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.

SANDIMMUNE (NDA-050625)

(CYCLOSPORINE)

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

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03/06/2026 (SUPPL-65)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: RECOMMENDATIONS FOR USE, USE WITH CORTICOSTERIODS, RISKS WITH INAPPROPRIATE SWITCHING, and MONITORING CYCLOSPORINE BLOOD LEVELS

Recommendations for Use

Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Sandimmune. Patients receiving Sandimmune should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

Use with Corticosteroids

Sandimmune should be administered with adrenal corticosteroids but not with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression.

Risks with Inappropriate Switching Between Neoral Capsules (MODIFIED) and Sandimmune Capsules

Do not switch between Sandimmune capsules, 25 mg to Neoral capsules, MODIFIED, 25 mg (or between Sandimmune capsules, 100 mg to Neoral capsules, MODIFIED 100 mg) on a mg-to-mg basis to achieve the same total daily cyclosporine dosage. Inappropriate switching may lead to increased cyclosporine exposure which may increase the risk of cyclosporine-associated adverse reactions or decreased cyclosporine exposure which may decrease the efficacy of cyclosporine.

Monitoring Cyclosporine Blood Levels

The absorption of cyclosporine during chronic administration of Sandimmune capsules was found to be erratic. It is recommended that patients taking the Sandimmune capsules over a period of time be monitored at repeated intervals for cyclosporine blood concentrations and subsequent dosage adjustments be made in order to avoid toxicity due to high concentrations and possible organ rejection due to low absorption of cyclosporine. This is of special importance in liver transplants.

Numerous assays are being developed to measure blood concentrations of cyclosporine. Comparison of concentrations in published literature to patient concentrations using current assays must be done with detailed knowledge of the assay methods employed (see DOSAGE AND ADMINISTRATION, Blood Concentration Monitoring).

4 Contraindications

Additions and/or revisions underlined:

Sandimmune capsules and Sandimmune injection are contraindicated in patients with a hypersensitivity reaction to cyclosporine.

Sandimmune injection is also contraindicated in patients with a history of a hypersensitivity reaction to Cremophor® EL (polyoxyethylated castor oil).

5 Warnings and Precautions

WARNINGS

Additions and/or revisions underlined:

. . .

Risks with Inappropriate Switching Between Neoral Capsules (MODIFIED) and Sandimmune Capsules

Do not switch between Sandimmune capsules to Neoral capsules, MODIFIED on a mg-to-mg basis to achieve the same total daily cyclosporine dosage.

Sandimmune (cyclosporine capsules), 25 mg and 100 mg and Neoral (cyclosporine capsules), MODIFIED 25 mg and 100 mg are not mutually substitutable on a mg-to-mg basis due to differences in pharmacokinetic profiles.

Inappropriate switching from Sandimmune capsules to Neoral capsules MODIFIED, increases cyclosporine exposure which may increase the risk of cyclosporine-associated adverse reactions.
Inappropriate switching from Neoral capsules, MODIFIED, to Sandimmune capsules decreases cyclosporine exposure which may decrease the efficacy of cyclosporine for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants or treatment of chronic rejection in patients previously treated with other immunosuppressive agents.

For recommendations on how to switch between Sandimmune capsules and Neoral capsules, including increasing the frequency of blood cyclosporine concentration monitoring, see DOSAGE AND ADMINISTRATION

PRECAUTIONS

Additions and/or revisions underlined:

Patients with Malabsorption

Patients with malabsorption may have difficulty in achieving therapeutic concentrations with Sandimmune capsules.

. . .

Information for Patients

Patients should be advised that a switch of their current cyclosporine formulation to another cyclosporine formulation should be made cautiously and only under health care provider supervision because it may result in the need for a change in dosage (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Patients should be informed of the necessity of repeated laboratory tests while they are receiving Sandimmune. They should be given careful dosage instructions, advised of the potential risks during pregnancy, and informed of the increased risk of neoplasia.

. . .

6 Adverse Reactions

Additions and/or revisions underlined:

. . .

Adverse Reactions in Clinical Studies

The following reactions occurred in 3% or greater of 892 patients involved in clinical trials of kidney, heart, and liver transplants:

Adverse reactions are in table format; no additions or revisions to report.

. . .

Adverse Reactions During Postmarketing Use

Hepatotoxicity

Cases of hepatotoxicity and liver injury, including cholestasis, jaundice, hepatitis, and liver failure; serious and/or fatal outcomes have been reported (see WARNINGS, Hepatotoxicity).

Increased Risk of Infections

Cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), sometimes fatal; and polyoma virus-associated nephropathy (PVAN), especially BK virus resulting in graft loss have been reported (see WARNINGS, Polyoma Virus Infection).

Headache, Including Migraine

Cases of migraine have been reported. In some cases, patients have been unable to continue cyclosporine, however, the final decision on treatment discontinuation should be made by the treating health care provider following the careful assessment of benefits versus risks.

. . .

8 Use in Specific Populations

Pediatric Use

Additions and/or revisions underlined:

Although no adequate and well-controlled studies have been conducted in children, patients as young as 6 months of age have received cyclosporine with no unusual adverse effects.

Geriatric Use

Additions and/or revisions underlined:

Clinical studies of Sandimmune did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients. Other reported clinical experience has not identified differences in responses between patients aged 65 and over and younger adult patients. In general, dosage selection for patients aged 65 and over should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

09/28/2023 (SUPPL-61)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

Information for Patients

Additions and/or revisions underlined:

…

Cyclosporine may impact the ability to drive and use machines. Patients should be advised to exercise care when driving or using machines if they experience neurological disturbances including confusion, somnolence, or dizziness and discuss with their healthcare provider (see WARNINGS and ADVERSE REACTIONS).

…

Drug Interactions

B. Effect of Cyclosporine on the Pharmacokinetics and/or Safety of Other Drugs or Agents

Additions and/or revisions underlined:

…

Interactions resulting in decrease of other drug levels

Cyclosporine inhibits the enterohepatic circulation of mycophenolic acid (MPA). Concomitant administration of cyclosporine and mycophenolate mofetil or mycophenolate sodium in transplant patients may decrease the mean exposure of MPA by 20 - 50% when compared with other immunosuppressants, which could reduce efficacy of mycophenolate mofetil or mycophenolate sodium. Monitor patients for alterations in efficacy of mycophenolate mofetil or mycophenolate sodium, when they are co-administered with cyclosporine.

…

Pregnancy

Extensive changes; please refer to label for complete information

Nursing Mothers

Additions and/or revisions underlined:

Cyclosporine and its metabolites are present in human milk following oral and intravenous administration. Adverse effects on the breastfed infant have not been reported. There are no data on the effects of the drug on milk production. The alcohol content of SANDIMMUNE should be taken into account when given to lactating women (see WARNINGS, Special Excipients). Lactating women are encouraged to avoid additional alcohol intake during treatment. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SANDIMMUNE and any potential adverse effects on the breastfed infant from SANDIMMUNE or from the underlying maternal condition.