Selumetinib
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From MedlinePlus, U.S. National Library of Medicine
Kinase Inhibitor
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Dosing in liver impairment
Recommended Dosage in Patients with Hepatic Impairment Severe Hepatic Impairment 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 ] . Moderate Hepatic Impairment The recommended dosage of KOSELUGO capsules (see Table 6) and KOSELUGO oral granules (see Table 7) for pediatric patients 1 year of age or older with moderate hepatic impairment (Child-Pugh B) is based on body surface area; 20 mg/m 2 orally twice daily, until disease progression or unacceptable toxicity [see Dosage and Administration ]. [See table below.] 40 [See table below.] – 0.59 m 2 10 10 0.60 – 0.69 m 2 12.5 12.5 0.70 – 0.89 m 2 15 15 0.90 – 1.09 m 2 20 20 1.10 – 1.29 m 2 25 25 1.30 – 1.49 m 2 30 25 1.50 – 1.69 m 2 35 30 1.70 – 1.89 m 2 35 35 ≥ 1.90 m 2 40 40
| 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 |
| Body Surface Area | Moderate Hepatic Impairment (Child‑Pugh B) (mg/dose) | |
|---|---|---|
| Morning | Evening | |
| 0.40 – 0.59 m2 | 10 | 10 |
| 0.60 – 0.69 m2 | 12.5 | 12.5 |
| 0.70 – 0.89 m2 | 15 | 15 |
| 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 |
Preparation and administration
Administration KOSELUGO is available in two dosage forms: KOSELUGO capsules and KOSELUGO oral granules. Prescribe KOSELUGO oral granules for patients who have difficulty swallowing whole capsules. KOSELUGO Capsules
Administer KOSELUGO capsules to patients who can swallow a whole capsule.
Swallow KOSELUGO capsules whole. Do not open, chew or crush KOSELUGO capsules.
KOSELUGO capsules may be administered with or without food. KOSELUGO Oral Granules Administer KOSELUGO oral granules to patients who have difficulty swallowing a whole capsule. Sprinkle KOSELUGO oral granules on or mix with a small amount (about 1 to 3 teaspoons) of smooth yogurt, or fruit puree containing the following fruits: apple, banana, pear, or strawberry and consume within 30 minutes of preparation.
If not consumed within 30 minutes of preparation, discard and prepare a new dose. If a dose has been partially consumed within 30 minutes of preparation, discard the remainder of the dose and do not prepare a new dose, aim to complete dosing within 30 minutes next time. The KOSELUGO oral granules should be free-flowing.
Do NOT use if the oral granules are clumped or stuck inside the capsule shell. Instruct the patient or caregiver to contact their pharmacy if this happens. Discard the empty capsule shells after use. Do NOT swallow, chew, or dissolve the capsule shells of KOSELUGO oral granules. Do NOT chew or crush the KOSELUGO oral granules.
Do NOT add oral granules to liquids. Do NOT mix KOSELUGO oral granules in grapefruit or any juice, fruit puree or jam containing Seville orange. Missed Dose If a dose of KOSELUGO capsules or KOSELUGO oral granules is missed, make up that dose unless the next dose is due within 6 hours. Vomiting If vomiting occurs after taking a dose of KOSELUGO capsules or KOSELUGO oral granules, do not take an additional dose.
Take the next dose at the regular scheduled time.
Drug interactions
Check selumetinib against a medication listLabel text (4 paragraphs)
7 DRUG INTERACTIONS • Strong or Moderate CYP3A4 Inhibitors or Fluconazole : Avoid coadministration of strong or moderate CYP3A4 inhibitors or fluconazole with KOSELUGO. If coadministration cannot be avoided, reduce the dose of KOSELUGO. ( 2.5 , 7.1 ) • Strong or Moderate CYP3A4 Inducers : Avoid concomitant use of strong and moderate CYP3A4 inducers. ( 7.1 )
7.1 Effect of Other Drugs on KOSELUGO Strong or Moderate CYP3A4 Inhibitors or Fluconazole Management • Avoid concomitant use of strong or moderate CYP3A4 inhibitors or fluconazole with KOSELUGO. If coadministration with strong or moderate CYP3A4 inhibitors or fluconazole cannot be avoided, reduce KOSELUGO dosage [see Dosage Modifications for Drug Interactions (2.5) ]. Clinical Impact • Concomitant use of KOSELUGO with a strong or moderate CYP3A4 inhibitor or fluconazole increased selumetinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions.
Strong or Moderate CYP3A4 Inducers Management • Avoid concomitant use of strong or moderate CYP3A4 inducers with KOSELUGO. Clinical Impact • Concomitant use of KOSELUGO with a strong or moderate CYP3A4 inducer decreased selumetinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may reduce KOSELUGO efficacy. Vitamin E Management • Supplemental vitamin E is not recommended if daily vitamin E intake (including the amount of vitamin E in KOSELUGO capsules and supplement) will exceed the recommended or safe limits. • Monitor for bleeding in patients administered a vitamin‑K antagonist or an anti‑platelet agent with KOSELUGO capsules.
Increase INR monitoring, as appropriate, in patients taking a vitamin‑K antagonist [see Warnings and Precautions (5.3) ] . Clinical Impact • KOSELUGO capsules contain vitamin E and daily vitamin E intake that exceeds the recommended or safe limits may increase the risk of bleeding. An increased risk of bleeding may occur in patients taking a vitamin‑K antagonist or an anti‑platelet agent with KOSELUGO capsules.
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , KOSELUGO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KOSELUGO in pregnant women to evaluate drug-associated risk. In animal reproduction studies, administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryofetal survival at exposures approximately > 5 times the human exposure at the clinical dose of 25 mg/m 2 twice daily ( see Data ). Advise pregnant women of the potential risk to the fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data In KOMET, a first trimester spontaneous abortion was reported in a patient receiving KOSELUGO. Animal Data In embryo-fetal development studies in mice at doses > 2.5 mg/kg twice daily (~5-times the human exposure based on area under the curve [AUC] at the clinical dose of 25 mg/m 2 twice daily), selumetinib caused increases in post-implantation loss, a reduction in mean fetal and litter weights, and an increased occurrence of open eye and cleft palate, but did not induce significant maternal toxicity.
Administration of selumetinib to pregnant mice from gestation Day 6 through lactation Day 20 resulted in reduced pup body weights and fewer pups met the pupil constriction criterion on day 21 post-partum. The incidence of malformations (e.g., prematurely open eye(s) and cleft palate) was increased even at the lowest dose of 0.5 mg/kg twice daily (maternal maximal concentration [C max ] of ~0.6 times the human C max at the clinical dose of 25 mg/m 2 twice daily).
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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