Rubraca

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 200 mg film-coated tablets 
Rubraca 250 mg film-coated tablets 
Rubraca 300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Rubraca 200 mg film-coated tablets 
 
Each tablet contains rucaparib camsylate corresponding to 200 mg rucaparib. 
 
Rubraca 250 mg film-coated tablets  
 
Each tablet contains rucaparib camsylate corresponding to 250 mg rucaparib. 
 
Rubraca 300 mg film-coated tablets  
 
Each tablet contains rucaparib camsylate corresponding to 300 mg rucaparib. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet.  
 
Rubraca 200 mg film-coated tablet 
 
Blue, 11 mm, round film-coated tablet, debossed with “C2”.  
 
Rubraca 250 mg film-coated tablet 
 
White, 11 x 15 mm, diamond-shaped film-coated tablet, debossed with “C25”. 
 
Rubraca 300 mg film-coated tablet 
 
Yellow, 8 x 16 mm, oval film-coated tablet, debossed with “C3”. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-
sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are 
in response (complete or partial) to platinum-based chemotherapy.  
 
Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or 
progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, 



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or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based 
chemotherapy, and who are unable to tolerate further platinum based chemotherapy. 
 
4.2 Posology and method of administration 
 
Treatment with rucaparib should be initiated and supervised by a physician experienced in the use of 
anticancer medicinal products. 
Detection of BRCA mutation 
 
There is no requirement for BRCA testing prior to using Rubraca for the maintenance treatment of 
adult patients with relapsed high-grade epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), 
or primary peritoneal cancer (PPC) who are in a complete or partial response to platinum-based 
chemotherapy. 
 
Before taking Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC, patients must have 
confirmation of deleterious germline or somatic mutations in the breast cancer 1 (BRCA1) or breast 
cancer 2 (BRCA2) gene using a validated test.  
 
Posology 
 
The recommended dose is 600 mg rucaparib taken twice daily, equivalent to a total daily dose of 
1,200 mg, until disease progression or unacceptable toxicity. 
 
For the maintenance treatment, patients should start the maintenance treatment with Rubraca no later 
than 8 weeks after completion of their final dose of the platinum containing regimen. 
 
If a patient vomits after taking Rubraca, the patient should not retake the dose and should take the next 
scheduled dose. 
 
Missed doses 
If a dose is missed, the patient should resume taking Rubraca with the next scheduled dose.  
 
Dose adjustments for adverse reactions 
 
Adverse reactions may be managed through dose interruptions and/or dose reductions for moderate to 
severe reactions (i.e. CTCAE Grade 3 or 4) such as neutropenia, anaemia and thrombocytopenia. 
 
Liver transaminase elevations (aspartate aminotransferase (AST) and/or alanine aminotransferase 
(ALT)) occur early in treatment and are generally transient. Grade 1-3 elevations in AST/ALT can be 
managed without change to the rucaparib dose, or with treatment modification (interruption and/or 
dose reduction). Grade 4 reactions require treatment modification (see Table 2). 
 
Other moderate to severe non-haematological adverse reactions such as nausea and vomiting, can be 
managed through dose interruption and/or reductions, if not adequately controlled by appropriate 
symptomatic management. 
 
Table 1.  Recommended dose adjustments 

Dose reduction Dose 
Starting dose 600 mg twice daily (two 300 mg tablets twice daily) 
First dose reduction 500 mg twice daily (two 250 mg tablets twice daily) 
Second dose reduction 400 mg twice daily (two 200 mg tablets twice daily) 
Third dose reduction 300 mg twice daily (one 300 mg tablet twice daily) 

 



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Table 2.  Management of Treatment-emergent AST/ ALT Elevations 
Grade of AST/ALT Elevation Management 
Grade 3 without other signs of liver dysfunction Monitor LFTs weekly until resolution to 

Grade ≤ 2 
Continue rucaparib provided bilirubin is < ULN 
and alkaline phosphatase is < 3 x ULN 
Interrupt treatment if AST/ALT levels do not 
decline within 2 weeks until Grade ≤ 2, then 
resume rucaparib at the same or at a reduced 
dose 

Grade 4 Interrupt rucaparib until values return to 
Grade ≤ 2; then resume rucaparib with a dose 
reduction and monitor LFTs weekly for 3 weeks 

 
Special populations 
 
Elderly 
No adjustment is recommended to the starting dose for elderly patients (≥ 65 years of age) (see 
sections 4.8 and 5.2). Greater sensitivity of some elderly patients (≥ 65 years of age) to adverse events 
cannot be ruled out. There are limited clinical data in patients aged 75 or over.  
 
Hepatic impairment 
No starting dose adjustment is required in patients with mild hepatic impairment (see section 5.2). 
There are limited clinical data in patients with moderate or severe hepatic impairment (ie, any total 
bilirubin greater than 1.5 times ULN), therefore rucaparib is not recommended for use in patients with 
moderate or severe hepatic impairment. 
 
Renal impairment 
No starting dose adjustment is required in patients with mild or moderate renal impairment (see 
section 5.2). There are no clinical data in patients with severe renal impairment (CLcr less than 
30 mL/min), therefore rucaparib is not recommended for use in patients with severe renal impairment. 
Rucaparib may only be used in patients with severe renal impairment if the potential benefit outweighs 
the risk. Patients with moderate or severe renal impairment should be carefully monitored for renal 
function and adverse reactions.  
 
Paediatric population 
The safety and efficacy of Rubraca in children or adolescents aged less than 18 years have not been 
established. No data are available. 
 
Method of administration 
 
Rubraca is for oral use and can be taken with or without food. The doses should be taken 
approximately 12 hours apart. See section 5.2. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Breast-feeding (see section 4.6) 
 
4.4 Special warnings and precautions for use 
 
Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been 
investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in 
this patient population is not recommended.  
 



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Haematological toxicity 
 
During treatment with rucaparib, events of myelosuppression (anaemia, neutropenia, 
thrombocytopenia) may be observed and are typically first observed after 8-10 weeks of treatment 
with rucaparib. These reactions are manageable with routine medical treatment and/or dose adjustment 
for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and 
monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered 
from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1).  
 
Supportive care and institutional guidelines should be implemented for the management of low blood 
counts for the treatment of anaemia and neutropenia. Rubraca should be interrupted or dose reduced 
according to Table 1 (see section 4.2) and blood counts monitored weekly until recovery. If the levels 
have not recovered to CTCAE Grade 1 or better after 4 weeks, the patient should be referred to a 
haematologist for further investigations. 
 
Myelodysplastic syndrome/acute myeloid leukaemia 
 
Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), including cases with fatal 
outcome, have been reported in patients who received rucaparib. The duration of therapy with 
rucaparib in patients who developed MDS/AML varied from less than 1 month to approximately 
28 months. 
 
If MDS/AML is suspected, the patient should be referred to a haematologist for further investigations, 
including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for 
prolonged haematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued. 
 
Photosensitivity 
 
Photosensitivity has been observed in patients treated with rucaparib. Patients should avoid spending 
time in direct sunlight because they may burn more easily during rucaparib treatment; when outdoors, 
patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection 
factor (SPF) of 50 or greater. 
 
Gastrointestinal toxicities 
 
Gastrointestinal toxicities (nausea and vomiting) are frequently reported with rucaparib, are generally 
low grade (CTCAE Grade 1 or 2), and may be managed with dose reduction (refer to Table 1) or 
interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, 
can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e., 
preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid 
prolonged or more severe events of nausea/vomiting which have the potential to lead to complications 
such as dehydration or hospitalisation. 
 
