Polivy

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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 
 
Polivy 30 mg powder for concentrate for solution for infusion. 
Polivy 140 mg powder for concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Polivy 30 mg powder for concentrate for solution for infusion 
 
Each vial of powder for concentrate for solution for infusion contains 30 mg of polatuzumab vedotin. 
After reconstitution, each mL contains 20 mg of polatuzumab vedotin. 
 
Polivy 140 mg powder for concentrate for solution for infusion 
 
Each vial of powder for concentrate for solution for infusion contains 140 mg of polatuzumab vedotin. 
After reconstitution, each mL contains 20 mg of polatuzumab vedotin. 
 
Polatuzumab vedotin is an antibody-drug conjugate composed of the anti-mitotic agent monomethyl 
auristatin E (MMAE) covalently conjugated to a CD79b-directed monoclonal antibody (recombinant 
humanized immunoglobulin G1 [IgG1], produced in Chinese Hamster Ovary cells by recombinant 
DNA technology). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion (powder for concentrate). 
 
White to greyish-white lyophilized cake. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Polivy in combination with bendamustine and rituximab is indicated for the treatment of adult patients 
with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for 
haematopoietic stem cell transplant. 
 
4.2 Posology and method of administration 
 
Polivy must only be administered under the supervision of a healthcare professional experienced in the 
diagnosis and treatment of cancer patients. 
 
Posology 
 
The recommended dose of Polivy is 1.8 mg/kg, given as an intravenous infusion every 21 days in 
combination with bendamustine and rituximab for 6 cycles. Polivy, bendamustine and rituximab can 
be administered in any order on Day 1 of each cycle. When administered with Polivy, the 
recommended dose of bendamustine is 90 mg/m2/day on Day 1 and Day 2 of each cycle and the 



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recommended dose of rituximab is 375 mg/m2 on Day 1 of each cycle. Due to limited clinical 
experience in patients treated with 1.8 mg/kg Polivy at a total dose >240 mg, it is recommended not to 
exceed the dose 240 mg/cycle. 
 
If not already premedicated, premedication with an antihistamine and anti-pyretic should be 
administered to patients prior to Polivy.  
 
Delayed or missed doses 
 
If a planned dose of Polivy is missed, it should be administered as soon as possible and the schedule of 
administration should be adjusted to maintain a 21-day interval between doses.  
 
Dose modifications 
 
The infusion rate of Polivy should be slowed or interrupted if the patient develops an infusion-related 
reaction. Polivy should be discontinued immediately and permanently if the patient experiences a 
life-threatening reaction. 
 
For dose modifications for peripheral neuropathy (section 4.4) see Table 1 below. 
 
Table 1 Polivy dose modifications for peripheral neuropathy (PN) 
 
Severity of PN on 
Day 1 of any cycle 

Dose modification 

Grade 2-3  Withhold Polivy dosing until improvement to ≤ Grade 1.  
If recovered to Grade ≤ 1 on or before Day 14, restart Polivy at a permanently 
reduced dose of 1.4 mg/kg.  
If a prior dose reduction to 1.4 mg/kg has occurred, discontinue Polivy. 
If not recovered to Grade ≤ 1 on or before Day 14, discontinue Polivy. 

Grade 4 Discontinue Polivy. 
 
For dose modifications for myelosuppression see Table 2.  
 
Table 2 Polivy, bendamustine and rituximab dose modifications for myelosuppression   
 
Severity of 
myelosuppression on 
Day 1 of any cycle 

Dose modification1 

Grade 3-4 
Neutropenia  
 
 
 
 
 
 
 
 

Withhold all treatment until ANC recovers to > 1000/µL.  
If ANC recovers to > 1000/µL on or before Day 7, resume all treatment 
without any additional dose reductions.  
If ANC recovers to > 1000/µL after Day 7: 

• restart all treatment with a dose reduction of bendamustine from 
90 mg/m2 to 70 mg/m2 or 70 mg/m2 to 50 mg/m2. 

• if a bendamustine dose reduction to 50 mg/m2 has already 
occurred, discontinue all treatment. 

Grade 3-4 
Thrombocytopenia 

Withhold all treatment until platelets recover to >75,000/µL.  
If platelets recover to > 75,000/µL on or before Day 7, resume all 
treatment without any dose reductions.  
If platelets recover to > 75,000/µL after Day 7: 

• restart all treatment with a dose reduction of bendamustine from 
90 mg/m2 to 70 mg/m2 or 70 mg/m2 to 50 mg/m2. 

• if a bendamustine dose reduction to 50 mg/m2 has already 
occurred, discontinue all treatment. 

1If primary cause is due to lymphoma, the dose of bendamustine may not need to be reduced. 



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For dose modifications for Infusion-related reactions see Table 3. 
 
Table 3: Polivy dose modifications for Infusion-related reactions (IRRs) 
 
Severity of IRR on Day 1 
of any cycle 

Dose modification 

Grade 1–3 
IRR 

Interrupt Polivy infusion and give supportive treatment. 

For the first instance of Grade 3 wheezing, bronchospasm, or 
generalized urticaria, permanently discontinue Polivy. 

For recurrent Grade 2 wheezing or urticaria, or for recurrence of any 
Grade 3 symptoms, permanently discontinue Polivy. 

Otherwise, upon complete resolution of symptoms, infusion may be 
resumed at 50% of the rate achieved prior to interruption. In the 
absence of infusion-related symptoms, the rate of infusion may be 
escalated in increments of 50 mg/hour every 30 minutes. 

For the next cycle, infuse Polivy over 90 minutes. If no infusion-
related reaction occurs, subsequent infusions may be administered 
over 30 minutes. Administer premedication for all cycles. 

Grade 4 
IRR 

Stop Polivy infusion immediately. 
Give supportive treatment. 
Permanently discontinue Polivy. 

 
Special populations 
 
Elderly  
No dose adjustment of Polivy is required in patients ≥ 65 years of age (see section 5.2). 
 
Renal impairment  
No dose adjustment of Polivy is required in patients with creatinine clearance (CrCL) ≥ 30 mL/min. A 
recommended dose has not been determined for patients with CrCL < 30mL/min due to limited data. 
 
Hepatic impairment  
The administration of Polivy in patients with moderate or severe hepatic impairment (bilirubin greater 
than 1.5 × upper limit of normal [ULN]) should be avoided.  
 
No adjustment in the starting dose is required when administering Polivy to patients with mild hepatic 
impairment (bilirubin greater than ULN to less than or equal to 1.5 × ULN or aspartate transaminase 
[AST] greater than ULN). 
 
Per studied population in mild hepatic impairment (defined as AST or ALT >1.0 to 2.5 × ULN or total 
bilirubin >1.0 to 1.5 × ULN), there was a 40% increase in unconjugated MMAE exposure, which was 
not deemed clinically significant. 
 
Paediatric population 
The safety and efficacy in children and adolescents less than 18 years have not been established. No 
data are available.  
 
Method of administration  
 
Polivy is for intravenous use. 
 
The initial dose of Polivy should be administered as a 90-minute intravenous infusion. Patients should 
be monitored for IRRs/hypersensitivity reactions during the infusion and for at least 90 minutes 
following completion of the initial dose.  



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If the prior infusion was well tolerated, the subsequent dose of Polivy may be administered as a 
30-minute infusion and patients should be monitored during the infusion and for at least 30 minutes 
after completion of the infusion. 
 
Polivy must be reconstituted and diluted using aseptic technique under the supervision of a healthcare 
professional. It should be administered as an intravenous infusion through a dedicated infusion line 
equipped with a sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2 or 
0.22 micrometer pore size) and catheter. Polivy must not be administered as intravenous push or bolus. 
 
