Opdivo

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Nivolumab 107 mg equivalent to 100mg/10mL;  ;  
Available from:
Bristol-Myers Squibb (NZ) Limited
INN (International Name):
Nivolumab 107 mg (=100mg/10mL)
Dosage:
100 mg/10mL
Pharmaceutical form:
Concentrate for infusion
Composition:
Active: Nivolumab 107 mg equivalent to 100mg/10mL     Excipient: Hydrochloric acid Mannitol Pentetic acid Polysorbate 80 Sodium chloride Sodium citrate dihydrate Sodium hydroxide Water for injection
Prescription type:
Prescription
Manufactured by:
Lonza Biologics Inc
Therapeutic indications:
Opdivo, as monotherapy is indicated for the treatment of patients with unresectable or metastatic melanoma. Opdivo, in combination with YERVOY (ipilimumab) is indicated for the treatment of patients with unresectable or metastatic melanoma. OPDIVO, as monotherapy, is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
Product summary:
Package - Contents - Shelf Life: Vial, glass, Type 1 clear. Closure: film coated butyl rubber stopper + al crimp seal - 1 dose units - 36 months from date of manufacture stored at 2° to 8°C (Refrigerate, do not freeze) protect from light 48 hours not refrigerated stored at or below 25°C 24 hours diluted stored at 2° to 8°C (Refrigerate, do not freeze). Product can be stored unrefrigerated (at or below 25 deg C) for up to 8 hours in this 24 hour period
Authorization number:
TT50-9916a
Authorization date:
2016-01-14

Read the complete document

OPDIVO CMI_V11.0

OPDIVO

®

(op-DEE-voh)

Nivolumab (nee-vol-u-mab)

Consumer Medicine Information

WHAT IS IN THIS

LEAFLET

This leaflet answers some common

questions about OPDIVO. It does not

contain all of the available

information. It does not take the

place of talking to your doctor or

pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you receiving OPDIVO

against the benefits they expect it

will have for you.

If you have any concerns about

taking this medicine, ask your

doctor.

You should read this leaflet

carefully and keep it in a safe place

to refer to it later.

WHAT IS OPDIVO

USED FOR

OPDIVO contains the active

substance nivolumab, a protein

which helps your immune system to

attack and destroy cancer cells.

Treatment with OPDIVO

OPDIVO is used to treat advanced

melanoma (unresectable or

metastatic). OPDIVO is also used to

treat skin cancer (melanoma) after

surgical removal of the cancer.

OPDIVO is used to treat a type of

lung cancer (advanced squamous and

non squamous

non-small cell lung

cancer), a type of kidney

cancer

(clear cell renal cell carcinoma)

and a

type of head and neck cancer

(squamous cell cancer of the head

and neck), a type of blood cancer

called classical Hodgkin lymphoma,

a type of bladder cancer (urothelial

carcinoma) and a type of liver cancer

(hepatocellular carcinoma), if your

cancer has not responded, or if it has

stopped responding, to earlier

treatment.

Treatment with OPDIVO in

combination with ipilimumab

OPDIVO in combination with

ipilimumab is used to treat advanced

melanoma in adults

nd a type of

advanced kidney cancer (renal cell

carcinoma).

Treatment with OPDIVO in

combination with ipilimumab

and chemotherapy

OPDIVO in combination with

ipilimumab and chemotherapy is

used to treat advanced lung cancer in

adults.

This medicine is available only with

a doctor's prescription.

OPDIVO will be given to you in

hospital under the supervision of an

experienced doctor.

Ask your doctor if you have any

questions about why OPDIVO has

been prescribed for you.

Your doctor will continue giving you

OPDIVO for as long as you keep

benefitting from it or until you no

longer tolerate the treatment.

Patients receiving OPDIVO after

surgical removal of melanoma may

require treatment for no longer than

one year.

BEFORE YOU ARE

GIVEN OPDIVO

You should not be given

OPDIVO

if you are allergic

(hypersensitive) to nivolumab or

any of the other ingredients of

OPDIVO. If you are not sure,

talk to your doctor.

Check with your doctor or nurse

before you are given OPDIVO if:

you have an autoimmune disease

(a condition where the body

attacks its own cells) like

Crohn's, ulcerative colitis or

lupus;

you have any history of

inflammation of the lungs

you have been told your cancer

has spread to your brain

you have melanoma of the eye

you were previously given

ipilimumab, another medicine

for the treatment of advanced

melanoma, and experienced side

effects because of this medicine.

you are taking any medicines

that suppress your immune

system, such as corticosteroids,

since these medicines may

interfere with the effect of

OPDIVO. However, once you

are treated with OPDIVO, your

OPDIVO CMI _V11.0

doctor may give you

corticosteroids to reduce any

possible side effects that you

may have during your treatment

and this will not impact the

effect of the medicine.

OPDIVO may cause:

Problems with your lungs such as

breathing difficulties, or cough.

These may be signs of

inflammation of the lungs

(pneumonitis or interstitial lung

disease).

Diarrhoea (watery, loose or soft

stools) or any symptoms of

inflammation of the intestines

(colitis), such as stomach pain

and mucus or blood in the stool.

Inflammation of the liver

(hepatitis).Signs and symptoms

of hepatitis may include

abnormal liver function tests,

eye or skin yellowing (jaundice),

pain on the right side of your

stomach area, or tiredness.

Inflammation or problems with

your kidneys. Signs and

symptoms may include abnormal

kidney function tests decreased

volume of urine, and kidney

failure.

Problems with your hormone

producing gland (including the

thyroid, parathyroid, pituitary,

and adrenal glands) that may

affect how these glands work.

Signs and symptoms that your

glands are not working properly

may include fatigue (extreme

tiredness), weight change or

headache, muscle aches or

cramps and visual disturbances.

Diabetes (symptoms include

excessive thirst, the passing of a

greatly increased amount of

urine, increase in appetite with a

loss of weight, feeling tired,

drowsy, weak, depressed,

irritable and generally unwell) or

diabetic ketoacidosis (acid in the

blood produced from diabetes).

Inflammation of the skin that can

lead to rash and itching. Severe

and possibly fatal peeling of the

skin (toxic epidermal necrolysis,

Steven-Johnson syndrome).

Loss of the covering around the

nerves (demyelination),

inflammation of the nerves

caused by the body attacking

itself, causing numbness,

weakness, tingling or burning

pain.