Embryofetal toxicity 
 
Rubraca 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 the period of organogenesis resulted in embryo-fetal toxicity at exposures 
below those in patients receiving the recommended human dose of 600 mg twice daily (see 
section 5.3). 
 
Pregnancy/contraception 
 
Pregnant women should be informed of the potential risk to a foetus. Women of reproductive potential 
should be advised to use effective contraception during treatment and for 6 months following the last 
dose of Rubraca (see section 4.6). A pregnancy test before initiating treatment is recommended in 
women of reproductive potential.  



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4.5 Interaction with other medicinal products and other forms of interaction 
 
Effect of other medicinal products on rucaparib 
 
Enzymes responsible for rucaparib metabolism have not been identified. Based on in vitro data, 
CYP2D6, and to a lesser extent CYP1A2 and CYP3A4, were able to metabolize rucaparib. 
Although in vitro rucaparib metabolism mediated by CYP3A4 was slow, a significant contribution of 
CYP3A4 in vivo cannot be excluded. Caution should be used for concomitant use of strong CYP3A4 
inhibitors or inducers. 
 
In vitro, rucaparib was shown to be a substrate of P-gp and BCRP. Effect of P-gp and BCRP inhibitors 
on rucaparib PK cannot be ruled out. Caution is recommended when rucaparib is co-administered with 
medicinal products that are strong inhibitors of P-gp. 
 
Effects of rucaparib on other medicinal products 
 
In a medicinal product interaction study in cancer patients, the effects of steady-state rucaparib at 
600 mg twice daily on CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp were evaluated with single 
oral doses of sensitive probes (caffeine, S-warfarin, omeprazole, midazolam, and digoxin, 
respectively). Data suggest that rucaparib is a moderate inhibitor of CYP1A2, and a mild inhibitor of 
CYP2C9, CYP2C19, and CYP3A. Rucaparib also marginally inhibits P-gp in the gut. 
 
CYP1A2 substrates 
Rucaparib showed no effect on Cmax of caffeine while moderately increasing AUCinf of caffeine by 
2.55 fold (90% CI: 2.12, 3.08). When co-administering medicinal products metabolized by CYP1A2, 
particularly medicines which have a narrow therapeutic index (e.g., tizanidine, theophylline), dose 
adjustments may be considered based on appropriate clinical monitoring. 
 
CYP2C9 substrates 
Rucaparib increased S-warfarin Cmax by 1.05 fold (90% CI: 0.99 to 1.12) and AUC0-96h by 1.49 fold 
(90% CI: 1.40 to 1.58), respectively. When co-administering medicinal products that are CYP2C9 
substrates with a narrow therapeutic index (e.g., warfarin, phenytoin), dose adjustments may be 
considered, if clinically indicated. Caution should be exercised and additional International 
Normalised Ratio (INR) monitoring with co-administration of warfarin and therapeutic drug level 
monitoring of phenytoin should be considered, if used concomitantly with rucaparib. 
 
CYP2C19 substrates 
Rucaparib increased omeprazole Cmax by 1.09 fold (90% CI: 0.93 to 1.27) and AUCinf by 1.55 fold 
(90% CI: 1.32 to 1.83). The risk for a clinically relevant effect of concomitant administration of proton 
pump inhibitors (PPIs) is likely small (see section 5.2). No dose adjustment is considered necessary 
for co-administered medicinal products that are CYP2C19 substrates.  
 
CYP3A substrates 
Rucaparib increased midazolam Cmax by 1.13 fold (90% CI: 0.95 to 1.36) and AUCinf by 1.38 fold 
(90% CI: 1.13 to 1.69). Caution is advised when co-administering medicinal products that are CYP3A 
substrates with a narrow therapeutic index (e.g., alfentanil, astemizole, cisapride, cyclosporine, 
dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine). 
Dose adjustments may be considered, if clinically indicated based on observed adverse reactions. 
Interactions between rucaparib and oral contraceptives have not been studied. 
 
P-gp substrates 
Rucaparib showed no effect on Cmax of digoxin while marginally increasing AUC0-72h by 1.20 fold 
(90% CI: 1.12 to 1.29). No dose adjustment is recommended for co-administered medicinal products 
that are P-gp substrates. 
 
Interaction of rucaparib with other enzymes and transporter was evaluated in vitro. Rucaparib is a 



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weak inhibitor of CYP2C8, CYP2D6, and UGT1A1. Rucaparib down regulated CYP2B6 in human 
hepatocytes at clinically relevant exposures. Rucaparib is a potent inhibitor of MATE1 and 
MATE2-K, a moderate inhibitor of OCT1, and a weak inhibitor of OCT2. As inhibition of these 
transporters could increase metformin renal elimination and decrease liver uptake of metformin, 
caution is advised when metformin is co-administered with rucaparib. In addition, rucaparib is an 
inhibitor of the BCRP with IC50 value suggesting potential BCRP inhibition and increased exposures 
of medicinal products that are BCRP substrates (e.g., rosuvastatin). The clinical relevance of UGT1A1 
inhibition by rucaparib is not clear. Caution should be used when rucaparib is co-administered with 
UGT1A1 substrates (i.e. irinotecan) to patients with UGT1A1*28 (poor metabolizer) due to a possible 
increase in the exposure of SN-38 (the active metabolite of irinotecan) and associated toxicities.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception in females 
 
Women of childbearing potential should be advised to avoid becoming pregnant while receiving 
rucaparib. Patients should be advised to use effective contraception during treatment and for 6 months 
following the last dose of rucaparib. 
 
Pregnancy 
 
There are no or limited data from the use of rucaparib in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). Based on its mechanism of action and preclinical data, 
rucaparib may cause fetal harm when administered to a pregnant woman. Rubraca should not be used 
during pregnancy unless the clinical condition of the woman requires treatment with rucaparib. A 
pregnancy test before initiating treatment is recommended in women of reproductive potential.  
 
Breast-feeding 
 
There are no animal studies on the excretion of rucaparib in breast milk. It is unknown whether 
rucaparib/or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be 
excluded. Rubraca must not be used during breast-feeding. 
 
Because of the potential for serious adverse reactions in breast-fed infants from rucaparib, 
breast-feeding is contraindicated during treatment with Rubraca and for 2 weeks after the final dose 
(see section 4.3).  
 
Fertility 
 
There are no data on the effect of rucaparib on human fertility. Based on the animal studies, impact on 
fertility associated with the use of rucaparib cannot be ruled out (see section 5.3). Moreover, according 
to its mechanism of action, rucaparib may impact human fertility.  
 
4.7 Effects on ability to drive and use machines 
 
Rubraca has minor influence on the ability to drive and use machines. Caution when driving or using 
machines is advised for patients who report fatigue, nausea, or dizziness during treatment with 
Rubraca (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The overall safety profile of rucaparib is based on data from 937 patients in clinical trials in ovarian 
cancer treated with rucaparib monotherapy. 
 
Adverse reactions occurring in ≥ 20% of patients receiving rucaparib were nausea, fatigue/asthenia, 



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vomiting, anaemia, abdominal pain, dysgeusia, ALT elevations, AST elevations, decreased appetite, 
diarrhoea, thrombocytopenia and creatinine elevations. The majority of adverse reactions were mild to 
moderate (Grade 1 or 2).  
 
The ≥ Grade 3 adverse reactions occurring in > 5% of patients were anaemia (23%), ALT elevations 
(10%), fatigue/asthenia (10%), neutropenia (8%), thrombocytopenia (6%), and nausea (5%). The only 
serious adverse reaction occurring in > 2% of patients was anaemia (5%).  
 
