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Brand Name
Koselugo
Generic Name
Selumetinib
View Brand Information FDA approval date: April 16, 2020
Classification: Kinase Inhibitor
Form: Granule, Capsule
What is Koselugo (Selumetinib)?
KOSELUGO is indicated for the treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas . KOSELUGO is a kinase inhibitor indicated for the treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas .
Approved To Treat
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Brand Information
KOSELUGO (SELUMETINIB)
1INDICATIONS AND USAGE
KOSELUGO is indicated for the treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN)
2DOSAGE FORMS AND STRENGTHS
Capsules:
- 10 mg selumetinib: white to off-white, opaque, hard capsule sealed with a clear band and marked with “SEL 10” in black ink.
- 25 mg selumetinib: blue, opaque, hard capsule sealed with a clear band and marked with “SEL 25” in black ink.
Oral Granules:
- 5 mg selumetinib: off-white to light-yellow free-flowing oral granules contained within capsules. The capsules have a yellow cap and white body. The cap is printed with “sel 5” in black ink, and body is printed with a sprinkle capsule image indicating opening.
- 7.5 mg selumetinib: off-white to light-yellow free-flowing oral granules contained within capsules. The capsules have a pink cap and white body. The cap is printed with “sel 7.5” in black ink, and body is printed with a sprinkle capsule image indicating opening.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Left Ventricular Dysfunction
- Ocular Toxicity
- Gastrointestinal Toxicity
- Skin Toxicity
- Increased Creatine Phosphokinase
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The NF1 PN pediatric safety pool described in the WARNINGS AND PRECAUTIONS reflects exposure to KOSELUGO at the recommended dosage in 134 pediatric patients in SPRINKLE (N = 36) (NCT05309668), SPRINT Phase I (N = 24) (NCT01362803), SPRINT Phase II Stratum 1 (N = 50)
In the KOMET adult NF1 PN study, 71 adult patients received KOSELUGO at the recommended dosage
Neurofibromatosis Type 1 (NF1) with Inoperable Plexiform Neurofibromas (PN)
Pediatrics 2-18 years of Age (SPRINT Phase II Stratum 1)
The safety of KOSELUGO was evaluated in SPRINT Phase II Stratum 1
Serious adverse reactions occurred in 24% of patients who received KOSELUGO. Serious adverse reactions that occurred in 2 or more patients were anemia, hypoxia and diarrhea.
Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received KOSELUGO. Adverse reactions resulting in permanent discontinuation of KOSELUGO included increased blood creatinine, increased weight, diarrhea, paronychia, malignant peripheral nerve sheath tumor, acute kidney injury, and skin ulcer.
Dosage interruptions and dose reductions due to adverse reactions occurred in 80% and 24% of patients who received KOSELUGO, respectively. Adverse reactions requiring a dosage interruption or reduction in ≥ 5% of patients were vomiting, paronychia, diarrhea, nausea, abdominal pain, rash, skin infection, influenza-like illness, pyrexia and weight gain.
The most common adverse reactions (≥ 40%) were vomiting, rash (all), abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, pyrexia, acneiform rash, stomatitis, headache, paronychia, and pruritus.
Table 10 presents the adverse reactions in SPRINT Phase II Stratum 1.
Clinically relevant adverse reactions that occurred < 20% of patients include:
- Eye: visual impairment and subretinal fluid.
- Gastrointestinal Disorders: dry mouth.
- General Disorders: facial edema, including periorbital edema and face edema.
- Metabolism and Nutrition: increased weight.
- Renal and Urinary System: acute kidney injury.
- Respiratory, Thoracic & Mediastinal: dyspnea, including exertional dyspnea and dyspnea at rest.
- Vascular: hypertension.
Table 11 presents the laboratory abnormalities in SPRINT Phase II Stratum 1.
Adults ≥ 18 years of Age (KOMET)
The safety of KOSELUGO was evaluated in KOMET
Serious adverse reactions occurred in 14% of patients who received KOSELUGO. Serious adverse reactions occurring in more than one patient included cellulitis (2.8%).
Permanent discontinuation due to an adverse reaction occurred in 13% of patients who received KOSELUGO. Adverse reactions resulting in permanent discontinuation of KOSELUGO included dermatitis acneiform, cellulitis, nausea, wound, neurofibrosarcoma, neurofibrosarcoma recurrent, psychiatric decompensation, ulcerative keratitis, and nail disorder.
Dosage interruptions and dose reductions due to adverse reactions occurred in 27% and 14% of patients who received KOSELUGO, respectively. Adverse reactions requiring a dosage reduction in 2 or more patients were paronychia, increased CPK, increased ALT, increased AST, rash, and alopecia. Adverse reactions requiring a dosage interruption in 2 or more patients were increased CPK, rash, headache, abdominal pain, nausea, and COVID‑19.