A condition in which the muscles

become weak and tire easily

(myasthenic syndrome)

A temporary inflammation of the

nerves that causes pain,

weakness and paralysis in the

extremities (Guillain-Barré

syndrome);

Inflammation of the brain

Inflammation of muscles causing

pain or stiffness

Inflammation of the heart

(myocarditis) characterised by

shortness of breath, fatigue,

palpitations or chest pain

Muscle breakdown/injury

(rhabdomyolysis) characterised

by muscle pain, weakness,

nausea or vomiting.

Solid organ transplant rejection

Tell your doctor immediately if

you have any signs or symptoms of

the possible side effects listed

above or if your symptoms get

worse.

Do not try to treat your symptoms

with other medicines.

Complications of stem cell transplant

that uses donor cells (allogeneic)

may occur after treatment with

Opdivo.

These complications can be severe

and can lead to death. Your

healthcare provider will monitor you

for signs of complications if you

have an allogeneic stem cell

transplant.

Using other medicines

Please tell your doctor if you are

taking or have recently taken any

other medicines, including medicines

obtained without a prescription. Ask

your doctor for advice before taking

any medicine during your treatment.

Children

It is not recommended to use this

medicine in children or an adolescent

(below 18 years) until further

information becomes available.

Take special care with

OPDIVO

OPDIVO is a medicine that

influences your immune system and

may cause inflammation in parts of

your body. Inflammation can cause

serious damage to your body and

some inflammatory conditions may

be life-threatening and need

treatment or withdrawal of OPDIVO.

Tell your doctor immediately if you

have any of the symptoms of

inflammation listed in "Possible Side

Effects".

Pregnancy and breast-

feeding

Tell your doctor if you are pregnant,

planning to become pregnant, or if

you are breast-feeding.

You must not use OPDIVO if you

are pregnant unless your doctor

specifically recommends it.

The effects of OPDIVO in pregnant

women are not known, but it is

possible that the active substance,

nivolumab, could harm an unborn

baby.

You must use effective

contraception while you are

being treated with OPDIVO if

you are a woman who could

become pregnant.

If you become pregnant while

using OPDIVO, tell your doctor.

You should stop breast-feeding if

you are being treated with

OPDIVO.

It is not known whether nivolumab

gets into breast milk. A risk to the

breast-fed infant cannot be excluded.

OPDIVO CMI _V11.0

Driving and using machines

No studies on the effects on the

ability to drive and use machines

have been performed. OPDIVO is

unlikely to affect your ability to drive

or use machines; however, use

caution when performing these

activities until you are sure that

OPDIVO does not adversely affect

you.

Important information about some

of the ingredients of OPDIVO

Tell your doctor if you are on a low-

sodium (low-salt) diet before you are

given OPDIVO. This medicine

contains 2.5 mg sodium per mL of

concentrate.

HOW OPDIVO IS

GIVEN

OPDIVO will be given to you in

hospital or clinic under the

supervision of an experienced doctor.

It will be given to you as an infusion

(a drip) into a vein (intravenously).

Your doctor will decide how many

treatments you need.

Dosage and frequency of

administration

The recommended dose and

frequency of OPDIVO can be

different depending on the type of

cancer it is being used to treat.

Some types of cancer are treated with

OPDIVO in combination

withipilimumab or ipilimumab and

chemotherapy.

Your doctor will advise you which

treatments you will be given and will

tell you about the dose and frequency

of these treatments.

Please refer to the package leaflet of

ipilimumabin order to understand the

use of this medicine. If you have

questions about this medicine, please

ask your doctor.

If you miss a dose of

OPDIVO

It is very important for you to keep

all appointments to receive OPDIVO.

If you miss an appointment, ask your

doctor when to schedule your next

dose.

If you stop using OPDIVO

Stopping your treatment may stop the

effect of the medicine. Do not stop

treatment with OPDIVO unless you

have discussed this with your doctor.

If you have any further questions

about your treatment or the use of

this medicine, ask your doctor.

WHILE YOU ARE

BEING TREATED

WITH OPDIVO

Things you must do

Tell your doctor immediately if

you have any signs or symptoms of

possible adverse effects or if they

get worse. See Possible Side

Effects.

Do not try to treat your symptoms

with other medicines on your own.

You doctor may

Give you other medicines in order

to prevent complications and

reduce your symptoms

Withhold the next dose of

OPDIVO

Or stop your treatment with

OPDIVO altogether.

Please note that these signs and

symptoms are sometimes delayed,

and may develop weeks or months

after your last dose. Before

treatment, your doctor will check

your general health. You will also

have blood tests during treatment.

Tell any other doctors, dentists,

and pharmacists who are treating

you that you are being given

OPDIVO.

If you are about to be started on

any new medicine, tell your doctor,

dentist or pharmacist that you are

being given OPDIVO.

Tell your doctor immediately if

you develop symptoms of an

allergic reaction.

These symptoms may be:

shortness of breath, wheezing or

difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin

POSSIBLE SIDE

EFFECTS

Like all medicines, OPDIVO can

cause side effects, although not

everybody gets them. Your doctor

will discuss these with you and will

explain the risks and benefits of your

treatment.

Do not try to treat your symptoms

with other medicines.

Do not be alarmed by possible side

effects.

You may not experience any of them.

Ask your doctor to answer any

questions you may have.

The following side effects have

been reported in clinical trials

when OPDIVO has been given

alone:

Very common (may affect more

than 1 in 10 people)

Decrease in some white blood

cells

Diarrhoea (watery, loose or soft

stools), nausea

Skin rash, itching

Feeling tired or weak

Common (may affect up to 1 in 10

people)

Infections of the upper respiratory

tract

Underactive thyroid gland, which

can cause tiredness or weight

gain, overactive thyroid gland,

OPDIVO CMI _V11.0

which can cause rapid heart rate,

sweating and weight loss

Decreased appetite

Inflammation of the nerves

causing numbness, weakness,

tingling or burning pain of the

arms and legs, headaches,

dizziness

Inflammation of the lungs

(pneumonitis), characterised by

coughing and difficulty breathing

Coughing shortness of breath

(dyspnoea)

Inflammation of the intestines

(colitis)

Stomach pain, constipation

Mouth ulcers and cold sores

(stomatitis), vomiting, dry mouth

Skin colour changes in patches

(vitiligo), dry skin, hair loss or

thinning

Pain in the muscles, bones and

joints

Fever, oedema (swelling)