Adverse reactions that most commonly led to dose reduction or interruption were anaemia (20%), 
fatigue/asthenia (18%), nausea (16%), thrombocytopenia (15%), and AST/ALT elevations (10%). 
Adverse reactions leading to permanent discontinuation occurred in 10% of patients, with 
thrombocytopenia, nausea, anaemia, and fatigue/asthenia being the most frequent adverse reactions 
leading to permanent discontinuation. 
 
Tabulated list of adverse reactions 
 
The adverse reaction frequency is listed by MedDRA System Organ Class (SOC) at the preferred term 
level. Frequencies of occurrence of adverse reactions are defined as: very common (≥ 1/10); common 
(≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare 
(< 1/10,000), not known (cannot be estimated from the available data). 
 
Table 3.  Tabulated list of adverse reactions by MedDRA system organ class 

 Adverse reactions 
MedDRA system organ 
class 

Frequency of all CTCAE grades Frequency of CTCAE grade 3 
and above 

Neoplasms benign, 
malignant and 
unspecified (including 
cysts and polyps) 

Common 
Myelodysplastic syndrome / 
Acute myeloid leukaemiaa  

Common 
Myelodysplastic syndrome / 
Acute myeloid leukaemia 

Blood and lymphatic 
system disorders 

Very common 
Anaemiab, Thrombocytopeniab, 
Neutropeniab 
Common 
Leukopeniab, Lymphopeniab, 
Febrile neutropenia 

Very common 
Anaemiab 
Common 
Thrombocytopeniab, 
Neutropeniab, Febrile 
neutropenia, Leukopeniab 
Uncommon 
Lymphopeniab 

Metabolism and nutrition 
disorders 

Very common 
Decreased appetite, Increased 
blood creatinineb 
Common 
Hypercholesterolaemiab, 
Dehydration 

Common 
Decreased appetite, Dehydration 
Uncommon 
Increased blood creatinine, 
Hypercholesterolaemiab 

Nervous system disorders Very common 
Dysgeusia, Dizziness 

Uncommon 
Dysgeusia, Dizziness,  

Respiratory, thoracic and 
mediastinal disorders 

Common 
Dyspnoea 

Uncommon 
Dyspnoea  

Gastrointestinal disorders Very common 
Nausea, Vomiting, Diarrhoea, 
Dyspepsia, Abdominal pain 

Common 
Nausea, Vomiting, Diarrhoea, 
Abdominal pain 
Uncommon 
Dyspepsia 

Hepatobiliary disorders 
 

Very common 
Increased alanine 
aminotransferase, Increased 
aspartate aminotransferase 
Common 

Common 
Increased alanine 
aminotransferase, Increased 
aspartate aminotransferase 
Uncommon 



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Increased transaminasesb Increased transaminases 
Skin and subcutaneous 
tissue disorders 

Very common 
Photosensitivity reaction, Rash 
Common 
Rash maculo-papular, Palmar-
plantar erythrodysaesthesia 
syndrome, Erythema 

Uncommon 
Photosensitivity reaction, Rash, 
Rash maculo-papular, Palmar-
plantar erythrodysaesthesia 
syndrome 

General disorders and 
administration site 
conditions 

Very common 
Fatiguec, Pyrexia 

Common 
Fatiguec 
Uncommon 
Pyrexia 

a  MDS/AML rate is based on overall total patient population of 1321 who have received one dose of oral 
rucaparib. 
b  Includes laboratory findings 
c  Includes fatigue, asthenia and lethargy 
 
Description of selected adverse reactions 
 
Haematological toxicity 
Haematological adverse reactions of all CTCAE Grades of anaemia, thrombocytopenia and 
neutropenia were reported in 42%, 26% and 16% of patients respectively. Thrombocytopenia and 
anaemia led to discontinuation in 1.8% and 2.1% of patients. Adverse reactions CTCAE Grade 3 or 
higher occurred in 23% (anaemia), 8% (neutropenia) and 6% (thrombocytopenia) of patients. The time 
of onset for adverse reactions of myelosuppression Grade 3 or higher was generally later in treatment 
(after 2 or more months). For risk mitigation and management, see section 4.4. 
 
Myelodysplastic syndrome/Acute myeloid leukaemia 
MDS/AML are serious adverse reactions that occur uncommonly (0.5%) in patients on treatment and 
during the 28 day safety follow up, and commonly (1.3%) for all patients including during the long 
term safety follow up (rate is calculated based on overall safety population of 1321 patients exposed to 
at least one dose of oral rucaparib in all clinical studies). In the pivotal Phase 3 study (ARIEL3), the 
incidence of MDS/AML during therapy in patients who received rucaparib was 0.8%. Although no 
cases were reported during therapy in patients who received placebo, one case has been reported in a 
placebo - treated patient during the long term safety follow up. All patients had potential contributing 
factors for the development of MDS/AML; in all cases, patients had received previous platinum-
containing chemotherapy regimens and/or other DNA damaging agents. For risk mitigation and 
management, see section 4.4. 
 
Gastrointestinal toxicities 
Vomiting and nausea were reported in 42% and 77% of patients, respectively and were generally low 
grade (CTCAE Grade 1 to 3). Abdominal pain (combined terms abdominal pain, abdominal pain 
lower, abdominal pain upper) was reported in 40.1% of rucaparib treated patients, but was also very 
common (33%) in placebo patients, most likely associated with underlying disease. For risk mitigation 
and management, see section 4.4. 
 
Photosensitivity 
Photosensitivity was reported in 13% of patients as low grade skin reactions (CTCAE Grade 1 or 2), 
and by 2 (0.2%) patients as ≥ CTCAE Grade 3 reaction. For risk mitigation and management, see 
section 4.4. 
 
Increases in serum aminotransferases (AST/ALT) 
Events related to increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
were observed in 38% (all grades) and 11% (≥ CTCAE Grade 3) of patients.  These events occurred 
within the first few weeks of treatment with rucaparib, were reversible, and were rarely associated 
with increases in bilirubin. Increased ALT was observed in 34.8% (all grades) and 9.9% (≥ CTCAE 
Grade 3) of patients, increased AST in 31.4% (all grades) and 2.8% (≥ CTCAE Grade 3) of patients 
and increased ALT and AST in 28.6% (all grades) and 2.1% (≥ CTCAE Grade 3) of patients. No 



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events met Hy’s Law criteria for drug-induced liver injury. AST/ALT elevations may need to be 
managed with treatment interruption and/or dose reduction as described in Table 2 (see section 4.2). 
Most patients could continue rucaparib with or without treatment modification without recurrence of 
Grade ≥ 3 LFT abnormalities.  
 
Elevations in serum creatinine 
Increases in serum creatinine, predominantly mild to moderate (CTCAE Grade 1 or 2), were observed 
in 20% of patients within the first few weeks of treatment with rucaparib. Four (0.4%) patients 
reported a CTCAE Grade 3 reaction. Elevations in creatinine with rucaparib treatment may be due to 
inhibition of the renal transporters MATE1 and MATE2-K (see section 4.5). These increases in serum 
creatinine were clinically asymptomatic. 
 
Elderly 
In patients ≥ 75 years old, frequencies of some adverse reactions increased: increased blood creatinine 
(32%), dizziness (20%), pruritus (15%), and memory impairment (4%) were higher than in patients 
< 75 years old (18%, 15%, 9% and 1% respectively). 
 
Patients with Renal Impairment 
In patients with moderate renal impairment (CLcr of 30-59 mL/min), frequencies of some adverse 
reactions increased: Grade 3 or 4 anaemia (31%), Grade 3 or 4 thrombocytopenia (12%), and Grade 3 
fatigue/asthenia (15%) were higher than in patients with mild renal impairment (CLcr 
> 59-80 mL/min) or normal renal function (CLcr > 80 mL/min) (21%, 5%, and 8%). 
 