The most common adverse reactions (≥ 40%) were rash (all), rash (acneiform), and diarrhea.
Table 12 presents the adverse reactions in the KOMET study. The 12 cycle (48 weeks) randomization period for KOSELUGO versus placebo was followed by a single arm treatment period where all patients received KOSELUGO (placebo patients crossed over to KOSELUGO at end of the randomized period). No new adverse reactions were identified during the open-label period.
Clinically relevant adverse reactions in < 20% of patients who received KOSELUGO versus placebo based on reported adverse reactions included hair changes (18% vs 11%), paronychia (13% vs 4%), pyrexia (7% vs 4%), stomatitis (18% vs 5%), and skin infection (6% vs 1%), respectively. Decreased ejection fraction in patients who received KOSELUGO versus placebo based on reported echocardiogram results occurred in 14% and 11% of patients, respectively.
Table 13 presents the laboratory abnormalities in the KOMET study.
Pediatrics > 1 year of Age on KOSELUGO Granules (SPRINKLE)
The safety of KOSELUGO oral granules was evaluated in SPRINKLE (NCT05309668), a dose-finding and activity estimating, single-arm, multicenter study in 36 pediatric patients ages 1 year to less than 7 years with a clinical diagnosis of NF1- related symptomatic, inoperable PN. The study evaluated the pharmacokinetics (PK), safety, efficacy, and tolerability of KOSELUGO oral granules. Study patients were to receive KOSELUGO oral granules for 25 cycles at a dose equivalent to 25 mg/m
In the SPRINKLE study, the median duration of KOSELUGO oral granules treatment in pediatric patients with neurofibromatosis type 1 (NF1) plexiform neurofibromas (PN) was 11 months (range: 3-25 months). Serious adverse reactions occurred in 6% of patients who received KOSELUGO oral granules. Serious adverse reactions occurred in 1 patient each and included pyrexia, gastroenteritis and upper respiratory infection. A total of 31% of patients had an adverse reaction leading to a dosage interruption. Adverse reactions requiring a dosage interruption in ≥ 5% of patients were pyrexia, vomiting, diarrhea, upper respiratory infection, gastroenteritis and eczema. The most common adverse reactions (≥ 40%) were pyrexia, dry skin, and paronychia.
The observed safety profile of KOSELUGO oral granules in the SPRINKLE study was consistent with the known safety profile of KOSELUGO capsules.
4.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of KOSELUGO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Eye disorders: RPED/CSR including detachment of retinal pigment epithelium, central serous chorioretinopathy, serous retinal detachment, serous retinopathy, and retinal detachment
5OVERDOSAGE
Dialysis is not effective as KOSELUGO is highly protein bound and is extensively metabolized.
6DESCRIPTION
KOSELUGO contains selumetinib sulfate, a kinase inhibitor. The chemical name is 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-6-[(2-hydroxyethoxy)carbamoyl]-1-methyl-1
Selumetinib sulfate is a white to yellow monomorphic crystalline powder that exhibits a pH dependent solubility. Selumetinib sulfate is freely soluble at pH < 1.5, sparingly soluble in the pH range at 1.5 to 3 and slightly soluble at pH > 3. Selumetinib sulfate has two ionizable functions with pKa values of 2.8 and 8.4.
KOSELUGO (selumetinib) 10 mg capsules for oral use, contain 10 mg selumetinib (equivalent to 12.1 mg selumetinib sulfate) and the excipient, vitamin E polyethylene glycol succinate. The capsule shell contains carnauba wax, carrageenan, hypromellose, potassium chloride, purified water, and titanium dioxide. The capsule is imprinted with black ink that contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac.
KOSELUGO (selumetinib) 25 mg capsules for oral use, contain 25 mg selumetinib (equivalent to 30.25 mg selumetinib sulfate) and the excipient, vitamin E polyethylene glycol succinate. The capsule shell contains carnauba wax and/or cornstarch, carrageenan, FD&C blue 2, ferric oxide yellow, hypromellose, potassium chloride, purified water, and titanium dioxide. The capsule is imprinted with black ink that contains carnauba wax, FD&C Blue 2 aluminum lake, ferric oxide red, ferric oxide yellow, glyceryl monooleate, and shellac.
KOSELUGO (selumetinib) 5 mg oral granules contain 5 mg selumetinib (equivalent to 6.05 mg selumetinib sulfate). The uncoated cores contain selumetinib sulfate, glyceryl dibehenate, and stearoyl polyoxylglycerides. The granule coating contains acetone, hypromellose acetate succinate, and stearic acid. The capsule shell contains ferric oxide yellow, hypromellose, and titanium dioxide. The capsule shell is imprinted with black ink that contains butyl alcohol, dehydrated alcohol, ferric oxide black, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.
