Indications for KOSELUGO:
Treatment of neurofibromatosis type 1 (NF1) in pediatric patients who have symptomatic, inoperable plexiform neurofibromas (PN).
<2yrs: not established. Swallow whole on an empty stomach. Do not consume food 2hrs before or 1hr after each dose. Base dose on body surface area (BSA <0.55m2: not established); see full labeling. ≥2yrs: 25mg/m2 twice daily (approx. every 12hrs) until disease progression or unacceptable toxicity. Hepatic impairment (moderate): 20mg/m2 twice daily; (severe): not established. Dose modifications for adverse reactions, hepatic impairment, drug interactions: see full labeling.
Cardiomyopathy. History of impaired LVEF or if baseline ejection fraction below LLN: not established. Assess ECG prior to initiation, every 3 months during 1st year, then every 6 months thereafter and as clinically indicated. If treatment interrupted for decreased LVEF, obtain ECG or cardiac MRI every 3–6 weeks. Ocular toxicity (eg, blurred vision, photophobia, cataracts). Perform ophthalmic exam prior to initiation, at regular intervals during therapy, and for visual changes. GI toxicity (eg, diarrhea). Monitor for severe skin rashes. Obtain serum CPK prior to initiation, periodically during, and as clinically indicated. Moderate or severe hepatic impairment (See Adults). Embryo-fetal toxicity. Pregnancy: exclude status prior to initiation. Advise females of reproductive potential and males (w. female partners) to use effective contraception during and for 1 week after the last dose. Nursing mothers: not recommended (during and for 1 week after the last dose).
Avoid concomitant strong or moderate CYP3A4 inhibitors (eg, fluconazole); if unavoidable, reduce dose (see full labeling). Concomitant supplemental Vitamin E: not recommended if daily limit is exceeded. Avoid concomitant strong or moderate CYP3A4 inducers. Increased risk of bleeding with vitamin-K antagonists or anti-platelet agents; monitor frequently for bleeding, anticoagulant assessments (including INR, PT).
Vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, pyrexia, acneiform rash, stomatitis, headache, paronychia, pruritus; retinal vein occlusion, retinal pigment epithelial detachment, serious GI toxicity (eg, perforation, colitis, ileus, intestinal obstruction), severe palmar-plantar erythrodysesthesia syndrome, rhabdomyolysis.
Fecal (59%), renal (33%). Half-life: ~6.2 hours.