Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

GENOTROPIN (BLA-020280)

(SOMATROPIN RECOMBINANT)

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

Download Data

Expand all

08/16/2024 (SUPPL-92)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

GENOTROPIN is contraindicated in patients with:

…

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies (rats and rabbits), there was no evidence of embryo-fetal or neonatal harm following somatropin administration during organogenesis at doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area (see Data).

The estimated background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

Animal reproduction studies with somatropin during the period of organogenesis at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously (SC) in pregnant rats and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in pregnant rabbits were not teratogenic (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area).

In perinatal and postnatal studies in rats, somatropin doses of 0.3, 1, and 3.3 mg/kg/day produced growth-promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed increased weight gain during suckling but the effect was not apparent by 10 weeks of age. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring due to somatropin.

8.2 Lactation

Newly added subsection:

Risk Summary

There is no information regarding the presence of somatropin in human milk. Limited published data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone. No adverse effects related to somatropin in the breastfeed infant have been reported. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GENOTROPIN and any potential adverse effects on the breastfed infant from GENOTROPIN or from the underlying maternal condition.

8.4 Pediatric Use

Newly added subsection:

Safety and effectiveness of GENOTROPIN in pediatric patients have been established in growth failure due to Prader-Willi syndrome (PWS), growth failure in children born small for gestational age (SGA) with no catch-up growth by age 2 years, growth failure associated with Turner syndrome, idiopathic short stature (ISS) and growth failure due to inadequate secretion of endogenous growth hormone.

Growth Failure Due to Prader-Willi Syndrome (PWS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with growth failure due to Prader-Willi syndrome based on data from two randomized, open-label, controlled clinical trials with GENOTROPIN in 43 pediatric patients. There have been reports of sudden death after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin [see Contraindications (4), Warnings and Precautions (5.2), Clinical Studies (14.2)].

Short Stature in Pediatric Patients Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2 Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature born SGA with no catch-up growth based on data from 4 randomized, open-label, controlled clinical trials with GENOTROPIN in 209 pediatric patients [see Clinical Studies (14.3)].

Short Stature associated with Turner Syndrome

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature associated with Turner syndrome based on data from two randomized, open-label, clinical trials with GENOTROPIN in 38 pediatric patients [see Clinical Studies (14.4)].

Idiopathic Short Stature (ISS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with ISS based on data from one randomized, open-label, clinical trial with GENOTROPIN in 102 pediatric patients [see Clinical Studies (14.5)].

12/13/2016 (SUPPL-88)

Approved Drug Label (PDF)

4 Contraindications

(revision underlined)

Hypersensitivity

GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products.

5 Warnings and Precautions

5.6 Severe Hypersensitivity

(subsection added)

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with post-marketing use of somatropin products.

Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs.

5.7 Fluid Retention

(addition underlined)

Fluid retention during somatropin replacement therapy in adults may occur. Clinical manifestations of fluid retention (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) are usually transient and dose dependent.

6 Adverse Reactions

(additions underlined)

The following important adverse reactions are also described elsewhere in the labeling:

· Increased mortality in patients with acute critical illness

· Fatalities in children with Prader-Willi syndrome

· Neoplasms

· Glucose intolerance and diabetes mellitus

· Intracranial hypertension

· Severe hypersensitivity

· Fluid retention

· Hypoadrenalism

· Hypothyroidism

· Slipped capital femoral epiphysis in pediatric patients

· Progression of preexisting scoliosis in pediatric patients

· Otitis media and cardiovascular disorders in patients with Turner syndrome •

· Lipoatrophy

· Pancreatitis

6.2 Post-Marketing Experience

(additions underlined)

Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with post-marketing use of somatropin products

09/06/2016 (SUPPL-79)

Approved Drug Label (PDF)

5 Warnings and Precautions

Acute Critical Illness

Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3–8 mg/day) compared to those receiving placebo. (This statement was previously in the Contraindications section under the subsection Acute Critical Illness)

Hypoadrenalism replaces Hypopituitarism

Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment.

6 Adverse Reactions

The following important adverse reactions are also described elsewhere in the labeling:

Acute critical illness (addition)
Hypoadrenalism
Otitis media and cardiovascular disorders in Turner Syndrome

Post-Marketing Experience

The following serious adverse reactions have been observed with use of somatropin (including events observed in patients who received brands of somatropin other than Genotropin): acute critical illness, sudden death, intracranial tumors, central hypothyroidism, cardiovascular disorders, and pancreatitis.
Slipped capital femoral epiphysis and Legg-Calve-Perthes disease (osteonecrosis/avascular necrosis; occasionally associated with slipped capital femoral epiphysis) have been reported in children treated with growth hormone. Cases have been reported with Genotropin.
The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and significant diabetic retinopathy.