For instructions on reconstitution and dilution of the medicinal product before administration, see 
section 6.6. 
 
Precaution to be taken before manipulating or administering the product 
 
Polivy contains a cytotoxic component which is covalently attached to the monoclonal antibody. 
Follow applicable proper handling and disposal procedure (see section 6.6). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Active severe infections (see section 4.4). 
 
4.4 Special warnings and precautions for use  
 
Traceability 
 
In order to improve traceability of biological medicinal products, the trade name and the batch number 
of the administered product should be clearly recorded. 
 
Myelosuppression 
 
Serious and severe neutropenia and febrile neutropenia have been reported in patients treated with 
Polivy as early as the first cycle of treatment. Prophylactic granulocyte colony stimulating factor 
(G-CSF) administration was required in the clinical development and should be considered. Grade 3 or 
4 thrombocytopenia or anaemia can also occur with Polivy. Complete blood counts should be 
monitored prior to each dose of Polivy. More frequent lab monitoring and/or Polivy delays or 
discontinuation should be considered for patients with Grade 3 or Grade 4 neutropenia and/or 
thrombocytopenia (see section 4.2). 
 
Peripheral neuropathy (PN) 
 
PN has been reported in patients treated with Polivy as early as the first cycle of treatment, and the risk 
increases with sequential doses. Patients with pre-existing PN may experience worsening of this 
condition. PN reported with treatment with Polivy is predominantly sensory PN. However, motor and 
sensorimotor PN have also been reported. Patients should be monitored for symptoms of PN such as 
hypoesthesia, hyperesthesia, paraesthesia, dysesthesia, neuropathic pain, burning sensation, muscle 
weakness, or gait disturbance. Patients experiencing new or worsening PN may require a delay, dose 
reduction, or discontinuation of Polivy (see section 4.2). 
 
Infections 
 
Serious, life threatening or fatal infections, including opportunistic infections, such as pneumonia 
(including pneumocystis jirovecii and other fungal pneumonia), bacteraemia, sepsis, herpes infection, 
and cytomegalovirus infection have been reported in patients treated with Polivy (see section 4.8). 
Reactivation of latent infections has been reported. Patients should be closely monitored during 
treatment for signs of bacterial, fungal, or viral infections and seek medical advice if signs and 



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symptoms appear. Anti-infective prophylaxis should be considered throughout treatment with Polivy. 
Polivy should not be administered in the presence of an active severe infection. Polivy and any 
concomitant chemotherapy should be discontinued in patients who develop serious infections.  
 
Human Immunodeficiency Virus (HIV) 
 
Polivy has not been evaluated in patients with HIV. With regard to co-administration of 
CYP3A-inhibitors see section 4.5. 
 
Immunization 
 
Live or live-attenuated vaccines should not be given concurrently with the treatment. Studies have not 
been conducted in patients who recently received live vaccines. 
 
Progressive multifocal leukoencephalopathy (PML) 
 
PML has been reported with Polivy treatment (see section 4.8). Patients should be monitored closely 
for new or worsening neurological, cognitive, or behavioural changes suggestive of PML. Polivy and 
any concomitant chemotherapy should be withheld if PML is suspected and permanently discontinued 
if the diagnosis is confirmed. 
 
Tumour lysis syndrome (TLS) 
 
Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of TLS. 
Appropriate measures/prophylaxis in accordance with local guidelines should be taken prior to 
treatment with Polivy. Patients should be monitored closely for TLS during treatment with Polivy. 
 
Infusion-related reactions 
 
Polivy can cause IRRs, including severe cases. Delayed IRRs as late as 24 hours after receiving Polivy 
have occurred. An antihistamine and antipyretic should be administered prior to the administration of 
Polivy, and patients should be monitored closely throughout the infusion. If an IRR occurs, the 
infusion should be interrupted and appropriate medical management should be instituted (see section 
4.2). 
 
Embryo-foetal toxicity 
 
Based on the mechanism of action and nonclinical studies, Polivy can be harmful to the foetus when 
administered to a pregnant woman (see section 5.3). Pregnant women should be advised regarding risk 
to the foetus.  
 
Women of childbearing potential should be advised to use effective contraception during treatment 
with Polivy and for at least 9 months after the last dose (see section 4.6). Male patients with female 
partners of childbearing potential should be advised to use effective contraception during treatment 
with Polivy and for at least 6 months after the last dose (see section 4.6). 
 
Fertility 
 
In non-clinical studies, polatuzumab vedotin has resulted in testicular toxicity, and may impair male 
reproductive function and fertility (see section 5.3). Therefore, men being treated with Polivy are 
advised to have sperm samples preserved and stored before treatment (see section 4.6). 
 
Elderly 
 
Among 151 previously treated DLBCL patients treated with Polivy  in combination with 
bendamustine and rituximab (BR) in Study GO29365, 103 (68%) were ≥65 years of age. Patients aged 
≥65 had a similar incidence of serious adverse reactions (55%) to patients aged <65 (56%). Clinical 



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studies of Polivy did not include sufficient numbers of patients aged ≥65 to determine whether they 
respond differently from younger patients. 
 
Hepatic toxicity 
 
Serious cases of hepatic toxicity that were consistent with hepatocellular injury, including elevations 
of transaminases and/or bilirubin, have occurred in patients treated with Polivy (see section 4.8). 
Pre-existing liver disease, elevated baseline liver enzymes, and concomitant medicinal products may 
increase the risk. Liver enzymes and bilirubin level should be monitored (see section 4.2). 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
No dedicated clinical drug-drug interaction studies with polatuzumab vedotin in humans have been 
conducted. 
 
Drug interactions with concomitant medicines that are CYP3A4 inhibitors, substrates or inducers and 
co-medications that are P-gp inhibitors 
 
Based on physiological-based pharmacokinetic (PBPK) model simulations of MMAE released from 
polatuzumab vedotin, strong CYP3A4 and P-gp inhibitors (e.g., ketoconazole) may increase the area 
under the concentration-time curve (AUC) of unconjugated MMAE by 48%. Caution is advised in 
case of concomitant treatment with CYP3A4 inhibitor. Patients receiving concomitant strong CYP3A4 
inhibitors (e.g., boceprevir, clarithromycin, cobicistat, indinavir, itraconazole, nefazodone, nelfinavir, 
posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) should be monitored more 
closely for signs of toxicities. 
 
Unconjugated MMAE is not predicted to alter the AUC of concomitant medicines that are CYP3A4 
substrates (e.g., midazolam). 
 
Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin, St John’s wort 
[Hypericum perforatum]) may decrease the exposure of unconjugated MMAE. 
 
Drug interactions of rituximab and bendamustine in combination with polatuzumab vedotin 
 
The pharmacokinetics (PK) of rituximab and bendamustine are not affected by co-administration with 
polatuzumab vedotin. Concomitant rituximab is associated with increased antibody conjugated 
MMAE (acMMAE) plasma AUC by 24% and decreased unconjugated MMAE plasma AUC by 37%, 
based on population PK analysis. No dose adjustment is required.  
Bendamustine does not affect acMMAE and unconjugated MMAE plasma AUC. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/Contraception in males and females 
 
Women 
Women of childbearing potential should be advised to use effective contraception during treatment 
with polatuzumab vedotin and for at least 9 months after the last dose. 
 
Men 
Male patients with female partners of childbearing potential should be advised to use effective 
contraception during treatment with polatuzumab vedotin and for at least 6 months after the last dose. 
 



