Olaratumab

Name: Olaratumab

Olaratumab Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, light-headed, chilled, flushed, feverish, or short of breath, or if you have a cold sweat, chest tightness, or trouble breathing.

Call your doctor at once if you have:

  • sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, cough, cold or flu symptoms;
  • swollen gums;
  • skin sores; or
  • trouble breathing.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, stomach pain, diarrhea, loss of appetite;
  • feeling tired;
  • muscle or joint pain;
  • numbness, weakness, or pain in your hands or feet;
  • hair loss; or
  • headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Olaratumab side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, light-headed, chilled, flushed, feverish, or short of breath, or if you have a cold sweat, chest tightness, or trouble breathing.

Call your doctor at once if you have:

  • sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  • fever, cough, cold or flu symptoms;

  • swollen gums;

  • skin sores; or

  • trouble breathing.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, stomach pain, diarrhea, loss of appetite;

  • feeling tired;

  • muscle or joint pain;

  • numbness, weakness, or pain in your hands or feet;

  • hair loss; or

  • headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Introduction

Antineoplastic agent; recombinant human IgG1 monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFR-α).1 2

Cautions for Olaratumab

Contraindications

  • No known contraindications.1

Warnings/Precautions

Infusion-related Effects

Infusion-related reactions (e.g., flushing, dyspnea, bronchospasm, fever/chills, severe hypotension, anaphylactic shock, cardiac arrest), sometimes fatal, reported; generally occur during first 2 cycles.1 2 8 Frequency of infusion-related reactions similar regardless of administration of premedication.1 Grade 1 or 2 infusion-related reactions recurred in 12 of 59 patients (20%) following resumption of infusion.1

Monitor patients for manifestations of infusion reactions during and following olaratumab infusion in a setting where resuscitation equipment is readily available.1

Premedicate with diphenhydramine and dexamethasone prior to first dose of olaratumab during cycle 1.1 (See Premedication for Infusion-related Reactions under Dosage and Administration.) If infusion-related reactions occur, temporary interruption followed by reduction in the infusion rate or permanent drug discontinuance may be required.1 (See Infusion-related Effects under Dosage and Administration.)

Combination Therapy

When used in combination with doxorubicin, consider cautions, precautions, and contraindications of doxorubicin.1

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1

Avoid pregnancy during therapy.1 Women of childbearing potential should use an effective contraceptive method while receiving olaratumab and for 3 months after the drug is discontinued.1 If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.1

Immunogenicity

Antibodies to olaratumab, including neutralizing antibodies to the drug, reported.1

Impairment of Fertility

May impair male fertility.1

Specific Populations

Pregnancy

May cause fetal harm.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether distributed into human milk.1 Discontinue nursing during therapy and for 3 months after drug discontinuance1

Effects of the drug on nursing infants or on human milk production are unknown.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1

Hepatic Impairment

Pharmacokinetics not affected by mild to moderate hepatic impairment (total bilirubin concentration at or below ULN with AST concentration exceeding ULN or total bilirubin concentration above ULN, but not >3 times the ULN, with any AST concentration).1

Not studied in patients with severe hepatic impairment (total bilirubin concentration >3 times the ULN with any AST concentration).1

Renal Impairment

Pharmacokinetics not affected by mild to moderate renal impairment (Clcr 30–89 mL/minute).1

Not studied in patients with severe renal impairment (Clcr 15–29 mL/minute).1

Common Adverse Effects

Lymphopenia,1 nausea,1 fatigue,1 2 neutropenia,1 2 musculoskeletal pain,1 2 thrombocytopenia,1 mucositis,1 2 alopecia,1 2 hyperglycemia,1 vomiting,1 2 leukopenia,2 diarrhea,1 2 increased aPTT,1 decreased appetite,1 2 abdominal pain,1 2 pyrexia,2 neuropathy,1 hypokalemia,1 hypophosphatemia,1 headache,1 increased alkaline phosphatase concentrations,1 hypomagnesemia,1 peripheral edema,2 infusion-related reactions (including hypersensitivity and angioedema),1 2 anxiety,1 dry eyes.1

Interactions for Olaratumab

Specific Drugs

Drug

Interaction

Doxorubicin

No substantial effect on systemic exposure to either drug1

Advice to Patients

  • Risk of infusion-related reactions; importance of reporting signs and symptoms of such reactions (e.g., flushing, dyspnea, bronchospasm, fever/chills).1

  • Risk of fetal harm.1 Necessity of advising women of childbearing potential that they should use an effective method of contraception while receiving the drug and for 3 months after discontinuance of therapy.1 Importance of women informing clinicians if they are pregnant.1 If pregnancy occurs, advise of potential fetal risk.1

  • Necessity of advising women to avoid breast-feeding during therapy and for 3 months after discontinuance of therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

What do I need to tell my doctor BEFORE I take Olaratumab?

  • If you have an allergy to olaratumab or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are breast-feeding. Do not breast-feed while you take olaratumab or for 3 months after your last dose.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Pronunciation

(oh lar AT ue mab)

Dosing Renal Impairment

CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, mild to moderate impairment has no clinically relevant impact on olaratumab pharmacokinetics.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing Adjustment for Toxicity

Hematologic toxicity: Neutropenic fever/infection or grade 4 neutropenia lasting longer than 1 week: Withhold olaratumab until the absolute neutrophil count (ANC) is ≥1,000/mm3 and then resume with the dose permanently reduced to 12 mg/kg.

Infusion reaction:

Grade 1 or 2: Interrupt infusion; after resolution resume with the rate reduced by 50%.

Grade 3 or 4: Discontinue permanently.

Note: Doxorubicin may also require dosage modification.

Other Comments

Administration advice:
-Do not administer as an IV push or bolus.
-Do not co-infuse with electrolytes or other medications through the same IV line. -Visually inspect the diluted solution for particulate matter and discoloration prior to administration; if particulate matter or discolorations are present, discard the solution.
-Administer the diluted solution as an IV infusion over 60 minutes; flush the line with sodium chloride 0.09% at the end of the infusion.

Storage requirements:
-The manufacturer product information should be consulted.

Reconstitution/preparation techniques:
-The manufacturer product information should be consulted.

IV compatibility:
-The manufacturer product information should be consulted.

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