Dosing & Uses
See Pediatric Dosing
Dosage Forms & Strengths
capsule
- 10mg
- 25mg
Type 1 Neurofibromatosis
Indicated for neurofibromatosis type 1 (NF1) in patients aged ≥2 years who have symptomatic, inoperable plexiform neurofibromas (PN)
<2 years or body surface area (BSA) <0.55 m2: Safety and efficacy not established
≥2 years
- BSA ≥0.55 m2: 25 mg/m2 PO BID (~q12hr)
-
Recommended dosage based on BSA
- 0.55-0.69 m2: 20 mg PO qAM and 10 mg PO qPM
- 0.7-0.89 m2: 20 mg PO BID
- 0.9-1.09 m2: 25 mg PO BID
- 1.1-1.29 m2: 30 mg PO BID
- 1.3-1.49 m2: 35 mg PO BID
- 1.5-1.69 m2: 40 mg PO BID
- 1.7-1.89 m2: 45 mg PO BID
- ≥1.9 m2: 50 mg PO BID
Dosage Modifications
Dose reductions for adverse reactions based on BSA
-
First dose reduction
- 0.55-0.69 m2: 10 mg BID
- 0.7-0.89 m2: 20 mg qAM and 10 mg qPM
- 0.9-1.09 m2: 25 mg qAM and 10 mg qPM
- 1.1-1.29 m2: 25 mg qAM and 20 mg qPM
- 1.3-1.49 m2: 25 mg BID
- 1.5-1.69 m2: 30 mg BID
- 1.7-1.89 m2: 35 mg qAM and 30 mg qPM
- ≥1.9 m2: 35 mg BID
-
Second dose reduction
- 0.55-0.69 m2: 10 mg qDay
- 0.7-1.09 m2: 10 mg BID
- 1.1-1.29 m2: 20 mg qAM and 10 mg qPM
- 1.3-1.49 m2: 25 mg qAM and 10 mg qPM
- 1.5-1.89 m2: 25 mg qAM and 20 mg qPM
- ≥1.9 m2: 25 mg BID
-
Subsequent dose reductions
- Permanently discontinue in patients unable to tolerate selumetinib after 2 dose reductions
Cardiomyopathy
- Asymptomatic decrease in left ventricular ejection fraction (LVEF) ≥10% from baseline and lower level of normal (LLN): Withhold until resolution; resume at reduced dose
- Symptomatic decreased LVEF OR Grade 3 or 4 decreased LVEF: Permanently discontinue
Ocular toxicity
- Retinal pigment epithelial detachment (RPED): Withhold until resolution; resume at reduced dose
- Retinal vein occlusion (RVO): Permanently discontinue
Gastrointestinal toxicity
- Grade 3 diarrhea: Withhold until improved to Grade <1; resume at same dose; permanently discontinue if no improvement within 3 days
- Grade 4 diarrhea OR Grade 3 or 4 colitis: Permanently discontinue
Skin toxicity
- Grade 3 or 4: Withhold until improvement; resume at reduced dose
Increased creatine phosphokinase (CPK)
- Grade 4 increased CPK OR any increased CPK and myalgia: Withhold until improved to Grade <1; resume at reduced dose; permanently discontinue if no improvement within 3 weeks
Other adverse reactions
- Intolerable Grade 2 OR Grade 3: Withhold until improved to Grade <1; resume at reduced dose
- Grade 4: Withhold until improved to Grade <1; resume at reduced dose; consider discontinuation
Dosage modifications for drug interactions
Strong or moderate CYP3A4 inhibitors or fluconazole
- Avoid coadministration
- If coadministration cannot be avoided, reduce selumetinib dosage based on the recommendations below
- Resume selumetinib after discontinuation of the strong or moderate CYP3A4 inhibitor or fluconazole for 3 elimination half-lives
- Reduce current dose by 5 mg/m2 (eg, 25 mg/m2 to 20 mg/m2 OR 20 mg/m2 to 15 mg/m2)
-
Dosage reduction to 20 mg/m2 based on BSA
- 0.55-0.69 m2: 10 mg BID
- 0.7-0.89 m2: 20 mg qAM and 10 mg qPM
- 0.9-1.09 m2: 20 mg BID
- 1.1-1.29 m2: 25 mg BID
- 1.3-1.49 m2: 30 mg qAM and 25 mg qPM
- 1.5-1.69 m2: 35 mg qAM and 30 mg qPM
- 1.7-1.89 m2: 35 mg BID
- ≥1.9 m2: 40 mg BID
-
Dosage reduction to 15 mg/m2 based on BSA
- 0.55-0.69 m2: 10 mg qDay
- 0.7-0.89 m2: 10 mg BID
- 0.9-1.09 m2: 20 mg qAM and 10 mg qPM
- 1.1-1.29 m2: 25 mg qAM and 10 mg qPM
- 1.3-1.49 m2: 25 mg qAM and 20 mg qPM
- 1.5-1.69 m2: 25 mg BID
- 1.7-1.89 m2: 30 mg qAM and 25 mg qPM
- ≥1.9 m2: 30 mg BID
Renal impairment
- No dosage adjustment necessary
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment necessary
-
Moderate (Child-Pugh B): Reduce recommended dose to 20 mg/m2 BID
- 0.55-0.69 m2: 10 mg BID
- 0.7-0.89 m2: 20 mg qAM and 10 mg qPM
- 0.9-1.09 m2: 20 mg BID
- 1.1-1.29 m2: 25 mg BID
- 1.3-1.49 m2: 30 mg qAM and 25 mg qPM
- 1.5-1.69 m2: 35 mg qAM and 30 mg qPM
- 1.7-1.89 m2: 35 mg BID
- ≥1.9 m2: 40 mg BID
- Severe (Child-Pugh C): Selumetinib unbound AUC increased 3.2-fold in subjects with severe hepatic impairment compared with normal hepatic function; no dosage recommended
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (96)
- amiodarone
amiodarone will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- amobarbital
amobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- aprepitant
aprepitant will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- armodafinil
armodafinil will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atazanavir
atazanavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- bexarotene
bexarotene will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bicalutamide
bicalutamide will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- bosentan
bosentan will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- brigatinib
brigatinib will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- chloramphenicol
chloramphenicol will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- clarithromycin
clarithromycin will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- clobazam
clobazam will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- conivaptan
conivaptan will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- crizotinib
crizotinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- cyclosporine
cyclosporine will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- dabrafenib
dabrafenib will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darunavir
darunavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- diltiazem
diltiazem will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- doxycycline
doxycycline will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- dronedarone
dronedarone will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.
- efavirenz
efavirenz will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- elagolix
elagolix will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- encorafenib
encorafenib will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin base
erythromycin base will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- etrasimod
etrasimod, selumetinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.
- etravirine
etravirine will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
fedratinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- fexinidazole
fexinidazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fluconazole
fluconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- fosamprenavir
fosamprenavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- fosaprepitant
fosaprepitant will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fostamatinib
fostamatinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- grapefruit
grapefruit will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- haloperidol
haloperidol will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- idelalisib
idelalisib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- iloperidone
iloperidone will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- imatinib
imatinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- indinavir
indinavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- isoniazid
isoniazid will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- itraconazole
itraconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- ivacaftor
ivacaftor will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- ivosidenib
ivosidenib will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ketoconazole
ketoconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- lapatinib
lapatinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- larotrectinib
larotrectinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- lenacapavir
lenacapavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with selumetinib. Refer to the prescribing information of selumetinib for further information on the dosage modifications.
- leniolisib
leniolisib will increase the level or effect of selumetinib by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
- letermovir
letermovir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- levoketoconazole
levoketoconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- lonafarnib
lonafarnib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lorlatinib
lorlatinib will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- metronidazole
metronidazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- mifepristone
mifepristone will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- mitotane
mitotane will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- nelfinavir
nelfinavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- pentobarbital
pentobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- primidone
primidone will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- repotrectinib
selumetinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- ribociclib
ribociclib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- rifabutin
rifabutin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritonavir
ritonavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- saquinavir
saquinavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- schisandra
schisandra will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- secobarbital
secobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sertraline
sertraline will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- St John's Wort
St John's Wort will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- stiripentol
stiripentol will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- telotristat ethyl
telotristat ethyl will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tetracycline
tetracycline will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- tipranavir
tipranavir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- tucatinib
tucatinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- verapamil
verapamil will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- voriconazole
voriconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
- voxelotor
voxelotor will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.
Monitor Closely (20)
- abciximab
abciximab and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- anagrelide
anagrelide and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- aspirin
aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- berotralstat
selumetinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.
- cangrelor
cangrelor and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- cilostazol
cilostazol and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- clopidogrel
clopidogrel and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- dipyridamole
dipyridamole and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- encorafenib
encorafenib will increase the level or effect of selumetinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.
