FREQUENTLY ASKED QUESTIONS
Q: What are the most common causes of infections?
Q: When should ZYVOX be prescribed?
Q: Has resistance to ZYVOX been studied?
Q: Is ZYVOX appropriate for empiric therapy?
Q: Are some pathogens resistant to all available treatments?
Q: What microorganisms is ZYVOX effective against?
Q: What were the most common drug-related adverse events associated with ZYVOX treatment?
Q: Are dosage adjustments necessary for special populations?
Q: Is there an association between thrombocytopenia (reduction in platelet count) and patients using ZYVOX?
Q: Can lactic acidosis occur with ZYVOX use?
Q: Can adverse events occur when ZYVOX is used concomitantly with MAOIs*?
Q: How is ZYVOX available?
Q: Does ZYVOX offer effective lung tissue penetration?
Q: Is ZYVOX well tolerated?
Q: What are the most common causes of infections?
A: In recent years, Gram-positive cocci and Candida species have replaced Gram-negative bacilli as the most common causes of nosocomial infections.62 For example, the frequency of infections caused by Escherichia coli has declined and the frequency of infections caused by staphylococci, enterococci, and Candida albicans has increased. Serious infections caused by streptococci and Mycobacterium species also have been quite common.
Q: When should ZYVOX be prescribed?
A: ZYVOX is indicated for the treatment of nosocomial (hospital acquired) pneumonia and complicated skin and skin structure infections, including cases due to methicillin-resistant Staphylococcus aureus. In addition, ZYVOX is approved for the treatment of community-acquired pneumonia and uncomplicated skin and skin structure infections. ZYVOX also is indicated for infections associated with vancomycin-resistant Enterococcus faecium, including cases with bacteremia.
Q: Is there an association between thrombocytopenia (reduction in platelet count) and patients using ZYVOX?
A: Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome is known, when ZYVOX was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive ZYVOX, particularly in those who receive ZYVOX for longer than 2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with ZYVOX should be considered in patients who develop or have worsening myelosuppression.
Within 7 phase 3 comparator-controlled trials, the reported ranges for thrombocytopenia among patients were 0.3% to 10.0% for ZYVOX-treated patients versus 0.4% to 7.0% for comparators.
It is important to note that the recommended treatment duration for ZYVOX indications of NP, including VAP, and cSSSI, including DFI, due to MRSA is 10 to 14 days.
Q: Has resistance to ZYVOX been studied?
A: In clinical trials, resistance to linezolid developed in 6 patients infected with Enterococcus faecium. In a compassionate use program, resistance to linezolid developed in 8 patients with E faecium and in 1 patient with Enterococcus faecalis. Reports of vancomycin-resistant E faecium becoming resistant to linezolid during its clinical use have been published. In one report, nosocomial spread of vancomycin- and linezolid-resistant E faecium occurred. There has been a report of Staphylococcus aureus (methicillin-resistant) developing resistance to linezolid during its clinical use. Resistance to linezolid has not been reported in Streptococcus spp, including Streptococcus pneumoniae.
The ZYVOX Annual Appraisal of Potency and Spectrum (ZAAPS) Program, a worldwide surveillance network, has compared MIC results for ZYVOX from 2002 to 2004, demonstrating no increase in resistance against 6 major organism groups.63
Data from the 2004 LEADER Surveillance Program conducted in the United States demonstrate that 99.5% of E faecalis and 96.4% of E faecium isolates were susceptible to ZYVOX, and that during the same time period, all 2872 strains of S aureus isolated were susceptible to ZYVOX.64
Q: Is ZYVOX appropriate for empiric therapy?
A: When MRSA is known or suspected, ZYVOX can be used empirically for all approved indications, including for susceptible strains in the treatment of NP, including VAP, and cSSSI, including DFI. Appropriate specimens should be taken and analyzed for culture and sensitivity, and antimicrobial selection should be adjusted accordingly based on those results. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX formulations and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Q: Are some pathogens resistant to all available treatments?
A: Some pathogens have developed resistance to virtually all antibiotic treatments.33 There is a need for the development of new antibiotics that have new mechanisms of action that may limit the development of resistance.
Q: What microorganisms is ZYVOX effective against?
A: ZYVOX has been shown to be active against most isolates of the following microorganisms:
Enterococcus faecium (vancomycin-resistant strains only)
Staphylococcus aureus (including methicillin-resistant strains)
Streptococcus agalactiae
Streptococcus pneumoniae (including multidrug-resistant isolates [MDRSP†])
Streptococcus pyogenes
Q: Is ZYVOX well tolerated?
A: In hospitalized patients with serious Gram-positive infections, ZYVOX had a low drug-related discontinuation rate in comparator-controlled studies. The most commonly reported drug-related adverse events leading to discontinuation in patients treated with ZYVOX were nausea, headache, diarrhea, and vomiting. Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.