Paediatric population 
 
No studies have been conducted to investigate the pharmacokinetics of rucaparib in paediatric patients. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other antineoplastic agents, ATC code: L01XX55 
 
Mechanism of action and pharmacodynamics effects 
 
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 involves inhibition of PARP enzymatic activity and the trapping of PARP-DNA 
complexes resulting in increased DNA damage, apoptosis, and cell death. 
 
Rucaparib has been shown to have in vitro and in vivo anti-tumour activity in BRCA mutant cell lines 
through a mechanism known as synthetic lethality, whereby the loss of two DNA repair pathways is 
required for cell death. Increased rucaparib-induced cytotoxicity and anti-tumour activity was 



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observed in tumour cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib 
has been shown to decrease tumour growth in mouse xenograft models of human cancer with or 
without deficiencies in BRCA. 
 
Clinical efficacy  
 
Maintenance treatment of recurrent ovarian cancer 
The efficacy of rucaparib was investigated in ARIEL3, a double-blind, multicentre clinical trial in 
which 564 patients with recurrent EOC, FTC or PPC who were in response to platinum-based 
chemotherapy were randomized (2:1) to receive Rubraca tablets 600 mg orally twice daily (n=375) or 
placebo (n=189). Treatment was continued until disease progression or unacceptable toxicity. All 
patients had achieved a response (complete or partial) to their most recent platinum-based 
chemotherapy and their cancer antigen 125 (CA-125) was below the upper limit of normal (ULN). 
Patients were randomised within 8 weeks of completion of platinum chemotherapy and no intervening 
maintenance treatment was permitted. Patients could not have received prior rucaparib or other PARP 
inhibitor therapy. Randomisation was stratified by best response to last platinum therapy (complete or 
partial), time to progression following the penultimate platinum therapy (6 to ≤ 12 months and > 12 
months), and tumour biomarker status (tBRCA, non-BRCA homologous recombination deficiency 
[nbHRD] and biomarker negative). 
 
The primary efficacy outcome was investigator-assessed progression-free survival (invPFS) evaluated 
according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1). PFS 
assessed by blinded independent radiology review (BIR) was a key secondary efficacy outcome.  
 
The mean age was 61 years (range: 36 to 85); most of the patients were white (80%); and all had an 
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The primary tumour in 
most patients was ovarian (84%); most patients (95%) had serous histology and 4% of patients 
reported endometrioid histology. All patients had received at least two prior platinum-based 
chemotherapies (range: 2 to 6) and 28% of patients had received at least three prior platinum-based 
chemotherapies. A total of 32% of patients were in complete response (CR) to their most recent 
therapy. The progression-free interval to penultimate platinum therapy was 6-12 months in 39% of 
patients and > 12 months in 61%. Prior bevacizumab therapy was reported for 22% of patients who 
received rucaparib and 23% of patients who received placebo. Demographics, baseline disease 
characteristics, and prior treatment history were generally well balanced between the rucaparib and 
placebo arms. 
 
None of the patients had received prior treatment with a PARP inhibitor. As such, efficacy of Rubraca 
in patients who have received prior treatment with a PARP inhibitor in the maintenance setting, has 
not been investigated and cannot be extrapolated from the available data. 
 
Tumour tissue samples for all of the patients (N=564) were tested centrally to determine HRD positive 
status (as defined by the presence of a deleterious tumour BRCA [tBRCA] mutation or high genomic 
loss of heterozygosity). Blood samples for 94% (186/196) of the tBRCA patients were evaluated using 
a central blood germline BRCA (gBRCA) test. Based on these results, 70% (130/186) of the tBRCA 
patients had a gBRCA mutation and 30% (56/186) had a somatic BRCA mutation. 
 
ARIEL3 demonstrated a statistically significant improvement in PFS for patients randomised to 
rucaparib as compared with placebo in the ITT population and in the HRD and tBRCA subgroups. 
IRR- assessment for the ITT population supported the primary endpoint. At the time of the analysis of 
PFS, OS data were not mature (with 22% of events). Efficacy results are summarised in Table 4 and 
Figure 1. 
 



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Table 4.  ARIEL3 Efficacy Results 

Parameter 
Investigator Assessment  IRR 

Rucaparib Placebo  Rucaparib Placebo 

ITT populationa   
Patients, n 375 189  375 189 
PFS events, n (%) 234 (62%) 167 (88%)  165 (44%)  133 (70%) 
PFS, median in months 
(95% CI) 

10.8 (8.3, 11.4) 5.4 (5.3-5.5)  13.7 (11.0, 19.1) 5.4 (5.1, 5.5) 

HR (95% CI) 0.36 (0.30, 0.45)  0.35 (0.28, 0.45) 
p-valueb < 0.0001  < 0.0001 
HRD Groupc    
Patients, n 236 118  236 118 
PFS events, n (%) 134 (57%) 101 (86%)  90 (38%) 74 (63%) 
PFS, median in months 
(95% CI) 

13.6 (10.9, 16.2) 5.4 (5.1, 5.6)  22.9 (16.2, NA) 5.5 (5.1, 7.4) 

HR (95% CI) 0.32 (0.24, 0.42)  0.34 (0.24, 0.47) 
p-valueb < 0.0001  < 0.0001 
tBRCA Groupd   
Patients, n 130 66  130 66 
PFS events, n (%) 67 (52%) 56 (85%)  42 (32%) 42 (64%) 
PFS, median in months 
(95% CI) 

16.6 (13.4, 22.9) 5.4 (3.4, 6.7)  26.8 (19.2, NA) 5.4 (4.9, 8.1) 

HR (95% CI) 0.23 (0.16, 0.34)  0.20 (0.13, 0.32) 
p-valueb < 0.0001  < 0.0001 
nonBRCA LOH+ Group    
Patients, n 106 52  106 52 
PFS events, n (%) 67 (63%) 45 (87%)  48 (45%) 32 (62%) 
PFS, median in months 
(95% CI) 

9.7 (7.9, 13.1) 5.4 (4.1, 5.7)  11.1 (8.2, NA) 5.6 (2.9, 2.8) 

HR (95% CI) 0.44 (0.29, 0.66)  0.554 (0.35, 0.89) 
p-valueb < 0.0001  0.0135 
nonBRCA LOH- Group    
Patients, n 107 54  107 54 
PFS events, n (%) 81 (73%) 50 (93%)  63 (59%) 46 (85%) 
PFS, median in months 
(95% CI) 

6.7 (5.4, 9.1) 5.4 (5.3, 7.4)  8.2 (5.6, 10.1) 5.3 (2.8, 5.5) 

HR (95% CI) 0.58 (0.40, 0.85)  0.47 (0.31, 0.71) 
p-valueb 0.0049  0.0003 

a. All randomised patients. 
b. Two-sided p-value 
c. HRD includes all patients with a deleterious germline or somatic BRCA mutation or non-tBRCA with 

high genomic loss of heterozygosity, as determined by the clinical trial assay (CTA). 
d. tBRCA includes all patients with a deleterious germline or somatic BRCA mutation, as determined by 

the CTA. 
 



13 

Figure 1. Kaplan-Meier Curves of Progression-Free Survival in ARIEL3 as Assessed by 
Investigator: ITT population  

 
 
In the ITT population, 38% of patients (141/375) in the rucaparib group and 35% of patients (66/189) 
in the placebo group had measurable disease at baseline. In an exploratory analysis in this subgroup, a 
response was noted in 18% (95% CI 12% – 26%) of patients (n=26) on rucaparib compared to 8% 
(95% CI 3% – 17%) of patients (n=5) on placebo (2-sided p-value = 0.0069), including 10 patients 
(7%) in the rucaparib group who achieved a complete remission. 
 
