Zyvox (linezolid) Use in Long Term Care

Zyvox (linezolid) is an antibiotic effective against a wide spectrum of gram-positive organisms, including resistant strains such as methicillin-resistant staphylococcus (MRSA) and vancomycin-resistant enterococci (VRE). It is often the topic of pharmacy recommendations due to the potential of serious side effects, drug interactions, inappropriate use and cost.

Antibiotic Stewardship and Appropriate Use

Antibiotic stewardship is the term used to describe the process of selecting the optimal antibiotic medication, dose, duration of therapy, and route of administration.¹ It requires that the most appropriate antibiotic be used in any given situation. Antibiotic stewardship decreases the likelihood of developing resistant organisms, maximizes cost effectiveness, and improves patient outcomes.

When applying the concept of antibiotic stewardship to Zyvox, we first need culture and sensitivity (C&S) results showing susceptibility to Zyvox. It is important to note that Zyvox is usually not appropriate for empiric therapy. Once susceptibility has been determined by C&S, Zyvox may be an appropriate antibiotic for treating a patient’s infection. Here are some examples of situations where Zyvox may be appropriate:

• The patient’s culture and sensitivity shows susceptibility to IV vancomycin and to Zyvox, but the patient is unable to tolerate IV vancomycin.
• The patient’s culture and sensitivity shows susceptibility to IV vancomycin and to Zyvox, but the IV access cannot be established.
• The patient’s culture and sensitivity shows vancomycin-resistant enterococcus (VRE) susceptible for Zyvox.

The following chart shows the indications for use of Zyvox in adult patients, along with the recommended dose and length of therapy. Courses of treatment longer than 28 days are not typical and increase the risk for additional side effects like lactic acidosis, peripheral neuropathy and optic neuropathy.²

Alternatives to Zyvox

Alternatives to Zyvox for treatment of MRSA may include IV vancomycin, daptomycin (Cubicin), and tigacycline (Tygacil), depending on the site of infection and the culture and sensitivity. IV vancomycin is by far the most cost-effective option, as Zyvox costs more than 10 times more than vancomycin. Zyvox is the only medication of this group to offer a PO route of administration (tablets and oral suspension).

Side Effects

Zyvox, like many antibiotics, can cause diarrhea, headache, nausea, and vomiting. However, when nausea and vomiting occurs with Zyvox, it may indicate lactic acidosis. Zyvox can also cause myelosuppression, including anemia, leukopenia, pancytopenia, and thrombocytopenia.  Optic neuropathy is also a possible side effect, especially when Zyvox is used for longer than 28 days.

Serotonin Syndrome

Serotonin syndrome is a condition caused by excess serotonin in the body. It is the most significant drug-drug interaction involving Zyvox. Signs and symptoms of serotonin syndrome may include stiff muscles, confusion, racing heartbeat, diarrhea, nausea, vomiting, high fever, shivering, hallucinations, very high or very low blood pressure, large pupils or sweating.

Monitoring

LABS: Complete blood count (CBC) weekly, due to the risk of myelosuppression. This is particularly important in patients who already have myelosuppression or who have a history of myelosuppression.

Nursing: Nurses should monitor the patient’s blood pressure, heart rate, and temperature daily and monitor for the signs and symptoms of serotonin syndrome and other side effects.

Pharmacy Recommendations

AlixaRx pharmacists will issue a recommendation to the provider when Zyvox is ordered for a patient on a medication that may increase the risk of serotonin syndrome. Many of these medications are antidepressants. A more detailed list of these medications can be found at the end of this article.³ Recommendations may request that an alternative antibiotic be considered, that an interacting drug be held until Zyvox is completed, or that CBC or other lab monitoring be initiated.

The drug interactions and side effects of Zyvox are important to watch out for, but equally important is its place in treating MRSA and VRE infections. With proper antibiotic stewardship, patient monitoring, and a clear understanding the risks and benefits of Zyvox, we can help our patients recover as quickly as possible

I. Serotonergic psychiatric drugs implicated in the AERS cases of serotonin syndrome with linezolid

Selective Serotonin Reuptake Inhibitors (SSRIs)

Generic Name            Found in Brand Names 

Paroxetine                  Paxil, Paxil CR

Fluvoxamine               Luvox, Luvox CR

Fluoxetine                  Prozac, Symbyax

Sertraline                    Zoloft

Citalopram                 Celexa

Escitalopram              Lexapro

Vilazodone                 Viibryd

Although the FDA has not received cases of serotonin syndrome to date involving vilazodone, the pharmacology of this drug places it in the SSRI category and suggests that it possesses a risk comparable to that of the SSRIs.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Generic Name                        Found in Brand Names     

Venlafaxine                            Effexor, Effexor XR

Desvenlafaxine                       Pristiq

Duloxetine                              Cymbalta

II. Other psychiatric drugs with varying degress of serotonergic activity for which the risk of serotonin syndrome with linezolid is unclear

Tricyclic Antidepressants (TCAs)

Generic Name                        Found in Brand Names    

clomipramine                                     Anafranil

amitriptyline                          Amitid, Amitril, Elavil, Endep, Etrafon,

amitriptyline

desipramine

imipramine

nortriptyline

doxepin                                  Sinequan, Zonalon, Silenor

trimipramine                                      Surmontil

Monoamine Oxidase Inhibitors (MAOIs)

Generic Name                        Found in Brand Names

isocarboxazid                         Marplan

phenelzine                              Nardil

transdermalselegiline           Emsam

tranylcypromine                     Parnate

Other Psychiatric Medications

Generic Name                        Found in Brand Names

amoxapine                             Asendin

maprotiline                            Ludiomil

nefazodone                            Serzone

trazodone                               Desyrel, Oleptro, Trialodine

bupropion                              Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin

buspirone                               Buspar

mirtazapine                            Remeron, RemeronSoltab

References:

1. Infectious Diseases Society of America, Arlington, VA. http://www.idsociety.org/Stewardship_Policy/. Accessed September 2, 2015.
2. Zyvox [package insert]. Pharmacia & Upjohn Co, New York, NY; June 2015. http://www.labeling.pfizer.com/showlabeling.aspx?id=649#section-2. Accessed September 2, 2015.
3. US Food and Drug Administration, Silver Spring, MD. http://www.fda.gov/Drugs/DrugSafety/ucm276251.htm. Accessed September 2, 2015

This article was originally published in our monthly issue of From the Front Lines – a monthly publication that shares best practices and medication-related challenges faced by “front line” staff in long-term care and post-acute (LTCPAC) facilities.

>>> From the Front Lines – September 2015 <<<