Q: What were the most common drug-related adverse events associated with ZYVOX treatment?
A: The most common drug-related adverse events associated with ZYVOX treatment were:
* Diarrhea (4%)
* Nausea (3.3%)
* Headache (1.9%)
Of reported adverse events, 85% were mild to moderate in nature. The treatment-related discontinuation rate was 2.1% to 3.5% for ZYVOX (versus 1.7% to 2.4% for comparators).
Q: Are dosage adjustments necessary for special populations?
A: No dosage adjustments are required because of renal insufficiency, mild to moderate hepatic impairment, or advanced age. ZYVOX is eliminated by dialysis. No information is available on the effect of peritoneal dialysis on the pharmacokinetics of ZYVOX. ZYVOX should be given after hemodialysis. The ATS/IDSA pneumonia management guidelines support the use of ZYVOX for NP and VAP patients with renal insufficiency.31
Q: Can lactic acidosis occur with ZYVOX use?
A: Lactic acidosis is a potential adverse event that can occur during ZYVOX therapy. However, there have been spontaneous postmarketing reports during ZYVOX therapy that lactic acidosis reverses upon discontinuation of ZYVOX. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation. 86-89
Q: Can adverse events occur when ZYVOX is used concomitantly with MAOIs*?
A: Serotonin syndrome has been reported in postmarketing experience in patients receiving concomitant serotonergic agents, including antidepressants such as SSRIs, and ZYVOX. Because ZYVOX is an inhibitor of MAO, it has the potential to interact with drugs known to increase neurotransmitter concentrations either directly or indirectly. However, unlike traditional MAOIs, which are potent inhibitors of MAO types A and B, ZYVOX was shown in a recent in vitro study to be a weak and reversible inhibitor of this enzyme. 41
Q: How is ZYVOX available?
A: ZYVOX is available as IV, tablet, and for oral suspension. It is
100% bioavailable in oral form.
Q: Does ZYVOX offer effective lung tissue penetration?
A: ZYVOX provides excellent lung penetration of linezolid. Plasma and epithelial lining fluid concentrations of linezolid in healthy volunteers exceed MIC90 values for enterococci, staphylococci, and streptococci through the dosing interval.10 Pharmacokinetics in healthy and active volunteers and in vitro activity do not necessarily imply a correlation with clinical effectiveness.
Q: When should ZYVOX be prescribed?
Q: Has resistance to ZYVOX been studied?
Q: Is ZYVOX appropriate for empiric therapy?
Q: Are some pathogens resistant to all available treatments?
Q: What microorganisms is ZYVOX effective against?
Q: What were the most common drug-related adverse events associated with ZYVOX treatment?
Q: Are dosage adjustments necessary for special populations?
Q: Is there an association between thrombocytopenia (reduction in platelet count) and patients using ZYVOX?
Q: Can lactic acidosis occur with ZYVOX use?
Q: Can adverse events occur when ZYVOX is used concomitantly with MAOIs*?
Q: How is ZYVOX available?
Q: Does ZYVOX offer effective lung tissue penetration?
Q: Is ZYVOX well tolerated?
Q: What are the most common causes of infections?
A: In recent years, Gram-positive cocci and Candida species have replaced Gram-negative bacilli as the most common causes of nosocomial infections.62 For example, the frequency of infections caused by Escherichia coli has declined and the frequency of infections caused by staphylococci, enterococci, and Candida albicans has increased. Serious infections caused by streptococci and Mycobacterium species also have been quite common.
Q: When should ZYVOX be prescribed?
A: ZYVOX is indicated for the treatment of nosocomial (hospital acquired) pneumonia and complicated skin and skin structure infections, including cases due to methicillin-resistant Staphylococcus aureus. In addition, ZYVOX is approved for the treatment of community-acquired pneumonia and uncomplicated skin and skin structure infections. ZYVOX also is indicated for infections associated with vancomycin-resistant Enterococcus faecium, including cases with bacteremia.
Q: Is there an association between thrombocytopenia (reduction in platelet count) and patients using ZYVOX?
A: Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome is known, when ZYVOX was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive ZYVOX, particularly in those who receive ZYVOX for longer than 2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with ZYVOX should be considered in patients who develop or have worsening myelosuppression.
Within 7 phase 3 comparator-controlled trials, the reported ranges for thrombocytopenia among patients were 0.3% to 10.0% for ZYVOX-treated patients versus 0.4% to 7.0% for comparators.
It is important to note that the recommended treatment duration for ZYVOX indications of NP, including VAP, and cSSSI, including DFI, due to MRSA is 10 to 14 days.
Q: Has resistance to ZYVOX been studied?