- eptifibatide
eptifibatide and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- fostemsavir
fostemsavir will increase the level or effect of selumetinib by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.
- momelotinib
momelotinib increases toxicity of selumetinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- oteseconazole
oteseconazole will increase the level or effect of selumetinib by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- ponesimod
ponesimod and selumetinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- prasugrel
prasugrel and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- ticagrelor
ticagrelor and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- ticlopidine
ticlopidine and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- tirofiban
tirofiban and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
- vitamin E
vitamin E and selumetinib both increase Other (see comment). Modify Therapy/Monitor Closely. Selumetinib contains vitamin E. Daily vitamin E intake (ie, amount in selumetinib, supplement, dietary) that exceeds recommendations may increase bleeding risk.
- vorapaxar
vorapaxar and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.
Minor (0)
Adverse Effects
>10%
All grades
- Vomiting (82%)
- Rash (80%)
- Increased CPK (79%)
- Abdominal pain (76%)
- Diarrhea (70%)
- Nausea (66%)
- Dry skin (60%)
- Musculoskeletal pain (58%)
- Fatigue (56%)
- Pyrexia (56%)
- Decreased albumin (51%)
- Acneiform rash (50%)
- Stomatitis (50%)
- Paronychia (48%)
- Headache (48%)
- Pruritus (46%)
- Increased AST (41%)
- Decreased hemoglobin (41%)
- Dermatitis (36%)
- Increased ALT (35%)
- Constipation (34%)
- Decreased neutrophils (33%)
- Increased lipase (32%)
- Hair changes (32%)
- Epistaxis (28%)
- Hematuria (22%)
- Proteinuria (22%)
- Decreased appetite (22%)
- Decreased ejection fraction (EF) (22%)
- Sinus tachycardia (20%)
- Skin infection (20%)
- Edema (20%)
- Decreased lymphocytes (20%)
- Visual impairment (<20%)
- Dry mouth (<20%)
- Facial edema, including periorbital and face edema (<20%)
- Increased weight (<20%)
- Acute kidney injury (<20%)
- Dyspnea, including exertional dyspnea and dyspnea at rest (<20%)
- Hypertension (<20%)
- Increased alkaline phosphatase (18%)
- Increased amylase (18%)
- Decreased potassium (18%)
- Increased sodium (18%)
- Decreased sodium (18%)
Grade 3 or 4
- Diarrhea (16%)
1-10%
Grade 3 or 4
- Pyrexia (8%)
- Increased CPK (7%)
- Rash (6%)
- Vomiting (6%)
- Paronychia (6%)
- Increased lipase (5%)
- Increased ALT (4%)
- Rash acneiform (4%)
- Dermatitis (4%)
- Increased potassium (4%)
- Decreased hemoglobin (4%)
- Decreased neutrophils (4%)
- Decreased lymphocytes (2%)
- Increased ALT (2%)
- Headache (2%)
- Hematuria (2%)
- Skin infection (2%)
- Nausea (2%)
- Decreased potassium (2%)
Warnings
Contraindications
None
Cautions
Rash occurred; other skin toxicities, including severe palmoplantar erythrodysesthesia syndrome, occurred; monitor for severe rashes
Increased CPK occurred; rhabdomyolysis occurred in an unapproved adult population who received selumetinib; obtain serum CPK before initiating, periodically during treatment, and as clinically indicated
May cause fetal harm when administered to a pregnant woman based on animal studies and mechanism of action
Gastrointestinal toxicity
- Diarrhea occurred
- Serious gastrointestinal toxicities (eg, perforation, colitis, ileus, intestinal obstruction) occurred in an unapproved population of adult patients
- Colitis occurred in an unapproved population of pediatric patients
- Advise to start an antidiarrheal agent (eg, loperamide) immediately after first episode of unformed, loose stool and to increase fluid intake during diarrhea episodes
Ocular toxicity
- Blurred vision, photophobia, cataracts, and ocular hypertension occurred
- Serious ocular toxicities, including RVO and RPED, occurred in an unapproved population of adult patients with multiple tumor types
- RPED occurred in the pediatric population during treatment and resulted in permanent discontinuation
- Conduct comprehensive ophthalmic assessments before initiating treatment, at regular intervals during treatment, and for new or worsening visual changes
Cardiomyopathy
- Cardiomyopathy (decreased in LVEF ≥10% below baseline) occurred; all patients with decreased LVEF were asymptomatic and identified during routine echocardiography
- Safety has not been established in patients with a history of impaired LVEF or a baseline ejection fraction below the institutional LLN
- Assess ejection fraction by echocardiogram before initiating treatment, q3months during the first year of treatment, q6months thereafter, and as clinically indicated.