In the tBRCA population, 31% of patients (40/130) in the rucaparib group and 35% of patients (23/66) 
in the placebo group had measurable disease at baseline. In an exploratory analysis, a response was 
noted in 38% (95% CI 23% – 54%) of patients (n=15) on rucaparib compared to 9% (95% CI 1% – 
28%) of patients (n=2) on placebo (2-sided p-value = 0.0055), including 7 (18%) patients in the 
rucaparib group who achieved a complete remission. 
 
Treatment of BRCA-mutated ovarian cancer after 2 or more chemotherapies 
The efficacy of rucaparib was investigated in 106 patients in 2 multicentre, single-arm, open-label 
clinical studies, Study 10 and ARIEL2, in patients with advanced BRCA-mutant epithelial ovarian, 
fallopian tube or primary peritoneal cancer who had progressed after 2 or more prior chemotherapies 
(the primary efficacy population). The tumour histology was high grade serous in 91.5% of patients, 
endometrioid in 2.8% and mixed histology in 4.7%. None of the patients had received prior treatment 
with a PARP inhibitor. BRCA status based on a local test was known for some patients at the time of 
enrollment. Central BRCA testing was performed retrospectively after patients were enrolled. All 106 
patients received rucaparib 600 mg twice daily. Patients who had been hospitalised for bowel 
obstruction in the last 3 months were excluded. 
 
The primary efficacy outcome measure of both studies was objective response rate (ORR) as assessed 
by the investigator according to RECIST version 1.1. An analysis of progression-free survival (PFS) 
was also performed. 
 
Study 10 population characteristics in 42 patients were: median age 57 years (range 42 to 84), white 
(83%), ECOG performance status 0 (62%) or 1 (38%), high grade ovarian cancer (100%), 3 or more 
prior lines of chemotherapy (36%), median time since ovarian cancer diagnosis 43 months [range: 6 - 
178], median progression-free interval from the last platinum treatment 8.0 months [range: 6.0 - 
116.4]. 



14 

 
ARIEL2 population characteristics in 64 patients were: median age 60 years (range 33 to 80), white 
(75%), ECOG performance status 0 (61%) or 1 (39%), high grade ovarian cancer (100%), 3 or more 
prior lines of chemotherapy (78%), median time since ovarian cancer diagnosis 53 months [range: 
22-197], median progression-free interval from the last platinum treatment 7.6 months [range: 
0.7-26.5]. 
 
Most of the primary efficacy population were platinum-sensitive (n=79, 74.5%); the remaining 
patients were platinum-resistant (n=20, 18.9%) or platinum-refractory (n=7, 6.6%). Patients with 
germline (g)BRCA (n=88, 83.0%) or somatic (s)BRCA (n=18, 17.0%) mutations were included. 
 
In the subset of 79 platinum-sensitive patients, progression free interval after last platinum dose was 
≥ 6 – 12 months for 55 (69.6%) patients and > 12 months for 24 (30.4%) patients. Platinum-sensitive 
patients had received 2 (n=47, 59.5%), 3 (n=28, 35.4%), or > 3 (n=4, 5.1%) prior lines of platinum-
based chemotherapy. The proportion of platinum-sensitive patients with gBRCA and sBRCA 
mutations was comparable to the primary efficacy population at n=66 (83.5%) and n=13 (16.5%) 
respectively. 
 
Efficacy results from all patients treated are summarized in Table 5. 
 
Table 5.  Summary of primary efficacy findings for patients with BRCA-mutant ovarian cancer 
who received rucaparib 600 mg twice daily and two or more prior chemotherapy regimens 
based on investigator assessment of response 

 Primary Efficacy 
N=106 

Platinum Sensitive 
N=79 

 
Objective response rate  (ORR) N 
% 
(95% CI) 

 
58 

54.7  
(44.8, 64.4) 

 
51 

64.6 
(53.0, 75.0) 

Complete response % 8.5 10.1 
Partial response % 46.2 54.4 
Median duration of responsea - days 
(95% CI) 

288  
(202-392) 

294 
(224-393) 

Median progression-free survival - days 
(95% CI)  
Censoring N (%) 

289 
(226-337) 
23 (21.7) 

332 
(255-391) 
19 (24.1) 

Median overall survival - months (95% 
CI) 
Censoring N (%) 

NA (21.7-NA) 

82 (77.4) 

NA (NA-NA) 

68 (86.1) 
a The median duration of response is determined from the patients who had an objective tumour 
response according to RECIST guidelines, following treatment with rucaparib. 
NA: Not Achieved 
CI: Confidence interval 

 
Four (5.1%) of 79 platinum sensitive patients overall had progressive disease as best response. ORR 
was similar for patients with germline BRCA-mutant ovarian cancer or somatic BRCA-mutant ovarian 
cancer and for patients with a BRCA1 gene mutation or BRCA2 gene mutation. 
 
The ORR, by independent radiology review for the platinum-sensitive population, was 42/79, 53.2% 
(95% CI [41.6-64.5]).  
 
For the platinum-resistant population (N=20), ORR by investigator review was 35.0% (95% CI [15.4, 
59.2], with a complete response rate of 5.0%, and a partial response rate of 30.0%. The median 
duration of response was 196 days (95% CI [113 – NA]). The median progression-free survival was 



15 

282 days (95% CI [218-335]), and the median overall survival was 18.8 months (95% CI [12.9-NA]).  
 
For the platinum-refractory population (N=7), there were no responders. The median progression-free 
survival was 162 days (95% CI [51-223]). Median overall survival was not achieved in this 
population. 
 
Cardiac electrophysiology 
 
Concentration-QTcF prolongation analysis was conducted using data from 54 patients with a solid 
tumour administered continuous rucaparib at doses ranging from 40 mg once daily to 840 mg twice 
daily (1.4 times the approved recommended dose). At the predicted median steady-state Cmax 
following 600 mg rucaparib twice daily, the projected QTcF increase from baseline was 11.5 msec 
(90% CI: 8.77 to 14.2 msec). Thus, the risk for clinically significant QTcF increase from baseline (i.e. 
> 20 msec) is low. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Rubraca in all subsets of the paediatric population in ovarian cancer (see section 4.2 for information 
on paediatric use). 
 
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This 
means that further evidence on this medicinal product is awaited. The European Medicines Agency 
will review new information on this medicinal product at least every year and this SmPC will be 
updated as necessary. 
 
5.2 Pharmacokinetic properties 
 
Plasma exposures of rucaparib, as measured by Cmax and AUC, were approximately dose proportional 
at evaluated doses (40 to 500 mg daily, 240 to 840 mg twice a day). Steady state was achieved after 
1 week of dosing. Following repeated twice daily dosing, the accumulation based on AUC ranged 
from 3.5 to 6.2 fold. 
 
Absorption 
 
In patients with cancer following rucaparib 600 mg taken twice daily, the mean steady-state Cmax was 
1940 ng/mL and AUC0-12h was 16900 h⋅ng/mL with Tmax of 1.9 hours. The mean absolute oral 
bioavailability following a single oral dose of 12 to 120 mg rucaparib was 36%. The absolute oral 
bioavailability at 600 mg has not been determined. In patients with cancer following a high-fat meal, 
the Cmax increased by 20%, the AUC0-24h increased by 38%, and the Tmax was delayed by 2.5 hours, as 
compared with dosing under fasted conditions. The food effect on PK was not considered clinically 
significant. Rubraca can be administered with or without food. 
 
Distribution 
 
The in vitro protein binding of rucaparib is 70.2% in human plasma at therapeutic concentration 
levels. Rucaparib preferentially distributed to red blood cells with a blood-to-plasma concentration 
ratio of 1.83. In patients with cancer, rucaparib had a steady-state volume of distribution of 113 L to 
262 L following a single intravenous dose of 12 mg to 40 mg rucaparib. 
 