A: In clinical trials, resistance to linezolid developed in 6 patients infected with Enterococcus faecium. In a compassionate use program, resistance to linezolid developed in 8 patients with E faecium and in 1 patient with Enterococcus faecalis. Reports of vancomycin-resistant E faecium becoming resistant to linezolid during its clinical use have been published. In one report, nosocomial spread of vancomycin- and linezolid-resistant E faecium occurred. There has been a report of Staphylococcus aureus (methicillin-resistant) developing resistance to linezolid during its clinical use. Resistance to linezolid has not been reported in Streptococcus spp, including Streptococcus pneumoniae.
The ZYVOX Annual Appraisal of Potency and Spectrum (ZAAPS) Program, a worldwide surveillance network, has compared MIC results for ZYVOX from 2002 to 2004, demonstrating no increase in resistance against 6 major organism groups.63
Data from the 2004 LEADER Surveillance Program conducted in the United States demonstrate that 99.5% of E faecalis and 96.4% of E faecium isolates were susceptible to ZYVOX, and that during the same time period, all 2872 strains of S aureus isolated were susceptible to ZYVOX.64
Q: Is ZYVOX appropriate for empiric therapy?
A: When MRSA is known or suspected, ZYVOX can be used empirically for all approved indications, including for susceptible strains in the treatment of NP, including VAP, and cSSSI, including DFI. Appropriate specimens should be taken and analyzed for culture and sensitivity, and antimicrobial selection should be adjusted accordingly based on those results. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX formulations and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Q: Are some pathogens resistant to all available treatments?
A: Some pathogens have developed resistance to virtually all antibiotic treatments.33 There is a need for the development of new antibiotics that have new mechanisms of action that may limit the development of resistance.
Q: What microorganisms is ZYVOX effective against?
A: ZYVOX has been shown to be active against most isolates of the following microorganisms:
Enterococcus faecium (vancomycin-resistant strains only)
Staphylococcus aureus (including methicillin-resistant strains)
Streptococcus agalactiae
Streptococcus pneumoniae (including multidrug-resistant isolates [MDRSP†])
Streptococcus pyogenes
Q: Is ZYVOX well tolerated?
A: In hospitalized patients with serious Gram-positive infections, ZYVOX had a low drug-related discontinuation rate in comparator-controlled studies. The most commonly reported drug-related adverse events leading to discontinuation in patients treated with ZYVOX were nausea, headache, diarrhea, and vomiting. Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.
Q: What were the most common drug-related adverse events associated with ZYVOX treatment?
A: The most common drug-related adverse events associated with ZYVOX treatment were:
* Diarrhea (4%)
* Nausea (3.3%)
* Headache (1.9%)
Of reported adverse events, 85% were mild to moderate in nature. The treatment-related discontinuation rate was 2.1% to 3.5% for ZYVOX (versus 1.7% to 2.4% for comparators).
Q: Are dosage adjustments necessary for special populations?
A: No dosage adjustments are required because of renal insufficiency, mild to moderate hepatic impairment, or advanced age. ZYVOX is eliminated by dialysis. No information is available on the effect of peritoneal dialysis on the pharmacokinetics of ZYVOX. ZYVOX should be given after hemodialysis. The ATS/IDSA pneumonia management guidelines support the use of ZYVOX for NP and VAP patients with renal insufficiency.31
Q: Can lactic acidosis occur with ZYVOX use?
A: Lactic acidosis is a potential adverse event that can occur during ZYVOX therapy. However, there have been spontaneous postmarketing reports during ZYVOX therapy that lactic acidosis reverses upon discontinuation of ZYVOX. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation. 86-89
Q: Can adverse events occur when ZYVOX is used concomitantly with MAOIs*?
A: Serotonin syndrome has been reported in postmarketing experience in patients receiving concomitant serotonergic agents, including antidepressants such as SSRIs, and ZYVOX. Because ZYVOX is an inhibitor of MAO, it has the potential to interact with drugs known to increase neurotransmitter concentrations either directly or indirectly. However, unlike traditional MAOIs, which are potent inhibitors of MAO types A and B, ZYVOX was shown in a recent in vitro study to be a weak and reversible inhibitor of this enzyme. 41
Q: How is ZYVOX available?
A: ZYVOX is available as IV, tablet, and for oral suspension. It is
100% bioavailable in oral form.
Q: Does ZYVOX offer effective lung tissue penetration?
A: ZYVOX provides excellent lung penetration of linezolid. Plasma and epithelial lining fluid concentrations of linezolid in healthy volunteers exceed MIC90 values for enterococci, staphylococci, and streptococci through the dosing interval.10 Pharmacokinetics in healthy and active volunteers and in vitro activity do not necessarily imply a correlation with clinical effectiveness.