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Pregnancy  
 
There are no data in pregnant women using Polivy. Studies in animals have shown reproductive 
toxicity (see section 5.3). Based on the mechanism of action and nonclinical studies, polatuzumab 
vedotin can be harmful to the foetus when administered to a pregnant woman. In women of 
childbearing potential, the pregnancy status shall be checked prior to treatment. Polivy is not 
recommended during pregnancy and in women of childbearing potential not using contraception 
unless the potential benefit for the mother outweighs the potential risk to the foetus. 
 
Breast-feeding  
 
It is not known whether polatuzumab vedotin or its metabolites are excreted in human breast milk. A 
risk for breast-feeding children cannot be excluded. Women should discontinue breast-feeding during 
treatment with Polivy and for at least 3 months after the last dose. 
 
Fertility 
 
In nonclinical studies, polatuzumab vedotin has resulted in testicular toxicity, and may impair male 
reproductive function and fertility (see section 5.3).  
Therefore, men being treated with this medicine are advised to have sperm samples preserved and 
stored before treatment. Men being treated with Polivy are advised not to father a child during 
treatment and for up to 6 months following the last dose. 
 
4.7 Effects on ability to drive and use machines 
 
Polivy has minor influence on the ability to drive and use machines. IRRs, PN, fatigue, and dizziness 
may occur during treatment with Polivy (see sections 4.4 and 4.8). 
 
4.8 Undesirable effects  
 
Summary of the safety profile 
 
For the clinical development program of Polivy as a whole, an estimated total of 1429 patients have 
received Polivy. The adverse drug reactions (ADRs) described in this section were identified during 
treatment and follow-up of previously treated DLBCL patients (n=151) from the pivotal clinical trial 
GO29365. This includes run-in phase patients (n=6), randomized patients (n=39), and extension 
cohort patients (n=106) who received Polivy plus BR compared to randomized patients (n=39) who 
received BR alone. Patients in the treatment arms received a median of 5 cycles of treatment while 
randomized patients in the comparator arm received a median of 3 cycles of treatment. 
 
The most frequently-reported (≥ 30%) ADRs in patients treated with Polivy in combination with BR 
were anaemia (31.8%), thrombocytopenia (32.5%), neutropenia (45.7%), diarrhoea (35.8%), nausea 
(33.1%), and peripheral neuropathy (30.5%). Serious adverse reactions were reported in 42.4% of 
Polivy plus BR treated patients. The most common serious adverse reactions were reported in > 5% of 
patients were febrile neutropenia (10.6%), sepsis (9.9%), IRRs (11.3%), pneumonia (8.6%), and 
pyrexia (7.9%). 
 
The ADR leading to treatment regimen discontinuation in >5% of patients was thrombocytopenia 
(6.0%). 
 
Tabulated list of ADRs from clinical trials 
 
The ADRs are listed below by MedDRA system organ class (SOC) and categories of frequency. The 
corresponding frequency category for each adverse drug reaction is based on the following 
convention: 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). Within each frequency grouping, adverse 
reactions are presented in the order of decreasing seriousness. 



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Table 4 Summary of ADRs occurring in relapsed or refractory DLBCL patients treated with 
Polivy in combination with BR 
 
Infections and infestations 

Very common sepsis, pneumoniaa, upper respiratory tract infection 

Common herpes virus infectiona, cytomegalovirus infection 

Blood and lymphatic system disorders 

Very common  febrile neutropenia, neutropenia, thrombocytopenia, anaemia, leukopenia, 
lymphopenia 

Common pancytopenia 

Metabolism and nutrition disorders 

Very common hypokalaemia, decreased appetite 

Common hypocalcaemia, hypoalbuminemia 

Nervous system disorders 

Very common neuropathy peripheral, dizziness 

Common gait disturbance, paraesthesia, hypoaesthesia 

Eye disorders 

Common vision blurred 

Respiratory, thoracic and mediastinal disorders 

Very common Cough 

Common Pneumonitis 

Gastrointestinal disorders 

Very common diarrhoea, nausea, constipation, vomiting, abdominal pain 

Common upper abdominal pain 

Skin and subcutaneous tissue disorders 

Common Pruritus 

Musculoskeletal disorders 

Common Arthralgia 

General disorders and administration site conditions 

Very common fatigue, pyrexia, asthenia 

Common Chills 

Investigations 

Very common weight decreased 

Common transaminase elevation, lipase increase, hypophosphataemia 

Injury, poisoning and procedural complications 

Very Common infusion-related reactions 
a ADR associated with fatal outcome 
Uncommon, rare and very rare ADRs: none  
 



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Description of selected adverse drug reactions  
 
In the Polivy plus BR arms, Grade 3 or higher neutropenia, thrombocytopenia, and anaemia were 
reported in 40.4%, 25.8%, and 12.6% of patients, respectively. 
 
Myelosuppression 
4% of patients in the Polivy plus BR arms discontinued Polivy due to neutropenia compared to 2.6% 
of patients in the BR arm who discontinued treatment due to neutropenia. Thrombocytopenia events 
led to discontinuation of treatment in 7.9% of patients in the Polivy plus BR arms and 5.1% of patients 
in the BR arm. No patients discontinued treatment due to anaemia in either the Polivy plus BR arms or 
BR arm. 
 
Peripheral neuropathy (PN) 
In the Polivy plus BR arms, Grade 1 PN and Grade 2 PN were reported in 15.9% and 12.6% of 
patients, respectively. In the BR arm, Grade 1 and 2 PN events were reported in 2.6% and 5.1% of 
patients, respectively. One Grade 3 PN event was reported in the Polivy plus BR arms and no patients 
reported PN events in the BR arm. No Grade 4-5 PN events were reported in either the Polivy plus BR 
arms or BR arm. 2.6% of patients discontinued Polivy treatment due to PN and 2.0% of patients had 
Polivy dose reduction due to PN. No patients in the BR arm discontinued treatment or had dose 
reductions due to PN. In the Polivy plus BR arms, the median onset to first event of PN was 1.6 
months, and 39.1% of patients with PN events reported event resolution. 
 
Infections 
Infections, including pneumonia and other types of infections, were reported in 48.3% of patients in 
the Polivy plus BR arms and 51.3% of patients in the BR arm. In the Polivy plus BR arms, serious 
infections were reported in 27.2% of patients and fatal infections were reported in 6.6% of patients. In 
the BR arm, serious infections were reported in 30.8% of patients and fatal infections were reported in 
10.3% of patients. Four patients (2.6%) in the Polivy plus BR arms discontinued treatment due to 
infection compared to 2 patients (5.1%) in the BR arm. 
 
Progressive multifocal leukoencephalopathy (PML) 
One case of PML, which was fatal, occurred in one patient treated with Polivy plus bendamustine and 
obinutuzumab. This patient had three prior lines of therapy that included anti-CD20 antibodies. 
 
Hepatic toxicity 
In another study, two cases of serious hepatic toxicity (hepatocellular injury and hepatic steatosis) 
were reported and were reversible.  
 
Gastrointestinal toxicity 
Gastrointestinal toxicity events were reported in 72.8% of patients in the Polivy plus BR arms 
compared to 66.7% of patients in the BR arm. Most events were Grade 1-2, and Grade 3-4 events were 
reported in 16.5% of patients in the Polivy plus BR arms compared to 12.9% of patients in the BR arm. 
The most common gastrointestinal toxicity events were diarrhoea and nausea.  
 
