(rituximab-pvvr)

Prescribing Information
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8 USE IN SPECIFIC POPULATIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on human data, rituximab products can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in-utero (see Clinical Considerations). In animal reproduction studies, intravenous administration of rituximab to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid B-cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Advise pregnant women of the risk to a fetus.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated populations is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies.

Clinical Considerations

Fetal/Neonatal Adverse Reactions
Observe newborns and infants for signs of infection and manage accordingly.

Data

Human Data
Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero.

Animal Data
An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum Days 20 through 50). Rituximab was administered as loading doses on post coitum (PC) Days 20, 21, and 22, at 15, 37.5, or 75 mg/kg/day, and then weekly on PC Days 29, 36, 43, and 50, at 20, 50, or 100 mg/kg/week. The 100 mg/kg/week dose resulted in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Rituximab crosses the monkey placenta. Exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue B cells.

A subsequent pre- and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of B cells and immune function in infants exposed to rituximab in-utero. Animals were treated with a loading dose of 0, 15, or 75 mg/kg every day for 3 days, followed by weekly dosing with 0, 20, or 100 mg/kg dose. Subsets of pregnant females were treated from PC Day 20 through postpartum Day 78, PC Day 76 through PC Day 134, and from PC Day 132 through delivery and postpartum Day 28. Regardless of the timing of treatment, decreased B cells and immunosuppression were noted in the offspring of rituximab-treated pregnant animals. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months postpartum.

8.2 Lactation

There are limited data on the presence of rituximab in human milk, and the effect on the breastfed child, and there are no data on the effect on milk production. Rituximab is detected in the milk of lactating cynomolgus monkeys, and maternal IgG is present in human breast milk. Rituximab has also been reported to be excreted at low concentrations in human breast milk. Given that the clinical significance of this finding for children is not known, advise women not to breastfeed during treatment with RUXIENCE and for 6 months after the last dose due to the potential of serious adverse reactions in breastfed children.

8.3 Females and Males of Reproductive Potential

Rituximab products can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating RUXIENCE.

Contraception

Females
Advise females of reproductive potential to use effective contraception during treatment with RUXIENCE and for 12 months after the last dose.

8.4 Pediatric Use

The safety and effectiveness of RUXIENCE have not been established in pediatric patients with NHL, CLL, PV or RA.

Rituximab was not studied in pediatric patients with polyarticular juvenile idiopathic arthritis (PJIA) due to concerns regarding the potential for prolonged immunosuppression as a result of B-cell depletion in the developing juvenile immune system.

8.5 Geriatric Use

Diffuse Large B-Cell NHL

Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received rituximab in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis.

Low-Grade or Follicular Non-Hodgkin's Lymphoma

Patients with previously untreated follicular NHL evaluated in NHL Study 5 were randomized to rituximab as single-agent maintenance therapy (n=505) or observation (n=513) after achieving a response to rituximab in combination with chemotherapy. Of these, 123 (24%) patients in the rituximab arm were age 65 or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other clinical studies of rituximab in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

Chronic Lymphocytic Leukemia

Among patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 rituximab-treated patients (36%) were 65 years of age or older; of these, 100 rituximab-treated patients (15%) were 70 years of age or older.

In exploratory analyses defined by age, there was no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 70 years of age or older in CLL Study 1 or in CLL Study 2; there was also no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 65 years of age or older in CLL Study 2 [see Clinical Studies (14.5)]. Patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of rituximab. In CLL Study 1, the dose intensity of rituximab was similar in older and younger patients, however in CLL Study 2 older patients received a lower dose intensity of rituximab.

The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (CLL Study 1); 56% vs. 39% (CLL Study 2)], febrile neutropenia [16% vs. 6% (NHL Study 10 (NCT00719472))], anemia [5% vs. 2% (CLL Study 1); 21% vs. 10% (CLL Study 2)], thrombocytopenia [19% vs. 8% (CLL Study 2)], pancytopenia [7% vs. 2% (CLL Study 1); 7% vs. 2% (CLL Study 2)], and infections [30% vs. 14% (CLL Study 2)].

Rheumatoid Arthritis

Among the 2,578 patients in global RA studies completed to date, 12% were 65–75 years old and 2% were 75 years old and older. The incidences of adverse reactions were similar between older and younger patients. The rates of serious adverse reactions, including serious infections, malignancies, and cardiovascular events were higher in older patients.

Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis

Of the 99 rituximab-treated GPA and MPA patients in GPA/MPA Study 1, 36 (36%) were 65 years old and over, while 8 (8%) were 75 years and over. No overall differences in efficacy were observed between patients that were 65 years old and over and younger patients. The overall incidence and rate of all serious adverse events was higher in patients 65 years old and over. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

In GPA/MPA Study 2, 30 (26%) of the enrolled patients were at least 65 years old, of which 12 patients were exposed to non-U.S.-licensed rituximab and 18 were exposed to azathioprine. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

Pemphigus Vulgaris

Of the 46 patients treated with non-U.S.-licensed rituximab, 15 (33%) patients were 65 years of age and older. The clinical study did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients.

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration     Revised: 4/2026

MEDICATION GUIDE
RUXIENCE® (RUKSee-ents)
(rituximab-pvvr)
injection

What is the most important information I should know about RUXIENCE?
RUXIENCE can cause serious side effects that can lead to death, including:

•
Infusion-related reactions. Infusion-related reactions are very common side effects of RUXIENCE treatment. Serious infusion-related reactions can happen during your infusion or within 24 hours after your infusion of RUXIENCE. Your healthcare provider should give you medicines before your infusion of RUXIENCE to decrease your chance of having a severe infusion-related reaction.
Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an infusion of RUXIENCE:
o
hives (red itchy welts) or rash
o
itching
o
swelling of your lips, tongue, throat or face
o
sudden cough
o
shortness of breath, difficulty breathing, or wheezing
o
weakness
o
dizziness or feel faint
o
palpitations (feel like your heart is racing or fluttering)
o
chest pain
•
Severe skin and mouth reactions. Tell your healthcare provider or get medical help right away if you get any of these symptoms at any time during your treatment with RUXIENCE:
o
painful sores or ulcers on your skin, lips or in your mouth
o
blisters
o
peeling skin
o
rash
o
pustules
•
Hepatitis B virus (HBV) reactivation. Before you receive your RUXIENCE treatment, your healthcare provider will do blood tests to check for HBV infection. If you have had hepatitis B or are a carrier of hepatitis B virus, receiving RUXIENCE could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems including liver failure, and death. You should not receive RUXIENCE if you have active hepatitis B liver disease. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving RUXIENCE.
Tell your healthcare provider right away if you get worsening tiredness, or yellowing of your skin or white part of your eyes, during treatment with RUXIENCE.
•
Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive RUXIENCE. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML.
Tell your healthcare provider right away if you have any new or worsening symptoms or if anyone close to you notices these symptoms:
o
confusion
o
dizziness or loss of balance
o
difficulty walking or talking
o
decreased strength or weakness on one side of your body
o
vision problems

See "What are the possible side effects of RUXIENCE?" for more information about side effects.

What is RUXIENCE?
RUXIENCE is a prescription medicine used to treat:

•
Adults with Non-Hodgkin's Lymphoma (NHL): alone or with other chemotherapy medicines.
•
Adults with Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
•
Adults with Rheumatoid Arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA in adults, after treatment with at least one other medicine called a Tumor Necrosis Factor (TNF) antagonist has been used and did not work well.
•
Adults with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA): with glucocorticoids, to treat GPA and MPA.
•
Adults with Pemphigus Vulgaris (PV): to treat moderate to severe PV.

RUXIENCE is not indicated for treatment of children.

Before you receive RUXIENCE, tell your healthcare provider about all of your medical conditions, including if you:

•
have had a severe reaction to RUXIENCE or another rituximab product
•
have a history of heart problems, irregular heart beat or chest pain
•
have lung or kidney problems
•
have an infection or weakened immune system
•
have or have had any severe infections including:
o
Hepatitis B virus (HBV)
o
Hepatitis C virus (HCV)
o
Cytomegalovirus (CMV)
o
Herpes simplex virus (HSV)
o
Parvovirus B19
o
Varicella zoster virus (chickenpox or shingles)
o
West Nile Virus
•
have had a recent vaccination or are scheduled to receive vaccinations. You should not receive certain vaccines before or during treatment with RUXIENCE.
•
are pregnant or plan to become pregnant. Talk to your healthcare provider about the risks to your unborn baby if you receive RUXIENCE during pregnancy.
Females who are able to become pregnant:
o
Your healthcare provider should do a pregnancy test to see if you are pregnant before starting RUXIENCE.
o
You should use effective birth control (contraception) during treatment with RUXIENCE and for 12 months after your last dose of RUXIENCE. Talk to your healthcare provider about effective birth control.
o
Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with RUXIENCE.
•
are breastfeeding or plan to breastfeed. RUXIENCE may pass into your breast milk. Do not breastfeed during treatment and for 6 months after your last dose of RUXIENCE.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take or have taken:

•
a Tumor Necrosis Factor (TNF) inhibitor medicine
•
a Disease Modifying Anti-Rheumatic Drug (DMARD)

If you are not sure if your medicine is one listed above, ask your healthcare provider.

