Drug Safety-related Labeling Changes (SrLC)
Get Email Alerts |
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.
STAXYN (NDA-200179)
(VARDENAFIL HYDROCHLORIDE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
04/24/2023 (SUPPL-7)
5 Warnings and Precautions
5.2 Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors
Subsection title revised
Additions and/or revisions underlined:
Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, ketoconazole, and cobicistat) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Do not use STAXYN in patients taking strong or moderate CYP3A4 inhibitors. [See Dosage and Administration (2.4), Drug Interactions (7.2) and Patient Counseling Information (17).]
7 Drug Interactions
7.2 Effect of Other Drugs on Vardenafil
Additions and/or revisions underlined:
In vitro studies
Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].
In vivo studies
Do not use STAXYN with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration (2.4)].
Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil area under the curve (AUC) and a 4-fold increase in maximum concentration (Cmax) when co-administered with vardenafil 5 mg in healthy volunteers. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]
Indinavir (800 mg t.i.d.) co-administered with vardenafil 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax and a 2-fold increase in vardenafil half-life. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]
Ritonavir (600 mg b.i.d.) co-administered
with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13-
fold increase in vardenafil Cmax. The interaction is a consequence
of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease
inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits
CYP2C9. [See Dosage and Administration
(2.4) and Warnings and Precautions (5.2).]
Cobicistat with STAXYN can result in increased plasma concentrations. STAXYN should not be used with cobicistat.
…
7.3 Effects of Vardenafil on Other Drugs
Additions and/or revisions underlined:
Vardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki >100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 Cmax values after an 80 mg vardenafil dose
In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses. While concomitant use of vardenafil did not significantly increase plasma concentrations of digoxin, a P-gp substrate, the effect on plasma concentrations of P-gp substrates that are more sensitive than digoxin (e.g. dabigatran) is not known.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
…
CAN OTHER MEDICATIONS AFFECT STAXYN?
…
Always check with your doctor before starting or stopping any medicines. Especially tell your doctor if you take any of the following:
Medicines called nitrates (see “What important information should you know about STAXYN?”).
Medicines containing cobicistat.
Medicines that treat abnormal heartbeat. These include quinidine, procainamide, amiodarone and sotalol.
Ritonavir (Norvir®) or indinavir sulfate (Crixivan®) saquinavir (Fortavase® or Invirase®) or atazanavir (Reyataz®) or other HIV protease inhibitors.
Ketoconazole or itraconazole (such as Nizoral® or Sporanox®).
Cobicistat
Erythromycin or clarithromycin.
- Other medicines or treatments for ED.
…