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.

SANCUSO (NDA-022198)

(GRANISETRON)

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

Download Data

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04/30/2020 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Progressive Ileus and Gastric Distention

(additions underlined)

Sancuso may mask a progressive ileus and/or gastric distention. This should be particularly considered before use of Sancuso in patients who have had recent abdominal surgery. Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction.

5.4 Increased Drug Exposure with Use of External Heat Sources

(additions underlined)

Prolonged exposure to heat results in increasing plasma concentrations of granisetron during the period of heat exposure. Do not apply a heat pad or heat lamp over or in the vicinity of the Sancuso transdermal system and avoid extended exposure to heat.

5.5 Phototoxicity with Ultraviolet Light Exposure

(additions underlined)

Granisetron may be affected by direct natural or artificial sunlight, including sunlamps. An in vitro study using Chinese hamster ovary cells suggests that granisetron has the potential for photogenotoxicity. To avoid a potential skin reaction, advise patients to cover the application site of the transdermal system with clothing if there is a risk of exposure to direct natural or artificial sunlight throughout the period of wear and for 10 days following its removal

6 Adverse Reactions

(additions underlined)

The following are serious or otherwise clinically significant adverse reactions reported in other sections of labeling:

Progressive ileus and gastric distention
Serotonin syndrome
Skin reactions
Increased drug exposure with use of external heat sources
Phototoxicity with ultraviolet light exposure

7 Drug Interactions

7.1 Serotonergic Drugs

(new subsection added, additions underlined)

…

Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Monitor for the emergence of serotonin syndrome. If symptoms occur, discontinue Sancuso and initiate supportive treatment

7.2 Concomitant Use Medications

(new subsection added)

There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs. However, in humans, granisetron hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron hydrochloride injection also does not appear to interact with emetogenic cancer therapies. In agreement with these data, no clinically relevant drug interactions have been reported in clinical studies with Sancuso.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Available published data and postmarketing reports with granisetron use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In a published ex vivo human placental perfusion model, no transplacental passage of granisetron was detected at a concentration (5 ng/mL) that mimics the plasma concentration achieved following transdermal application of Sancuso. In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits administered granisetron hydrochloride during organogenesis at intravenous doses up to 24 times and 16 times, respectively, the maximum recommended human dose delivered by the Sancuso transdermal system, based on body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits administered granisetron hydrochloride at intravenous doses up to 24 times and 16 times, respectively, the maximum recommended human dose delivered by the Sancuso transdermal system, based on body surface area (see Data).

Data

Animal Data

Reproduction studies with granisetron hydrochloride have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m2/day, about 24 times the recommended human dose delivered by the Sancuso transdermal system, based on body surface area) and oral doses up to 125 mg/kg/day (750 mg/m2/day, about 326 times the recommended human dose with Sancuso based on body surface area). Reproduction studies have been performed in pregnant rabbits at intravenous doses up to 3 mg/kg/day (36 mg/m2/day, about 16 times the human dose with Sancuso based on body surface area) and at oral doses up to 32 mg/kg/day (384 mg/m2/day, about 167 times the human dose with Sancuso based on body surface area). These studies did not reveal any harm to the fetus due to granisetron.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of granisetron in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sancuso and any potential adverse effects on the breastfed child from Sancuso or from the underlying maternal condition.

8.6 Renal Impairment or Hepatic Impairment

(additions underline)

Although no studies have been performed to investigate the pharmacokinetics of Sancuso in patients with renal or hepatic impairment, pharmacokinetic information is available for intravenous granisetron. No dosage adjustment is recommended for renal or hepatic impairment.

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

PATIENT COUNSELING INFORMATION

(additions underlined)

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Progressive Ileus and Gastric Distention

Advise the patient to report new or worsening constipation to their healthcare provider and seek immediate medical care if symptoms of an ileus (pain or swelling in their abdomen) occur.

…

Increased Drug Exposure with Use of External Heat Sources

Advise the patient to avoid prolonged exposure to heat and not to apply a heat pad or heat lamp over or near the Sancuso transdermal system and avoid extended exposure to heat.

Phototoxicity with Ultraviolet Light Exposure

Advise the patient to avoid direct sunlight or exposure to sunlamps and to cover the application site of the transdermal system with clothing, if there is a risk of exposure to sunlight or sunlamps throughout the period of wear and for 10 days following its removal .

Application and Removal Instructions

Instruct the patient on how to apply and remove the transdermal system:

Only wear one transdermal system at any time.
Do not cut the transdermal system.
Apply the transdermal system to clean, dry, nearly hairless, intact healthy skin on the upper outer arm.
After the transdermal system is applied, wash hands thoroughly.
Remove the transdermal system by peeling off gently from the skin.
Upon removal, fold the used transdermal system in half with the sticky side together, and discard in household trash in a manner that prevents accidental contact or ingestion by children, pets or others.
Sancuso contains granisetron. Do not use other granisetron-containing products with Sancuso

PATIENT INFORMATION

(additions and revisions, please refer to label for complete information)