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.

FLO-PRED (NDA-022067)

(PREDNISOLONE ACETATE)

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

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06/05/2024 (SUPPL-15)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Immunosuppression and Increased Risk of Infection

Additions and revisions underlined:

Subsection title revised

Corticosteroids, including Flo-Pred suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can:

Reduce resistance to new infections
Exacerbate existing infections
Increase the risk of disseminated infections
Increase the risk of reactivation or exacerbation of latent infections
Mask some signs of infection

Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages.

Monitor for the development of infection and consider Flo-Pred withdrawal or dosage reduction as needed.

Tuberculosis

If Flo-Pred is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged Flo-Pred therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis.

Varicella Zoster and Measles Viral Infections

Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including Flo-Pred. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles:

If a Flo-Pred treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered.
If a Flo-Pred-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated.

Hepatitis B Virus Reactivation

Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including Flo-Pred. Reactivation can also occur infrequently in corticosteroid-treatedpatients who appear to have resolved hepatitis B infection.Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with Flo-Pred. For patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy.

Fungal Infections

Corticosteroids, including Flo-Pred, may exacerbate systemic fungal infections; therefore, avoid Flo-Pred use in the presence of such infections unless Flo-Pred is needed to control drug reactions. For patients on chronic Flo-Pred therapy who develop systemic fungal infections, Flo-Pred withdrawal or dosage reduction is recommended.

Amebiasis

Corticosteroids, including Flo-Pred, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating Flo-Pred in patients who have spent time in the tropics or patients with unexplained diarrhea.

Strongyloides Infestation

Corticosteroids, including Flo-Pred, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Cerebral Malaria

Avoid corticosteroids, including Flo-Pred, in patients with cerebral malaria.

07/15/2021 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Embryo-Fetal Toxicity

(Subsection title revised; Additions and/or revisions underlined)

Prednisolone can cause fetal harm when administered to a pregnant woman. Human studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester of pregnancy. Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. Intrauterine growth restriction and decreased birth weight have also been reported with corticosteroid use during pregnancy, however the underlying maternal condition may also contribute to these risks. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, advise the patient about the potential harm to the fetus [see Use in Specific Populations (8.1)].

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Based on findings from human and animal studies, corticosteroids, including Flo-Pred, can cause fetal harm when administered to a pregnant woman (see Data) [see Warnings and Precautions (5.10)]. Published epidemiological studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester. Intrauterine growth restriction and decreased birth weight have also been reported with maternal use of corticosteroids during pregnancy; however, the underlying maternal condition may also contribute to these risks (see Clinical Considerations). Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring (see Data). Advise a pregnant woman about the potential harm to a fetus.

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 risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Infants born to pregnant women who have received corticosteroids should be carefully monitored for signs and symptoms of hypoadrenalism [see Warnings and Precautions (5.1)].

Data

Human Data

Published epidemiological studies on the association between prednisolone and fetal outcomes have reported inconsistent findings and have important methodological limitations. Multiple cohort and case-controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the incidence of cleft lip with or without cleft palate from about 1/1000 infants to 3 to 5/1000 infants; however, a risk for orofacial clefts has not been observed in all studies. Methodological limitations of these studies include non- randomized design, retrospective data collection, and the inability to control for confounders such as underlying maternal disease and use of concomitant medications.

Two prospective case control studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero. In humans, the risk of decreased birth weight appears to be dose related an may be minimized by administering lower corticosteroid doses. It is likely that underlying maternal conditions contribute to intrauterine growth restriction and decreased birth weight, but it is unclear to what extent these maternal conditions contribute to the increased risk of orofacial clefts.

Animal Data

Prednisolone, administered during the period of organogenesis, has been shown to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. In teratogenicity studies, cleft palate along with elevation of fetal lethality (or increase in resorptions) and reductions in fetal body weight were seen in rats at maternal doses of 30 mg/kg (equivalent to 290 mg in a 60 kg individual based on mg/m2 body surface comparison) and higher. Cleft palate was observed in mice at a maternal dose of 20 mg/kg (equivalent to 100 mg in a 60 kg individual based on mg/m2 comparison). Additionally, constriction of the ductus arteriosus has been observed in fetuses of pregnant rats exposed to prednisolone.

8.2 Lactation

(PLLR conversion)

Risk Summary

Prednisolone has been found to be present in human milk following administration to lactating women. Published reports suggest infant daily doses are estimated to be less than 1% of the maternal daily dose. No adverse effects in the breastfed infant have been reported following maternal exposure of prednisolone during breastfeeding. There are no available data on the effects of prednisolone on milk production. High doses of corticosteroids administered to lactating women for long periods could potentially produce problems in the breastfed infant including growth and development and interfere with endogenous corticosteroid production (see Clinical Considerations) (see Use in Specific Populations (8.4)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Flo-Pred and any potential adverse effects on the breastfed child from Flo-Pred or from the mother’s underlying condition.

Clinical Considerations

In order to minimize exposure, the lowest dose should be prescribed to lactating women to achieve the desired clinical effect.

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Patients should be warned not to discontinue the use of Flo-Pred abruptly or without medical supervision, to advise any medical attendants that they are taking it, and to seek medical advice at once should they develop fever or other signs of infection. Patients should be told to take Flo-Pred exactly as prescribed, follow the instructions on the prescription label, and not stop taking Flo-Pred without first checking with their healthcare providers, as there may be a need for gradual dose reduction.

Patients should discuss with their physician if they have had recent or ongoing infections or if they have recently received a vaccine. Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

There are a number of medicines that can interact with Flo-Pred. Patients should inform their healthcare provider of all the medicines they are taking, including over-the-counter and prescription medicines (such as phenytoin, diuretics, digitalis or digoxin, rifampin, amphotericin B, cyclosporine, insulin or diabetes medicines, ketoconazole, estrogens including birth control pills and hormone replacement therapy, blood thinners such as warfarin, aspirin or other NSAIDs, barbiturates), dietary supplements, and herbal products. If patients are taking any of these drugs, alternate therapy, dosage adjustment, and/or special testing may be needed during the treatment.

For missed doses, patients should be told to take the missed dose as soon as they remember. If it is almost time for the next dose, the missed dose should be skipped and the medicine taken at the next regularly scheduled time. Patients should not take an extra dose to make up for the missed dose.

Patients should be told to take Flo-Pred with food to avoid GI irritation.

Patients should be advised of common adverse reactions that could occur with Flo-Pred use to include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.10) and Use in Specific Populations (8.1)].

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