LAROTID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAROTID (LAROTID).
Larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) A, B, and C. It inhibits TRK kinase activity by binding to the ATP-binding site, leading to inhibition of downstream signaling pathways, which results in reduced cell proliferation and tumor growth in tumors with NTRK gene fusions.
| Metabolism | Larotrectinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. |
| Excretion | Renal: 70-80% unchanged by glomerular filtration and tubular secretion; Biliary/Fecal: <10% as inactive metabolites. |
| Half-life | 30 minutes; prolonged in renal impairment (up to 20 hours in anuria). |
| Protein binding | 20% bound, primarily to albumin. |
| Volume of Distribution | 0.3-0.4 L/kg; indicates distribution into total body water with low tissue penetration. |
| Bioavailability | Oral: 75-90% (variable with food); IM: 100%. |
| Onset of Action | Oral: 30-60 minutes; IM/IV: immediate (within 5 minutes). |
| Duration of Action | 4-6 hours; may be extended in renal impairment. |
| Molecular Weight | 365.4 |
Larotrectinib 100 mg orally twice daily, with or without food, for adult patients.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 75 mg twice daily. Larotrectinib has not been studied in patients with end-stage renal disease requiring hemodialysis. |
| Liver impairment | For Child-Pugh Class A (mild) or Class B (moderate) hepatic impairment, no dose adjustment. For Child-Pugh Class C (severe), reduce dose to 75 mg twice daily. |
| Pediatric use | Body surface area (BSA)-based dosing: 100 mg/m², up to a maximum of 100 mg, orally twice daily. Administer with or without food. |
| Geriatric use | No specific dose adjustment in elderly patients beyond standard dosing. Monitor renal function and adjust if severe impairment present. |
| 1st trimester | Avoid during first trimester unless benefit outweighs risk. Animal studies suggest no teratogenicity but limited human data. |
| 2nd trimester | Use with caution. No known fetal harm in second trimester; monitor for maternal allergic reactions. |
| 3rd trimester | Use near term may increase risk of kernicterus in neonates due to displacement of bilirubin from albumin binding sites. |
Clinical note
Comprehensive clinical and safety monograph for LAROTID (LAROTID).
| Placental transfer | Amoxicillin crosses the placenta; fetal serum levels reach about 30% of maternal levels. No known teratogenicity. |
| Breastfeeding | Larotid (amoxicillin) is excreted into breast milk in low concentrations. No adverse effects reported in nursing infants, but theoretical risk of altering infant gut flora or causing hypersensitivity. Use with caution; monitor infant for rash, diarrhea, or candidiasis. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to amoxicillin or any penicillinHistory of anaphylactic reaction to beta-lactam antibioticsInfectious mononucleosis (increases risk of rash)
| Precautions | Neurologic adverse reactions (including dizziness, gait disturbance, and paresthesia), hepatotoxicity, prolonged QT interval, embryo-fetal toxicity. |
| Food/Dietary | No significant food interactions. Absorption is unaffected by food. Avoid alcohol as it may increase side effects like nausea. |
| Clinical Pearls |
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| Lactation Rating | L1 (Safe - Compatible) |
| Teratogenic Risk | Larotid (amoxicillin) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate well-controlled studies in pregnant women exist. However, amoxicillin is widely used in pregnancy without evidence of teratogenicity. First trimester: Low risk, no documented malformations. Second trimester: Safe for treating infections. Third trimester: No specific risks, but use only when clearly needed. |
| Fetal Monitoring | No specific monitoring required beyond standard prenatal care. Monitor for allergic reactions, superinfection, and gastrointestinal disturbances. In prolonged therapy, monitor renal and hepatic function. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies have not shown impaired fertility. |
| LAROTID (amoxicillin) is a broad-spectrum penicillin antibiotic. It is first-line for acute otitis media in children; give with probenecid if renal impairment. High doses (e.g., 3 g twice daily) are used for endocarditis prophylaxis. Always check for penicillin allergy before administration. Can cause false-positive urine glucose tests with Clinitest but not with glucose oxidase methods. |
| Patient Advice | Take exactly as prescribed until the full course is finished, even if you feel better. · Swallow capsules whole; do not crush or chew. For oral suspension, shake well and use a measuring device. · Take with or without food, but if stomach upset occurs, take with a meal. · Report any rash, hives, or difficulty breathing immediately. · Store at room temperature; discard any unused suspension after 14 days. |