RUBRACA*
Manufacturer DetailsCLOVIS ONCOLOGY INC.
Clovis Oncology, Inc. Boulder, CO 80301
Compositions:
Rucaparib mg tablets,
Rucaparib mg tablets,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | tablets |
List of Related Indications:
- Ovarian cancer
List Of Drugs:
- Rucaparib -Rubraca -@-(Sep 2016)- anti-cancer
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
RUBRACA safely and effectively.
See full prescribing information for RUBRACA.
RUBRACA (rucaparib) tablets, for oral use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated
as monotherapy for the treatment of patients with deleterious
BRCA mutation (germline and/or somatic) associated advanced ovarian cancer
who have been treated with two or more chemotherapies.
Select patients for therapy based on an FDA-approved companion
diagnostic for RUBRACA.
This indication is approved under accelerated approval based on objective
response rate and duration of response. Continued approval for this indication
may be contingent upon verification and description of clinical benefit in
confirmatory trials.
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
21. Rubraca Rucaparib 12/19/2016
To treat women with certain type of ovarian cancer
Press release
Drug Trials Snapshot
Adverse Reaction:
ADVERSE REACTIONS.
Most common adverse reactions (. 20%) were nausea, fatigue (including
asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation,
decreased appetite, diarrhea, thrombocytopenia, and dyspnea. (6.1)
Most common laboratory abnormalities (. 35%) were increase in creatinine,
increase in ALT, increase in AST, decrease in hemoglobin, decrease in
lymphocytes, increase in cholesterol, decrease in platelets,
and decrease in absolute neutrophil count.
Contra-Indications:
CONTRAINDICATIONS
NONE
WARNINGS AND PRECAUTIONS
.
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):
MDS/AML occurred in patients exposed to RUBRACA, including one fatal
event of AML.
Monitor patients for hematological toxicity at baseline and monthly
thereafter. Discontinue if MDS/AML is confirmed.
.
Embryo-Fetal Toxicity: RUBRACA can cause fetal harm.
Advise females of reproductive potential of the potential risk to a fetus and
to use effective contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated
as monotherapy for the treatment of patients with deleterious
BRCA mutation (germline and/or somatic) associated advanced ovarian cancer
who have been treated with two or more chemotherapies.
Select patients for therapy based on an FDA-approved companion
diagnostic for RUBRACA.
This indication is approved under accelerated approval based on objective
response rate and duration of response. Continued approval for this indication
may be contingent upon verification and description of clinical benefit in
confirmatory trials.
DOSAGE AND ADMINISTRATION
Recommended dose is 600 mg orally twice daily with or without food.
Continue treatment until disease progression or unacceptable toxicity.
For adverse reactions, consider interruption of treatment or dose reduction.
DOSAGE FORMS AND STRENGTHS
Tablets: 200 mg and 300 mg
OVERDOSAGE
There is no specific treatment in the event of Rubraca overdose, and symptoms
of overdose are not established. In the event of suspected overdose
physicians should follow general supportive measures and should treat
symptomatically.
Patient Information:
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
MDS/AML: Advise patients to contact their healthcare provider if they experience
weakness, feeling tired, fever, weight loss, frequent infections, bruising,
bleeding easily, breathlessness, blood in urine or stool, and/or laboratory
findings of low blood cell counts, or a need for blood transfusions.
These may be signs of hematological toxicity or a more serious uncommon
bone marrow problem called ‘myelodysplastic syndrome’ (MDS)
or ‘acute myeloid leukemia’ (AML) which have been reported in patients
treated with Rubraca
Embryo-Fetal Toxicity:
Advise females to inform their healthcare provider if they are pregnant or
become pregnant. Inform female patients of the risk to a fetus and potential
loss of the pregnancy
Advise females of reproductive potential to use effective contraception
during treatment and for 6 months after receiving the last dose of Rubraca .
Photosensitivity:
Advise patients to use appropriate sun protection due to the increased
susceptibility to sunburn while taking Rubraca
Lactation:
Advise females not to breastfeed during treatment and for 2 weeks after
the last dose of Rubraca
Dosing Instructions:
Instruct patients to take Rubraca orally twice daily with or without food.
Doses should be taken approximately 12 hours apart.
Advise patients that if a dose of Rubraca is missed or if the patient
vomits after taking a dose of Rubraca, patients should not take an extra dose,
but take the next dose at the regular time
Distributed by:
Clovis Oncology, Inc.
Boulder, CO 80301
1-844-258-7662
Rubraca is a trademark of Clovis Oncology, Inc.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action
Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes,
including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair
In vitro studies have shown that rucaparib-induced cytotoxicity may involve
inhibition of PARP enzymatic activity and increased formation of PARP-DNA
complexes resulting in DNA damage, apoptosis, and cell death. Increased
rucaparib-induced cytotoxicity was observed in tumor cell lines with
deficiencies in BRCA1/2 and other DNA repair genes.
Rucaparib has been shown to decrease tumor growth in mouse xenograft models
of human cancer with or without deficiencies in BRCA.
2. Pharmacokinetics
All pharmacokinetics of rucaparib were characterized in patients with cancer.
Rucaparib demonstrated linear pharmacokinetics over a dose range from
240 to 840 mg twice daily with time-independence and dose-proportionality.
The mean steady-state rucaparib Cmax was 1940 ng/mL
(54% coefficient of variation [CV]) and AUC0-12h was 16900 h·ng/mL (54% CV)
at the approved recommended dosage. Accumulation was 3.5 to 6.2 fold.
Median terminal half-life (T1/2) was 17 hours following a single intravenous
dose of 12 to 40 mg rucaparib.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1.Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action, Rubraca can
cause fetal harm when administered to pregnant women. There are no available
data in pregnant women to inform the drug-associated risk.
2. Lactation
Risk Summary
There is no information regarding the presence of rucaparib in human milk, or on its
effects on milk production or thebreast-fed infant.
Because of the potential for serious adverse reactions in breast-fed infants
from Rubraca, advise lactating women not to breastfeed during treatment with
Rubraca and for 2 weeks after the final dose.
3. Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior
to initiating Rubraca.
Contraception
Females
Rubraca can cause fetal harm when administered to a pregnant woman .
. Advise females of reproductive potential to use effective contraception
during treatment and for 6 months following the final dose of Rubraca.
4. Pediatric Use
The safety and effectiveness of Rubraca in pediatric patients have not
been established.
5. Geriatric Use
One hundred and sixty (42%) of the 377 ovarian cancer patients in clinical trials
of Rubraca were 65 years of age or older.
No overall differences in safety were observed between these patients and
younger patients, but greater sensitivity of some older individuals
cannot be ruled out.
The effectiveness of Rubraca in patients with BRCA-mutant ovarian cancer
who were 65 years of age or older could not be assessed due to the
small number of patients (N=38).
6. Hepatic Impairment
No starting dose adjustment is recommended for patients with mild hepatic
impairment (total bilirubin less than or equal to upper limit of normal
[ULN] and AST greater than ULN, or total bilirubin between 1.0 to 1.5 times
ULN and any AST).
No recommendation of starting dose adjustment is available for patients
with moderate to severe hepatic impairment (total bilirubin greater than
1.5 times ULN) due to a lack of data.
7. Renal Impairment
No starting dose adjustment is recommended for patients with mild to moderate
renal impairment (creatinine clearance [CLcr] between 30 and 89 mL/min,
as estimated by the Cockcroft-Gault method). There is no recommended
starting dose for patients with CLcr less than 30 mL/min or patients on dialysis
due to a lack of data.