KOSELUGO (selumetinib) 7.5 mg oral granules contain 7.5 mg selumetinib (equivalent to 9.08 mg selumetinib sulfate). The uncoated cores contain selumetinib sulfate, glyceryl dibehenate, and stearoyl polyoxylglycerides. The granule coating contains acetone, hypromellose acetate succinate, and stearic acid. The capsule shell contains ferric oxide red, hypromellose, and titanium dioxide. The capsule shell is imprinted with black ink that contains butyl alcohol, dehydrated alcohol, ferric oxide black, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Selumetinib Capsules
Selumetinib Oral Granules
Storage
KOSELUGO Capsules
Store KOSELUGO capsules at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense and store in the original bottle to protect from light and moisture. Do not remove desiccant. Keep the bottle tightly closed after first opening.
KOSELUGO Oral Granules
Store and transport KOSELUGO oral granules refrigerated at 2°C to 8°C (36°F to 46°F). After receipt, patients may store at room temperature 20°C to 25°C (68°F to 77°F). Do NOT exceed 30°C (86°F). KOSELUGO oral granules may clump together or stick to the capsule shell if exposed to high temperatures, which may lead to underdose. Dispense and store in the original bottle to protect from light and moisture. Do not remove desiccant. Keep the bottle tightly closed after first opening.
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Left Ventricular Dysfunction
Advise patients and caregivers that KOSELUGO can cause a reduction in LVEF and to immediately report any signs or symptoms of cardiomyopathy to their healthcare provider
Ocular Toxicity
Advise patients and caregivers that KOSELUGO can cause ocular toxicity that can lead to blindness and to contact their healthcare provider if the patient experiences any changes in their vision
Gastrointestinal Toxicity
Advise patients and caregivers that KOSELUGO can cause diarrhea, nausea, vomiting, and stomatitis and to contact their healthcare provider at the first sign of gastrointestinal toxicity
Skin Toxicity
Advise patients and caregivers that KOSELUGO can cause serious skin toxicities and to contact their healthcare provider for severe skin changes
Increased Creatine Phosphokinase
Advise patients and caregivers that KOSELUGO can cause increased CPK and rhabsomyolysis to report any signs and symptoms of muscle pain or weakness to their healthcare provider
Increased Vitamin E Levels and Increased Risk of Bleeding (KOSELUGO Capsules)
Advise patients and caregivers to notify their healthcare provider if they are taking a supplement containing vitamin E, a vitamin-K antagonist or an anti-platelet agent
Embryo-Fetal Toxicity
- Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy
- Advise females of reproductive potential to use effective contraception during treatment with KOSELUGO and for 1 week after the last dose
- Advise males with female partners of reproductive potential to use effective contraception during treatment with KOSELUGO and for 1 week after the last dose
Lactation
Advise women not to breastfeed during treatment with KOSELUGO and for 1 week after the last dose
Drug Interactions
Advise patients and caregivers to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products. Inform patients to avoid St. John’s wort, grapefruit or grapefruit juice, and Seville orange while taking KOSELUGO
Dosing and Administration
Inform patients and caregivers on how to take KOSELUGO and what to do for missed or vomited doses
Distributed by:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
© AstraZeneca 20XX
9Instructions for Use
This Instructions for Use has been approved by the U.S. Food and Drug Administration. Approved: Sep/2025
10PACKAGE/LABEL PRINCIPAL DISPLAY PANEL 10mg
NDC 0310-0610-28
Koselugo
(selumetinib)
capsules
10 mg
Rx only
Dispense in original bottle.
desiccant. Protect from moisture.
Keep the bottle tightly closed.
28 Capsules AstraZeneca
11PACKAGE/LABEL PRINCIPAL DISPLAY PANEL 25mg
NDC 0310-0625-28
Koselugo
(selumetinib)
capsules
25 mg
Rx only
Dispense in original bottle.
desiccant. Protect from moisture.
Keep the bottle tightly closed.
28 Capsules AstraZeneca
12Package/Label Display Panel 5 mg
NDC 0310-0635-60
Koselugo
(selumetinib)
Oral granules
7.5 mg
Sprinkle oral granules on or mix
with smooth yogurt or fruit puree.
Dispense and store in original
bottle
protect from light and moisture.
60 Capsules
Rx only Astrazeneca
13Package/Label Display Panel 7.5 mg
NDC 0310-0640-60
Koselugo
(selumetinib)
Oral granules
7.5 mg
Sprinkle oral granules on or mix
with smooth yogurt or fruit puree.
Dispense and store in original
bottle
protect from light and moisture.
60 Capsules
Rx only Astrazeneca
