concentration changes may lead to increased adverse reactions . If coadministration cannot be avoided , follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling .
Drugs that Prolong QT Interval
RETEVMO is associated with QTc interval prolongation . Monitor the QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong the QT interval .
USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary
Based on findings from animal studies , and its mechanism of action , RETEVMO can cause fetal harm when administered to a pregnant woman . There are no available data on RETEVMO use in pregnant women to inform drug-associated risk . Administration of selpercatinib to pregnant rats during the period of organogenesis resulted in embryolethality and malformations at maternal exposures that were approximately equal to the human exposure at the clinical dose of 160 mg twice daily . Advise pregnant women of the potential risk to a 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 Animal Data
Selpercatinib administration to pregnant rats during the period of organogenesis at oral doses ≥ 100 mg / kg [ approximately 3.6 times the human exposure based on the area under the curve ( AUC ) at the clinical dose of 160 mg twice daily ] resulted in 100 % postimplantation loss . At the dose of 50 mg / kg [ approximately equal to the human exposure ( AUC ) at the clinical dose of 160 mg twice daily ], 6 of 8 females had 100 % early resorptions ; the remaining 2 females had high levels of early resorptions with only 3 viable fetuses across the 2 litters . All viable fetuses had decreased fetal body weight and malformations ( 2 with short tail and one with small snout and localized edema of the neck and thorax ).
Lactation Risk Summary
There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production . Because of the potential for serious adverse reactions in breastfed children , advise women not to breastfeed during treatment with RETEVMO and for 1 week after the final dose .
Females and Males of Reproductive Potential
Based on animal data , RETEVMO can cause embryolethality and malformations at doses resulting in exposures less than or equal to the human exposure at the clinical dose of 160 mg twice daily .
Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating RETEVMO .
Pediatric Use
The safety and effectiveness of RETEVMO have been established in pediatric patients aged 12 years and older for medullary thyroid cancer ( MTC ) who require systemic therapy and for advanced RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory ( if radioactive iodine is appropriate ). Use of RETEVMO for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged 12 years and older . The safety and effectiveness of RETEVMO have not been established in these indications in patients less than 12 years of age .
The safety and effectiveness of RETEVMO have not been established in pediatric patients for other indications .
Animal Toxicity Data
In 4-week general toxicology studies in rats , animals showed signs of physeal hypertrophy and tooth dysplasia at doses resulting in exposures ≥ approximately 3 times the human exposure at the 160 mg twice daily clinical dose . Minipigs also showed signs of minimal to marked increases in physeal thickness at the 15 mg / kg high dose level ( approximately 0.3 times the human exposure at the 160 mg twice daily clinical dose ). Rats in both the 4- and 13-week toxicology studies had malocclusion and tooth discoloration at the high dose levels ( ≥1.5 times the human exposure at the 160 mg twice daily clinical dose ) that persisted during the recovery period .
Monitor growth plates in adolescent patients with open growth plates . Consider interrupting or discontinuing therapy based on the severity of any growth plate abnormalities and based on an individual risk-benefit assessment .
Geriatric Use
Of 702 patients who received RETEVMO , 34 % ( 239 patients ) were ≥ 65 years of age and 10 % ( 67 patients ) were ≥ 75 years of age . No overall differences were observed in the safety or effectiveness of RETEVMO between patients who were ≥65 years of age and younger patients .
Renal Impairment
No dosage modification is recommended for patients with mild to severe renal impairment [ estimated Glomerular Filtration Rate ( eGFR ) ≥15 to 89 mL / min estimated by Modification of Diet in Renal Disease ( MDRD ) equation ]. The recommended dosage has not been established for patients with end-stage renal disease .
Hepatic Impairment
Reduce the dose when administering RETEVMO to patients with severe [ total bilirubin greater than 3 to 10 times upper limit of normal ( ULN ) and any AST ] hepatic impairment . No dosage modification is recommended for patients with mild ( total bilirubin less than or equal to ULN with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST ) or moderate ( total bilirubin greater than 1.5 to 3 times ULN and any AST ) hepatic impairment . Monitor for RETEVMO-related adverse reactions in patients with hepatic impairment .
Rx only .
Additional information can be found at www . retevmo . com .
Contraception Females
Advise female patients of reproductive potential to use effective contraception during treatment with RETEVMO and for 1 week after the final dose .
Males
Advise males with female partners of reproductive potential to use effective contraception during treatment with RETEVMO and for 1 week after the final dose .
Infertility RETEVMO may impair fertility in females and males of reproductive potential .
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RETEVMO ® ( selpercatinib ) capsules , for oral use SE HCP BS 25MAR2021 RETEVMO ® ( selpercatinib ) capsules , for oral use SE HCP BS 25MAR2021