Rucaparib is a pharmaceutical drug used in the treatment of certain types of cancer. It belongs to a class of medications known as poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is an enzyme involved in repairing damaged DNA within cells. When PARP is inhibited, cancer cells with defects in their DNA repair mechanisms become more susceptible to damage, which can lead to their death.

Rucaparib is primarily used to treat advanced ovarian cancer, specifically in patients with certain genetic mutations like BRCA1 or BRCA2. These mutations are associated with an increased risk of developing ovarian cancer, and drugs like rucaparib can be effective in targeting cancer cells in individuals with these mutations.

Rucaparib (Rubraca) inhibits PARP enzymes (poly ADP-ribose polymerase) that play an essential role in cell replication. It is used in the treatment of advanced or recurrent ovarian cancer.

Rucaparib Uses:

• Advanced Ovarian cancer:
  • It is used in the treatment of deleterious germline and/or somatic BRCA mutations associated ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who have been treated with two or more chemotherapy regimens before.
  • Note: The mutations should be detected by approved labs
• Maintenance treatment of recurrent ovarian cancer:
  • It is used in the maintenance treatment of recurrent ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who have a complete or partial response to platinum-based chemotherapy.

Rucaparib (Rubraca) Dose in Adults

Note:

• Only give rucaparib to patients who have a specific kind of genetic mutation called BRCA, which can be found through a special test.
• Rucaparib might make people feel like they want to throw up, so they might need medicine to stop them from feeling sick.

Rucaparib (Rubraca) Dose in the treatment of advanced ovarian cancer:

• In treating advanced ovarian cancer with rucaparib, the typical dose is 600 milligrams taken by mouth twice a day.
• Patients continue this dosing schedule until their cancer either gets worse or they experience side effects that they cannot tolerate.
• This information is based on studies from 2017.

Rucaparib (Rubraca) Dose in the maintenance treatment of recurrent ovarian cancer:

• For recurrent ovarian cancer (maintenance treatment), take Rucaparib by mouth.
• The dose is 600 milligrams twice a day.
• Keep taking it until your cancer gets worse or you can't handle the side effects.

Missed Dose:

• If you forget a dose, take the next one at the usual time.
• Don't take an extra dose if you throw up the medicine.

Use in Children:

Not indicated.

Pregnancy Risk Category: D

• Rucaparib can be harmful to a developing fetus based on how it works and what we know from studies in animals.
• Before using it, check if a woman who can have children is pregnant.
• If a woman can have children, she should use a reliable form of birth control while taking rucaparib and for six months after the last dose. This helps prevent pregnancy and the potential harm it could cause to the fetus.

Use while breastfeeding

• We don't know if rucaparib can get into breast milk.
• Because it could harm the baby, the manufacturer suggests not breastfeeding while taking rucaparib and for two weeks after the last dose.
• This is to make sure the baby doesn't get exposed to any potential risks from the medication.

Rucaparib Dose in Kidney Disease:

• If your kidney function, measured as CrCl, is 30 mL/minute or higher when you start taking rucaparib, you typically don't need to change the dose.
• If your CrCl is less than 30 mL/minute, the manufacturer's label doesn't give specific instructions on dose adjustments because this hasn't been studied enough.
• For individuals on hemodialysis, there are also no specific dose adjustments mentioned in the manufacturer's instructions because this hasn't been studied either.

Rucaparib Dose in Liver disease:

• If you have mild liver impairment, which means your total bilirubin levels are either within the normal range or slightly elevated, and your AST (aspartate aminotransferase) levels are elevated, or if your total bilirubin is between 1 to 1.5 times the upper limit of normal (ULN) with any AST elevation, you typically don't need to adjust your rucaparib dosage.
• If you have moderate to severe liver impairment, where your total bilirubin levels are more than 1.5 times the upper limit of normal, the manufacturer's label doesn't provide specific dosage adjustments because this hasn't been studied enough in this patient group.

Common Side Effects of Rucaparib (Rubraca):

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
  • Dizziness Headache
  • Insomnia
  • Depression
• Dermatologic:
  • Skin Rash
• Endocrine & Metabolic:
  • Increased Serum Cholesterol
• Gastrointestinal:
  • Nausea
  • Abdominal Distention
  • Abdominal Pain
  • Dysgeusia
  • Constipation
  • Vomiting
  • Diarrhea
  • Stomatitis
  • Decreased Appetite
  • Dyspepsia
• Hematologic & Oncologic:
  • Decreased White Blood Cell Count
  • Anemia
  • Decreased Absolute Lymphocyte Count
  • Thrombocytopenia
  • Neutropenia
• Hepatic:
  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Alkaline Phosphatase
• Neuromuscular & Skeletal:
  • Weakness
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Dyspnea
• Miscellaneous:
  • Fever

Contraindication to Rucaparib (Rubraca):

• The manufacturer's labeling for rucaparib does not list any specific contraindications.

