Rubraca

Name: Rubraca

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What is the most important information I should know about rucaparib?

Rucaparib can cause leukemia or serious bone marrow problems. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, blood in your urine or stools, shortness of breath, or signs of infection (fever, feeling weak or tired, weight loss).

Cautions for Rubraca

Contraindications

None.1

Warnings/Precautions

Myelodysplastic Syndrome/Acute Myeloid Leukemia

Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) was reported in 2 of 377 (0.5%) patients with ovarian cancer treated with rucaparib camsylate. The duration of rucaparib camsylate treatment prior to the diagnosis of MDS/AML was 57 days and 539 days. Both patients received prior treatment with platinum and other DNA damaging agents.1

In addition, AML was reported in 2 (<1%) patients with ovarian cancer enrolled in a blinded, randomized trial evaluating rucaparib camsylate versus placebo. One case of AML was fatal. The duration of treatment prior to the diagnosis of AML was 107 days and 427 days. Both patients had received prior treatment with platinum and other DNA damaging agents.1

Monitor complete blood count testing at baseline and monthly thereafter. Do not start rucaparib camsylate until patients have recovered from hematological toxicity caused by previous chemotherapy (≤grade 1). For prolonged hematological toxicities, interrupt rucaparib camsylate and monitor blood counts weekly until recovery. If the levels have not recovered to grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue rucaparib camsylate.1

Embryo-fetal Toxicity

Rucaparib camsylate can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposure that were 0.04 times the AUC in patients receiving the recommended dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of rucaparib camsylate.1

Specific Populations

Pregnancy

Based on findings from animal studies and its mechanism of action, rucaparib camsylate can cause fetal harm when administered to pregnant women. There are no available data in pregnant women to inform the drug-associated risk. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposure that were 0.04 times the AUC0-24h in patients receiving the recommended dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus.1

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

In a dose range-finding embryo-fetal development study, pregnant rats received oral doses of 50, 150, 500, or 1000 mg/kg/day of rucaparib during the period of organogenesis. Post-implantation loss (100% early resorptions) was observed in all animals at doses greater than or equal to 50 mg/kg/day (with maternal systemic exposures approximately 0.04 times the human exposure at the recommended dose based on AUC0-24h).1

Lactation

There is no information regarding the presence of rucaparib in human milk, or on its effects on milk production or the breast-fed infant. Because of the potential for serious adverse reactions in breast-fed infants from rucaparib camsylate, advise lactating women not to breastfeed during treatment with rucaparib camsylate and for 2 weeks after the final dose.1

Females and Males of Reproductive Potential

Pregnancy testing is recommended for females of reproductive potential prior to initiating rucaparib camsylate.1

Rucaparib camsylate 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 rucaparib camsylate. 1

Pediatric Use

The safety and effectiveness of rucaparib camsylate in pediatric patients have not been established.1

Geriatric Use

One hundred and sixty (42%) of the 377 ovarian cancer patients in clinical trials of rucaparib camsylate 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 rucaparib camsylate 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).1

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.1

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.1

Common Adverse Effects

  • Most common adverse reactions (≥20%) were nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea.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.1

Commonly used brand name(s)

In the U.S.

  • Rubraca

Available Dosage Forms:

  • Tablet

Therapeutic Class: Antineoplastic Agent

What are some things I need to know or do while I take Rubraca?

  • Tell all of your health care providers that you take Rubraca. This includes your doctors, nurses, pharmacists, and dentists.
  • A bone marrow problem called myelodysplastic syndrome (MDS) and a type of leukemia have rarely happened in patients treated with this medicine. One case of leukemia was deadly. Talk with your doctor.
  • Low blood cell counts may happen with Rubraca. Low blood cell counts may raise the chance of needing a blood transfusion or getting an infection or bleeding. If you have questions, talk with your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • It is common to have diarrhea, upset stomach, throwing up, or stomach pain with this medicine. Call your doctor if any of these side effects get very bad, bother you, or do not go away.
  • If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
  • You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant.
  • If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting Rubraca. Talk with your doctor.
  • Use birth control that you can trust to prevent pregnancy while taking this medicine and for 6 months after stopping Rubraca.
  • If you get pregnant while taking this medicine or within 6 months after your last dose, call your doctor right away.

Use in specific populations

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. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposure that were 0.04 times the AUC0-24h in patients receiving the recommended dose of 600 mg twice daily [see Data]. Apprise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In a dose range-finding embryo-fetal development study, pregnant rats received oral doses of 50, 150, 500, or 1000 mg/kg/day of rucaparib during the period of organogenesis. Post-implantation loss (100% early resorptions) was observed in all animals at doses greater than or equal to 50 mg/kg/day (with maternal systemic exposures approximately 0.04 times the human exposure at the recommended dose based on AUC0-24h).

Lactation

Risk Summary

There is no information regarding the presence of rucaparib in human milk, or on its effects on milk production or the breast-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.

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 [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the final dose of Rubraca.

Pediatric Use

The safety and effectiveness of Rubraca in pediatric patients have not been established.

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).

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 [See Clinical Pharmacology (12.3)].

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 [See Clinical Pharmacology (12.3)].

Rubraca Description

Rucaparib is an inhibitor of the mammalian polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme. The chemical name is 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt. The chemical formula of rucaparib camsylate is C19H18FN3O•C10H16O4S and the relative molecular mass is 555.67 Daltons.

The chemical structure of rucaparib camsylate is shown below:

Rucaparib camsylate is a white to pale yellow powder; formulated into a tablet for oral use. Rucaparib shows pH-independent low solubility of approximately 1 mg/mL across the physiological pH range.

Rubraca (rucaparib) tablets contain rucaparib camsylate as the active ingredient. Each 200 mg tablet contains 344 mg rucaparib camsylate equivalent to 200 mg rucaparib free base. Each 250 mg tablet contains 430 mg rucaparib camsylate equivalent to 250 mg rucaparib free base. Each 300 mg tablet contains 516 mg rucaparib camsylate equivalent to 300 mg rucaparib free base.

The inactive ingredients in Rubraca tablets include: microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, and magnesium stearate. The cosmetic blue film coating for 200 mg tablets, cosmetic white film coating for 250 mg tablets, and cosmetic yellow film coating for 300 mg tablets is Opadry II containing polyvinyl alcohol, titanium dioxide, polyethylene glycol/macrogol, and talc. The coating is colorized as blue using brilliant blue aluminum lake and indigo carmine aluminum lake, or yellow using yellow iron oxide.

Important information

Rubraca can cause leukemia or serious bone marrow problems. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, blood in your urine or stools, shortness of breath, or signs of infection (fever, feeling weak or tired, weight loss).

How should I take Rubraca?

Take Rubraca exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Rubraca is usually taken once every 12 hours. Follow your doctor's dosing instructions very carefully.

You may take Rubraca with or without food.

If you vomit shortly after taking this medicine, do not take another dose. Wait until your next scheduled dose to take the medicine again, but do not take 2 doses at the same time.

Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Store at room temperature away from moisture and heat.

Rubraca dosing information

Usual Adult Dose for Ovarian Cancer:

600 mg orally twice a day
Duration of therapy: Continue treatment until disease progression or unacceptable toxicity.

Comments:
-Administer each dose about 12 hours apart, with or without food.
-Select patients based on the results of the approved test for the detection of a tumor BRCA mutation in patients with ovarian cancer; the test is available at http://www.fda.gov/CompanionDiagnostics.

Use: Monotherapy for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with 2 or more chemotherapies.

What should I avoid while taking Rubraca?

Avoid exposure to sunlight or tanning beds. Rucaparib can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

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