Source: FDA, National Drug Code (US) Revision Year: 2020
KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
The recommended dosage of KOSELUGO is 25 mg/m2 orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity.
Take KOSELUGO on an empty stomach. Do not consume food 2 hours before each dose or 1 hour after each dose [see Clinical Pharmacology (12.3)]. The recommended dose of KOSELUGO based on body surface area (BSA) is shown in Table 1.
Table 1. Recommended Dosage Based on Body Surface Area:
| Body Surface Area* | Recommended Dosage |
|---|---|
| 0.55-0.69 m2 | 20 mg in the morning and 10 mg in the evening |
| 0.70-0.89 m2 | 20 mg twice daily |
| 0.90-1.09 m2 | 25 mg twice daily |
| 1.10-1.29 m2 | 30 mg twice daily |
| 1.30-1.49 m2 | 35 mg twice daily |
| 1.50-1.69 m2 | 40 mg twice daily |
| 1.70-1.89 m2 | 45 mg twice daily |
| ≥1.90 m2 | 50 mg twice daily |
* The recommended dosage for patients with a BSA less than 0.55m has not been established.
Swallow KOSELUGO capsules whole with water. Do not chew, dissolve or open capsule.
Do not administer to patients who are unable to swallow a whole capsule.
Do not take a missed dose of KOSELUGO unless it is more than 6 hours until the next scheduled dose.
If vomiting occurs after KOSELUGO administration, do not take an additional dose, but continue with the next scheduled dose.
The recommended dose reductions for adverse reactions are provided in Table 2.
Table 2. Recommended Dose Reductions for KOSELUGO for Adverse Reactions:
| Body Surface Area | First Dose Reduction(mg/dose) | Second Dose Reduction*(mg/dose) | ||
|---|---|---|---|---|
| Morning | Evening | Morning | Evening | |
| 0.55-0.69 m2 | 10 | 10 | 10 once daily | |
| 0.70-0.89 m2 | 20 | 10 | 10 | 10 |
| 0.90-1.09 m2 | 25 | 10 | 10 | 10 |
| 1.10-1.29 m2 | 25 | 20 | 20 | 10 |
| 1.30-1.49 m2 | 25 | 25 | 25 | 10 |
| 1.50-1.69 m2 | 30 | 30 | 25 | 20 |
| 1.70-1.89 m2 | 35 | 30 | 25 | 20 |
| ≥1.90 m2 | 35 | 35 | 25 | 25 |
* Permanently discontinue KOSELUGO in patients unable to tolerate KOSELUGO after two dose reductions.
Dosage modifications for adverse reactions are in Table 3.
Table 3. Recommended Dosage Modifications for KOSELUGO for Adverse Reactions:
| Severity of Adverse Reaction | Recommended Dosage Modifications for KOSELUGO |
|---|---|
| Cardiomyopathy [see Warnings and Precautions (5.1)] | |
| • Asymptomatic decrease in left ventricular ejection (LVEF) of 10% or greater from baseline and less than lower level of normal | Withhold until resolution. Resume at reduced dose. |
| • Symptomatic decreased LVEF • Grade 3 or 4 decreased LVEF | Permanently discontinue. |
| Ocular Toxicity [see Warnings and Precautions (5.2)] | |
| • Retinal Pigment Epithelial Detachment (RPED) | Withhold until resolution. Resume at reduced dose. |
| • Retinal vein occlusion (RVO) | Permanently discontinue. |
| Gastrointestinal Toxicity[see Warnings and Precautions (5.3)] | |
| • Grade 3 Diarrhea | Withhold until improved to Grade 0 or 1. Resume at same dose. Permanently discontinue if no improvement within 3 days. |
| • Grade 4 Diarrhea | Permanently discontinue. |
| • Grade 3 or 4 Colitis | Permanently discontinue. |
| Skin Toxicity [see Warnings and Precautions (5.4)] | |
| • Grade 3 or 4 | Withhold until improvement. Resume at reduced dose. |
| Increased Creatine Phosphokinase (CPK) [see Warnings and Precautions (5.5)] | |
| • Grade 4 Increased CPK • Any Increased CPK and myalgia | Withhold until improved to Grade 0 or 1. Resume at reduced dose. Permanently discontinue if no improvement within 3 weeks. |
| • Rhabdomyolysis | Permanently discontinue. |
| Other Adverse Reactions [see Adverse Reactions (6.1)] | |
| • Intolerable Grade 2 • Grade 3 | Withhold KOSELUGO until improve to Grade 0 or 1. Resume at reduced dose. |
| • Grade 4 | Withhold KOSELUGO until improved to Grade 0 or 1. Resume at reduced dose. Consider discontinuation. |
* Per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Reduce the recommended dosage of KOSELUGO to 20 mg/m2 orally twice daily in patients with moderate hepatic impairment (Child-Pugh B). The recommended dosage of KOSELUGO for use in patients with severe hepatic impairment (Child-Pugh C) has not been established [see Use in Specific Populations (8.7)].
Table 4. Recommended Dosage of KOSELUGO for Moderate Hepatic Impairment:
| Body Surface Area | Moderate Hepatic Impairment (Child-Pugh B) (mg/dose) | |
|---|---|---|
| Morning | Evening | |
| 0.55-0.69 m2 | 10 | 10 |
| 0.70-0.89 m2 | 20 | 10 |
| 0.90-1.09 m2 | 20 | 20 |
| 1.10-1.29 m2 | 25 | 25 |
| 1.30-1.49 m2 | 30 | 25 |
| 1.50-1.69 m2 | 35 | 30 |
| 1.70-1.89 m2 | 35 | 35 |
| ≥1.90 m2 | 40 | 40 |
Avoid coadministration of strong or moderate CYP3A4 inhibitors or fluconazole with KOSELUGO. If coadministration with strong or moderate CYP3A4 inhibitors or fluconazole cannot be avoided, reduce the KOSELUGO dosage as recommended in Table 5. After discontinuation of the strong or moderate CYP3A4 inhibitor or fluconazole for 3 elimination half-lives, resume the KOSELUGO dose that was taken prior to initiating the inhibitor or fluconazole [see Drug Interactions (7.1)].
Table 5. Recommended Dosage of KOSELUGO for Coadministration with Strong or Moderate CYP3A4 Inhibitors or Fluconazole:
| Body Surface Area | If the current dosage is 25 mg/m2 twice daily, reduce to 20 mg/m2 twice daily (mg/dose) | If the current dosage is 20 mg/m2 twice daily, reduce to 15 mg/m2 twice daily (mg/dose) | ||
|---|---|---|---|---|
| Morning | Evening | Morning | Evening | |
| 0.55-0.69 m2 | 10 | 10 | 10 mg once a day | |
| 0.70-0.89 m2 | 20 | 10 | 10 | 10 |
| 0.90-1.09 m2 | 20 | 20 | 20 | 10 |
| 1.10-1.29 m2 | 25 | 25 | 25 | 10 |
| 1.30-1.49 m2 | 30 | 25 | 25 | 20 |
| 1.50-1.69 m2 | 35 | 30 | 25 | 25 |
| 1.70-1.89 m2 | 35 | 35 | 30 | 25 |
| ≥1.90 m2 | 40 | 40 | 30 | 30 |
Dialysis is not helpful as KOSELUGO is highly protein bound and is extensively metabolized.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Dispense in original bottle. Do not remove desiccant. Protect from moisture.
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