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Dose reductions due to an adverse reaction occurred in 31 % of patients who received RETEVMO . Adverse reactions requiring dosage reductions in > 2 % of patients included ALT increased , AST increased , QT prolongation and fatigue .
The most common adverse reactions , including laboratory abnormalities , ( ≥ 25 %) were increased aspartate aminotransferase ( AST ), increased alanine aminotransferase ( ALT ), increased glucose , decreased leukocytes , decreased albumin , decreased calcium , dry mouth , diarrhea , increased creatinine , increased alkaline phosphatase , hypertension , fatigue , edema , decreased platelets , increased total cholesterol , rash , decreased sodium , and constipation .
Table 1 summarizes the adverse reactions in LIBRETTO-001 .
Table 1 : Adverse Reactions (> 15 %) in Patients Who Received RETEVMO in LIBRETTO-001
Adverse Reaction
Grades 1-4 (%)
RETEVMO ( n = 702 )
Grade 3-4 (%)
Gastrointestinal Dry Mouth
39
0
Diarrhea 1
37
3.4 *
Constipation
25
0.6 *
Nausea
23
0.6 *
Abdominal pain 2
23
1.9 *
Vomiting
15
0.3 *
Vascular Hypertension
35
18
General
Fatigue 3
35
2 *
Edema 4
35
0.3 *
Skin
Rash 5
27
0.7 *
Nervous System
Headache 6
23
1.4 *
Respiratory
Cough 7
18
0
Dyspnea 8
16
2.3
Investigations Prolonged QT interval
17
4 *
Blood and Lymphatic System
Hemorrhage 9
15
1.9
1
Diarrhea includes diarrhea , defecation urgency , frequent bowel movements , and anal
incontinence
2
Abdominal pain includes abdominal pain , abdominal pain upper , abdominal pain lower ,
abdominal discomfort , gastrointestinal pain
3
Fatigue includes fatigue , asthenia , malaise .
4
Edema includes edema , edema peripheral , face edema , periorbital edema , eye edema ,
eyelid edema , orbital edema , localized edema , lymphedema , scrotal edema , peripheral
swelling , scrotal swelling , swelling , swelling face , eye swelling
5
Includes rash , rash erythematous , rash macular , rash maculopapular , rash morbilliform ,
rash pruritic
6
Headache includes headache , sinus headache , tension headache ,
7
Includes cough , productive cough
8
Includes dyspnea , dyspnea exertional , dyspnea at rest
9
Hemorrhage includes epistaxis , hematuria , hemoptysis , contusion , rectal hemorrhage ,
vaginal hemorrhage , ecchymosis , hematochezia , petechiae , traumatic hematoma ,
anal hemorrhage , blood blister , blood urine present , cerebral hemorrhage , gastric
hemorrhage , hemorrhage intracranial , spontaneous hematoma , abdominal wall
hematoma , angina bullosa hemorrhagica , diverticulum intestinal hemorrhagic , eye
hemorrhage , gastrointestinal hemorrhage , gingival bleeding , hematemesis , hemorrhagic
anemia , intraabdominal hemorrhage , lower gastrointestinal hemorrhage , melena , mouth
hemorrhage , occult blood positive , pelvic hematoma , periorbital hematoma , pharyngeal
hemorrhage , pulmonary contusion , purpura , retroperitoneal hematoma , subarachnoid
hemorrhage , subdural hemorrhage , upper gastrointestinal hemorrhage , vessel puncture
site hematoma
* Only includes a grade 3 adverse reaction .
Clinically relevant adverse reactions in < 15 % of patients who received RETEVMO include hypothyroidism and tumor lysis syndrome .
Table 2 summarizes the laboratory abnormalities in LIBRETTO-001 .
Table 2 : Select Laboratory Abnormalities ( ≥ 20 %) Worsening from Baseline in Patients Who Received RETEVMO in LIBRETTO-001
Laboratory Abnormality
RETEVMO 1
Grades 1-4 (%)
Grades 3-4 (%)
Chemistry Increased AST
51
8
Increased ALT
45
9
Increased glucose
44
2.2
Decreased albumin
42
0.7
Decreased calcium
41
3.8
Increased creatinine
37
1.0
Increased alkaline phosphatase
36
2.3
Increased total cholesterol
31
0.1
Decreased sodium
27
7
Decreased magnesium
24
0.6
Increased potassium
24
1.2
Increased bilirubin
23
2.0
Decreased glucose
22
0.7
Hematology Decreased leukocytes
43
1.6
Decreased platelets
33
2.7
1
Denominator for each laboratory parameter is based on the number of patients
with a baseline and post-treatment laboratory value available , which ranged from 675 to
692 patients .
Increased Creatinine
In healthy subjects administered RETEVMO 160 mg orally twice daily , serum creatinine increased 18 % after 10 days . Consider alternative markers of renal function if persistent elevations in serum creatinine are observed .
DRUG INTERACTIONS Effects of Other Drugs on RETEVMO Acid-Reducing Agents
Concomitant use of RETEVMO with acid-reducing agents decreases selpercatinib plasma concentrations , which may reduce RETEVMO anti-tumor activity . Avoid concomitant use of PPIs , H2 receptor antagonists , and locally acting antacids with RETEVMO . If coadministration cannot be avoided , take RETEVMO with food ( with a PPI ) or modify its administration time ( with a H2 receptor antagonist or a locally acting antacid ).
Strong and Moderate CYP3A Inhibitors
Concomitant use of RETEVMO with a strong or moderate CYP3A inhibitor increases selpercatinib plasma concentrations , which may increase the risk of RETEVMO adverse reactions , including QTc interval prolongation . Avoid concomitant use of strong and moderate CYP3A inhibitors with RETEVMO . If concomitant use of strong and moderate CYP3A inhibitors cannot be avoided , reduce the RETEVMO dosage and monitor the QT interval with ECGs more frequently .
Strong and Moderate CYP3A Inducers
Concomitant use of RETEVMO with a strong or moderate CYP3A inducer decreases selpercatinib plasma concentrations , which may reduce RETEVMO anti-tumor activity . Avoid coadministration of strong or moderate CYP3A inducers with RETEVMO .
Effects of RETEVMO on Other Drugs CYP2C8 and CYP3A Substrates
RETEVMO is a moderate CYP2C8 inhibitor and a weak CYP3A inhibitor . Concomitant use of RETEVMO with CYP2C8 and CYP3A substrates increases their plasma concentrations , which may increase the risk of adverse reactions related to these substrates . Avoid coadministration of RETEVMO with CYP2C8 and CYP3A substrates where minimal
RETEVMO ® ( selpercatinib ) capsules , for oral use SE HCP BS 25MAR2021 RETEVMO ® ( selpercatinib ) capsules , for oral use SE HCP BS 25MAR2021