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 experience with overdose in human clinical trials. The highest dose tested to date is 
2.4 mg/kg administered as an intravenous infusion; it was associated with a higher frequency and 
severity of PN events. Patients who experience overdose should have immediate interruption of their 
infusion and be closely monitored.  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties  
 
Pharmacotherapeutic group: antineoplastic agents; other antineoplastic agents; monoclonal antibodies 
ATC code: L01XC37 
 
Mechanism of action 
 
Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent 
anti-mitotic agent (monomethyl auristatin E, or MMAE) to B-cells, which results in the killing of 
malignant B-cells. The polatuzumab vedotin molecule consists of MMAE covalently attached to a 
humanized immunoglobulin G1 monoclonal antibody via a cleavable linker. The monoclonal antibody 
binds with high affinity and selectivity to CD79b, a cell surface component of the B-cell receptor. 
CD79b expression is restricted to normal cells within the B-cell lineage (with the exception of plasma 
cells) and malignant B-cells; it is expressed in > 95% of diffuse large B-cell lymphoma. Upon binding 
CD79b, polatuzumab vedotin is rapidly internalized and the linker is cleaved by lysosomal proteases 
to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by 
inhibiting cell division and inducing apoptosis. 
 
Pharmacodynamic effects 
 
Cardiac electrophysiology  
 
Polatuzumab vedotin did not prolong the mean QTc interval to any clinically relevant extent based on 
ECG data from two open-label studies in patients with previously treated B-cell malignancies at the 
recommended dosage.  
 
Clinical efficacy and safety 
 
The efficacy of Polivy was evaluated in an international, multicentre, open-label study (GO29365) 
which included a randomized cohort of 80 patients with previously treated DLBCL. Patients were 
randomized 1:1 to receive Polivy plus BR or BR alone for six 21-day cycles. Patients were stratified 
by duration of response to last prior treatment of ≤ 12 months or > 12 months.  
 
Eligible patients were not candidates for autologous haematopoietic stem cell transplant (HSCT) and 
had relapsed or refractory disease after receiving at least one prior systemic chemotherapy regimen. 
The study excluded patients with prior allogeneic HSCT, central nervous system lymphoma, 
transformed indolent lymphoma, grade 3b FL, significant cardiovascular or pulmonary disease, active 
infections, AST or alanine transaminase (ALT) >2.5× ULN or total bilirubin ≥1.5 x ULN, creatinine 
>1.5 x ULN (or CrCl  <40 mL/min) unless due to underlying lymphoma. 
 
Polivy was given intravenously at 1.8 mg/kg administered on Day 2 of Cycle 1 and on Day 1 of 
Cycles 2-6. Bendamustine was administered at 90 mg/m2 intravenously daily on Days 2 and 3 of 
Cycle 1 and on Days 1 and 2 of Cycles 2-6. Rituximab was administered at 375 mg/m2 on Day 1 of 
Cycles 1-6. 
 
Among the 80 patients who were randomized to receive Polivy plus BR (n=40) or BR alone (n = 40) 
the majority were white (71%) and male (66%). The median age was 69 years (range: 30-86 years). 
Sixty-four out of 80 patients (80%) had ECOG performance score (PS) of 0-1 and 14 out of 80 
patients (18%) had ECOG PS of 2. The majority of patients (98%) had DLBCL not otherwise 
specified (NOS). Overall, 48% of patients had activated B-cell (ABC) DLBCL and 40% had germinal 
center B-cell like (GCB) DLBCL. Primary reasons patients were not candidates for HSCT included 
age (40%), insufficient response to salvage therapy (26%) and prior transplant failure (20%). The 
median number of prior therapies was 2 (range: 1-7), with 29% (n = 23) receiving one prior therapy, 



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25% (n = 20) receiving 2 prior therapies, and 46% (n = 37) receiving 3 or more prior therapies. All 
except one patient in the pola+BR arm of the randomized Phase II were naïve to bendamustine 
treatment. 80% of patients had refractory disease. For patients who received polatuzumab vedotin plus 
BR and had CD3+ lymphocyte count evaluated, the absolute CD3+ lymphocyte count was > 200 
cells/μL in 95%, 79% and 83% of patients analyzed at prior to therapy (n=134), end of treatment 
(n=72) and 6 months after end of treatment (n=18), respectively. 
 
The primary endpoint of the study was complete response (CR) rate at end of treatment (6-8 weeks 
after Day 1 of Cycle 6 or last study treatment) as assessed by PET-CT by an Independent Review 
Committee (IRC).  
 
Table 5  Summary of efficacy in patients with previously treated DLBCL from study GO29365 
 
 Polivy + bendamustine 

+ rituximab 
N = 40 

Bendamustine + 
rituximab 

N = 40 
 Median observation time 22 months 
Primary endpoint  
Complete Response Rate* (IRC-assessed) at End 
of treatment**  

  

Responders (%) 16 (40.0) 7 (17.5) 
Difference in response rate (%) [95% CI] 22.5 [2.6, 40.2] 
p-value (CMH chi-squared test***) 0.0261 

Key secondary and exploratory endpoints   
Duration of response (INV-assessed)   

Number of patients included in analysis 
Number (%) of patients with event  

28 
17 (60.7) 

13 
11 (84.6) 

Median DOR (95% CI), months 
HR [95% CI] 

10.3 (5.6, NE) 4.1 (2.6, 12.7) 
0.44 [0.20, 0.95] 

p-value (Log-Rank test, stratified***) 0.0321 
Overall Response Rate* (INV-assessed) at End of 
Treatment** 

 
 

Responders (%) (CR, PR) 19 (47.5) 7 (17.5) 
Difference in response rate (%) [95% CI] 30.0 [9.5, 47.4] 
p-value (CMH chi-squared test***) 0.0036 

Complete Response (%) (CR) 17 (42.5) 6 (15.0) 
Difference in response rate (%) [95% CI] 27.5 [7.7, 44.7] 
p-value (CMH chi-squared test***) 0.0061 

Partial Response (%) (PR) 
95% CI Clopper-Pearson 

2 (5.0) 
[0.6, 16.9] 

1 (2.5) 
[0.06, 13.2] 

Best Overall Response Rate* (INV-assessed)   
Responders (%) (CR, PR) 28 (70.0) 13 (32.5) 

Difference in response rate (%) [95% CI] 37.5 [15.6, 54.7] 
Complete Response (%) (CR) 23 (57.5) 8 (20.0) 

95% CI Clopper-Pearson [40.9, 73.0] [9.1, 35.7] 
Partial Response (%) (PR) 

95% CI Clopper-Pearson 
5 (12.5) 

[4.2, 26.8] 
5 (12.5) 

[4.2, 26.8] 
CI: Confidence Interval; CMH: Cochran-Mantel-Haenszel; CR: Complete Response; DOR: Duration of Response; HR: 
Hazard Ratio; INV: Investigator; IRC: Independent Review Committee; NE: Not evaluable; PR: Partial Response  
*Per modified Lugano 2014 criteria: Bone marrow confirmation of PET-CT CR required. PET-CT PR required meeting both 
PET-CT criteria and CT criteria. 
**6-8 weeks after Day 1 of Cycle 6 or last study treatment 
*** Stratification by duration of response to prior therapy (≤ 12 months vs > 12 months) 
 
Overall survival (OS) was an exploratory endpoint which was not type 1 error controlled. The median 
OS in the Polivy plus BR arm was 12.4 months (95% CI: 9.0, NE) vs 4.7 months (95% CI: 3.7, 8.3) in 
the control arm. The unadjusted estimate for OS HR was 0.42. When accounting for the influence of 



13 

baseline covariates the OS HR was adjusted to 0.59. Covariates included primary refractory status, 
number of prior lines of therapy, IPI, and prior stem cell transplant. 
 
