Larotrectinib

REMS

Solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or are likely to result in severe morbidity with surgical resection, and have either progressed following treatment or have no satisfactory alternative therapy.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy (may cause fetal harm)
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment (↓ dose)
Rep: Women of reproductive potential and men with female partners of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema.

EENT: nasal congestion.

GI: abdominal pain, constipation, diarrhea, hypoalbuminemia, hepatotoxicity, ↑liver enzymes, nausea, vomiting.

GU: dehydration, ↓ fertility.

Hemat: anemia, neutropenia.

Metab: ↓appetite, ↑weight.

MS: arthralgia, muscle weakness, myalgia.

Neuro: dizziness, fatigue, falls, headache, delirium, dysarthria, gait disturbance, memory impairment, paresthesia, tremor.

Resp: cough, dyspnea.

Misc: fever.

Interactions ⬆ ⬇

Drug-Drug:

Strong CYP3A4 inhibitors, including itraconazole, may significantly ↑ levels; avoid concurrent use; if need to use strong CYP3A4 inhibitor, ↓ larotrectinib dose.
Strong CYP3A4 inducers, including rifampin, may significantly ↓ levels; avoid concurrent use; if need to use strong CYP3A4 inducer, double larotrectinib dose.
May ↑ levels of CYP3A4 substrates; avoid concurrent use with CYP3A4 substrates with a narrow therapeutic index.

Drug-Natural Products:

St. John's wort may significantly ↓ levels; avoid concurrent use.

Drug-Food:

Grapefruit juice may significantly ↑ levels; avoid concurrent use.

Availability ⬆ ⬇

Capsules: 25 mg; 100 mg;
Oral solution: 20 mg/mL;

Route/Dosage ⬆ ⬇

PO (Adults and Children with BSA 1 m²): 100 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 50 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inducer — 200 mg twice daily until disease progression or unacceptable toxicity.
PO (Children with BSA <1 m²): 100 mg/m² twice daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 50 mg/m² twice daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inducer — 200 mg/m² twice daily until disease progression or unacceptable toxicity.

Hepatic Impairment

(Adults and Children with BSA 1 m²): Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment — 50 mg twice daily until disease progression or unacceptable toxicity.

Hepatic Impairment

(Children with BSA <1 m²): Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment — 50 mg/m² twice daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes), which ultimately inhibits growth of cancer cell lines.

Therapeutic Effects:

Decreased spread of certain solid tumors.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 34% absorbed following oral administration; absorption reduced with high-fat meals.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme. 58% excreted in feces (5% as unchanged drug), 39% excreted in urine (20% as unchanged drug).

Half-life: 2.9 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take larotrectinib as directed. If vomiting occurs after dose, omit dose and take next dose at scheduled time. Take missed doses as soon as remembered up to 6 hr before next dose. Do not change dose or stop taking larotrectinib without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to avoid grapefruit juice during therapy.
Caution patient that larotrectinib may cause dizziness. Advise patient to avoid driving or other activities requiring alertness until response to drug is known.
Advise patient to notify health care professional if signs and symptoms of new or worsening neurotoxicity (confusion; difficulty speaking; dizziness; coordination problems; tingling, numbness, or burning sensation in hands and feet) or liver problems (loss of appetite, nausea or vomiting, pain on upper right side of stomach) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort.
Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception and to avoid breastfeeding during and for 1 wk after last dose. May impair female fertility.
Emphasize importance of regular lab tests to monitor for side effects.

Pronunciation ⬆ ⬇

Code ⬆

NDC Code^*

50419- Bayer HealthCare Pharmaceuticals Inc.
50419-390- VITRAKVI 50419-390-01- 60 CAPSULE in 1 BOTTLE (50419-390-01)

50419- Bayer HealthCare Pharmaceuticals Inc.
50419-391- VITRAKVI 50419-391-01- 60 CAPSULE in 1 BOTTLE (50419-391-01)

50419- Bayer HealthCare Pharmaceuticals Inc.
50419-392- VITRAKVI 50419-392-01- 100 mL in 1 BOTTLE (50419-392-01)

71777- Loxo Oncology, Inc.
71777-390- VITRAKVI 71777-390-01- 60 CAPSULE in 1 BOTTLE (71777-390-01)

71777- Loxo Oncology, Inc.
71777-391- VITRAKVI 71777-391-01- 60 CAPSULE in 1 BOTTLE (71777-391-01)

71777- Loxo Oncology, Inc.
71777-392- VITRAKVI 71777-392-01- 100 mL in 1 BOTTLE (71777-392-01)

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Indications ⬇