Blincyto

1. Blincyto

Medicines can interact with certain foods. In some cases this may be harmful and your doctor may advise you to avoid certain foods. In the case of Blincyto, there are no specific foods that you must exclude from your diet when receiving this medication.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of blinatumomab injection in the elderly. However, elderly patients are more likely to have unwanted effects (eg, confusion, encephalopathy, infections) in patients which may require caution in patients receiving blinatumomab injection.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Antineoplastic agent; a CD3 T-cell-engaging anti-CD19 monoclonal antibody.1 11 12 13 15

Contraindications

• Known hypersensitivity to blinatumomab or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Cytokine release syndrome, sometimes life-threatening or fatal, reported;1 2 peak cytokine release observed within 2 days following initiation of blinatumomab.9

Serious adverse effects associated with cytokine release syndrome include pyrexia, headache, nausea, asthenia, hypotension, and elevated ALT, AST, and bilirubin concentrations; most patients in clinical studies did not require discontinuance of therapy.1 Disseminated intravascular coagulation, capillary leak syndrome, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome also reported.1 Infusion-related reactions may be clinically indistinguishable from manifestations of cytokine release syndrome.1

Closely monitor patients for signs and symptoms of cytokine release syndrome.1 (See Advice to Patients.) Interruption or discontinuance of therapy may be necessary.1 (See Cytokine Release Syndrome under Dosage and Administration.)

Neurologic toxicities occur commonly;1 2 median time to onset is 7 days.1 Severe, life-threatening, or fatal toxicity (e.g., encephalopathy, seizures, speech impairment, disturbances in consciousness, confusion and disorientation, coordination and balance disorders) can occur.1 Patients should not drive a motor vehicle or engage in hazardous occupations or activities (e.g., operating hazardous machinery) while receiving the drug.1

Neurologic toxicity generally resolves following treatment interruption; however, discontinuance of therapy may be necessary.1 In the principal efficacy study, grade 1 or 2 neurologic toxicities were managed with dexamethasone without treatment interruption.2

Monitor patients for manifestations of neurologic toxicities.1 (See Advice to Patients.) Interruption or discontinuance of therapy may be necessary.1 (See Neurologic Toxicity under Dosage and Administration.)

Other Warnings and Precautions

Serious infections (e.g., sepsis, pneumonia, bacteremia, opportunistic infections, catheter-site infections), sometimes life-threatening or fatal, reported.1

Initiate prophylactic anti-infective therapy as appropriate and employ surveillance testing during blinatumomab therapy.1 Monitor patients for signs and symptoms of infection; initiate appropriate anti-infective treatment as clinically indicated.1

Tumor lysis syndrome, sometimes life-threatening or fatal, reported.1

Monitor patients for signs and symptoms of tumor lysis syndrome; interruption or discontinuance of blinatumomab therapy may be necessary.1 Initiate appropriate prophylactic measures (e.g., pretreatment nontoxic cytoreduction, adequate hydration during therapy).1

Neutropenia and febrile neutropenia, sometimes life-threatening, reported.1

Monitor CBC, including differential.1 If prolonged neutropenia occurs, interrupt therapy.1

Transient increases in hepatic enzyme concentrations reported; median time to onset is 15 days.1 Mostly occurs in association with cytokine release syndrome.1

Evaluate serum ALT, AST, γ-glutamyltransferase (γ-glutamyltranspeptidase, GGT, GGTP), and total bilirubin concentrations prior to and during blinatumomab therapy.1 If ALT and/or AST concentrations >5 times the ULN or total bilirubin concentrations >3 times the ULN occur, interrupt blinatumomab therapy.1

Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy reported, particularly in those who previously received cranial irradiation and antileukemic chemotherapy (including systemic high-dose methotrexate or intrathecal cytarabine).1 The clinical importance of these changes is not known.1

Medication errors resulting in underdosage or overdosage of blinatumomab have occurred.1 Exercise extra care to ensure proper preparation and administration of the drug.1 (See Preparation and Administration Precautions under Dosage and Administration.)

Antibodies to blinatumomab, including neutralizing antibodies to the drug, reported.1 Pharmacokinetics may be affected.1 No clinically important effects on safety observed to date.1

Specific Populations

Category C.1

May cause fetal harm, including B-cell lymphocytopenia.1 Embryofetal toxicity and teratogenicity not observed in animal studies; however, the surrogate molecule crossed the placenta.1 B-cell and T-cell depletion occurred in pregnant mice; however, hematologic effects were not assessed in fetuses.1

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.1

Not known whether blinatumomab is distributed into milk.1 Discontinue nursing or the drug.1

Limited experience in pediatric patients.1

Dose-limiting toxicity was cytokine release syndrome in pediatric patients (2–17 years of age) with relapsed or refractory pre-B-ALL;1 6 7 10 incidence decreased with stepwise dosing of blinatumomab (5 mcg/m2 daily initially for 7 days, then 15 mcg/m2 daily).6 Fatal respiratory failure and grade 4 cytokine release syndrome resulting in fatal cardiac failure and life-threatening GI hemorrhage reported following administration of blinatumomab 15–30 mcg/m2 daily.1 6 7

Pharmacokinetic parameters similar to those reported in adults with relapsed or refractory pre-B-ALL who received equivalent dosages based on body surface area.1 6 (See Special Populations under Pharmacokinetics.)