Allergic reaction, reaction related

to the infusion of the medicine

High blood pressure

(hypertension)

Uncommon (may affect up to 1 in

100 people)

Serious lung infection

(pneumonia), bronchitis

Decreased secretion of hormones

produced by adrenal glands

(glands situated above the

kidneys), underactive function

(hypopituitarism) or

inflammation (hypophysitis) of

the pituitary gland situated at the

base of the brain, swelling of the

thyroid gland, diabetes

Inflammation of the pancreas,

inflammation of the stomach

(gastritis)

Dehydration

Increased acid level in the blood

Increase in some white blood

cells

Inflammation of the eye, which

causes pain and redness, blurred

vision, dry eyes

Inflammation in the kidney,

kidney failure

Fast heart rate

Arthritis

Damage to nerves causing

numbness and weakness

(polyneuropathy), inflammation

of the nerves caused by the body

attacking itself, causing

numbness, weakness, tingling and

burning pain

Inflammation of the liver

(hepatitis)

Fluid around the lungs

Severe condition of the skin that

causes red, often itchy spots,

similar to rash of measles, which

starts on the limbs and sometimes

on the face and the rest of the

body (erythema multiforme), skin

disease with thickened patches of

red skin, often silvery scales

(psoriasis), skin conditions of the

face where the nose and cheeks

are unusually red (rosacea), hives

(itchy, bumpy rash)

Pain, chest pain

Rare (may affect up to 1 in 1000

people)

Life threatening allergic reaction

Severe and possibly fatal peeling

of the skin (toxic epidermal

necrolysis, Steven-Johnson

Syndrome)

Loss of the covering around the

nerves (demyelination)

A condition in which the muscles

become weak and tire easily

(myasthenic syndrome)

A temporary inflammation of the

nerves that causes pain, weakness

and paralysis in the extremities

(Guillain-Barré syndrome)

Inflammation of the brain

Ulcer of the small intestine

Blockage of the bile ducts

Fluid in lungs

Acid in the blood produced from

diabetes (diabetic ketoacidosis)

A disease causing inflammation

or enlargement of a lymph node

(Kikuchi lymphadenitis)

Changes in the rhythm or rate of

the heart, abnormal heart rhythm

Inflammation of the heart

(myocarditis) characterised by

shortness of breath, fatigue,

palpitations or chest pain.

Inflammation of muscles causing

pain or stiffness

Muscle breakdown/injury

(rhabdomyolysis) characterised

by muscle pain, weakness, nausea

or vomiting.

Myopathy (aching muscles,

muscle tenderness or weakness,

not caused by exercise)

Inflammatory disease of blood

vessels

Disease in which the immune

system attacks the glands that

make moisture for the body, such

as tears and saliva (Sjogren's

syndrome)

decrease in parathyroid hormone

blood disorder caused by

overactive immune cells

Changes in test results

OPDIVO may cause changes in the

results of tests carried out by your

doctor. These include:

Abnormal liver function tests

Abnormal kidney function tests

A decreased number of red blood

cells (which carry oxygen), white

blood cells (which are important

in fighting infection) or platelets

(cells which help the blood clot)

Abnormal levels of calcium,

potassium, magnesium or sodium

in your blood

Decrease in body weight

Higher levels of sugar in your

blood (hyperglycaemia)

The following side effects have

been reported in clinical trials

OPDIVO CMI _V11.0

when OPDIVO has been given in

combination withipilimumab:

Very common (may affect more

than 1 in 10 people)

Overactive thyroid gland, which

can cause rapid heart rate,

sweating and weight loss

Underactive thyroid gland, which

can cause tiredness or weight gain

Decreased appetite

Headache

Shortness of breath (dyspnoea)

Inflammation of the intestines

(colitis), diarrhoea (watery, loose

or soft stools), vomiting, nausea,

stomach pain

Skin rash sometimes with blisters,

itching

Pain in the joints, muscles and

bones

Feeling tired or weak, fever

Common (may affect up to 1 in 10

people)

Infections of the upper respiratory

tract, serious lung infection

(pneumonia)

Increase in some white blood

cells

Decreased secretion of hormones

produced by adrenal glands

(glands situated above the

kidneys); underactive function

(hypopituitarism) or

inflammation (hypophysitis) of

the pituitary gland situated at the

base of the brain; inflammation of

the thyroid gland

(hyperthyroidism); swelling of

the thyroid gland, high sugar

levels in the blood

(hyperglycaemia)

Dehydration

Inflammation of the nerves

causing numbness, weakness,

tingling or burning pain of the

arms and legs; dizziness

Inflammation of the eye, which

causes pain and redness, blurred

vision

Fast heart rate

High blood pressure

(hypertension)

Inflammation of the lungs

(pneumonitis), characterised by

coughing and difficulty breathing,

blood clots, cough

Mouth ulcers and cold sores

(stomatitis), inflammation of the

pancreas (pancreatitis),

constipation, dry mouth

Inflammation of the liver

Skin colour change in patches

(vitiligo), dry skin, redness of the

skin, unusual hair loss or

thinning, hives (itchy rash)

Pain in the muscles and bones

Kidney failure (including abrupt

loss of kidney function)

Oedema (swelling), pain

Allergic reaction, reactions

related to the infusion of the

medicine

Uncommon (may affect up to 1 in

100 people)

Inflammation of the brain,

Bronchitis

Chronic diseases associated with

a build-up of inflammatory cells

in various organs and tissues,

most commonly the lungs

(sarcoidosis)

Acid in the blood produced from

diabetes (diabetic ketoacidosis),

diabetes

A temporary inflammation of the

nerves that causes pain, weakness

and paralysis in the extremities

(Guillain-Barré syndrome);

damage to nerves causing

numbness and weakness

(polyneuropathy); inflammation

of the nerves; foot drop (peroneal

nerve palsy); inflammation of the

nerves caused by the body

attacking itself, causing

numbness, weakness, tingling or

burning pain

Changes in the rhythm or rate of

the heart beat, abnormal heart

rhythm

Fluid around the lungs

Intestinal perforation,

inflammation of th stomach

(gastritis), inflammation of the

duodenum

Skin disease with thickened

patches of red skin, often with

silvery scales (psoriasis)

Chronic disease of joints

(spondyloarthropathy)

Disease in which the immune

system attacks the glands that

make moisture for the body, such

as tears and saliva (Sjogren’s

syndrome)

Inflammation of the joints

(arthritis)

Inflammation of muscles

(myositis) causing pain or

stiffness

Inflammation of the kidney

(nephritis)

Chest pain

Inflammation of the heart

(myocarditis) characterised by

shortness of breath, fatigue,

palpitations or chest pain.

