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.

GANCICLOVIR (NDA-209347)

(GANCICLOVIR )

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

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09/20/2017 (SUPPL-1)

Approved Drug Label (PDF)

4 Contraindications

(additions underlined)

GANZYK-RTU is contraindicated in patients who have experienced a clinically significant hypersensitivity reaction (e.g., anaphylaxis) to ganciclovir, valganciclovir, or any component of the formulation.

5 Warnings and Precautions

5.1 Hematologic Toxicity

(additions underlined)

…

Due to the frequency of neutropenia, anemia and thrombocytopenia in patients receiving GANZYK-RTU, complete blood counts with differential and platelet counts should be performed frequently in all patients, especially in patients with renal impairment and in patients in whom ganciclovir or other nucleoside analogues have previously resulted in leukopenia, or in whom neutrophil counts are less than 1000 cells/µL at the beginning of treatment.

6 Adverse Reactions

6.1 Clinical Trials Experience in Adult Patients

(additions underlined)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions and laboratory abnormalities reported in at least 20% of patients were pyrexia, diarrhea, leukopenia, nausea, anemia, asthenia, headache, cough, decreased appetite, dyspnea, abdominal pain, sepsis, hyperhidrosis, and blood creatinine increased.

Selected adverse reactions that occurred during clinical trials of intravenous ganciclovir are summarized below, according to the participating study patient population.

…

Other Adverse Reactions in Clinical Trials in Patients with CMV Retinitis and in Transplant Recipients

Other adverse reactions with intravenous ganciclovir or ganciclovir capsules in controlled clinical trials in either subjects with AIDS or transplant recipients are listed below. All these events occurred in at least 3 subjects.

Blood and lymphatic disorders: pancytopenia, bone marrow failure

Cardiac disorders: arrhythmias

Ear and labyrinth disorders: tinnitus, ear pain, deafness

Eye disorders: visual impairment, vitreous disorders, eye pain, conjunctivitis, macular edema

Gastrointestinal disorders: nausea, abdominal pain, dyspepsia, flatulence, constipation, mouth ulceration, dysphagia, abdominal distention, pancreatitis, gastrointestinal perforation, eructation, dry mouth

General disorders and administration site conditions: fatigue, injection site inflammation, edema, pain, malaise, asthenia, chest pain, multiple organ failure

Blood Immune system disorders: hypersensitivity

Infections and infestations: candida infections including oral candidiasis, upper respiratory infection, influenza, urinary tract infections, cellulitis

Investigations: blood alkaline phosphatase increased, hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine clearance decreased

Metabolism and nutrition disorders: weight decreased

Musculoskeletal and connective tissue disorders: back pain, myalgia, arthralgia, muscle spasms, leg cramps, myasthenia

Nervous system disorders: headache, insomnia, dizziness, paresthesia, hypoaesthesia, seizures, somnolence, dysgeusia (taste disturbance), tremor

Psychiatric disorders: depression, confusional state, anxiety, agitation, psychotic disorder, thinking abnormal, abnormal dreams

Renal and urinary disorders: kidney failure, renal function abnormal, urinary frequency, hematuria

Respiratory, thoracic and mediastinal disorders: cough, dyspnea

Skin and subcutaneous tissues disorders: dermatitis, alopecia, dry skin, urticaria, rash

Vascular disorders: hypotension, hypertension, phlebitis, vasodilation

6.2 Postmarketing Experience

(additions underlined)

The following adverse reactions have been identified during post-approval use of intravenous ganciclovir or ganciclovir capsules. Because these reactions 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.

Blood and lymphatic disorders: hemolytic anemia, agranulocytosis, granulocytopenia

Cardiac disorders: cardiac arrest, conduction disorder, torsade de pointes, ventricular tachycardia

Congenital, familial and genetic disorders: congenital anomaly

Endocrine disorders: inappropriate antidiuretic hormone secretion

Eye disorders: cataracts, dry eyes

Gastrointestinal disorders: intestinal ulcer

Hepatobiliary disorders: cholelithiasis, cholestasis, hepatic failure, hepatitis

Immune system disorders: anaphylactic reaction, allergic reaction, vasculitis

Investigations: blood triglycerides increased

Metabolism and nutrition disorders: acidosis, hypercalcemia, hyponatremia

Musculoskeletal and connective tissue disorders: arthritis, rhabdomyolysis

Nervous system disorders: dysesthesia, dysphasia, extrapyramidal disorder, facial paralysis, amnesia, anosmia, myelopathy, cerebrovascular accident, third cranial nerve paralysis, aphasia, encephalopathy, intracranial hypertension

…

7 Drug Interactions

(additions underlined)

Drug-drug interaction studies were conducted in patients with normal renal function. Patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug following concomitant administration of GANZYK-RTU and drugs excreted by the same pathway as ganciclovir. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug.

…

8 Use in Specific Populations

8.1 Pregnancy

(additions underlined)

…

Clinical considerations

Disease-associated maternal and/or fetal risk

Most maternal CMV infections are subclinical or they may be associated with a mononucleosis-like syndrome. However, in immunocompromised patients, CMV infections are often symptomatic and are associated with significant morbidity and mortality. The transmission of CMV to the fetus is a result of maternal viremia and transplacental infection. CMV infection can also occur perinatally from mother to infant by exposure to CMV in cervicovaginal secretions. Approximately 10% of children with congenital CMV infection are symptomatic at birth. Mortality in symptomatic infants is about 10%, and approximately 50 to 90% of symptomatic surviving newborns experience significant problems, including sensorineural hearing loss, mental retardation, and other neurologic deficits. The risk and severity of congenital CMV infection appear to be higher in infants born to mothers with primary CMV infection than in those born to mothers with reactivation of CMV infection.

…

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

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Impairment of Cognitive Ability

Based on the adverse reaction profile, ganciclovir may affect cognitive abilities including on the ability to drive and operate machinery as seizures, dizziness, and/or confusion have been reported with the use of ganciclovir.

Ophthalmological Examination in Patients with CMV Retinitis

Inform patients that GANZYK-RTU is not a cure for CMV retinitis, and they may continue to experience progression of retinitis during or following treatment. Advise patients to have frequent ophthalmological examinations while being treated with GANZYK-RTU to monitor disease status and for other retinal abnormalities. More frequent ophthalmological follow-up may be needed in some cases.

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