Indications
Larogen Capsule is used for:
Indicated for treatment of patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment
Adult Dose
Solid Tumors
Indicated for treatment of patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment
100 mg PO BID
Continue until disease progression or until unacceptable toxicity
Hepatic impairment
Mild (Child-Pugh A): No dosage adjustment necessary
Moderate to severe (Child-Pugh B or C): Reduce starting dose by 50%
Child Dose
Solid Tumors
Indicated for treatment of patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment
Body surface area (BSA) <1 m²: 100 mg/m² PO BID
BSA >1 m²: 100 mg PO BID
Continue until disease progression or until unacceptable toxicity
Renal Dose
Renal impairment
Mild to severe: No dosage adjustment necessary
Administration
Capsules or oral solution may be used interchangeably
Contra Indications
Precautions
Neurologic adverse reactions (any grade) occurred; majority of neurologic adverse reactions occurred within first 3 months of treatment; advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions
Increased transaminases of any grade occurred; median time to onset of increased AST/ALT was 2 months; monitor liver tests every 2 weeks during first month of treatment, then monthly thereafter, and as clinically indicated
Can cause fetal harm when administered to pregnant women
Pregnancy-Lactation
Pregnancy
Based on literature reports, findings from animal studies, and its mechanism of action, embryo-fetal harm may occur when administered to a pregnant woman
There are no available data on use in pregnant women
Verify pregnancy status in females of reproductive potential prior to initiation
Animal data
Administration of larotrectinib to pregnant rats and rabbits during organogenesis resulted in malformations at maternal exposures were ~11- and 0.7-times (observed at 100 mg PO BID)
Contraception
Females of reproductive potential: Advise to use of effective contraception during treatment and for at least 1 week after last dose
Males: Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after last dose
Infertility
Based on histopathological findings in reproductive tracts of female rats in a 1-month repeated-dose study, fertility may be reduced
Lactation
There are no data on presence of larotrectinib or its metabolites in human milk and its effects on the breastfed child or on milk production
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after final dose
Interactions
Larotrectinib is a substrate of CYP3A4 (major); also a P-gp and BCRP substrate
Larotrectinib moderately inhibits CYP3A4
Strong CYP3A4 inhibitors
Coadministration with a strong CYP3A4 inhibitor may increase larotrectinib plasma concentrations and potentially result in higher incidence of adverse reactions
Avoid use with strong CYP3A4 inhibitors, including grapefruit or grapefruit juice; if coadministration of strong CYP3A4 inhibitors cannot be avoided, modify dose as recommended
Strong CYP3A4 inducers
Coadministration with a strong CYP3A4 inducer may decrease larotrectinib plasma concentrations, which may decrease efficacy
Avoid use with strong CYP3A4 inducers; if coadministration of strong CYP3A4 inducers cannot be avoided, modify dose as recommended
Sensitive CYP3A4 substrates
Coadministration with sensitive CYP3A4 substrates may increase their plasma concentrations, which may increase incidence and/or severity of adverse reactions
Avoid use with sensitive CYP3A4 substrates; if coadministration of these sensitive CYP3A4 substrates cannot be avoided, monitor for increased adverse reactions of these drugs
Side Effects
Side effects of Larotrectinib :
>10%
Increased AST/ALT (45%)
Anemia (42%)
Fatigue (37%)
Hypoalbuminemia (35%)
Increased alkaline phosphatase (30%)
Nausea (29%)
Dizziness (28%)
Vomiting (26%)
Cough (26%)
Constipation (23%)
Neutropenia (23%)
Diarrhea (22%)
Pyrexia (18%)
Dyspnea (18%)
Peripheral edema (15%)
Increased weight (15%)
Headache (14%)
Arthralgia (14%)
Myalgia (14%)
Muscular weakness (13%)
Decreased appetite (13%)
Abdominal pain (13%)
Back pain (12%)
Pain in extremity (12%)
Hypertension (11%)
1-10%
Nasal congestion (10%)
Fall (10%)
Anemia, Grade 3 or 4 (10%)
Neutropenia, Grade 3 or 4 (7%)
Increased weight, Grade 3 or 4 (4%)
Fatigue, Grade 3 or 4 (3%)
Increased alkaline phosphatase, Grade 3 or 4 (3%)
Increased AST/ALT, Grade 3 or 4 (45%)
Diarrhea, Grade 3 or 4 (2%)
Dyspnea, Grade 3 or 4 (2%)
Decreased appetite, Grade 3 or 4 (2%)
Hypertension, Grade 3 or 4 (2%)
Hypoalbuminemia, Grade 3 or 4 (3%)
Pyrexia, Grade 3 or 4 (1%)
Nausea, Grade 3 or 4 (1%)
Vomiting, Grade 3 or 4 (1%)
Arthralgia, Grade 3 or 4 (1%)
Myalgia, Grade 3 or 4 (1%)
Back pain, Grade 3 or 4 (1%)
Pain in extremity, Grade 3 or 4 (1%)
Fall, Grade 3 or 4 (1%)
Constipation, Grade 3 or 4 (1%)
Dizziness, Grade 3 or 4 (1%)
Mode of Action
Highly selective inhibitor of tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC
TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3; chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines
In tumor models, larotrectinib demonstrates antitumor activity in cells by activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK overexpression
Note
Larogen 25 mg Capsule generic name is Larotrectinib. Larogen 25 mg Capsule is manufactured by General Pharmaceuticals Ltd.Larogen is availble in all over Bangladesh.
Mes BD drug index information on Larogen Capsule is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.