Dosage of 5 mcg/m2 daily on days 1–7 followed by 15 mcg/m2 daily on days 8–28 of cycle 1, then 15 mcg/m2 daily on days 1–28 of subsequent cycles, recommended for phase 2 studies.1 7

In clinical studies in patients with relapsed or refractory ALL, approximately 13% of patients were ≥65 years of age.1 Efficacy and safety of the drug was generally similar regardless of patient age, except for increased incidence of neurologic toxicities (e.g., cognitive disorder, encephalopathy, confusion) and serious infections in patients ≥65 years of age.1

Pharmacokinetics not studied in patients with hepatic impairment.1

Formal pharmacokinetic studies not conducted in patients with renal impairment.1 Clearance affected by moderate renal impairment; however, high interpatient variability was apparent.1 (See Special Populations under Pharmacokinetics.)

Not studied in patients with severe renal impairment (Clcr <30 mL/minute) or in those receiving hemodialysis.1

Common Adverse Effects

Pyrexia,1 2 infection,1 headache,1 2 peripheral edema,1 2 febrile neutropenia,1 2 nausea,1 2 hypokalemia,1 2 rash,1 constipation,1 2 diarrhea,1 tremor.1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of blinatumomab injection in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of blinatumomab injection in the elderly. However, elderly patients are more likely to have unwanted effects (eg, confusion, encephalopathy, infections) in patients which may require caution in patients receiving blinatumomab injection.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Aminophylline
• Artemether
• Astemizole
• Carbamazepine
• Cisapride
• Cyclosporine
• Dihydroergotamine
• Ergotamine
• Fentanyl
• Fosphenytoin
• Iloperidone
• Lumefantrine
• Paclitaxel
• Phenytoin
• Pimozide
• Quinidine
• Sirolimus
• Tacrolimus
• Terfenadine
• Theophylline
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Encephalopathy or
• Liver disease or
• Neutropenia (low number of white blood cells) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.

• Infections—May decrease your body's ability to fight infections.

It is very important that your doctor check your or your child's progress at regular visits to make sure this medicine is working properly. Blood tests are needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control during treatment and for at least 48 hours after your treatment ends to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may cause cytokine release syndrome (CRS) and infusion reactions. This may be life-threatening and requires immediate attention. Tell your doctor right away if you or your child have any of the following symptoms: a fever, chills, headache, nausea, lightheadedness, dizziness, fainting, skin rash, trouble breathing, or tiredness or weakness.

Check with your doctor right away if you or your child have seizures, loss of balance, loss of consciousness, confusion, disorientation, difficulty with speaking, or slurred speech.

This medicine can temporarily lower the number of white blood cells in your blood, which increases the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you or your child are getting an infection or if you have a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

This medicine may cause a serious reaction, called tumor lysis syndrome (TLS). Your doctor may give you a medicine to help prevent this. Call your doctor right away if you or your child have a change in how much or how often you urinate, muscle or joint pain, rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you or your child have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

This medicine may make youdizzy, confused, or less alert than youare normally. Do not drive or do anything else that could be dangerous until you or your child know how this medicine affects you.

While you are being treated with blinatumomab, do not have any immunizations (vaccinations) without your doctor's approval. Live virus vaccinations should not be given for at least 2 weeks before start of treatment, during treatment, and until recovery following the last cycle of this medicine.

Some preparations of this medicine may contain benzyl alcohol which may cause serious reactions (including gasping syndrome) to newborn or premature infants.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Agitation
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• chest pain
• confusion
• cough or hoarseness
• dizziness
• fever or chills
• headache
• irritability
• lower back or side pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• rapid, shallow breathing
• seeing, hearing, or feeling things that are not there
• seizures
• sore throat
• stiff neck
• tightness in the chest
• tingling of the hands or feet
• troubled breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting

• Cloudy urine
• darkened urine
• discouragement
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• extremely high fever or body temperature
• eye pain
• feeling sad or empty
• general feeling of illness
• irritability
• lack or loss of strength
• loss of interest or pleasure
• mood or mental changes
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent bleeding or oozing from puncture sites, mouth, or nose
• pounding in the ears
• problems with speech or speaking
• rash
• slow or fast heartbeat
• stomach pain
• sweating
• swelling of the hands, ankles, feet, or lower legs
• trouble sleeping
• ulcers, sores, or white spots in the mouth
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bone, joint, or muscle pain
• change in urination
• decreased appetite
• diarrhea
• difficulty having a bowel movement
• dry mouth
• increased hunger or thirst
• irregular heartbeat
• muscle pain or cramps
• pain in the arms or legs
• shakiness in the legs, arms, hands, or feet

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Overdoses have been observed, including one adult patient who received 133-fold the recommended therapeutic dose of Blincyto delivered over a short duration.