Muscle breakdown/injury

(rhabdomyolysis) characterised

by muscle pain, weakness, nausea

or vomiting.

Rare (may affect up to 1 in 1000

people)

Severe and possibly fatal peeling

of the skin (toxic epidermal

necrolysis, Steven-Johnson

syndrome)

decrease in parathyroid hormone

blood disorder caused by

overactive immune cells

Changes in test results

OPDIVO in combination with

ipilimumab may cause changes in the

results of tests carried out by your

doctor. These include:

Abnormal liver function tests

Abnormal kidney function tests

A decreased number of red blood

cells (which carry oxygen), white

blood cells (which are important

OPDIVO CMI _V11.0

in fighting infection) or platelets

(cells which help the blood to

clot)

An increased level of the enzyme

that breaks down fats and of the

enzyme that breaks down starch.

Abnormal levels of calcium,

potassium, magnesium or sodium

in your blood

Higher blood levels of bilirubin

Decrease in body weight

Higher (hyperglycaemia) or lower

(hypoglycaemia) levels of sugar

in your blood

The following side effects have

been reported in clinical trials

when OPDIVO has been given in

combination with ipilimumab and

chemotherapy:

Very common (may affect more

than 1 in 10 people)

Underactive thyroid gland, which

can cause tiredness or weight gain

Decreased appetite

diarrhoea (watery, loose or soft

stools), vomiting, nausea

Skin rash sometimes with blisters,

itching

Feeling tired or weak

Common (may affect up to 1 in 10

people)

Conjunctivitis

Serious lung infection

(pneumonia), infections of the

upper respiratory tract

Increase in some white blood

cells

Allergic reaction, reactions

related to the infusion of the

medicine

Decreased secretion of hormones

produced by adrenal glands

(glands situated above the

kidneys), inflammation

(hypophysitis) of the pituitary

gland situated at the base of the

brain, overactive thyroid gland,

which can cause rapid heart rate,

sweating and weight loss,

swelling of the thyroid gland

Inflammation of the nerves

causing numbness, weakness,

tingling or burning pain of the

arms and legs; dizziness

dry eyes

headache

Shortness of breath (dyspnoea)

Inflammation of the lungs

(pneumonitis), characterised by

coughing and difficulty breathing,

blood clots, cough

Inflammation of the intestines

(colitis)

Mouth ulcers and cold sores

(stomatitis), inflammation of the

pancreas (pancreatitis),

constipation, dry mouth

Inflammation of the liver

dry skin, redness of the skin,

unusual hair loss or thinning

Pain in the joints, muscles and

bones, inflammation of the joints

Kidney failure (including abrupt

loss of kidney function)

Fever

Oedema (swelling)

Uncommon (may affect up to 1 in

100 people)

underactive function

(hypopituitarism) of the pituitary

gland situated at the base of the

brain, decrease in parathyroid

hormone

damage to nerves causing

numbness and weakness

(polyneuropathy); inflammation

of the nerves caused by the body

attacking itself, causing

numbness, weakness, tingling or

burning pain (autoimmune

neuropathy), inflammation of the

brain

blurred vision

Changes in the rhythm or rate of

the heart beat, abnormal heart

rhythm

High blood pressure

(hypertension), low blood

pressure (hypotension)

Fluid around the lungs, bronchitis

Skin disease with thickened

patches of red skin, often with

silvery scales (psoriasis)

Severe and possibly fatal peeling

of the skin (Steven-Johnson

syndrome)

Inflammation of muscles

(myositis) causing pain or

stiffness

Inflammation of the kidney

(nephritis)

Chest pain

Changes in test results

OPDIVO in combination with

ipilimumab and chemotherapy may

cause changes in the results of tests

carried out by your doctor. These

include:

Abnormal liver function tests

Abnormal kidney function tests

A decreased number of red blood

cells (which carry oxygen), white

blood cells (which are important

in fighting infection) or platelets

(cells which help the blood to

clot)

An increased level of the enzyme

that breaks down fats and of the

enzyme that breaks down starch.

Abnormal levels of calcium,

potassium, magnesium or sodium

in your blood

Higher levels of sugar in your

blood (hyperglycaemia)

Higher blood levels of bilirubin

FURTHER

INFORMATION

What OPDIVO contains

The active substance is

nivolumab.

Each vial contains either 40 mg

(in 4mL) or 100 mg (in 10mL) of

nivolumab.

The other ingredients are sodium

citrate dihydrate, sodium

OPDIVO CMI _V11.0

chloride, mannitol (E421),

pentetic acid, polysorbate 80,

sodium hydroxide, hydrochloric

acid and water for injection.

What OPDIVO looks like and

contents of the pack

OPDIVO concentrate for solution for

infusion is a clear to opalescent,

colourless to pale yellow liquid that

may contain light (few) particles.

It is available in packs containing

either 1 vial of 40 mg in4 mL or 1

vial of 100 mg in 10 mL.

HOW TO STORE OPDIVO

It is unlikely that you will be asked to

store OPDIVO yourself. It will be

stored in the hospital or clinic where

it is given to you.

Sponsored by

Bristol-Myers Squibb (NZ) Limited

88 Shortland Street

Auckland 1010

NEW ZEALAND

Date of preparation:

March 2021

OPDIVO

(nivolumab) is a

registered trademark of Bristol-

Myers Squibb Company

Read the complete document

OPDIVO V21.0

DATA SHEET

1

PRODUCT NAME

OPDIVO 10 mg/mL concentrate for solution for infusion.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 mL of concentrate contains 10 mg of nivolumab.

Each 40 mg/4mL vial contains 40 mg of nivolumab in 4mL of solution.

Each 100 mg/10mL vial contains 100 mg of nivolumab in 10mL of solution.

OPDIVO (nivolumab (rch)) is a fully human anti-PD-1 monoclonal antibody (IgG4) produced in

mammalian (Chinese hamster ovary) cells by recombinant DNA technology.

Excipient with known effect

Each 1 mL of concentrate contains 0.1 mmol (or 2.5 mg) sodium.

