Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

SELZENTRY (NDA-208984)

(MARAVIROC)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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10/30/2020 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

Clinical Trials Experience in Pediatric Subjects

HIV-1–Infected Pediatric Subjects: Trial A4001031 is an open-label trial in which

103 treatment-experienced, CCR5-tropic, HIV-1–infected pediatric subjects aged 2 to less than 18 years weighing at least 10 kg received SELZENTRY twice daily in combination with OBT. The dose of SELZENTRY was based on body surface area (BSA) and on whether the subject was receiving potent CYP3A inhibitors and/or inducers. The median duration of therapy with SELZENTRY was 131 weeks with 72% of subjects receiving study treatment for greater than 48 weeks and 62% of subjects receiving study treatment for 96 weeks.

HIV-1–Exposed Neonates: The IMPAACT P2007 trial was an open-label trial in which 47 full- term HIV-1–exposed neonates (born to HIV-1–infected mothers) received at least one dose of SELZENTRY in combination with other antiretrovirals, mostly zidovudine and/or nevirapine [see Clinical Pharmacology (12.3)]. Cohort 1 received 2 single doses of SELZENTRY: the first within 3 days of birth and the second at 7 to 14 days of age. Cohort 2 received SELZENTRY twice daily for 6 weeks beginning within 3 days of birth and continued through Week 6. Both cohorts received SELZENTRY with or without exposure to maternal efavirenz (in utero only in Cohort 1, and both in utero and after birth while breastfeeding in Cohort 2). The population was 51% male and 81% black. All infants were followed for safety through 16 weeks, with a total of 37 infants evaluable for safety.

There were no additional adverse reactions observed in neonates compared with those seen in adults. All adverse reactions reported were mild to moderate. The most common adverse reaction (all grades) reported with SELZENTRY was hemoglobin decreased (14%). One subject (3%) discontinued due to an adverse event (Grade 3 staphylococcal sepsis).

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions underlined)

The safety, and efficacy of SELZENTRY have been established in pediatric patients aged from birth to less than 18 years. The use of SELZENTRY in pediatric patients was supported by pharmacokinetic and safety data described below and by previous demonstration of efficacy in adult patients [see Indications and Usage (1)], Dosage and Administration (2.4)].

HIV-1–Infected Pediatric Patients Aged 2 to Less Than 18 Years: The safety, pharmacokinetic profile, and antiviral activity of SELZENTRY were evaluated in treatment-experienced, CCR5- tropic, HIV-1-–infected pediatric subjects aged 2 to less than 18 years weighing at least 10 kg in an open-label, multicenter clinical trial, A4001031 [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Pharmacokinetics were evaluated in a total of 98 pediatric subjects: 85 subjects received SELZENTRY and concomitant medications that included potent CYP3A inhibitors with or without potent CYP3A inducers, 10 subjects received SELZENTRY and noninteracting medications (not containing potent CYP3A inhibitors or potent CYP3A inducers), and three subjects received SELZENTRY and medications that included potent CYP3A inducers without potent CYP3A inhibitors [see Clinical Pharmacology (12.3)].

HIV-1–Infected Pediatric Patients Aged Older Than 6 Weeks to Less Than 2 Years: No clinical trials have been conducted in children aged older than 6 weeks to less than 2 years. Dosing recommendations for SELZENTRY in this population when concomitantly receiving noninteracting medications are based on population pharmacokinetic modeling and simulation only [see Dosage and Recommendations (2.4), Clinical Pharmacology (12.3)].

HIV-1–Infected Neonates Aged from Birth to 6 Weeks: The recommendation of SELZENTRY for the treatment of HIV-1 infection in this pediatric population is based on safety and pharmacokinetic data obtained from clinical trial IMPAACT P2007. In IMPAACT P2007, the safety and pharmacokinetic profiles of SELZENTRY were evaluated in full-term HIV-1– exposed neonates (born to HIV-1–infected mothers) aged from birth through 6 weeks [see Adverse Reactions (6.1)]. Pharmacokinetics were evaluated in 38 of 47 enrolled neonates who received SELZENTRY as a single dose (n = 13) or multiple doses (n = 25) up to 6 weeks of age concomitantly with other antiretrovirals (mostly zidovudine and/or nevirapine) with or without maternal exposure to efavirenz. HIV-1 status was assessed by nucleic acid test at birth, Week 6, and Week 16; all 47 enrolled neonates were HIV-1 negative at completion of the study [see Clinical Pharmacology (12.3)].

There are insufficient data to make dosing recommendations for use of SELZENTRY in pediatric patients concomitantly receiving potent CYP3A inhibitors and weighing less than 10 kg, or in any pediatric patients concomitantly receiving potent CYP3A inducers without a potent CYP3A inhibitor [see Dosage and Administration (2.4, 2.5)].

SELZENTRY is not recommended in pre-term neonates or in pediatric patients weighing less than 2 kg.

07/18/2018 (SUPPL-1)

Approved Drug Label (PDF)

7 Drug Interactions

7.1 Effect of Concomitant Drugs on the Pharmacokinetics of Maraviroc

(additions underlined)

Maraviroc is metabolized by CYP3A, and is also a substrate for P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP)1B1, and multidrug resistance-associated protein (MRP)2. The pharmacokinetics of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A and P-gp, and may be modulated by inhibitors of OATP1B1 and MRP2.

Therefore, a dosage adjustment may be required when maraviroc is coadministered with those drugs.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(addition underlined)

…

How should I store SELZENTRY?

Store SELZENTRY tablets and oral solution at room temperature between 68°F to 77°F (20°C to 25°C).
Throw away any unused oral solution 60 days after first opening the bottle.
Keep SELZENTRY and all medicines out of the reach of children.
…