Warnings and precautions

Suppression of bone marrow

• Rucaparib can affect your bone marrow, which is responsible for making blood cells.
• Common effects include anemia (low red blood cells), neutropenia (low white blood cells called neutrophils), lymphocytopenia (low lymphocytes, another type of white blood cell), and thrombocytopenia (low platelets, which help blood clot).
• It's important to regularly check your blood counts while on rucaparib treatment. Your healthcare provider will decide how often this needs to be done.
• Before starting rucaparib, you should wait until your blood counts have recovered from any previous chemotherapy, ideally to grade 1 or lower (indicating a safer level of blood counts).
• If you experience prolonged blood count issues lasting more than 4 weeks, your healthcare provider may stop or reduce your rucaparib dose and keep a close eye on your blood counts, checking them weekly until they recover to a safe level.

Toxicity to the gastrointestinal tract:

• Rucaparib can cause gastrointestinal (GI) problems.
• It has the potential to make you feel like you want to vomit (emetogenic), but it's not the strongest in this regard.

Secondary malignancy

• In rare cases, rucaparib has been associated with the development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), which are serious blood disorders that can be potentially fatal.
• Some of these cases have occurred during or within 28 days following rucaparib treatment.
• The duration of rucaparib therapy before the diagnosis of MDS/AML has varied, ranging from 1 month to approximately 28 months.
• These cases are often similar to secondary MDS or AML, which can develop as a result of previous chemotherapy with platinum agents and/or other DNA-damaging medications.
• To monitor for potential blood-related issues, your healthcare provider will check your blood counts before you start rucaparib and then monthly thereafter.
• If you experience prolonged hematological toxicities (lasting more than 4 weeks), your healthcare provider may interrupt your treatment and/or reduce the dose. They will closely monitor your blood counts on a weekly basis until they return to a safer level.
• If your blood counts do not recover to a grade 1 level after 4 weeks or if MDS/AML is suspected, further evaluation by a hematologist (including bone marrow and cytogenetic analyses) is necessary.
• If MDS/AML is confirmed, rucaparib treatment should be discontinued.

Rucaparib: Drug Interaction

Monitoring parameters:

BRCA Mutation Testing (For Advanced Ovarian Cancer Treatment):

• Make sure you have the BRCA genetic mutation that this treatment is meant for.

Baseline and Ongoing Check-ups:

• Get a complete blood count before starting treatment and then monthly or as your doctor suggests.
• If you have prolonged blood issues, your blood counts will be checked weekly until they improve.

Pregnancy Test (For Women Who Can Get Pregnant):

• If you're a woman capable of having children, get a pregnancy test before starting rucaparib.

Monitor for Signs of Blood Disorders (MDS/AML):

• Keep an eye out for any unusual signs or symptoms that might indicate blood problems, like MDS or AML.

Watch for Adherence:

• Make sure you're taking the medication as prescribed.

How to administer Rucaparib?

Preventing Nausea and Vomiting:

• Rucaparib can make you feel like you want to vomit, but it's not the strongest in this regard.
• Your doctor might give you antiemetic medications to prevent nausea and vomiting.

How to Take Rucaparib:

• Take it by mouth twice a day, with about 12 hours between doses.
• You can take it with or without food, whichever you prefer.

Important Note:

• If you throw up after taking a dose, do not take another dose to make up for it.

Mechanism of action of Rucaparib:

• Rucaparib is a medicine that works by blocking certain enzymes called PARP, which play a role in how DNA works inside our cells.
• When Rucaparib stops PARP, it can make more PARP-DNA combinations in cells, leading to damaged DNA, cell death, and a way to fight cancer.
• It's especially effective in cancer cells that have problems with genes like BRCA1/2 and others that repair DNA.

Absorption:

• Rucaparib is absorbed better when taken with a high-fat meal, increasing the amount in the bloodstream by 20%, and the total exposure to the drug by 38%. It also takes about 2.5 hours longer to reach its peak level in the body compared to when taken on an empty stomach.

Distribution:

• After an intravenous (IV) dose, rucaparib spreads throughout the body, with a volume ranging from 113 to 262 liters.

Protein Binding:

• Rucaparib mostly attaches itself to proteins in the blood, with about 70% of the drug binding to these proteins.

Metabolism:

• The liver mainly processes rucaparib, primarily through an enzyme called CYP2D6. There are also minor pathways involving other enzymes like CYP1A2 and CYP3A4.

Bioavailability:

• When taken orally, about 36% of the rucaparib you ingest actually enters your bloodstream, although this can vary from 30% to 45%.

Half-life Elimination:

• Rucaparib stays in your system for quite some time, with a terminal half-life of 17 to 19 hours after taking a single 600 mg oral dose.

Time to Peak:

• It takes approximately 1.9 hours for rucaparib to reach its highest concentration in the body after being taken.

International Brand names of Rucaparib:

• Rubraca

Rucaparib Brand Names in Pakistan:

Not available.