Drug Safety-related Labeling Changes (SrLC)
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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.
INVIRASE (NDA-021785)
(SAQUINAVIR MESYLATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
12/19/2019 (SUPPL-24)
03/28/2019 (SUPPL-23)
03/15/2018 (SUPPL-22)
4 Contraindications
(additions underlined)
…
INVIRASE/ritonavir is contraindicated in patients receiving the following co-administered drugs; however, it should be noted that this list is not intended to be exhaustive.
Alpha 1-adrenoreceptor antagonist: alfuzonsin
Antiarrhythmics: amiodarone, bepridil, deofeilide, flecainide, lidocaine (systemic), propafenone, quinidine
Antidepressant: trazodone
Anti-infectives: clarithromycin, erythromycin, halofantrine, pentamidine
Antimycobacterial Agents: rifampin
Antipsychotics: lurasidone, clozapine, haloperidol, pimozide, sertindole, ziprasidone, phenothiazines (e.g. chlorpromazine, mesoridazine, thioridazine).
Ergot Derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine
HIV-1 Protease Inhibitor: atazanavir
HMG-CoA Reductase Inhibitors: lovastatin, simvastatin
Immunosuppressant: tacrolimus
Non-nucleoside reverse transcriptase inhibitor (NNRTI): rilpivirine (concomitant use and switching from rilpivirine to INVIRASE/ritonavir without a washout period of at least 2 weeks is contraindicated)
PDE5 Inhibitors: sildenafil (Revatio®)[for treatment of pulmonary arterial hypertension]
Sedative/Hypnotics: triazolam, and orally administered midazolam
Tyrosine kinase inhibitors: dasatinib, sunatinib
Other drugs that are CYP3A substrates: disopyramide, quinine
5 Warnings and Precautions
5.1 Importance of Co-administration with Ritonavir(new subsection header added)
INVIRASE must be used in combination with ritonavir. Please refer to the ritonavir full prescribing information for additional precautionary measures.
INVIRASE is not
recommended for use in combination with cobicistat. Dosing recommendations for this combination have not
been established. Cobicistat is also not recommended in combination with
regimens containing ritonavir due to similar effects of cobicistat and
ritonavir on CYP3A. Please refer to the cobicistat full prescribing information
for additional precautionary measures.
(additions underlined)
…
If a serious or severe toxicity occurs during treatment with INVIRASE/ritonavir, discontinue INVIRASE/ritonavir. For concomitantly used drugs including antiretroviral agents used in combination with INVIRASE/ritonavir, physicians should refer to the complete product information for these drugs for dose adjustment recommendations and for information regarding drug-associated adverse reactions.
(additions underlined)
INVIRASE/ritonavir prolongs the PR interval in a dose-dependent fashion. Cases of second or third degree atrioventricular block have been reported rarely. Patients with underlying structural heart disease, pre-existing conduction system abnormalities, cardiomyopathies and ischemic heart disease may be at increased risk for developing cardiac conduction abnormalities. ECG monitoring is recommended in these patients. Discontinue INVIRASE/ritonavir if significant arrhythmias, QT or PR prolongation occur.
The impact on the PR interval of coadministration of INVIRASE/ritonavir with other drugs that prolong the PR interval (including calcium channel blockers, beta-adrenergic blockers, digoxin and atazanavir) has not been evaluated. As a result, coadministration of INVIRASE/ritonavir with these drugs should be undertaken with caution, particularly with those drugs metabolized by CYP3A, and clinical monitoring is recommended.
For concomitantly used drugs, including antiretroviral agents used in combination with INVIRASE/ritonavir, physicians should refer to the complete product information for these drugs for dose adjustment recommendations and for information regarding drug- associated adverse reactions.
(additions underline)
…
For concomitantly used drugs including antiretroviral agents used in combination with INVIRASE/ritonavir, refer to the complete product information for these drugs for dose adjustment recommendations and for information regarding drug- associated adverse reactions.Discontinue INVIRASE/ritonavir if significant arrhythmias, QT or PR prolongation occurs.
Patients initiating
therapy with INVIRASE/ritonavir:
An ECG should be performed prior to initiation of treatment. Patients with a QT interval ? 450 msec should not initiate treatment with INVIRASE/ritonavir.
Treatment-naïve patients initiating treatment with INVIRASE/ritonavir should receive a reduced starting dose of INVIRASE 500 mg twice daily with ritonavir 100 mg twice daily for the first 7 days of treatment followed by INVIRASE/ritonavir 1000/100 mg twice daily due to potential for an increased risk of PR and QT interval prolongation with the standard 1000/100 mg twice daily dose.
For patients with a baseline QT interval < 450 msec, an on-treatment ECG is recommended after approximately 10 days of therapy. Discontinue INVIRASE/ritonavir in patients with a QT interval prolongation > 20 msec over pre-treatment.
…
(additions underlined)
In patients with underlying hepatitis B or C, cirrhosis, chronic alcoholism or other underlying liver abnormalities, there have been reports of worsening of the underlying liver disease and development of portal hypertension after starting INVIRASE/ritonavir. Jaundice and exacerbation of chronic liver disease with grade 4 elevated liver function tests were also observed. No dosage adjustment is necessary for patients with mild or moderate hepatic impairment based on limited data. INVIRASE/ritonavir is contraindicated in patients with severe hepatic impairment. If a serious or severe toxicity occurs during treatment with INVIRASE/ritonavir, discontinue INVIRASE/ritonavir.
7 Drug Interactions
7.3 Established and Other Potentially Significant Drug Interactions(additions underlined)
…
Table 2 provides examples of established or potentially clinically significant drug interactions. This table includes potentially significant interactions but is not all inclusive. Alteration in dose or avoidance of the combination may be recommended depending on the interaction.
(please refer to label to view Table 2)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(additions and revisions, please refer to label)
(reorganized and reordered, please refer to label)