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Indications & Uses
Larotrectinib is used to treat adults and children who have solid tumours with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion, as long as there is no known acquired resistance mutation. The tumour must also be metastatic, or surgery to remove it must be likely to cause severe morbidity. On top of that, there should be no satisfactory alternative treatments, or the tumour should have progressed after treatment.
Pharmacology
Larotrectinib blocks the tropomyosin receptor kinases (TRK), which are TRKA, TRKB and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited all three with IC50 values between 5 and 11 nM. One other kinase, TNK2, was inhibited at concentrations approximately 100-fold higher. TRKA, B and C are encoded by the genes NTRK1, NTRK2 and NTRK3. When chromosomal rearrangements fuse these genes in-frame with various partners, the result can be constitutively activated chimeric TRK fusion proteins. These can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.
Absorption: The mean absolute bioavailability of larotrectinib capsules was 34% (range: 32% to 37%).
Distribution: After intravenous administration in healthy subjects, the mean (CV%) volume of distribution (Vss) of larotrectinib is 48 (38%) L. In vitro, larotrectinib is 70% bound to human plasma proteins, and the binding does not depend on drug concentration. The blood-to-plasma concentration ratio is 0.9.
Elimination: After oral administration in healthy subjects, the mean (CV%) clearance (CL/F) of larotrectinib is 98 (44%) L/h and the half-life is 2.9 hours.
Metabolism: Larotrectinib is metabolized mainly by CYP3A4. Healthy subjects were given a single oral 100 mg dose of [14C] radiolabeled larotrectinib. Among the major circulating radioactive drug components in plasma, unchanged larotrectinib made up 19% and an O-linked glucuronide made up 26%.
Excretion: In the same kind of study, with a single oral 100 mg dose of [14C] radiolabeled larotrectinib given to healthy subjects, 58% of the administered radioactivity was recovered in feces (5% unchanged) and 39% in urine (20% unchanged).
Dosage Reference
Reference Information Only
Dosages shown are general references from official sources. Always consult your doctor or pharmacist for personalized dosing.
Adults:
For adult and pediatric patients with a body surface area of at least 1 m2, the recommended dosage of Larotrectinib is 100 mg taken by mouth twice daily, with or without food, until disease progression or until unacceptable toxicity. For pediatric patients with a body surface area less than 1 m2, the recommended dosage is 100 mg/m2 by mouth twice daily, with or without food, again until disease progression or until unacceptable toxicity. Swallow the capsules whole with water, and don't chew or crush them. If a dose is missed, don't make it up within 6 hours of the next scheduled dose. If vomiting occurs after a dose of Larotrectinib, take the next dose at the scheduled time. Or, as directed by the registered physicians.
Side Effects
Larotrectinib commonly causes neurotoxicity and hepatotoxicity.
Cautions & Contraindications
Warnings & Precautions
Neurotoxicity Among the 176 patients who received Larotrectinib, 53% had neurologic adverse reactions of some grade. Grade 3 reactions occurred in 6% of patients and Grade 4 in 0.6%. Most of them (65%) appeared within the first three months of treatment, though the timing ranged from 1 day to 2.2 years. The Grade 3 reactions were delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%) and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Reactions that led to a change in dose were dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%) and tremor (1%). Patients and caretakers should be told about these risks. Anyone who has neurologic adverse reactions should not drive or operate hazardous machinery. Treatment should be withheld or stopped permanently, depending on how severe the reaction is. If it is withheld, the dose should be modified when treatment is resumed. Hepatotoxicity Among the same 176 patients, 45% had increased transaminases of some grade. Grade 3 increased AST or ALT occurred in 6% of patients, and one patient (0.6%) had Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). For increased ALT it was also 2 months (range: 1 month to 1.1 years). Increased AST led to dose modification in 4% of patients and increased ALT in 6%. In 2% of patients, increased AST or ALT led to permanent discontinuation. Liver tests, including ALT and AST, should be checked every 2 weeks during the first month of treatment, then monthly, and whenever clinically indicated. Larotrectinib should be withheld or permanently discontinued based on severity. If it is withheld, the dose should be modified when treatment is resumed. Embryo-Fetal Toxicity Larotrectinib can cause fetal harm when given to a pregnant woman. This is based on literature reports in people born with congenital mutations that change TRK signaling, on findings from animal studies, and on how the medicine works. Women should be told about the possible risk to a fetus. Females of reproductive potential should use an effective method of contraception during treatment and for 1 week after the final dose.
Contraindications
Larotrectinib must not be given to anyone who is known to be hypersensitive to larotrectinib or to any other component of the product.
Pregnancy & Breastfeeding
Larotrectinib can harm an unborn baby when it is given to a pregnant woman. There are no data on its use in pregnant women, so a pregnant woman should be told about the possible risk to the fetus.
We also don't know whether Larotrectinib or its metabolites pass into human milk. There are no data on what it might do to a breastfed child or to milk production. Because breastfed children could have serious adverse reactions, women should be advised not to breastfeed during treatment with Larotrectinib and for 1 week after the final dose.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Use in Special Populations
Females: Women who could become pregnant should be advised to use effective contraception while taking Larotrectinib and for at least 1 week after the last dose.
Males: Men whose female partners could become pregnant should be advised to use effective contraception during treatment with Larotrectinib and for 1 week after the last dose.
Pediatric Use: The safety and effectiveness of Larotrectinib in children were established from data of three multicenter, open-label, single-arm clinical trials. These trials included adult patients and paediatric patients aged 28 days and older.
Geriatric Use: Clinical studies of Larotrectinib did not include enough subjects aged 65 and over to say whether they respond differently from younger subjects.
Storage
Keep Larotrectinib in a cool, dry place below 30°C, away from sunlight. Make sure children can't reach it.
Common questions about Larocent 100 mg
What is Larocent 100 mg Capsule?
Larocent 100 mg Capsule is a medicine that contains Larotrectinib. It is made by Incepta Pharmaceuticals Ltd. It belongs to the Cytotoxic Chemotherapy group of medicines.
What is Larocent used for?
Larotrectinib is used to treat adults and children who have solid tumours with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion, as long as there is no known acquired resistance mutation. The tumour must also be metastatic, or surgery to remove it must be likely to cause severe morbidity.
What are the side effects of Larocent?
Larotrectinib commonly causes neurotoxicity and hepatotoxicity.
Can I take Larocent during pregnancy or while breastfeeding?
Larotrectinib can harm an unborn baby when it is given to a pregnant woman. There are no data on its use in pregnant women, so a pregnant woman should be told about the possible risk to the fetus. Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
How should I store Larocent?
Keep Larotrectinib in a cool, dry place below 30°C, away from sunlight. Make sure children can't reach it.
Is there a cheaper medicine with the same ingredient?
Larocent is already among the lowest-priced brands of Larotrectinib at this strength.
Do I need a prescription for Larocent?
Larocent is a prescription (Rx) medicine. Take it as your doctor advises.