Biotransformation 
 
In vitro, rucaparib is metabolised primarily by CYP2D6, and to a lesser extent by CYP1A2, and 
CYP3A4. In a population PK analysis, no clinically relevant PK differences were observed among 
patients with different CYP2D6 phenotypes (including poor metabolizers, n=9; intermediate 
metabolizers, n=71; normal metabolizers, n=76; and ultra-rapid metabolizers, n=4) or patients with 
different CYP1A2 phenotypes (including normal metabolizers, n=28; hyperinducers, n=136). The 



16 

results should be interpreted with caution due to the limited representation of some subgroup 
phenotypes. 
 
Following administration of a single oral dose of [14C]-rucaparib to patients with solid tumours, 
unchanged rucaparib accounted for 64.0% of the radioactivity in plasma. Oxidation, N-demethylation, 
N-methylation, glucuronidation, and N-formylation were the major metabolic pathways for rucaparib. 
The most abundant metabolite was M324, an oxidative deamination product of rucaparib, accounting 
for 18.6% of the radioactivity in plasma. In vitro, M324 was at least 30 fold less potent than rucaparib 
against PARP-1, PARP-2, and PARP-3. Other minor metabolites accounted for 13.8% of the 
radioactivity in plasma. Rucaparib accounted for 44.9% and 94.9% of radioactivity in urine and 
faeces, respectively; while M324 accounted for 50.0% and 5.1% of radioactivity in urine and faeces, 
respectively. 
 
Elimination 
 
The clearance ranged from 13.9 to 18.4 L/hour, following a single intravenous dose of rucaparib 
12 mg to 40 mg. Following administration of a single oral dose of [14C]-rucaparib 600 mg to patients, 
the overall mean recovery of radioactivity was 89.3%, with a mean recovery of 71.9% in faeces and 
17.4% in urine by 288 hours post dose. Ninety percent of the observed faecal recovery was achieved 
within 168 hours postdose. The mean half-life (t1/2) of rucaparib was 25.9 hours. 
 
Medicinal product interactions 
 
In vitro, rucaparib was shown to be a substrate of P-gp and BCRP, but not a substrate of renal uptake 
transporters OAT1, OAT3, and OCT2, or hepatic transporters OAPT1B1 and OATP1B3. Effect of P-
gp and BCRP inhibitors on rucaparib PK cannot be ruled out. 
 
In vitro, rucaparib reversibly inhibited CYP1A2, CYP2C19, CYP2C9, and CYP3A, and to a lesser 
extent CYP2C8, CYP2D6, and UGT1A1. Rucaparib induced CYP1A2, and down regulated CYP2B6 
and CYP3A4 in human hepatocytes at clinically relevant exposures. 
  
In vitro, rucaparib is a potent inhibitor of MATE1 and MATE2-K, a moderate inhibitor of OCT1, and 
a weak inhibitor of OCT2. At clinical exposures, rucaparib did not inhibit bile salt export pump 
(BSEP), OATP1B1, OATP1B3, OAT1 and OAT3. Inhibition of MRP4 by rucaparib cannot be fully 
ruled out at clinical exposures. No interaction with MRP2 or MRP3 was observed in vitro at the 
clinical exposure of rucaparib, however, mild bi-phasic activation and inhibition of MRP2 and 
concentration dependent inhibition of MRP3 were observed at concentrations higher than the observed 
plasma Cmax of rucaparib. The clinical relevance MRP2 and MRP3 interaction in the gut is not known. 
In vitro, rucaparib is an inhibitor of the BCRP and P-gp efflux transporters. Potential in vivo BCRP 
inhibition cannot be excluded. No significant P-gp inhibition was observed in vivo (section 4.5). 
 
Population PK analysis suggested that concomitant use of PPIs is unlikely to have clinically 
meaningful impact on rucaparib PK. A firm conclusion cannot be made regarding the effect of 
co-administration of rucaparib and PPIs because dose level and time of administration have not been 
documented in detail for the PPIs. 
 
Pharmacokinetics in specific populations 
 
Age, race, and body weight 
Based on population PK analysis, no clinically significant relationships were identified between 
predicted steady-state exposure and patient’s age, race, and body weight. Patients included in the 
population PK study were aged 21 to 86 years (58% < 65 years, 31% 65-74 years, and 11% > 75 
years), 82% were Caucasian, and had body weights between 41 and 171 kg (73% had body weight 
> 60 kg). 
 
Hepatic impairment 
No formal studies of rucaparib in patients with hepatic impairment have been conducted. A population 



17 

PK analysis was performed to evaluate the effect of hepatic impairment on the clearance of rucaparib 
in patients receiving rucaparib 600 mg twice daily. No clinically important differences were observed 
between 34 patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN or total 
bilirubin > 1.0 to 1.5 times ULN and any AST) and 337 patients with normal hepatic function. Limited 
data are available for patients with moderate or severe hepatic impairment (see section 4.2). 
 
Renal impairment 
No formal studies of rucaparib in patients with renal impairment have been conducted. A population 
PK analysis was performed to evaluate the effect of renal impairment on the clearance of rucaparib in 
patients receiving rucaparib 600 mg twice daily. Patients with mild renal impairment (N=149; CLcr 
between 60 and 89 mL/min, as estimated by the Cockcroft-Gault method) and those with moderate 
renal impairment (N=76; CLcr between 30 and 59 mL/min) showed approximately 15% and 33% 
higher steady-state AUC, respectively, compared to patients with normal renal function (N=147; CLcr 
greater than or equal to 90 mL/min). The pharmacokinetic characteristics of rucaparib in patients with 
CLcr less than 30 mL/min or patients on dialysis are unknown (see section 4.2).  
 
5.3 Preclinical safety data 
 
General toxicology 
 
The findings in non-clinical toxicology studies performed with oral rucaparib were generally 
consistent with the adverse events observed in clinical studies. In repeat-dose toxicity studies of up to 
3 months duration in rats and dogs, the target organs were the gastrointestinal, haematopoietic, and 
lymphopoietic systems. These findings occurred at exposures below those observed in patients treated 
at the recommended dose, and were largely reversible within 4 weeks of cessation of dosing. In vitro, 
the IC50 of rucaparib against the human ether-à-go-go related gene (hERG) was 22.6 µM, which is 
approximately 13-fold higher than the Cmax in patients at the recommended dose. 
 
Intravenous administration of rucaparib in the rat and dog induced cardiac effects at a high Cmax (5.4 to 
7.3-fold higher than patients), but not at a lower Cmax (1.3 to 3.8-fold higher than patients). No cardiac 
effects were observed with oral dosing of rucaparib in repeat-dose toxicology studies at a rucaparib 
Cmax comparable to that observed in patients. Although no cardiac effects were observed following 
oral dosing, based on the findings in the intravenous studies and safety margins, cardiac effects in 
patients cannot be excluded when rucaparib is given orally. 
 
Carcinogenicity 
 
Carcinogenicity studies have not been performed with rucaparib.  
 
Genotoxicity 
 
Rucaparib was not mutagenic in a bacterial reverse mutation (Ames) assay. Rucaparib induced 
structural chromosomal aberrations in the in vitro human lymphocyte chromosomal aberration assay.  
 
Reproductive toxicology 
 
In an embryo-foetal development study in rats, rucaparib was associated with post-implantation loss at 
exposures of approximately 0.04 times the human AUC at the recommended dose. 
 