For the full list of excipients, see section 6.1 List of excipients.

3

PHARMACEUTICAL FORM

Concentrate for solution for infusion.

Clear to opalescent, colorless to pale yellow liquid that may contain few light particles. The solution

has a pH of approximately 6.0 and an osmolarity of approximately 340 mOsm/kg.

4

CLINICAL PARTICULARS

4.1

THERAPEUTIC INDICATIONS

Melanoma

OPDIVO, as monotherapy, is indicated for the adjuvant treatment of patients with melanoma with

involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO, as monotherapy, is indicated for the treatment of patients with unresectable or metastatic

melanoma.

OPDIVO, in combination with ipilimumab, is indicated for the treatment of patients with unresectable

or metastatic melanoma. The approval of this indication is based on a pre-specified comparison to

ipilimumab

monotherapy.

analyses

comparing

nivolumab

monotherapy

with

nivolumab/ipilimumab combination are descriptive.

Non-Small Cell Lung Cancer (NSCLC)

OPDIVO, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy, is indicated

for the first-line treatment of patients with metastatic or recurrent non-small cell lung cancer (NSCLC)

with no EGFR or ALK genomic tumour aberrations.

OPDIVO, as monotherapy, is indicated for the treatment of locally advanced or metastatic squamous

non-small cell lung cancer (NSCLC) with progression on or after prior chemotherapy.

OPDIVO, as monotherapy is indicated for the treatment of locally advanced or metastatic non squamous

non-small cell lung cancer (NSCLC) with progression on or after prior chemotherapy. In patients with

OPDIVO V21.0

tumour EGFR or ALK genomic aberrations, OPDIVO should be used after progression on or after

targeted therapy.

Renal Cell Carcinoma (RCC)

OPDIVO,

combination

with

ipilimumab,

indicated

treatment

patients

with

intermediate/poor-risk, previously untreated advanced renal cell carcinoma.

OPDIVO, as monotherapy, is indicated for the treatment of patients with advanced clear cell renal cell

carcinoma after prior anti-angiogenic therapy.

Classical Hodgkin lymphoma (cHL)

OPDIVO, as monotherapy, is indicated for the treatment of adult patients with relapsed or refractory

classical

Hodgkin

lymphoma

(cHL)

after

autologous

stem

cell

transplant

treatment

with

brentuximab vedotin. The approval of this indication is based on objective response rate. See

CLINICAL TRIALS.

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

OPDIVO, as monotherapy is indicated for the treatment of recurrent or metastatic squamous cell cancer

of the head and neck in adults progressing on or after platinum based therapy.

Urothelial Carcinoma (UC)

OPDIVO, as monotherapy, is indicated for the treatment of patients with locally advanced unresectable

or metastatic urothelial carcinoma after prior platinum-containing therapy. The approval of this

indication is based on objective response rate and duration of response in a single arm study.

Hepatocellular Carcinoma (HCC)

OPDIVO, as monotherapy, is indicated for the treatment of patients with hepatocellular carcinoma

after prior sorafenib therapy. This indication is approved based on objective response rate and duration

of response in a single arm study. An improvement in survival or disease-related symptoms has not

been established.

4.2

DOSE AND METHOD OF ADMINISTRATION

Treatment must be initiated and supervised by specialist physicians experienced in the treatment of

cancer.

Dose escalation or reduction is not recommended. Guidelines for permanent discontinuation or

withholding of doses are described in Table 1. Detailed guidelines for the management of immune-

related adverse reactions are described in Section 4.4.

Nivolumab was originally developed using every two weeks dosing when used as monotherapy (see

Section 5.1 Pharmacodynamic Properties – Clinical efficacy and safety). Subsequent approval of the

every four weeks dosing when used as monotherapy was based on pharmacokinetic modelling and

exposure-response modelling and simulations and supportive clinical safety data. Therefore, when

selecting a dosing regimen for nivolumab monotherapy, clinicians should consider individual patient

factors and that there is more clinical evidence to support every two weeks dosing.

OPDIVO MONOTHERAPY

Unresectable or metastatic melanoma, Squamous NSCLC, non squamous NSCLC, renal cell

carcinoma, relapsed/refractory classical Hodgkin lymphoma, recurrent or metastatic squamous

cell carcinoma of the head and neck, urothelial carcinoma, melanoma with involvement of lymph

nodes or metastatic disease after complete resection and hepatocellular carcinoma.

OPDIVO V21.0

The recommended dose of OPDIVO as a monotherapy administered intravenously over 30 minutes is

3mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks . Treatment should be

continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient.

The maximum treatment duration with OPDIVO as monotherapy for adjuvant melanoma is 12 months.

OPDIVO IN COMBINATION WITH IPILIMUMAB

OPDIVO and ipilimumab should be administered and monitored under the supervision of

physicians experienced with the use of immunotherapy.

Please review the full prescribing information for ipilimumab prior to initiation of OPDIVO in

combination with ipilimumab.

In the initial combination phase, administer OPDIVO and ipilimumab on the same day. Use separate

infusion bags and filters for each infusion. Administer OPDIVO first followed by ipilimumab, after

completion of the OPDIVO infusion.

Unresectable or metastatic melanoma

Combination Phase:

The recommended dose of OPDIVO in the combination phase is 1mg/kg administered intravenously

over 30 minutes every 3 weeks for the first 4 doses in combination with ipilimumab 3mg/kg

administered intravenously over 90 minutes. This should be followed by OPDIVO monotherapy

therapy in the single-agent phase (see below).

Single-agent Phase:

The recommended dose of OPDIVO in the single-agent phase is administered intravenously over 30

minutes is 3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks. Following the

last dose of the combination of nivolumab and ipilimumab, the first dose of nivolumab monotherapy

should be administered after 3 weeks when using 3 mg/kg or 240 mg or 6 weeks when using 480 mg.

Treatment with OPDIVO in the single agent phase, should be continued as long as clinical benefit is

observed or until treatment is no longer tolerated by the patient.

RCC

Combination Phase:

The recommended dose is 3 mg/kg nivolumab administered as an intravenous infusion over 30 minutes

every 3 weeks for the first 4 doses in combination with 1 mg/kg ipilimumab administered intravenously

over 30 minutes.