Investigator-assessed progression free survival (PFS) was an exploratory endpoint which was not type 
1 error controlled. The median PFS in the Polivy plus BR arm was 7.6 months (95% CI: 6.0, 17.0) vs 
2.0 months (95% CI: 1.5, 3.7) in the control arm. The unadjusted estimate for PFS HR was 0.34. 
 
Immunogenicity  
 
As with all therapeutic proteins, there is the potential for an immune response in patients treated with 
polatuzumab vedotin. Across all arms of study GO29365, 8 out of 134 (6.0%) patients tested positive 
for anti-polatuzumab vedotin antibodies at one or more post-baseline time points. Across seven 
clinical studies, 14 out of 536 (2.6%) patients tested positive for anti-polatuzumab vedotin antibodies 
at one or more post-baseline time points. Due to the limited number of anti-polatuzumab vedotin 
antibody positive patients, no conclusions can be drawn concerning a potential effect of 
immunogenicity on efficacy or safety. 
 
Immunogenicity assay results are highly dependent on several factors including assay sensitivity and 
specificity, assay methodology, sample handling, timing of sample collection, concomitant 
medications and underlying disease. For these reasons, comparison of incidence of antibodies to 
polatuzumab vedotin with the incidence of antibodies to other products may be misleading. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit results of studies with Polivy in 
all subsets of the paediatric population for the treatment of mature B-cell neoplasms (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 
 
Antibody-conjugated MMAE (acMMAE) plasma exposure increased dose-proportionally over the 0.1 
to 2.4 mg/kg polatuzumab vedotin dose range. After the first 1.8 mg/kg polatuzumab vedotin dose, the 
acMMAE mean maximum concentration (Cmax) was 803 (± 233) ng/mL and the area under the 
concentration-time curve from time zero to infinity (AUCinf) was 1860 (±966) day•ng/mL. Based on 
the population PK analysis, Cycle 3 acMMAE AUC increased by approximately 30% over Cycle 1 
AUC, and achieved more than 90% of the Cycle 6 AUC. The terminal half-life at Cycle 6 was 
approximately 12 days (95% CI of 8.1-19.5 days) for acMMAE. Based on population PK analysis, the 
predicted acMMAE concentration at the end of cycle 6 is approximately 80% of the theoretical steady-
state value. Exposures of unconjugated MMAE, the cytotoxic component of polatuzumab vedotin, 
increased dose proportionally over the 0.1 to 2.4 mg/kg polatuzumab vedotin dose range. MMAE 
plasma concentrations followed formation rate limited kinetics. After the first 1.8 mg/kg polatuzumab 
vedotin dose, the Cmax was 6.82 (± 4.73) ng/mL, the time to maximum plasma concentration is 
approximately 2.5 days, and the terminal half-life is approximately 4 days. Plasma exposures of 
unconjugated MMAE are < 3% of acMMAE exposures. Based on the population PK analysis there is 
a decrease of plasma unconjugated MMAE exposure (AUC) after repeated every-three-week dosing.  
 
Based on population pharmacokinetics simulations, a sensitivity analysis predicted exposure to 
unconjugated MMAE for patients with bodyweight over 100 kg to be increased by 27%.  
 
Absorption  
 
Polivy is administered as an intravenous infusion. There have been no studies performed with other 
routes of administration. 
 



14 

Distribution 
 
The population estimate of central volume of distribution for acMMAE was 3.15 L, which 
approximated plasma volume. In vitro, MMAE is moderately bound (71%-77%) to human plasma 
proteins. MMAE does not significantly partition into human red blood cells in vitro; the blood to 
plasma ratio is 0.79 to 0.98. 
 
In vitro data indicate that MMAE is a P-gp substrate but does not inhibit P-gp at clinically relevant 
concentrations.  
 
Biotransformation 
 
Polatuzumab vedotin is expected to undergo catabolism in patients, resulting in the production of 
small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE related catabolites. The 
levels of MMAE metabolites have not been measured in human plasma. 
 
In vitro studies indicate that MMAE is a substrate for CYP3A4/5 but does not induce major CYP 
enzymes. MMAE is a weak time-dependent inhibitor of CYP3A4/5 but does not competitively inhibit 
CYP3A4/5 at clinically relevant concentrations.  
 
MMAE does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. 
 
Elimination 
 
Based on a population PK analysis, the conjugate (acMMAE) is primarily eliminated by non-specific 
linear clearance pathway with a value of 0.9 L/day. In vivo studies in rats dosed with polatuzumab 
vedotin (radiolabel on MMAE) demonstrate that the majority of radioactivity is excreted in faeces and 
the minority of radioactivity is excreted in urine. 
 
Paediatric population 
 
No studies have been conducted to investigate the pharmacokinetics of polatuzumab vedotin in the 
paediatric population (<18 years old). 
 
Elderly 
 
Age did not have an effect on the pharmacokinetics of acMMAE and unconjugated MMAE based on a 
population PK analysis with patients aged 20-89 years. No significant difference was observed in the 
pharmacokinetics of acMMAE and unconjugated MMAE among patients < 65 years of age (n = 187) 
and patients ≥ 65 years of age (n = 273).  
 
Renal impairment 
 
In patients with mild (CrCL 60-89 mL/min, n = 161) or moderate (CrCL 30- 59 mL/min, n = 109) 
renal impairment, acMMAE and unconjugated MMAE exposures are similar to patients with normal 
renal function (CrCL ≥ 90 mL/min, n = 185), based on a population PK analysis. There are insufficient 
data to assess the impact of severe renal impairment (CrCL 15-29 mL/min, n = 3) on PK. No data are 
available in patients with end-stage renal disease and/or who are on dialysis. 
 
Hepatic impairment 
 
In patients with mild hepatic impairment [AST or ALT >1.0 to 2.5 × ULN or total bilirubin >1.0 to 
1.5 × ULN], n = 54], acMMAE exposures are similar whereas unconjugated MMAE AUC are 40% 
higher compared to patients with normal hepatic function (n = 399), based on a population PK analysis. 
 



15 

There are insufficient data to assess the impact of moderate hepatic impairment (total 
bilirubin > 1.5-3×ULN, n = 2) on PK. No data are available in patients with severe hepatic impairment 
or liver transplantation. 
 
5.3 Preclinical safety data 
 
Systemic toxicity  
 
In both rats and cynomolgus monkeys, the predominant systemic toxicities associated with 
administration of MMAE and polatuzumab vedotin included reversible bone marrow toxicity and 
associated peripheral blood cell effects. 
 
Genotoxicity 
 
No dedicated mutagenicity studies have been performed with polatuzumab vedotin. MMAE was not 
mutagenic in the bacterial reverse mutation assay (Ames test) or the L5178Y mouse lymphoma 
forward mutation assay. 
 
MMAE was genotoxic in the rat bone marrow micronucleus study probably through an aneugenic 
mechanism. This mechanism is consistent with the pharmacological effect of MMAE as a microtubule 
disrupting agent. 
 
Carcinogenicity 
 
No dedicated carcinogenicity studies have been performed with polatuzumab vedotin and/or MMAE. 
 
Impairment of fertility 
 
No dedicated fertility studies in animals have been performed with polatuzumab vedotin. However, 
results of the 4-week rat toxicity study indicate the potential for polatuzumab vedotin to impair male 
reproductive function and fertility. Testicular seminiferous tubule degeneration did not reverse 
following a 6-week treatment-free period and correlated with decreased testes weight and gross 
findings at recovery necropsy of small and/or soft testes in males given ≥ 2 mg/kg. 
 
Reproductive toxicity 
 
No dedicated teratogenicity studies in animals have been performed with polatuzumab vedotin. 
However, treatment of pregnant rats with MMAE at 0.2 mg/kg caused embryolethality and foetal 
malformations (including protruding tongue, malrotated limbs, gastroschisis, and agnathia). Systemic 
exposure (AUC) in rats at a dose of 0.2 mg/kg MMAE is approximately 50% of the AUC in patients 
who received the recommended dose of 1.8 mg/kg Polivy every 21-days. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Succinic acid 
Sodium hydroxide (for pH-adjustment) 
Sucrose 
Polysorbate 20 (E 432) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed or diluted with other medicinal products except those 
mentioned in section 6.6. 
 



16 

6.3 Shelf life 
 
Unopened vial 
 
2 years  
 
Reconstituted solution  
 
From a microbiological point of view, the reconstituted solution should be used immediately. If not 
used immediately, in-use storage times and conditions prior to use are the responsibility of the user 
and would normally not be longer than 24 hours refrigerated (2 °C − 8 °C), unless reconstitution has 
taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of 
the reconstituted solution has been demonstrated for up to 72 hours refrigerated (2 °C − 8 °C) and up 
to 24 hours at room temperature (9 °C − 25 °C).  
 
Diluted solution  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours refrigerated (2 °C − 8 °C), unless dilution has 
taken place in controlled and validated aseptic conditions. Chemical and physical stability of the 
prepared solution for infusion has been demonstrated for the durations listed in Table 6. The diluted 
solution must be discarded if storage time exceeds the limits specified in Table 6.  
 
Table 6   Durations for which chemical and physical stability of the prepared solution for 
infusion have been demonstrated 
 

Diluent used to prepare solution 
for infusion 

Solution for infusion  
storage conditions1 

Sodium chloride 9 mg/mL (0.9%)  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 4 hours at room temperature (9 °C − 25 °C)  

Sodium chloride 4.5 mg/mL (0.45%)  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 8 hours at room temperature (9 °C − 25 °C) 

5% Glucose  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 8 hours at room temperature (9 °C − 25 °C) 

1 To ensure product stability, do not exceed specified storage durations. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C - 8 °C). 
 
Do not freeze. 
 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Polivy 30 mg powder for concentrate for solution for infusion: 
 
6 mL vial (colourless Type 1 glass) closed with a stopper (fluororesin laminate), with an aluminium 
seal with plastic flip-off cap containing 30 mg polatuzumab vedotin. Pack size of one vial.  



17 

 
Polivy 140 mg powder for concentrate for solution for infusion: 
 
20 mL vial (colourless Type 1 glass) closed with a stopper (fluororesin laminate), with an aluminium 
seal with plastic flip-off cap containing 140 mg polatuzumab vedotin. Pack size of one vial.  
 
6.6 Special precautions for disposal and other handling 
 
General precautions 
 
Polivy contains a cytotoxic component. To be administered under the supervision of a physician 
experienced in the use of cytotoxic agents. Procedures for proper handling and disposal of 
antineoplastic and cytotoxic medicines should be used. 
 
The reconstituted product contains no preservative and is intended for single-dose only. Proper aseptic 
technique throughout the handling of this medicinal product should be followed.  
 
Polivy must be reconstituted using sterile water for injection and diluted into an intravenous infusion 
bag containing sodium chloride 9 mg/mL (0.9%) solution for injection, or sodium chloride 4.5 mg/ml 
(0.45%) solution for injection, or 5% glucose prior to administration. 
 
The reconstituted solution and solution for infusion should not be frozen or exposed to direct sunlight.  
 
Instructions for reconstitution 
 
• Polivy 30 mg: Using a sterile syringe, slowly inject 1.8 mL of sterile water for injection into the 

30 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin. 
Direct the stream toward the wall of the vial and not directly on the lyophilized cake. 

• Polivy 140 mg: Using a sterile syringe, slowly inject 7.2 mL of sterile water for injection into 
the 140 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab 
vedotin. Direct the stream toward the wall of the vial and not directly on the lyophilized cake. 

• Swirl the vial gently until completely dissolved. Do not shake. 
• Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted 

solution should appear colourless to slightly brown, clear to slightly opalescent, and free of 
visible particulates. Do not use if the reconstituted solution is discoloured, is cloudy, or contains 
visible particulates. 

 
Instructions for dilution 
 
1. Polivy must be diluted to a final concentration of 0.72-2.7 mg/mL in an intravenous infusion 

bag, with a minimum volume of 50 mL, containing 9 mg/mL sodium chloride solution for 
injection, or 4.5 mg/mL sodium chloride solution for injection, or 5% glucose. 

2. Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose 
(see below): 

Total Polivy dose (mL) to be further diluted = Polivy dose (mg/kg) X patient’s weight (kg) Reconstituted vial concentration (20 mg/mL) 
3. Withdraw the required volume of reconstituted solution from the Polivy vial using a sterile 

syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial. 
4. Gently mix the intravenous bag by slowly inverting the bag. Do not shake. 
5. Inspect the intravenous bag for particulates and discard if present. 

 
Avoid transportation of the prepared solution for infusion as agitation stress can result in aggregation. 
If the prepared infusion will be transported, remove air from the infusion bag and limit transportation 
to 30 minutes room temperature (9°C − 25°C) or 24 hours refrigerated (2°C − 8°C). If air is removed, 
an infusion set with a vented spike is required to ensure accurate dosing during the infusion. The total 
storage plus transportation times of the diluted product should not exceed the storage duration 
specified in Table 6 (see section 6.3). 



18 

 
Polivy must be administered using a dedicated infusion line equipped with sterile, non-pyrogenic, 
low-protein binding in-line or add-on filter (0.2 or 0.22 micrometer pore size) and catheter.  
 
Polivy is compatible with intravenous infusion bags with product contacting materials of polyvinyl 
chloride (PVC) or polyolefins such as polyethylene (PE) and polypropylene. In addition, no 
incompatibilities have been observed with infusion sets or infusion aids with product contacting 
materials of PVC, PE, polyurethane, polybutadiene, acrylonitrile butadiene styrene, polycarbonate, 
polyetherurethane, fluorinated ethylene propylene, or polytetrafluorethylene and with filter 
membranes composed of polyether sulfone or polysulfone. 
 
Disposal  
 
Polivy is for single-use only. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1388/001 
EU/1/19/1388/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 16 January 2020 
 
 
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. 
 
  

http://www.ema.europa.eu/


19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND 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  

 
 
 
 
 
 
 
 
 
 

 
 
 



20 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Lonza Ltd.  
Lonzastrasse  
CH-3930 Visp  
Switzerland 
 
Name and address of the manufacturer responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
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 (PSURs) 
 
The requirements for submission of PSURs 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 (MAH) shall submit the first PSUR 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 marketing authorisation holder (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. 

 
 



21 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE CONDITIONAL MARKETING AUTHORISATION 

 
This being a conditional marketing authorisation and pursuant to Article 14-a(4) of Regulation (EC) 
No 726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 
Description Due date 
In order to provide further evidence of efficacy and safety of polatuzumab vedotin 
in DLBCL, the MAH will provide Study GO39942, a randomized, double-blind, 
placebo controlled trial that evaluates polatuzumab vedotin in combination with 
R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) versus R-CHOP 
in patients with previously untreated diffuse large B-cell lymphoma. 

