Rucaparib Camsylate

L01X - Other antineoplastic agents ATC L01XK03 Small molecule approved 2016 Oral

JFDA label: Rubraca

Mechanism of Action

Inhibitor of PARP 1, 2 and 3 — PARP 1, 2 and 3 inhibitor

Target	Action	Gene / class
PARP 1, 2 and 3 efficacy	INHIBITOR

Indications

Approved

Ovarian cancer, advanced

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer's labeling Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Very Common dizziness · Fatigue

Hepatobiliary disorders (2)

Very Common Increased serum ALT · increased serum AST

Renal and urinary disorders (1)

Very Common Increased serum creatinine

Blood and lymphatic system disorders (6)

Very Common anemia · decreased absolute lymphocyte count · Decreased hemoglobin · neutropenia · thrombocytopenia

Common Febrile neutropenia

Metabolism and nutrition disorders (1)

Very Common Increased serum cholesterol

Gastrointestinal disorders (7)

Very Common abdominal pain · constipation · decreased appetite · diarrhea · dysgeusia · Nausea · vomiting

Skin and subcutaneous tissue disorders (4)

Very Common Skin rash

Common palmar-plantar erythrodysesthesia · pruritus · Skin photosensitivity

Musculoskeletal and connective tissue disorders (1)

Very Common Weakness

General disorders and administration site conditions (1)

Very Common Fever

Respiratory, thoracic and mediastinal disorders (1)

Very Common Dyspnea

Dosing

Source: Lexicomp

Note: Administer only to patients with deleterious germline and/or somatic BRCA mutation, as detected by an approved test. Rucaparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting. Ovarian cancer, advanced: Oral: 600 mg twice daily until disease progression or unacceptable toxicity. Missed doses: If a dose is missed, administer the next dose at its scheduled time. Do not repeat a vomited dose.

Refer to adult dosing.

CrCl ≥30 mL/minute: No dosage adjustment is necessary CrCl Hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment is necessary. Moderate to severe impairment (total bilirubin > 1.5 times ULN): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Bone marrow suppression

Anemia, neutropenia, lymphocytopenia, and thrombocytopenia were commonly observed in clinical trials. Monitor blood counts as clinically necessary. Do not initiate treatment until after hematologic recovery (to grade 1 or lower) from prior chemotherapy. Prolonged hematologic toxicity may require therapy interruption. ·

GI toxicity

Rucaparib is associated with a moderate emetic potential; antiemetics may be needed to prevent nausea and vomiting.

Secondary malignancy

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and AML have been reported (rarely) in a clinical trial of patients with ovarian cancer receiving rucaparib monotherapy. The duration of therapy prior to development of MDS/AML and AML ranged from 57 days to ~1.5 years and 107 days to 427 days, respectively; all patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications. Monitor blood counts at baseline and then monthly and as clinically indicated. If prolonged hematologic toxicity occurs and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.

Pregnancy & Lactation

Pregnancy

Based on animal reproduction studies and its mechanism of action, rucaparib may be expected to cause adverse events to the fetus. Women of reproductive potential should use effective contraception during therapy and for 6 months after the last dose. Pregnancy testing is recommended prior to therapy initiation.

Lactation

Avoid

It is not known if rucaparib is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended by the manufacturer during treatment and for 2 weeks after the last dose.

Monitoring

Clinical pearl	Complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity); monitor for signs/symptoms of MDS/AML. Monitor adherence.

Chemistry & Properties

Formula	C29H34FN3O5S
Molecular weight	555.67 g/mol
IUPAC name	[(1S,4R)-7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl]methanesulfonic acid;6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one
CAS	1859053-21-6
PubChem CID	121490161
InChIKey	`INBJJAFXHQQSRW-STOWLHSFSA-N`
logP	2.98
Polar surface area	56.92 Å²
H-bond acceptors / donors	2 / 3
Drug-likeness (QED)	0.69
Lipinski violations	0

SMILES

CC1(C)[C@@H]2CC[C@@]1(CS(=O)(=O)O)C(=O)C2.CNCc1ccc(-c2[nH]c3cc(F)cc4c3c2CCNC4=O)cc1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	0.903 h
Volume of distribution	2.914 L/kg
Protein binding	74.3%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)P-gp (Inhibitor)BCRP (Substrate)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Amiodarone	major
Amisulpride	major
Anagrelide	major
Arsenic trioxide	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Bedaquiline	major
Bepridil	major
Berotralstat	major
Brexpiprazole	major
Cabozantinib	major
Ceritinib	major
Certolizumab pegol	major
Chloroquine	major
Cisapride	major
Citalopram	major
Cladribine	major
Clozapine	major
Crizotinib	major
Deferiprone	major
Disopyramide	major
Dofetilide	major
Dolasetron	major
Dronedarone	major
Droperidol	major
Efavirenz	major
Escitalopram	major
Etanercept	major
Fingolimod	major
Gatifloxacin	major
Golimumab	major
Grepafloxacin	major
Halofantrine	major
Haloperidol	major
Hydroxychloroquine	major
Ibutilide	major
Iloperidone	major
Infliximab	major
Ivabradine	major

Showing 40 of 100+.

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Rubraca	Tablet (equivalent to 250 mg Rucaparib): Rucaparib Camsylate 429.6 mg	60 tab	Hikma Pharmaceuticals LLC Amman- Jordan	—
Rubraca	Tablet (equivalent to 300 mg Rucaparib): Rucaparib Camsylate 515.5 mg	60 tab	Hikma Pharmaceuticals LLC Amman- Jordan	—
Rubraca	Tablet (Equivalent to 200 mg Rucaparib): Rucaparib Camsylate 343.7 mg	60 tab	Hikma Pharmaceuticals LLC Amman- Jordan	—