LARTRUVO
Clinical safety rating
cautionComprehensive clinical and safety monograph for LARTRUVO (LARTRUVO).
Comprehensive clinical and safety monograph for LARTRUVO (LARTRUVO).
Treatment of adult patients 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, in combination with doxorubicin.
Olaratumab is a recombinant human IgG1 monoclonal antibody that binds to platelet-derived growth factor receptor alpha (PDGFRα), blocking PDGF-AA, -BB, and -CC binding and receptor activation, thereby inhibiting tumor growth.
| Metabolism | Olaratumab is a monoclonal antibody expected to be degraded into small peptides and amino acids via general protein catabolism. No specific metabolic pathways identified. |
| Excretion | Olaratumab is cleared primarily via proteolytic catabolism; no specific renal or biliary excretion studies have been conducted. In patients, only trace amounts are excreted in urine (<1% of dose). |
| Half-life | Terminal elimination half-life is approximately 11 days (range 4–20 days), supporting a 3-week dosing interval when combined with doxorubicin. |
| Protein binding | Approximately 90% bound to plasma proteins (primarily IgG, as a monoclonal antibody). |
| Volume of Distribution | Central volume of distribution is approximately 4.1 L (0.058 L/kg for a 70 kg patient), indicating limited extravascular distribution, consistent with a large monoclonal antibody. |
| Bioavailability | 100% (intravenous administration only; not bioavailable orally). |
| Onset of Action | Not applicable; onset of clinical effect (e.g., tumor response) typically requires several weeks of treatment. For intravenous infusion, no immediate pharmacological effect. |
| Duration of Action | Sustained receptor blockade persists for several weeks after a single dose, corresponding to the half-life. Clinical effects (e.g., progression-free survival benefit) are assessed over cycles. |
| Molecular Weight | 395.24 Da |
10 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CLcr 30-89 mL/min). Not studied in severe renal impairment (CLcr <30 mL/min) or end-stage renal disease; use only if benefit outweighs risk. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate or severe (Child-Pugh B or C): not studied; use only if benefit outweighs risk. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No dose adjustment based on age; monitor for adverse reactions more frequently due to higher incidence of underlying renal or hepatic impairment and comorbidities. |
| 1st trimester | Avoid use during first trimester due to potential for fetal harm based on its mechanism of action (PDGFRα inhibition). No adequate human data; animal studies show embryotoxicity. |
| 2nd trimester | Avoid use during second trimester as PDGFRα inhibition may interfere with normal fetal development. |
| 3rd trimester | Avoid use during third trimester due to risk of fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for LARTRUVO (LARTRUVO).
| Placental transfer | Larotrectinib is likely to cross the placenta based on its molecular weight and pharmacokinetic properties; however, specific human data are lacking. Animal studies indicate placental transfer. |
| Breastfeeding | It is unknown if larotrectinib or its metabolites are excreted in human milk. However, due to the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for at least 1 week after the last dose. |
| Lactation Rating | Avoid |
| Teratogenic Risk | Based on its mechanism of action (PDGFR-alpha inhibitor) and animal studies, LARTRUVO (olaratumab) is expected to cause fetal harm when administered to pregnant women. There are no adequate human data. In animal reproduction studies, administration of olaratumab to pregnant monkeys during organogenesis resulted in embryofetal toxicity including increased abortion and fetal anomalies. Use is contraindicated in pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose. Risks apply throughout all trimesters. |
| Fetal Monitoring | Monitor for infusion-related reactions (e.g., pyrexia, chills, hypotension) during administration. Monitor complete blood counts, including platelet count, regularly due to risk of thrombocytopenia and neutropenia. Monitor electrolytes and renal function. If used inadvertently during pregnancy, perform fetal monitoring with ultrasound and consider serial growth assessments due to potential fetal harm. |
| Fertility Effects | There are no human data on the effect of olaratumab on fertility. Based on animal studies, olaratumab impairs male and female fertility. In female monkeys, irregular menstrual cycles and reduced ovarian weights were observed. In male monkeys, decreased sperm motility and testicular degeneration were noted. Advise patients of potential risk to reproductive capacity. |
■ FDA Black Box Warning
WARNING: INFUSION-RELATED REACTIONS (IRRs), INCLUDING DEATH. Serious and sometimes fatal infusion-related reactions can occur. Premedicate and monitor during infusion. Interrupt or permanently discontinue based on severity.
| Serious Effects |
None reported
| Precautions | Infusion-related reactions (including severe and fatal); embryo-fetal toxicity; neutropenia; cardiotoxicity (left ventricular dysfunction); and increased adverse reactions in patients with baseline left ventricular ejection fraction (LVEF) below normal. |
| Food/Dietary | No specific food interactions known. However, doxorubicin may cause nausea and vomiting; advise taking antiemetics as prescribed and eating small, frequent meals. Avoid grapefruit and grapefruit juice as they may affect CYP3A4 metabolism of doxorubicin. |
| Clinical Pearls | LARTRUVO (olaratumab) is a PDGFRα inhibitor used in combination with doxorubicin for advanced soft tissue sarcoma not amenable to surgery or radiotherapy. Monitor for infusion-related reactions and pre-medicate with antihistamines and corticosteroids. Assess cardiac function via echocardiogram or MUGA scan before each cycle due to doxorubicin cardiotoxicity. Neutropenia is common; monitor CBCs before each cycle and hold for ANC <1000/mm3. Olaratumab does not require dose adjustment for mild to moderate hepatic impairment but avoid in severe impairment. No dose adjustment for renal impairment. Pregnancy category D: advise effective contraception during and for 3 months after treatment. |
| Patient Advice | This medication is given as an intravenous infusion over 60 minutes on Day 1 and Day 8 of each 21-day cycle. · You will receive it together with another chemotherapy drug called doxorubicin. · Common side effects include nausea, fatigue, low white blood cell counts, and infusion-related reactions (fever, chills, shortness of breath). · Report any signs of infection (fever, sore throat) or unusual bleeding/bruising immediately. · Avoid pregnancy and breastfeeding while on this treatment; use effective birth control during and for 3 months after the last dose. · Do not take any other medications, supplements, or herbal products without consulting your doctor. |
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