Single-agent Phase:

recommended

dose

OPDIVO

single

agent

phase

administered

intravenously

over30 minutes is 3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks. Following

the last dose of the combination of nivolumab and ipilimumab, the first dose of nivolumab monotherapy

should be administered after 3 weeks when using 3 mg/kg or 240 mg or 6 weeks when using 480 mg.

Treatment with OPDIVO in the single-agent phase should be continued as long as clinical benefit is

observed or until treatment is no longer tolerated by the patient.

NSCLC

The recommended dose is 360 mg OPDIVO administered as an intravenous infusion over 30 minutes

every 3 weeks in combination with 1 mg/kg ipilimumab administered as an intravenous infusion over

30 minutes every 6 weeks, and platinum chemotherapy administered every 3 weeks. After completion

of 2 cycles of chemotherapy, treatment is continued with 360 mg OPDIVO administered as an

intravenous infusion every 3 weeks in combination with 1 mg/kg ipilimumab every 6 weeks until

disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

OPDIVO V21.0

RECOMMENDED

TREATMENT

MODIFICATIONS

FOR

OPDIVO

AS

MONOTHERAPY

AND

OPDIVO

IN

COMBINATION

WITH

OTHER

THERAPEUTIC AGENTS

Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required

based on individual safety and tolerability.

When OPDIVO is administered in combination with ipilimumab, if either agent is withheld, the other

agent should also be withheld.

Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first

few months followed by tumour shrinkage) have been observed. It is recommended to continue

treatment with nivolumab for clinically stable patients with initial evidence of disease progression until

disease progression is confirmed.

Table 1: Recommended treatment modifications for OPDIVO as monotherapy or OPDIVO in

combination with other therapeutic agents

Immune-related

adverse reaction

Severity of Adverse Reaction

a

Treatment modification

Immune-related

pneumonitis

Grade 2 pneumonitis

Withhold dose(s) until symptoms

resolve, radiographic abnormalities

improve, and management with

corticosteroids is complete.

Grade 3 or 4 pneumonitis

Permanently discontinue treatment.

Immune-related colitis

Grade 2 diarrhoea or colitis

Withhold dose(s) until symptoms

resolve and management with

corticosteroids, if needed, is complete.

Grade 3 diarrhoea or colitis

- OPDIVO monotherapy

Withhold dose(s) until symptoms

resolve and management with

corticosteroids is complete.

Grade 3 diarrhoea or colitis

- OPDIVO+ipilimumab

Permanently discontinue treatment.

Grade 4 diarrhoea or colitis

Immune-related

hepatitis

Patients with normal AST/ALT/bilirubin

at baseline:

Grade 2 elevation in aspartate

aminotransferase (AST), alanine

aminotransferase (ALT), or total bilirubin

Withhold dose(s) until laboratory

values return to baseline and

management with corticosteroids, if

needed, is complete.

Grade 3 or 4 elevation in AST, ALT, or

total bilirubin

Permanently discontinue treatment.

OPDIVO V21.0

Table 1: Recommended treatment modifications for OPDIVO as monotherapy or OPDIVO in

combination with other therapeutic agents

Immune-related

adverse reaction

Severity of Adverse Reaction

a

Treatment modification

HCC patients with elevated AST/ALT at

baseline:

Grade 1 elevation in AST/ALT at

baseline (>1 to 3 times upper limit of

normal [ULN]) and on-treatment

AST/ALT elevation at >5-10 times the

ULN.

Grade 2 elevation in AST/ALT at

baseline (>3 to 5 times ULN) and

on-treatment AST/ALT elevation at

>8-10 times ULN.

Withhold dose(s) until laboratory

values return to baseline and

management with corticosteroids, if

needed, is complete.

AST/ALT >10 time ULN or Grade 3 or 4

elevation in total bilirubin.

Permanently discontinue treatment.

Immune-related

nephritis and renal

dysfunction

Grade 2 or 3 creatinine elevation

Withhold dose(s) until creatinine

returns to baseline and management

with corticosteroids is complete.

Grade 4 creatinine elevation

Permanently discontinue treatment.

Immune-related

endocrinopathies

Symptomatic Grade 2 or 3

hypothyroidism, hyperthyroidism,

hypophysitis

Grade 2 adrenal insufficiency

Grade 3 diabetes

Withhold dose(s) until symptoms

resolve and management with

corticosteroids (if needed for

symptoms of acute inflammation) is

complete. OPDIVO should be

continued in the presence of hormone

replacement therapy

as long as no

symptoms are present.

Grade 4 hypothyroidism

Grade 4 hyperthyroidism

Grade 4 hypophysitis

Grade 3 or 4 adrenal insufficiency

Grade 4 diabetes

Permanently discontinue treatment.

Immune-related skin

adverse reactions

Grade 3 rash

Withhold dose(s) until symptoms

resolve and management with

corticosteroids is complete.

Suspected Stevens-Johnson syndrome

(SJS) or toxic epidermal necrolysis

(TEN)

Withhold dose(s).

Grade 4 rash

Confirmed SJS/TEN

Permanently discontinue treatment.

Immune-related

neurological adverse

reactions

New onset moderate or severe neurologic

signs or symptoms

Withhold dose(s) until symptoms

resolve and management with

corticosteroids is complete.

OPDIVO V21.0

Table 1: Recommended treatment modifications for OPDIVO as monotherapy or OPDIVO in

combination with other therapeutic agents

Immune-related

adverse reaction

Severity of Adverse Reaction

a

Treatment modification

Immune-related encephalitis

Immune-related myasthenic

syndrome/myasthenia gravis

Permanently discontinue treatment.

Immune-related

myocarditis

Grade 2 myocarditis

Withhold dose(s) until symptoms

resolve and management with

corticosteroids is complete.

Retreatment may be considered after

recovery.

Grade 3 myocarditis

Permanently discontinue treatment.

Other immune-related

adverse reactions

Other Grade 3 adverse reaction

First occurrence

Withhold dose(s) until symptoms

resolve and management with

corticosteroids is complete.

Recurrence of same Grade 3 adverse

reaction

Permanently discontinue treatment.

Grade 3 myotoxicity

Permanently discontinue treatment.

Life-threatening or Grade 4 adverse

reaction

Permanently discontinue treatment.

Inability to reduce corticosteroid dose to

10 mg prednisone or equivalent per day

Persistent Grade 2 or 3 adverse reactions

despite treatment modification

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events

Version 4.0 (NCI-CTCAE v4).

Recommendation for the use of hormone replacement therapy is provided in Section 4.4 Precautions.