Fertility studies have not been conducted with rucaparib. No effects on male and female fertility were 
observed in 3-month general toxicology studies in rats and dogs at exposures of 0.09 to 0.3 times the 
human AUC at the recommended dose. A potential risk cannot be ruled out based on the safety margin 
observed. In addition, according to its mechanism of action rucaparib may have the potential to impair 
fertility in humans. 
 
 
6. PHARMACEUTICAL PARTICULARS 



18 

 
6.1 List of excipients 
 
Tablet core 
 
Microcrystalline cellulose 
Sodium starch glycolate (Type A) 
Colloidal anhydrous silica 
Magnesium stearate  
 
Rubraca 200 mg film-coated tablets 
 
Tablet coating 
Polyvinyl alcohol (E1203) 
Titanium dioxide (E171) 
Macrogol 4000 (E1521) 
Talc (E553b) 
Brilliant blue FCF aluminium lake (E133) 
Indigo carmine aluminium lake (E132) 
 
Rubraca 250 mg film-coated tablets 
 
Tablet coating 
Polyvinyl alcohol (E1203) 
Titanium dioxide (E171) 
Macrogol 4000 (E1521) 
Talc (E553b) 
 
Rubraca 300 mg film-coated tablets 
 
Tablet coating 
Polyvinyl alcohol (E1203) 
Titanium dioxide (E171) 
Macrogol 4000 (E1521) 
Talc (E553b) 
Iron oxide yellow (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
HDPE bottle, with a polypropylene (PP) induction seal closure, containing 60 tablets. Each carton 
contains one bottle. 
 
6.6 Special precautions for disposal 
 



19 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  

 
EU/1/17/1250/001 
EU/1/17/1250/002 

 EU/1/17/1250/003 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 24 May 2018 
Date of latest renewal: 13 March 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING  

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
 EFFECTIVE USE OF THE MEDICINAL PRODUCT  
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION  
 



21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
Almac Pharma Services Ltd 
Seagoe Industrial Estate 
Craigavon  
County Armagh 
BT63 5UA 
United Kingdom 
 
Almac Pharma Services (Ireland) Ltd 
Finnabair Industrial Estate 
Dundalk 
County Louth 
A91 P9KD 
Ireland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed  subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached.  
 
 
• Obligation to conduct post-authorisation measures 



22 

 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 
PAES: In order to further investigate the efficacy of rucaparib maintenance 
treatment in patients with relapsed high-grade epithelial ovarian, fallopian tube, 
or primary peritoneal cancer who are in response (complete or partial) to 
platinum-based chemotherapy, the MAH should submit the final analysis of OS 
and updated analyses of PFS2, chemotherapy-free interval and time to start of 
subsequent anti-cancer treatment of the phase 3, randomised, double-blind study 
CO-338-014 

31 December 
2022 

 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE CONDITIONAL MARKETING AUTHORISATION  
 
This being a conditional marketing authorisation and pursuant to Article 14(7) of Regulation (EC) No 
726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 

Description Due date 
In order to further confirm the safety and efficacy of rucaparib in the treatment of 
platinum sensitive, relapsed or progressive, BRCA mutated (germline and/ or 
somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal 
cancer, the MAH should submit the results of study CO-338-043 (ARIEL4), a 
phase 3, multicentre, open-label, randomised study evaluating the efficacy and 
safety of rucaparib versus chemotherapy for treatment of relapsed ovarian cancer.  

Due date: Q2 
2023 

 

  



23 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 200 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 200 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



26 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/001 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 200 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN: 
NN:  
  



27 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 200 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 200 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



28 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/001 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 250 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 250 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



30 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/002 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 250 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN: 
NN:  
  



31 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 250 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 250 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



32 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/002 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 250 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 300 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 300 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



34 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/003  
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 300 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN: 
NN:  
  



35 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rubraca 300 mg film-coated tablets 
rucaparib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains rucaparib camsylate corresponding to 300 mg rucaparib. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



36 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1250/003  
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rubraca 300 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



38 

Package leaflet: Information for the patient 
 

Rubraca 200 mg film-coated tablets 
Rubraca 250 mg film-coated tablets 
Rubraca 300 mg film-coated tablets 

rucaparib  
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again.  
• If you have any further questions, ask your doctor, pharmacist or nurse. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Rubraca is and what it is used for  
2. What you need to know before you take Rubraca  
3. How to take Rubraca 
4. Possible side effects  
5. How to store Rubraca  
6. Contents of the pack and other information 
 
 
1. What Rubraca is and what it is used for 
 
What Rubraca is and how it works 
Rubraca contains the active substance rucaparib. Rubraca is an anti-cancer medicine, also known as a 
‘PARP (poly adenosine diphosphate-ribose polymerase) inhibitor’. 
 
Patients with changes (mutations) in genes called BRCA are at risk of developing a number of types of 
cancer. Rubraca blocks an enzyme that repairs damaged DNA in the cancer cells, resulting in their 
death.  
 
What Rubraca is used for 
Rubraca is used to treat a type of cancer of the ovary. It is used after the cancer has responded to 
previous chemotherapy treatments. 
 
Rubraca can be used as maintenance therapy immediately after a course of chemotherapy that has 
caused the tumour to shrink. 
 
Rubraca can also be used if your cancer has progressed after chemotherapy has been used and you 
have an abnormality of the BRCA gene. 
 
If you take Rubraca because your cancer has progressed you will need to have a clinical test to identify 
an abnormality in the BRCA gene. 
 
 



39 

2. What you need to know before you take Rubraca 
 
Do not take Rubraca: 
• if you are allergic to rucaparib or any of the other ingredients of this medicine (listed in 

section 6). 
• if you are breast-feeding 

 
If you are not sure, talk to your doctor, pharmacist or nurse before taking Rubraca. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before or during taking Rubraca. 
 
Blood tests 
Your doctor or nurse will perform blood tests to check your blood cell-counts: 

• before treatment with Rubraca 
• every month during treatment with Rubraca 

 
This is because Rubraca can cause low blood counts of: 
• red blood-cells, white blood-cells, or platelets. See section 4 for more information. The signs 

and symptoms of low blood cell counts include fever, infection, bruising or bleeding.  
• a low blood-cell count may be a sign of a serious bone marrow problem - such as 

‘myelodysplastic syndrome’ (MDS) or ‘acute myeloid leukaemia’ (AML). Your doctor may test 
your bone marrow to check for any problems.  
 

Your doctor may also do weekly tests, if you have low blood cell counts for a long time. They may 
stop treatment with Rubraca until your blood cell counts improve. 

 
Take care in direct sunlight 
You may get sunburn more easily during treatment with Rubraca. This means you should: 
• keep out of direct sunlight and not use sunbeds while you are taking Rubraca 
• wear clothing that covers your head, arms and legs 
• use a sunscreen and lip balm with a sun protection factor (SPF) of 50 or higher. 

 
Symptoms you should be aware of 
Talk to your doctor if you feel sick (nauseous), have been sick (vomiting) or you have had diarrhoea. 
These may be signs and symptoms that Rubraca is affecting your stomach. 
 
Children and adolescents 
Children unde 18 years of age should not be given Rubraca, This medicine has not beem studied in 
this age group. 
 
Other medicines and Rubraca 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken, or might take any other 
medicines. This is because Rubraca can affect the way some other medicines work. Also some other 
medicines can affect the way Rubraca works. 
 