How will I receive RUXIENCE?

•
RUXIENCE is given by infusion through your central catheter or through a needle placed in a vein (intravenous infusion), in your arm. Talk to your healthcare provider about how you will receive RUXIENCE.
•
Your healthcare provider may prescribe medicines before each infusion of RUXIENCE to reduce infusion side effects such as fever and chills.
•
Your healthcare provider should do blood tests regularly to check for side effects to RUXIENCE.
•
Before each RUXIENCE treatment, your healthcare provider or nurse will ask you questions about your general health. Tell your healthcare provider or nurse about any new symptoms.

What are the possible side effects of RUXIENCE?
RUXIENCE can cause serious side effects, including:

•
See "What is the most important information I should know about RUXIENCE?"
•
Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause you to have:
o
kidney failure and the need for dialysis treatment
o
abnormal heart rhythm
 
TLS can happen within 12 to 24 hours after an infusion of RUXIENCE. Your healthcare provider may do blood tests to check you for TLS. Your healthcare provider may give you medicine to help prevent TLS.
Tell your healthcare provider right away if you have any of the following signs or symptoms of TLS:
o
nausea
o
vomiting
o
diarrhea
o
lack of energy
•
Serious infections. Serious infections can happen during and after treatment with RUXIENCE, and can lead to death. RUXIENCE can increase your risk of getting infections and can lower the ability of your immune system to fight infections. Types of serious infections that can happen with RUXIENCE include bacterial, fungal, and viral infections. After receiving RUXIENCE, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these people with low antibody levels developed infections. People with serious infections should not receive RUXIENCE. Tell your healthcare provider right away if you have any symptoms of infection:
o
fever
o
cold symptoms, such as runny nose or sore throat that do not go away
o
flu symptoms, such as cough, tiredness, and body aches
o
earache or headache
o
pain during urination
o
cold sores in the mouth or throat
o
cuts, scrapes or incisions that are red, warm, swollen or painful
•
Heart problems. RUXIENCE may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your heart during and after treatment with RUXIENCE if you have symptoms or heart problems or have a history of heart problems. Tell your healthcare provider right away if you have chest pain or irregular heartbeats during treatment with RUXIENCE.
•
Kidney problems, especially if you are receiving RUXIENCE for NHL. RUXIENCE can cause severe kidney problems that lead to death. Your healthcare provider should do blood tests to check how well your kidneys are working.
•
Stomach and Serious bowel problems that can sometimes lead to death. Bowel problems, including blockage or tears in the bowel can happen if you receive RUXIENCE with chemotherapy medicines. Tell your healthcare provider right away if you have any severe stomach-area (abdomen) pain or repeated vomiting during treatment with RUXIENCE.

Your healthcare provider will stop treatment with RUXIENCE if you have severe, serious or life-threatening side effects.
The most common side effects of RUXIENCE include:

o
infusion-related reactions (see "What is the most important information I should know about RUXIENCE?")
o
infections (may include fever, chills)
o
body aches
o
tiredness
o
nausea

In adults with GPA or MPA the most common side effects of RUXIENCE also include:

o
low white and red blood cells
o
swelling
o
diarrhea
o
muscle spasms

Other side effects with RUXIENCE include:

o
aching joints during or within hours of receiving an infusion
o
more frequent upper respiratory tract infection

These are not all of the possible side effects with RUXIENCE.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of RUXIENCE.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about RUXIENCE that is written for healthcare providers.

What are the ingredients in RUXIENCE?
Active ingredient: rituximab-pvvr
Inactive ingredients: edetate disodium dihydrate, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for Injection.

Manufactured by Pfizer Ireland Pharmaceuticals Unlimited Company, Cork, Ireland, P43 X336

U.S. License No. 2060
Distributed by Pfizer Labs Division of Pfizer Inc. New York, NY 10001
LAB-1274-7.0

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For more information, go to www.pfizer.com or call 1-800-438-1985.

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