Special populations

Paediatric population

The safety and efficacy of OPDIVO in children below 18 years of age have not been established. No

data are available. OPDIVO should not be used in children below 18 years of age.

Elderly

No overall differences in safety or efficacy were reported between elderly (≥ 65 years) and younger

patients (< 65 years). No dose adjustment is required for elderly patients (≥ 65 years) (see section 5.2).

Renal impairment

The safety and efficacy of OPDIVO have not been studied in patients with severe renal impairment.

Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with

mild or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment

are too limited to drawn conclusions from this population.

OPDIVO V21.0

Hepatic impairment

The safety and efficacy of OPDIVO have not been studied in patients with severe hepatic impairment

or with cirrhosis of Child-Pugh B or C severity. OPDIVO must be administered with caution in these

patients. Data from patients with moderate hepatic impairment are too limited

Method of administration

OPDIVO infusion must not be administered as an intravenous push or bolus injection.

Administer the OPDIVO infusion intravenously over a period of 30 minutes.

OPDIVO infusion should not be infused at the same time in the same intravenous line with other agents.

Use a separate infusion line for the infusion.

Administer OPDIVO in combination with other therapeutic agents as follows:

With ipilimumab: administer OPDIVO first followed by ipilimumab on the same day.

With platinum-doublet chemotherapy: administer OPDIVO first followed by

platinum-doublet chemotherapy on the same day.

With ipilimumab and platinum-doublet chemotherapy: administer OPDIVO first followed by

ipilimumab and then platinum-doublet chemotherapy on the same day.

Use separate infusion bags and filters for each infusion. Administer OPDIVO first followed by

ipilimumab, no earlier than 30 minutes after completion of the OPDIVO infusion.

Use an infusion set and an in-line, sterile, non-pyrogenic, low protein binding filter (pore size of 0.2 μm

to 1.2 μm).

OPDIVO infusion is compatible with:

PVC or non-PVC containers

Polyolefin containers

Glass bottles

PVC infusion sets

In-line filters with polyethersulfone membranes with pore sizes of 0.2 μm to 1.2 μm.

After administration of dose, flush the line with sodium chloride 9 mg/mL (0.9%) solution for injection

or 50 mg/mL (5%) glucose solution for injection.

Calculating the dose

More than one vial of OPDIVO concentrate may be needed to give the total dose for the patient.

When the prescribed dose for the patient is 240 mg, 360 mg or 480 mg, it is given regardless of body

weight.

When the prescribed dose for the patient is 3 mg/kg or 1 mg/kg, calculate the total dose to be given.

Each 4 mL vial of OPDIVO concentrate contains 40 mg of nivolumab; each 10 mL vial of OPDIVO

contains 100 mg of nivolumab.

The total nivolumab dose in mg = the patient’s weight in kg × the prescribed dose in mg/kg.

The volume of OPDIVO concentrate to prepare the dose (mL) = the total dose in mg, divided by 10

(the OPDIVO concentrate strength is 10 mg/mL).

OPDIVO V21.0

Preparing the infusion

Preparation should be performed by trained personnel in accordance with good practice rules, especially

with respect to asepsis.

OPDIVO can be used for intravenous administration without dilution, after transfer to an infusion

container using an appropriate sterile syringe.

OPDIVO can also be used for intravenous administration after diluting with either sodium chloride

9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection. For 3

mg/kg or 1 mg/kg dose, the final infusion concentration should range between 1 and 10 mg/mL.

For 240 mg, 360 mg or 480 mg, the concentrate may be diluted to not exceed a total infusion

volume of 160 mL. For patients with body weight less than 40 kg, the total volume of infusion must

not exceed 4 mL/kg of body weight.

STEP 1

Inspect the OPDIVO concentrate for particulate matter or discoloration. Do not shake.

OPDIVO concentrate is a clear to opalescent, colourless to pale yellow liquid that may contain

a few light particles. Discard the vial if the solution is cloudy, is discoloured, or contains

particulate matter other than a few translucent-to-white particles.

Withdraw the required volume of OPDIVO concentrate using an appropriate sterile syringe.

STEP 2

Transfer the concentrate into a sterile, evacuated glass bottle or IV container (PVC, non-PVC

or polyolefin).

If applicable, dilute with the required volume of sodium chloride 9 mg/mL (0.9%) solution for

injection or 50 mg/mL (5%) glucose solution for injection. For ease of preparation, the

concentrate can also be transferred directly into a pre-filled bag containing the appropriate

volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose

solution for injection.

Gently mix the infusion by manual rotation. Do not shake.

4.3

CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients.

4.4

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Early identification of adverse reactions and intervention are an important part of the safe use of

OPDIVO with or without ipilimumab.

OPDIVO monotherapy is associated with immune-related adverse reactions. In clinical trials, immune-

related adverse reactions have occurred at higher frequencies when OPDIVO was administered in

combination with ipilimumab compared with OPDIVO as a monotherapy. Most immune-related

adverse

reactions

improved

resolved

with

appropriate

management,

including

initiation

corticosteroids and dose modifications.

Patients should be monitored continuously as an adverse reaction with OPDIVO monotherapy or

OPDIVO in combination with ipilimumab may occur at any time during or after discontinuation of

therapy. The majority of these initially manifested during treatment; however, a minority occurred

weeks to months after discontinuation.

Clinicians should consider immune-related adverse reactions for all unexplained illnesses. Adequate

evaluation should be performed to confirm aetiology or exclude other causes.

OPDIVO V21.0

Based on the severity of the adverse reaction, OPDIVO monotherapy or OPDIVO in combination with

ipilimumab should be withheld (see Section 4.2) and corticosteroids administered.

If immunosuppression with corticosteroids is used to treat an adverse reaction, a taper of at least one

month duration should be initiated upon improvement. Rapid tapering may lead to worsening or

recurrence of the adverse reaction.

Non-corticosteroid

immunosuppressive

therapy

should

added

there

worsening

improvement despite corticosteroid use.

OPDIVO monotherapy or OPDIVO in combination with ipilimumab should not be resumed while the

patient is receiving immunosuppressive doses of corticosteroids or other immunosuppressive therapy.

Prophylactic antibiotics should be used to prevent opportunistic infections in patients receiving

immunosuppressive therapy.