Tell your doctor, pharmacist or nurse if you are taking any of the following medicines: 
• anticoagulant medicines which helps the blood flow freely, such as warfarin 
• anticonvulsant medicines used to treat fits (seizures) and epilepsy - such as phenytoin 
• medicines to lower blood cholesterol levels- such as rosuvastatin 
• medicines to treat stomach problems - such as cisapride, omeprazole 
• medicines which suppress the immune system - such as ciclosporin, sirolimus or tacrolimus  
• medicines to treat migraines and headaches - such as dihydroergotamine or ergotamine 
• medicines to treat severe pain - such as alfentanil or fentanyl 
• medicines used to treat uncontrolled movement or mental disorders - such as pimozide 
• medicines to lower blood sugar levels and treat diabetes - such as metformin 



40 

• medicines to treat irregular heartbeats - such as digoxin or quinidine 
• medicines to treat allergic reactions - such as astemizole or terfenadine 
• medicines used to cause sleepiness or drowsiness - such as midazolam 
• medicines used to relax muscles – such as tizanidine 
• medicines used to treat asthma – such as theophylline  
 
Pregnancy, breast-feeding and contraception 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor, nurse or pharmacist for advice before taking this medicine. 
 
Pregnancy 
• Rubraca is not recommended during pregnancy. This is because it may harm your unborn baby. 
• For women who are able to become pregnant, a pregnancy test is recommended before starting 

treatment with Rubraca  
 

Breast-feeding 
• Do not breast-feed during treatment with Rubraca, and for two weeks after taking the last dose. 

This is because it is not known if rucaparib passes into breast milk. 
 

Contraception 
• Women who are able to become pregnant must use effective birth control (contraception): 

- during treatment with Rubraca and 
- for 6 months after taking the last dose of Rubraca. 

This is because rucaparib may affect the unborn baby. 
 
• Talk to your doctor or pharmacist about the most effective methods of contraception. 
 
Driving and using machines 
Rubraca may affect your ability to drive or use tools or machines. Take care if you feel tired or feel 
sick (nauseous).  
 
 
3. How to take Rubraca 
 
Always take this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your 
doctor, pharmacist, or nurse if you are not sure. 
 
How much to take 
• The usual recommended dose is 600 mg twice a day. This means you take a total of 1,200 mg 

each day. If you have certain side effects your doctor may recommend a lower dose, or 
temporarily stop your treatment. 

• Rubraca is available as either 200 mg, 250 mg or 300 mg tablets. 
 
Taking this medicine 
• Take the tablets once in the morning and once in the evening, approximately 12 hours apart. 
• You can take the tablets with or without food. 
• If you are sick (vomit) after taking Rubraca, do not take an extra dose. Take your next dose at 

your regular time. 
 
If you take more Rubraca than you should 
If you take more tablets than you should, tell your doctor, pharmacist or nurse straight away. You may 
need medical help. 
 
If you forget to take Rubraca 
• If you forget to take a dose, skip the missed dose. Then take your next dose at the usual time. 



41 

• Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Rubraca 
• It is important to keep taking Rubraca every day – as long as your doctor prescribes it for you. 
• Do not stop taking this medicine without talking to your doctor first. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor straight away if you notice any of the following side effects – you may need 
urgent medical treatment: 
 
Very common (may affect more than 1 in 10 people): 
• being short of breath, feeling tired, having pale skin, or fast heart beat - these may be signs of a 

low red blood cell count (anaemia) 
• bleeding or bruising for longer than usual if you hurt yourself - these may be signs of a low 

blood platelet count (thrombocytopenia) 
• fever or infection – these may be signs of a low white blood cell count (neutropenia) 
 
Other side effects include:  
 
Very common (may affect more than 1 in 10 people): 
• feeling sick (nausea) 
• feeling tired 
• being sick (vomiting) 
• pain in the stomach 
• changes in the way food tastes 
• abnormal blood tests - increase in levels of liver enzymes  
• loss of appetite 
• diarrhoea 
• abnormal blood tests - increase in blood creatinine levels  
• difficulty breathing 
• feeling dizzy 
• sunburn 
• heartburn  
• rash 

 
Common (may affect up to 1 in 10 people): 
• high cholesterol levels 
• indigestion  
• dehydration 
• itching 
 
Uncommon (may affect up to 1 in 100 people): 
• redness, swelling, and pain on the palms of the hands and, or the soles of the feet 
• red patches on the skin 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 



42 

system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Rubraca 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the bottle and the carton after EXP. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Rubraca contains  

 
• The active substance is rucaparib. 
 

Rubraca 200 mg film-coated tablets: Each film-coated tablet contains rucaparib camsylate 
corresponding to 200 mg of rucaparib. 
 
Rubraca 250 mg film-coated tablets: Each film-coated tablet contains rucaparib camsylate 
corresponding to 250 mg of rucaparib. 
 
Rubraca 300 mg film-coated tablets: Each film-coated tablet contains rucaparib camsylate 
corresponding to 300 mg of rucaparib. 
 

• The other ingredients are: 
• Tablet content: Microcrystalline cellulose, sodium starch glycolate (Type A), colloidal 

anhydrous silica and magnesium stearate. 
• Tablet coating:  

- Rubraca 200 mg film-coated tablets  
Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 4000 (E1521), talc 
(E553b), brilliant blue FCF aluminium lake (E133) and indigo carmine aluminium 
lake (E132). 

- Rubraca 250 mg film-coated tablets 
Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 4000 (E1521), and 
talc (E553b) 
 

- Rubraca 300 mg film-coated tablets  
Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 4000 (E1521), talc 
(E553b), and iron oxide yellow (E172). 

 
 
What Rubraca looks like and contents of the pack 
• Rubraca 200 mg film-coated tablets are blue, round, film-coated tablets with “C2” marked on 

one side. 
• Rubraca 250 mg film-coated tablets are white, diamond-shaped, film-coated tablets with “C25” 

marked on one side. 
• Rubraca 300 mg film-coated tablets are yellow, oval, film-coated tablets with “C3” marked on 

one side. 
 



43 

Rubraca is supplied in plastic bottles. Each bottle contains 60 film-coated tablets. 
 
Marketing Authorisation Holder  
Clovis Oncology Ireland Ltd. 
Regus Dublin Airport 
Skybridge House - Dublin Airport 
Swords 
County Dublin 
K67 P6K2, Ireland 
 
Manufacturer  
Almac Pharma Services Limited 
Seagoe Industrial Estate,  
Portadown, 
Craigavon, 
BT63 5UA 
United Kingdom 
 
or 
 
Almac Pharma Services (Ireland) Ltd 
Finnabair Industrial Estate 
Dundalk 
County Louth 
A91 P9KD 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

Deutschland 
Clovis Oncology Germany GmbH 
Tel: +49 (0)8005892665 
 
España 
Clovis Oncology Spain, S.L. 
Tel: +34 800099526 
 
France 
Clovis Oncology France SAS 
Tél: +33 (0)805631633 
 
Ireland 
Clovis Oncology Ireland Limited 
Tel: +353 16950030 
 

Italia 
Clovis Oncology Italy IT S.r.l. 
Tel: +39 800194716 
 
Nederland  
Clovis Oncology France SAS 
Tel: +31 (0)8000227859 
 
Österreich 
Clovis Oncology Germany GmbH 
Tel: +43 (0)800005924  
 
United Kingdom 
Clovis Oncology UK Limited  
Tel: +44 (0)800 0093361 
 

België/Belgique/Belgien, България, Česká republika, Danmark, Eesti, Ελλάδα, Hrvatska, 
Ísland, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, Malta, 
Norge, Polska, Portugal, România, Slovenija, Slovenská republika,  
Suomi/Finland, Sverige:  
 
Clovis Oncology Ireland Limited  
Tel: +353 16950030 
 
This leaflet was last revised in  
 



44 

This medicine has been given ‘conditional approval’. This means that there is more evidence to come 
about this medicine. The European Medicines Agency will review new information on this medicine at 
least every year and this leaflet will be updated as necessary. 
 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURESFOR THE CONDITIONAL MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET