.
The manufacturer makes no specific dosage recommendations for geriatric patients.
In clinical studies evaluating rucaparib in women with ovarian cancer, 41% of patients were 65 years of age or older and 10% were 75 years of age or older. In clinical studies evaluating rucaparib in men with metastatic castration-resistant prostate cancer, 77% of patients were 65 years of age or older and 33% were 75 years of age or older.
No major differences in safety were observed between geriatric patients and younger adults with ovarian cancer or metastatic castration-resistant prostate cancer.
In pharmacokinetic population analyses, age did not have a clinically important effect on systemic exposure to rucaparib.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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