- If dose is withheld, obtain an echocardiogram or a cardiac MRI every 3-6 weeks, then every 2-3 months or as directed by the cardiologist once resolved
Drug interaction overview
Selumetinib is a substrate of CYP3A4, BCRP, and P-gp transporters
-
Antiplatelet antagonists or vitamin K antagonists
- Capsules contain vitamin E and daily intake of vitamin E that exceeds the recommended or safe limits may increase the risk of bleeding
- An increased risk of bleeding in patients may occur when coadministered with vitamin K antagonists or antiplatelet antagonists
- Supplemental vitamin E is not recommended if daily vitamin E intake will exceed the recommended or safe limits
- Monitor for bleeding and international normalized ratio
-
Strong and moderate CYP3A4 inhibitors
- Coadministration with a strong or moderate CYP3A4 inhibitor or fluconazole may increase selumetinib plasma concentration
- Avoid coadministration
-
Strong or moderate CYP3A4 inducers
- Coadministration with a strong or moderate CYP3A4 inducer decreased selumetinib plasma concentrations
- Avoid coadministration
Pregnancy & Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
No data available on use in pregnant women to evaluate drug-associated risk
Verify pregnancy status before initiating treatment
Animal data
- Administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryofetal survival at exposures approximately >5x the human exposure at the clinical dose of 25 mg/m2 BID
- Advise pregnant women of the potential risk to the fetus
Contraception
- Females of reproductive potential or males with females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
Lactation
There are no data on the presence of selumetinib or its active metabolite in human milk or their effects on breastfed child or milk production
Selumetinib and its active metabolite were present in the milk of lactating mice
Advise femalesnot to breastfeed during treatment and for 1 week after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibitor of mitogen-activated protein kinases 1 and 2 (MEK1/2)
MEK 1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway
Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway
In genetically modified mouse models, oral dosing of selumetinib inhibited ERK phosphorylation and reduced neurofibroma numbers, volume, and proliferation
Absorption
- Oral bioavailability (adults): 62%
- Peak plasma distribution (pediatric patients): 731 ng/mL (first dose); 783 ng/mL (steady-state)
- Peak plasma time (pediatric patients): 1-1.5 hr (steady-state)
- AUC (pediatric patients): 2000 ng⋅hr/mL (first dose); 1958 ng⋅hr/mL (steady-state)
-
Effect of food
- High-fat meal (1000 calories, 50% fat): Mean peak plasma concentration and AUC of selumetinib decreased by 50% and 16%, respectively, in healthy adults administered a single dose of 75 mg; peak plasma time was delayed by ~1.5 hr
- Low-fat meal (400 calories, 25% fat): Peak plasma concentration and AUC decreased by 60% and 38%, respectively, in healthy adults administered a single dose of 50 mg; peak plasma time was delayed by ~0.9 hr
Distribution
Vd (steady-state in pediatric patients): 78 L (20 mg/m2); 171 L (30 mg/m2)
Protein bound: 98%; binds to serum albumin (96%) and alpha-1 acid glycitein (<35%)
Metabolism
Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19, CYP1A2, CYP2C9, CYP2E1, and CYP3A5
Undergoes glucuronidation by UGT1A1 and UGT1A3
N-desmethyl selumetinib (active metabolite of selumetinib) is generated by CYP2C19 and CYP1A2 with additional contribution by CYP2C9 and CYP2A6, and metabolized through the same routes as selumetinib
Elimination
Oral clearance: 8.8 L/hr (pediatric patients)
Half-life (pediatric patients): 6.2 hr (25 mg/m2)
Excretion: 59% (feces [19% unchanged]); 33% (urine [<1% unchanged])
Administration
Oral Administration
Take on an empty stomach; do not consume food 2 hr before or within 1 hr after each dose
Swallow capsules whole with water; do not chew, dissolve, or open capsule
Do not administer to patients who are unable to swallow a whole capsule
Missed dose
- Do not take a missed dose unless it is >6 hr until the next scheduled dose
- If vomiting occurs after administration, do not take an additional dose, but continue with the next scheduled dose
Storage
Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
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