Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Lartruvo: 190 mg/19 mL (19 mL); 500 mg/50 mL (50 mL)
Pharmacology
Mechanism of Action
Olaratumab is a human (recombinant) IgG1 antibody which expressly binds to platelet-derived growth receptor alpha (PDGFR-α) to prevent binding of PDGF-AA, PDGF-BB, and PDGF-CC and block receptor activation and disrupt PDGF receptor signaling. The PDGF-alpha receptor has a role in cell differentiation, growth, and angiogenesis and has demonstrated antitumor activity in sarcomas (Tap 2016).
Pharmacokinetics/Pharmacodynamics
Distribution
Vss: 7.7 L
Half-Life Elimination
~11 days (range: 6 to 24 days)
Use: Labeled Indications
Soft tissue sarcoma: Treatment (in combination with doxorubicin) of adults with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.
Note: A phase III confirmatory trial in patients with unresectable locally advanced or metastatic STS comparing olaratumab plus doxorubicin to placebo plus doxorubicin found no improvement in overall survival due to the addition of olaratumab to doxorubicin (Tap 2019). Due to the trial results, the manufacturer is withdrawing olaratumab from the market.
Contraindications
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to olaratumab or any component of the formulation.
Dosage and Administration
Dosing: Adult
Note: A phase III confirmatory trial in patients with unresectable locally advanced or metastatic soft tissue sarcoma comparing olaratumab plus doxorubicin to placebo plus doxorubicin found no improvement in overall survival due to the addition of olaratumab to doxorubicin (Tap 2019). Due to the trial results, the manufacturer is withdrawing olaratumab from the market.
Soft tissue sarcoma: IV: 15 mg/kg on days 1 and 8 every 3 weeks (in combination with doxorubicin) for 8 cycles; after 8 cycles are completed, continue olaratumab (as a single agent) until disease progression or unacceptable toxicity. Dexrazoxane was allowed on day 1 of cycles 5 to 8 to reduce the potential for doxorubicin-related cardiotoxicity (Tap 2016).
Premedications: On day 1 of cycle 1, premedicate with diphenhydramine (25 to 50 mg IV) and dexamethasone (10 to 20 mg IV) prior to olaratumab.
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.
Reconstitution
Withdraw calculated dose volume and dilute in NS to a total volume of 250 mL. Gently invert to mix (do not shake). Do not freeze the diluted solution. Dilute with NS only; do not use dextrose-containing or other solutions.
Administration
IV: Infuse over 60 minutes. Do not administer as an IV push or bolus. Flush the IV line with normal saline at the end of infusion. Do not coadminister electrolytes or other medications through the same IV line.
If refrigerated, allow infusion solution to reach room temperature prior to administration. Infusion must be completed within 28 hours of dilution (when stored appropriately; see Storage/Stability).
Storage
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Keep in original carton to protect from light. Do not shake. Solutions diluted for infusion may be stored for up to 24 hours refrigerated and for an additional 4 hours at room temperature (infusion must be completed within this time frame). If refrigerated, allow infusion solution to reach room temperature prior to administration.
Drug Interactions
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Fatigue (69%), neuropathy (22%), headache (20%), anxiety (11%)
Dermatologic: Alopecia (52%)
Endocrine & metabolic: Hyperglycemia (52%), hypokalemia (21%), hypophosphatemia (21%), hypomagnesemia (16%)
Gastrointestinal: Nausea (73%), mucositis (53%), vomiting (45%), diarrhea (34%), decreased appetite (31%), abdominal pain (23%)
Hematologic & oncologic: Lymphocytopenia (77%, grades 3/4: 44%), neutropenia (65%, grades 3/4: 48%), thrombocytopenia (63%, grades 3/4: 6%), prolonged partial thromboplastin time (33%, grades 3/4: 5%)
Hepatic: Increased serum alkaline phosphatase (16%)
Neuromuscular & skeletal: Musculoskeletal pain (64%)
Ophthalmic: Xerophthalmia (11%)
Miscellaneous: Infusion related reaction (13% to 14%)
1% to 10%: Immunologic: Development of IgG antibodies (4%; all patients had neutralizing antibodies; however, therapeutic effects of antibodies could not be assessed)
Warnings/Precautions
Concerns related to adverse effects:
- GI toxicity: Nausea, vomiting, diarrhea, mucositis, and abdominal pain have been reported, with a higher incidence in patients treated with olaratumab and doxorubicin, compared to doxorubicin alone.
- Hematologic toxicity: A higher incidence of grade 3 and 4 lymphopenia and neutropenia have been reported in patients treated with olaratumab and doxorubicin, compared to doxorubicin alone. Thrombocytopenia (all grades) also had a higher incidence in the combination arm.
- Infusion reaction: Olaratumab is associated with infusion reactions; most infusion reactions occurred with the first or second cycle. Grade 3 or higher reactions have occurred, including a fatal case. Symptoms of infusion reactions have included flushing, dyspnea, bronchospasm, and/or fever/chills; severe cases included hypotension, anaphylactic shock, or cardiac arrest. Premedication with diphenhydramine and dexamethasone is recommended. Monitor for signs/symptoms of infusion reactions during and after infusion (resuscitation equipment should be readily available). May require treatment interruption (followed by rate reduction) or permanent discontinuation.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitoring Parameters
CBC with differential. Monitor for signs/symptoms of infusion reactions.
Pregnancy
Pregnancy Considerations
Based on its mechanism of action, olaratumab would be expected to cause fetal harm if administered to a pregnant woman. Females of reproductive potential should use effective contraception during therapy and for at least 3 months after the last olaratumab dose.
Patient Education
What is this drug used for?
- It is used to treat soft tissue sarcoma.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Mouth sores
- Mouth irritation
- Back pain
- Bone pain
- Joint pain
- Diarrhea
- Lack of appetite
- Abdominal pain
- Muscle pain
- Hair loss
- Headache
- Anxiety
- Dry eyes
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
- Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting
- Bruising
- Bleeding
- Severe loss of strength and energy
- Burning or numbness feeling
- Infusion reaction like chest pain, flushing, shortness of breath, severe dizziness, or passing out
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
