ACN_7.13_Full Issue | Page 38

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 (%)

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

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