In the dose evaluation phase of the Phase 1/2 study in pediatric and adolescent patients with relapsed or refractory B-cell precursor ALL, one patient experienced a fatal cardiac failure event in the setting of life-threatening cytokine release syndrome (CRS) at a 30 mcg/m2/day (higher than the maximum tolerated/recommended) dose [see Warnings and Precautions (5.1) and Adverse Reactions (6)]. 

Overdoses resulted in adverse reactions, which were consistent with the reactions observed at the recommended therapeutic dose and included fever, tremors, and headache. In the event of overdose, interrupt the infusion, monitor the patient for signs of toxicity, and provide supportive care [see Warnings and Precautions (5.10)]. Consider re-initiation of Blincyto at the correct therapeutic dose when all toxicities have resolved and no earlier than 12 hours after interruption of the infusion [see Dosage and Administration (2.1)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Cytokine Release Syndrome (CRS)
Advise patients of the risk of CRS and infusion reactions, and to contact their healthcare professional for signs and symptoms associated with CRS or infusion reactions (pyrexia, fatigue, nausea, vomiting, chills, hypotension, rash, and wheezing) [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

Neurological Toxicities
Advise patients of the risk of neurological toxicities, and to contact their healthcare professional for signs and symptoms associated with this event (convulsions, speech disorders, and confusion) [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

Infections
Advise patients of the risk of infections, and to contact their healthcare professional for signs or symptoms of infection [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

Inform patients of the importance of keeping the skin clean around the intravenous catheter to reduce the risk of infection.

Pancreatitis
Advise patients of the risk of pancreatitis and to contact their healthcare provider for signs or symptoms of pancreatitis which include severe and persistent stomach pain, with or without nausea and vomiting [see Warnings and Precautions (5.8) and Adverse Reactions (6.2)].

Driving and Engaging in Hazardous Occupations
Advise patients to refrain from driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while Blincyto is being administered.  Patients should be advised that they may experience neurological events [see Warnings and Precautions (5.6)]. 

Infusion Pump Errors
Inform patients they should not adjust the setting on the infusion pump. Any changes to pump function may result in dosing errors. If there is a problem with the infusion pump or the pump alarms, patients should contact their doctor or nurse immediately.

Blincyto® (blinatumomab)

Manufactured by:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, California 91320-1799
U.S. License No. 1080

Patent: http://pat.amgen.com/Blincyto/

© 2014-2017 Amgen Inc. All rights reserved.

v5            

This Medication Guide has been approved by the U.S. Food and Drug Administration.                         Revised: 07/2017

PRINCIPAL DISPLAY PANEL
1 Blincyto® Single-Dose Vial
1 IV Solution Stabilizer Vial
NDC 55513-160-01
AMGEN®
Blincyto®
(blinatumomab)
for Injection
35 mcg/vial
35 mcg/vial
For Intravenous Infusion Only
Store at 2°C to 8°C (36°F to 46°F).
Store in carton to protect from light.
DO NOT SHAKE reconstituted solution.
Dispense the enclosed Medication Guide to each patient.
No Preservative
Single-Dose Vial –
Discard unused portion.
Rx Only

Applies to blinatumomab: intravenous powder for solution

Along with its needed effects, blinatumomab (the active ingredient contained in Blincyto) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking blinatumomab:

• Agitation
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• chest pain
• confusion
• cough or hoarseness
• dizziness
• fever or chills
• headache
• irritability
• lower back or side pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• rapid, shallow breathing
• seeing, hearing, or feeling things that are not there
• seizures
• sore throat
• stiff neck
• tightness in the chest
• tingling of the hands or feet
• troubled breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting

• Cloudy urine
• darkened urine
• discouragement
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• extremely high fever or body temperature
• eye pain
• feeling sad or empty
• general feeling of illness
• irritability
• lack or loss of strength
• loss of interest or pleasure
• mood or mental changes
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent bleeding or oozing from puncture sites, mouth, or nose
• pounding in the ears
• problems with speech or speaking
• rash
• slow or fast heartbeat
• stomach pain
• sweating
• swelling of the hands, ankles, feet, or lower legs
• trouble sleeping
• ulcers, sores, or white spots in the mouth
• yellow eyes or skin

Some side effects of blinatumomab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bone, joint, or muscle pain
• change in urination
• decreased appetite
• diarrhea
• difficulty having a bowel movement
• dry mouth
• increased hunger or thirst
• irregular heartbeat
• muscle pain or cramps
• pain in the arms or legs
• shakiness in the legs, arms, hands, or feet