Q4 2021 

 
  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Polivy 140 mg powder for concentrate for solution for infusion  
polatuzumab vedotin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 140 mg of polatuzumab vedotin. 
After reconstitution each mL contains 20 mg of polatuzumab vedotin. 
 
 
3. LIST OF EXCIPIENTS 
 
succinic acid, sodium hydroxide, sucrose, polysorbate 20. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use after reconstitution and dilution 
Read the package leaflet before 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 
 
Cytotoxic 
Do not shake 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



25 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Keep the vial in the outer carton in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1388/001  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Polivy 140 mg powder for concentrate  
polatuzumab vedotin 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
IV after reconstitution and dilution 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
140 mg 
 
 
6. OTHER 
 
Cytotoxic 
  



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Polivy 30 mg powder for concentrate for solution for infusion  
polatuzumab vedotin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 30 mg of polatuzumab vedotin. 
After reconstitution each mL contains 20 mg of polatuzumab vedotin. 
 
 
3. LIST OF EXCIPIENTS 
 
succinic acid, sodium hydroxide, sucrose, polysorbate 20. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use after reconstitution and dilution 
Read the package leaflet before 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 
 
Cytotoxic 
Do not shake 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



28 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Keep the vial in the outer carton in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1388/002  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



29 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Polivy 30 mg powder for concentrate  
polatuzumab vedotin 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
IV after reconstitution and dilution 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 mg 
 
 
6. OTHER 
 
Cytotoxic 
  



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



31 

Package leaflet: Information for the patient 
 

Polivy 30 mg powder for concentrate for solution for infusion 
Polivy 140 mg powder for concentrate for solution for infusion 

polatuzumab vedotin 
 

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 are given 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 or nurse. 
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1.  What Polivy is and what it is used for  
2.  What you need to know before you are given Polivy 
3.  How Polivy is given  
4.  Possible side effects  
5.  How to store Polivy  
6.  Contents of the pack and other information 
 
 
1. What Polivy is and what it is used for 
 
What Polivy is 
 
Polivy is a cancer medicine that contains the active substance polatuzumab vedotin. 
 
What Polivy is used for 
 
Polivy is given to treat “diffuse large B-cell lymphoma” that has come back or has not got better with 
at least one previous therapy and when you cannot receive a stem cell transplant.  
 
Diffuse large B-cell lymphoma is a cancer that develops from B lymphocytes also called B-cells. 
These are a type of blood cells.  
 
How Polivy works 
 
The active substance in Polivy is made up of a monoclonal antibody linked to MMAE, a substance 
that can kill cancer cells. The monoclonal antibody part of the medicine attaches to a target on B cells. 
Once attached to B cells, the medicine releases MMAE into the B cells and kills them. 
 
What other medicines Polivy is given with 
 
Polivy is given in combination with two other cancer medicines called rituximab and bendamustine. 
 
 
2. What you need to know before you are given Polivy  
 
You must not be given Polivy 
 



32 

• if you are allergic to polatuzumab vedotin or any of the other ingredients of this medicine (listed 
in section 6).  

 
If you are not sure, talk to your doctor or nurse before you are given Polivy. 
 
Warnings and precautions  
 
Talk to your doctor or nurse before you are given Polivy if any of the following apply to you (or you 
are not sure):  
• you have ever had brain or nerve problems such as:  

- memory problems 
- difficulty moving or sensations in your body such as feeling pins and needles, burning, 

pain and discomfort even from slight touch 
- eyesight problems 

• you have ever had liver problems 
• you think you have an infection or have had long-lasting or repeated infections such as herpes 

(see “Infections” in section 4) 
• you are due to have a vaccine or you know you may need to have one in the near future 
 
If any of the above apply to you (or you are not sure) talk to your doctor or nurse before you are given 
Polivy.  
 
Pay attention to the following side effects 
 
Polivy can cause some serious side effects that you need to tell your doctor or nurse about straight 
away. These include:  
 
Myelosuppression 
 
Myelosuppression is a condition in which the production of blood cells is decreased, resulting in fewer 
red blood cells, white blood cells, and platelets. Your doctor will do blood tests to check your blood 
cell count.  
 
Tell your doctor or nurse straight away if you:  
• develop chills or shivering 
• have a fever 
• have headaches 
• feel tired 
• feel dizzy 
• look pale  
• have unusual bleeding, bruising under the skin, bleeding longer than usual after your blood has 

been drawn, or bleeding from your gums. 
 
Peripheral neuropathy 
 
Tell your doctor or nurse straight away if you have any problems with a change in the sensitivity of 
your skin, especially in your hands or feet, such as: 
• numbness 
• tingling 
• a burning sensation 
• pain 
• discomfort or weakness. 
 
If you had any of these symptoms before treatment with Polivy, tell your doctor straight away if you 
notice any changes in them.  
 



33 

If you have symptoms of peripheral neuropathy, your doctor may lower your dose. 
 
Infections 
 
Signs and symptoms of infections vary between individuals, tell your doctor or nurse straight away if 
you develop symptoms of an infection such as:  
• fever 
• cough 
• chest pain  
• tiredness  
• painful rash  
• sore throat  
• burning pain when passing urine  
• feeling weak or generally unwell. 
 
Progressive multifocal leukoencephalopathy (PML) 
 
PML is a very rare and life threatening infection in the brain, that has occured in one patient treated 
with Polivy together with bendamustine and another medicine called obinutuzumab.  
 
Tell your doctor or nurse straight away if you have: 
• memory loss 
• trouble speaking 
• difficulty walking 
• problems with your eyesight. 

 
If you had any of these symptoms before treatment with Polivy, tell your doctor straight away if you 
notice any changes in them. You may need medical treatment. 
 
Tumour lysis syndrome  
 
Some people may develop unusual levels of some substances (such as potassium and uric acid) in the 
blood caused by the fast breakdown of cancer cells during treatment. This is called tumour lysis 
syndrome. Your doctor, pharmacist or nurse will do blood tests to check for the condition. 
 
Infusion-related reactions 
 
Infusion-related reactions, allergic or anaphylactic (more severe allergic) reactions can happen. Your 
doctor or nurse will check for side effects during your infusion and for 30 to 90 minutes afterwards. If 
you get any serious reaction, your doctor may stop treatment with Polivy.  
 
Liver damage 
 
This medicine can cause inflammation or damage to cells in the liver that affect the normal function of 
the liver. Injured liver cells may leak high amounts of certain substances (liver enzymes and bilirubin) 
into the bloodstream, in which can be detected by blood tests.  
 
In most cases you will not have any symptoms but tell your doctor or nurse straight away if you get: 
• yellowing of your skin and of the whites of your eyes (jaundice). 
 
Your doctor will check your blood to test your liver function before and regularly during treatment. 
 
Children and adolescents 
 
This medicine should not be used in children or young people under the age of 18. This is because 
there is no information about its use in this age group.  



34 

 
Other medicines and Polivy  
 
Tell your doctor or nurse if you are taking, have recently taken or might start taking any other 
medicines. This includes medicines obtained without a prescription and herbal medicines. 
 
Contraception (women and men)  
 
If you are a woman of childbearing age, you must use effective contraception during treatment and for 
9 months after the last dose of Polivy. 
Men must use contraception during treatment and for 6 months after the last dose of Polivy. 
 
Pregnancy  
 
It is important to tell your doctor before and during treatment if you are pregnant, think you may be 
pregnant, or are planning to get pregnant. This is because Polivy can affect your baby’s health. You 
should not use this medicine if you are pregnant unless you and your doctor decide that the 
benefit to you outweighs possible risk to the unborn baby.  
 