OPDIVO monotherapy or OPDIVO in combination with ipilimumab must be permanently discontinued

for any severe immune related adverse reaction that recurs and for any life threatening immune related

adverse reaction (see Section 4.2).

Immune-related pneumonitis

Severe pneumonitis or interstitial lung disease, including fatal cases, has been observed with OPDIVO

monotherapy or OPDIVO in combination with ipilimumab.

Patients should be monitored for signs and symptoms of pneumonitis such as radiographic changes

(e.g., focal ground glass opacities, patchy filtrates), dyspnoea, and hypoxia. Infectious and disease-

related aetiologies should be ruled out.

For Grade 3 or 4 pneumonitis, OPDIVO monotherapy or OPDIVO in combination with ipilimumab,

must be permanently discontinued and corticosteroids should be initiated at a dose of 2 to 4 mg/kg/day

methylprednisolone equivalents.

For Grade 2 (symptomatic) pneumonitis, OPDIVO monotherapy or OPDIVO in combination with

ipilimumab,

should

withheld

corticosteroids

initiated

dose

mg/kg/day

methylprednisolone

equivalents.

Upon

improvement,

OPDIVO

monotherapy

OPDIVO

combination with ipilimumab, may be resumed (after corticosteroid taper). If worsening or no

improvement occurs despite initiation of corticosteroids, corticosteroid dose should be increased to 2 to

4 mg/kg/day methylprednisolone equivalents and OPDIVO monotherapy or OPDIVO in combination

with ipilimumab, must be permanently discontinued.

Immune-related colitis

Severe diarrhoea or colitis has been observed with OPDIVO monotherapy or OPDIVO in combination

with ipilimumab. Patients should be monitored for diarrhoea and additional symptoms of colitis, such

as abdominal pain and mucus or blood in stool. Infectious and disease-related aetiologies should be

ruled

out.

Cytomegalovirus

(CMV)

infection/reactivation

been

reported

patients

with

corticosteroid-refractory immune-related colitis. Stool infections work-up (including CMV, other viral

aetiology, culture, Clostridium difficile, ova, and parasite) should be performed upon presentation of

diarrhoea or colitis to exclude infectious or other alternate aetiologies.

For Grade 4 diarrhoea or colitis, OPDIVO monotherapy or OPDIVO in combination with ipilimumab,

must be permanently discontinued and corticosteroids should be initiated at a dose of 1 to 2 mg/kg/day

methylprednisolone equivalents.

For Grade 3 diarrhoea or colitis observed with OPDIVO in combination with ipilimumab, permanently

discontinue both agents and follow the management guideline for Grade 4 diarrhoea or colitis above.

OPDIVO monotherapy should be withheld for Grade 3 diarrhoea or colitis and corticosteroids initiated

dose

of 1 to 2 mg/kg/day

methylprednisolone

equivalents.

Upon

improvement,

OPDIVO

OPDIVO V21.0

monotherapy may be resumed (after corticosteroid taper). If worsening or no improvement occurs

despite initiation of corticosteroids, OPDIVO monotherapy must be permanently discontinued.

For Grade 2 diarrhoea or colitis, OPDIVO monotherapy or OPDIVO in combination with ipilimumab,

should be withheld. Persistent diarrhoea or colitis should be managed with corticosteroids at a dose of

0.5 to 1 mg/kg/day methylprednisolone equivalents. Upon improvement, OPDIVO monotherapy or

OPDIVO in combination with ipilimumab, may be resumed (after corticosteroid taper). If worsening or

no improvement occurs despite initiation of corticosteroids, corticosteroid dose should be increased to

mg/kg/day

methylprednisolone

equivalents

OPDIVO

monotherapy

OPDIVO

combination with ipilimumab, must be permanently discontinued.

The experience from clinical trials on the management of corticosteroid-refractory diarrhoea or colitis

is limited. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or

replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-

related colitis if other causes are excluded (including CMV infection/reactivation evaluated with viral

PCR on biopsy, and other viral, bacterial, and parasitic aetiology).

Immune-related hepatitis

Severe hepatitis has been observed with OPDIVO monotherapy or OPDIVO in combination with

ipilimumab. Infectious and disease-related aetiologies should be ruled out.

Elevations in liver function tests may develop in the absence of clinical symptoms. Monitor patients for

abnormal liver tests prior to and periodically during treatment as indicated based on clinical evaluation.

For Grade 3 or 4 transaminase or total bilirubin elevation, OPDIVO monotherapy or OPDIVO in

combination with ipilimumab, must be permanently discontinued and corticosteroids should be initiated

at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents.

Grade

transaminase

total

bilirubin

elevation,

OPDIVO

monotherapy

OPDIVO

combination with ipilimumab should be withheld. Persistent elevations in these laboratory values

should be managed with corticosteroids at a dose of 0.5 to 1 mg/kg/day methylprednisolone equivalents.

Upon improvement OPDIVO monotherapy or OPDIVO in combination with ipilimumab, may be

resumed (after corticosteroid taper).

If worsening or no improvement occurs despite initiation of corticosteroids, corticosteroid dose should

be increased to 1 to 2 mg/kg/day methylprednisolone equivalents and OPDIVO monotherapy or

OPDIVO in combination with ipilimumab must be permanently discontinued.

Management

of

transaminase

elevation

in

patients

with

HCC

(see

also

DOSAGE

ADMINISTRATION)

In patients with HCC, nivolumab monotherapy should be withheld or permanently discontinued based

on the following criteria and corticosteroids initiated at a dose of 1 to 2 mg/kg methylprednisolone

equivalent.

For Grade 1 transaminase levels at baseline (>1 to 3 times ULN) and on-treatment transaminase

elevation at >5 to 10 times ULN, nivolumab should be withheld

For Grade 2 transaminase levels at baseline (> 3 to 5 times ULN) and on-treatment transaminase

elevation at >8 to 10 times ULN, nivolumab should be withheld

Regardless of baseline transaminase levels, nivolumab must be permanently discontinued for on-

treatment transaminase increases > 10 times ULN or Grade 3 or 4 total bilirubin increases.

Immune-related nephritis and renal dysfunction

Severe nephritis and renal dysfunction have been observed with OPDIVO monotherapy or OPDIVO in

combination with ipilimumab. Disease-related aetiologies should be ruled out.

Creatinine elevations may develop in the absence of clinical symptoms. Monitor patients for elevated

serum creatinine prior to and periodically during treatment as indicated based on clinical evaluation.

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