Changes to the Mavyret product labeling for use in pediatrics

FDA approved Mavyret (glecaprevir and pibrentasvir) oral pellets (100mg/40mg) for the treatment of pediatric patients 3 to less than 12 years of age weighing less than 45 kg with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis.  The approval is based on a phase 2/3, open-label study to investigate the pharmacokinetics, safety and efficacy of Mavyret in HCV infected children 3 to less than 12 years of age. Below is a summary of the major changes to the product labeling. 1 INDICATIONS AND USAGE Revised the minimum patient age from 12 to 3 years of age. Removed the minimum patient body weight requirement. 2 DOSAGE AND ADMINISTRATION Revised section 2.4 to include dosage recommendations for pediatric patients 3 years of age and older as follows: The recommended dosage of MAVYRET in pediatric patients 3 to less than 12 years of age is based on weight. MAVYRET oral pellets are recommended for pediatric patients 3 to less than 12 years old weighing less than 45 kg. MAVYRET oral pellets in packets are a fixed combination drug product containing glecaprevir 50 mg and pibrentasvir 20 mg in each packet. The recommended dosage of MAVYRET in pediatric patients 12 years of age and older, or in pediatric patients weighing at least 45 kg, is three tablets taken at the same time once daily with food (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg). Less than 20 kg: Take three 50mg/20 mg packets of Mavyret oral pellets once daily 20 kg to less than 30 kg: Take four 50 mg/20 mg packets of Mavyret oral pellets once daily 30 kg to less than 45 kg: Take five 50 mg/20 mg packets of Mavyret oral pellets once daily 45 kg and greater or 12 years of age and older: Take three 100 mg/40 mg tablets once daily. (those who care unable to swallow tablets may take six 50 mg/20 mg packets of Mavyret oral pellets once daily) Addition of subsection 2.5, entitled, "Preparation and Administration of Oral Pellets". See the MAVYRET oral pellets full Instructions for Use for details on the preparation and administration. The oral pellets should be taken together, with food, once daily. In addition, the oral pellets for the total daily dose should be sprinkled on a small amount of soft food with a low water content that will stick to a spoon and should be swallowed without chewing (e.g., peanut butter, chocolate hazelnut spread, cream cheese, thick jam, or Greek yogurt). The entire mixture of food and oral pellets should be swallowed within 15 minutes of preparation; the oral pellets should not be crushed or chewed. Liquids or foods that would drip or slide off the spoon are not recommended as the drug may dissolve quickly and become less effective. 6 ADVERSE REACTIONS Added adverse reaction data for pediatric subjects 3 and older The safety of MAVYRET in HCV GT 1, 2, 3, or 4 infected pediatric subjects aged 3 years to less than 12 years is based on data from a Phase 2/3 open-label trial in 80 subjects aged 3 to less than 12 years without cirrhosis treated with weight-based MAVYRET oral pellets in packets for 8, 12 or 16 weeks (DORA-Part 2). The adverse reactions observed in subjects 3 years to less than 12 years of age were consistent with those observed in clinical trials of MAVYRET in adults with the exception of vomiting (occurring at 8%), rash, and abdominal pain upper (each occurring at 4%) which were observed more frequently in pediatric subjects less than 12 years of age compared to adults. Other adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET in DORA-Part 2 include fatigue and headache, each occurring at 8%. One subject discontinued treatment due to an adverse reaction of erythematous rash (Grade 3). All other adverse reactions were Grade 1 or 2 and no subjects interrupted treatment due to an adverse reaction 8 USE IN SPECIFIC POPULATIONS 8.4 Pediatric use o  Updated with data from pediatric patients 3 years and older The recommended dosage of MAVYRET in pediatric patients 3 to less than 12 years of age is based on weight The safety, efficacy, and pharmacokinetics of MAVYRET in HCV GT1, 2, 3, or 4 infected pediatric patients 3 years and older is based on data from an open-label trial in 127 subjects without cirrhosis aged 3 years to less than 18 years who were either treatment-naïve (n=114) or treatment-experienced (n=13) and received MAVYRET for 8, 12 or 16 weeks (DORA-Part 1 and Part 2).  The adverse reactions observed in subjects 3 years to less than 18 years of age were consistent with those observed in clinical trials of MAVYRET in adults with the exception of vomiting, rash and abdominal pain upper which were observed more frequently in pediatric subjects less than 12 years of age compared to adults. The efficacy results observed in this trial were consistent with those observed in clinical trials of MAVYRET in adults. In pediatric patients with cirrhosis, history of a kidney and/or liver transplant, or HCV GT5 or 6 infection, the safety and efficacy of MAVYRET are supported by the comparable glecaprevir and pibrentasvir exposures observed between pediatric subjects 12 CLINICAL PHARMACOLOGY 12.3 Pharmacokinetics o  Under Specific Populations:  Pediatric Patients subsection, the pharmacokinetic data from patients 3 and older were added. Geometric mean ratios (GMRs) of glecaprevir and pibrentasvir Cmax and AUC24 in HCV-infected pediatrics vs. adults ranged from 1.58-2.68 and 0.965-1.64, respectively. GMRs of glecaprevir Ctrough ranged from 0.292-0.954 and GMRs of pibrentasvir Ctrough ranged from 0.794-1.93. All pediatric glecaprevir and pibrentasvir PK parameter values fell within the range observed in adult subjects. These differences were not considered clinically significant. 14 CLINICAL STUDIES 14.10 Clinical Trials in Pediatric Subjects o  Updated to include data from pediatric subjects 3 to less than 6 years of age. Eighty subjects aged 3 years to less than 12 years were enrolled in DORA (Part 2) and received weight-based dosing of MAVYRET oral pellets for 8, 12, or 16 weeks. The median age was 7 years (range: 3 years to 11 years); the mean weight was 26 kg (range: 13 kg to 44 kg); 55% were female; 69% were White, 18% were Asian, and 4% were Black; 73% had HCV genotype 1, 3% had HCV genotype 2, 23% had HCV genotype 3, and 3% had HCV genotype 4; 97.5% were HCV TN; 2.5% were treatment-experienced to interferon; 1% had HIV-coinfection; none had cirrhosis. Sixty-two subjects received the weight-based recommended dosage. Eighteen subjects received doses lower than the recommended weight-based dosage and were not included in the efficacy assessment. The overall SVR12 rate for the subjects who received the recommended dosage was 98.4% (61/62); the subject who did not achieve SVR12 discontinued treatment due to an adverse reaction Manage Subscriptions  |  Unsubscribe All  |  Help This email was sent to ooseims.archieves@blogger.com using GovDelivery Communications Cloud on behalf of: U.S. Food and Drug Administration ·  10903 New Hampshire Ave · Silver Spring, MD ·  20993-0002 ·  1-888-INFO-FDA