Breast-feeding  
 
Do not breast-feed while receiving Polivy and for at least 3 months after the last dose, because small 
amount of Polivy may pass into your breast milk.  
 
Fertility  
 
Men being treated with this medicine are advised to have sperm samples preserved and stored before 
treatment.  
 
Driving and using machines  
 
Polivy has a minor influence on your ability to drive, cycle or use any tools or machines. If you get 
infusion-related reactions or nerve damage, or if you feel tired, weak or dizzy (see section 4) do not 
drive, cycle or use tools or machines until the reaction stops.  
 
See section 4 for more information about side effects. 
 
Polivy contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How Polivy is given  
 
Polivy is given under the supervision of a doctor experienced in giving such treatments. It is given into 
a vein, as a drip over 90 minutes.  
 
How much Polivy is given  
 
The dose of this medicine depends on your body weight.  
• The usual starting dose is 1.8 mg for each kilogram of your body weight.  
• If you have peripheral neuropathy, your doctor may lower your dose to 1.4 mg for each 

kilogram of your body weight.  
 
You will be given 6 treatment cycles of Polivy in combination with two other medicines called 
rituximab and bendamustine.  



35 

 
Each cycle lasts 21 days.  
 
If you miss a dose of Polivy 
 
If you miss an appointment, make another one straight away. For the treatment to be fully effective, it 
is very important not to miss a dose. 
 
If you stop receiving Polivy 
 
Do not stop treatment with Polivy unless you have discussed this with your doctor. This is because 
stopping treatment may make your condition worse.  
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects have been reported with this medicine: 
 
Serious side effects 
 
Tell your doctor or nurse straight away if you notice any of the following serious side effects – you 
may need urgent medical treatment. These may be new symptoms or a change in your current 
symptoms. 
 
• fevers and chills 
• rash/hives 
• severe infections 
• pneumonia (lung infection) 
• herpes infection 
• viral infections 
• unusual bleeding or bruising under the skin 
• memory loss, trouble speaking, difficulty walking or problems with your eyesight 
• yellowing of skin or whites of your eyes  
 
Other side effects 
 
Tell your doctor or nurse if you notice any of the following side effects: 
 
Very common (may affect more than 1 in 10 people) 
• severe infections 
• fever 
• cough  
• vomiting 
• pneumonia (lung infection) 
• diarrhoea or constipation 
• feeling sick (nausea) 
• abdominal (belly) pain 
• feeling tired (anaemia)  
• not feeling hungry  
• loss of weight 
• infusion-related reactions 
• common cold 
• dizziness 



36 

• unusual sensations 
 

Common (may affect up to 1 in 10 people) 
• chills 
• viral infections 
• herpes infection  
• problems walking 
• inflammation of the lungs 
• raised liver enzymes 
• joint pain 
• itchiness 
 
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 
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 Polivy 
 
Polivy will be stored by the healthcare professionals at the hospital or clinic. The storage details are as 
follows 
• 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 carton and the vial after 

EXP. The expiry date refers to the last day of that month. 
• Store in a refrigerator (2°C – 8°C). 
• Do not freeze. 
• Keep the container in the outer carton in order to protect from light. 
 
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 Polivy contains  
 
• The active substance is polatuzumab vedotin.  
• Polivy 30 mg: Each vial contains 30 milligrams (mg) polatuzumab vedotin. 
• Polivy 140 mg: Each vial contains 140 milligrams (mg) polatuzumab vedotin.  
• After reconstitution each millilitre (mL) contains 20 mg polatuzumab vedotin. 
• The other ingredients are: succinic acid, sodium hydroxide, sucrose, polysorbate 20. See section 

“Polivy contains sodium”. 
 
What Polivy looks like and contents of the pack 
 
Polivy powder for concentrate for solution for infusion is a white to slightly greyish-white cake 
provided in a glass vial. 
 
Each pack of Polivy consists of one vial. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


37 

Marketing Authorisation Holder 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. O. 
Tel: +420 - 2 20382111 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
  

Malta 
Irreferi għall-Irlanda  

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140  

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380  
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E. 
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o. 
Tel: +385 1 4722 333 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 



38 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland 
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika 
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy 
Puh/Tel: +358 (0) 10 554 500 
 

Κύπρος 
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

 
This leaflet was last revised in {MM/YYYY} 
 
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/  
 
  

http://www.ema.europa.eu/


39 

------------------------------------------------------------------------------------------------------------------------ 
 

The following information is intended for healthcare professionals only: 
 
Procedures for proper handling and disposal of anticancer medicinal products should be considered. 
 
Instructions for reconstitution 
 
• Polivy 30 mg: Using a sterile syringe, slowly inject 1.8 mL of sterile water for injection into the 

30 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin. 
Direct the stream toward the wall of the vial and not directly on the lyophilized cake. 

• Polivy 140 mg: Using a sterile syringe, slowly inject 7.2 mL of sterile water for injection into 
the 140 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab 
vedotin. Direct the stream toward the wall of the vial and not directly on the lyophilized cake. 

• Swirl the vial gently until completely dissolved. Do not shake. 
• Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted 

solution should appear colourless to slightly brown, clear to slightly opalescent, and free of 
visible particulates. Do not use if the reconstituted solution is discoloured, is cloudy, or contains 
visible particulates. 

 
Instructions for dilution 
 
1. Polivy must be diluted to a final concentration of 0.72-2.7 mg/mL in an intravenous infusion 

bag, with a minimum volume of 50 mL, containing 9 mg/mL sodium chloride solution for 
injection, or 4.5 mg/mL sodium chloride solution for injection, or 5% glucose. 

2. Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose 
(see below): 

Total Polivy dose (mL) to be further diluted = Polivy dose (mg/kg) X patient’s weight (kg) Reconstituted vial concentration (20 mg/mL) 
3. Withdraw the required volume of reconstituted solution from the Polivy vial using a sterile 

syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial. 
4. Gently mix the intravenous bag by slowly inverting the bag. Do not shake. 
5. Inspect the intravenous bag for particulates and discard if present. 
 
Reconstituted solution  
 
From a microbiological point of view, the reconstituted solution should be used immediately. If not 
used immediately, in-use storage times and conditions prior to use are the responsibility of the user 
and would normally not be longer than 24 hours refrigerated (2 °C − 8 °C), unless reconstitution has 
taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of 
the reconstituted solution has been demonstrated for up to 72 hours refrigerated (2 °C − 8 °C) and up 
to 24 hours at room temperature (9 °C − 25 °C).  
 
Diluted solution  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours refrigerated (2 °C − 8 °C), unless dilution has 
taken place in controlled and validated aseptic conditions. Chemical and physical stability of the 
prepared solution for infusion has been demonstrated for the durations listed in Table 1. Discard 
diluted Polivy solution if storage time exceeds the limits specified in Table 1.  
 



40 

Table 1   Durations for which chemical and physical stability of the prepared solution for 
infusion have been demonstrated 
 

Diluent used to prepare solution 
for infusion 

Solution for infusion  
storage conditions1 

Sodium chloride 9 mg/mL (0.9%)  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 4 hours at room temperature (9 °C − 25 °C)  

Sodium chloride 4.5 mg/mL (0.45%)  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 8 hours at room temperature (9 °C − 25 °C) 

5% Glucose  Up to 72 hours refrigerated (2 °C − 8 °C) or 
up to 8 hours at room temperature (9 °C − 25 °C) 

1 To ensure product stability, do not exceed specified storage durations. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET