Drug of the Month Linezolid (Zyvox ®) by Pharmacia-UpJohn Company and marketed by Pzifer Pharmaceuticals
When presented with a patient that has methicillan resistant S. aureus (MRSA), one of the most common terms that first come to mind is resistance. Resistance with MRSA has become a very familiar topic within the healthcare community. With evolving topics such as the occurrence of vancomycin resistant Enterococcus (VRE) and vancoymcin treatment failures with MRSA, new therapies have or are being developed to combat this resistance. One of the newly emerged antibiotics on the market that has demonstrated efficacy with resistant MRSA is linezolid.
What is Linezolid (4)?
Linezolid is the first of a new class of antibiotics, the oxazolidinones, which act by inhibiting protein synthesis. The mechanism of action of linezolid is unique since it has not been entirely defined though it is theorized to inhibit the initiation complex of bacterial protein synthesis. This is unlike other inhibitors of protein synthesis which interfere with protein synthesis in the elongation or termination stages.
Zyvox ® is FDA approved for nosocomial pneumonia, complicated skin and skin structure infections (cSSI), diabetic foot infections without osteomyelitis, community aquired pneumonia and uncomplicated skin and skin structure infections (ucSSI).
Linezolid has a broad spectrum of activity against gram-positive infections of which include MRSA, VRA, VRE, E. faecalis and E. faecium. In addition to its gram-positive coverage, linezolid has activity against some gram-negative and anaerobic bacteria such as Clostridium perfringens, C. difficile, Peptostreptocococcus species and Bacteroides fragilis. Linezolid is bactericidal against the Streptococcal species and bacteriostatic against most Staphylococcus and Enterococcus species.
Despite its broad spectrum activity, linezolid has only moderate activity against Haemophilus influenzae and Moraxella catarrhalis. It also has no significant activity against Enterobacteriaceae or Pseudomonas species.
How is Linezolid provided and prepared?
Linezolid is currently available in both injectable and oral formulations.
Tablets: Film-coated tablet at doses of 400 mg and 600 mg. The tablets contain a sodium content of 1.95 mg per 400 mg tablet and 2.92 mg per 600 mg tablet.
Suspension: Dry powder for reconstitution that provides 150 mL of 100 mg / 5 mL of an orange-flavored suspension. Every 5 mL contains 20mg of phenylalanine and 8.52 mg of sodium.
IV: Premixed solution with dextrose in 100 mL and 300 mL bags at a concentration of 2 mg/mL. The IV solution also contains a sodium content of 0.38 mg/mL.
The Zyvox ® IV solution is compatible with D5W, NS and lactate Ringer’s injection. No additives should be introduced into the solution. It is incompatible with Y-site administration with ceftriaxone, Bactrim ® and a multitude of other medications. Thus it is important to flush all sequential infusion lines before and after infusion with Zyvox ®.
What are the associated with adverse reaction during infusion?
With any injectable medication watching for common injection site pain and allergic reactions is essential. Aside from the norm, Linezolid has been associated with numerous amounts of side effects.
The most common adverse events included headache, candidiasis (particularly oral and vaginal candidiasis) or fungal infection, diarrhea, nausea, vomiting, abnormal liver function tests and taste perversion (metallic taste) . The more serious side effects that can occur are thrombocytopenia and myelosuppression. This is a usually dose dependent response and it more prominent after 2 weeks of administration. Other serious side effects that should be noted are lactic acidosis and serotonin syndrome (especially with concomitant serotonin reuptake inhibitors).
A unique side effect that has bee associated with linezolid therapy is a significant increase in blood pressure with large consumptions of tyramine containing foods (ie wine, cheese and meats such as sausage, bologna, pepperoni and salami). This is also prominent with concomitant administration of pseudoephedrine.
What must be monitored while on Linezolid therapy?
CBC with differential, Vital signs (especially blood pressure)
How is Linezolid administered at home?
Zyvox ® comes in premixed single use IV bags that have a protective foil over-wrap to each individual bag. The over-wrapped bags are stored at room temperature and should not be kept frozen. Once the foil over-wrap is opened, it is recommended to use the solution immediately and while infusing, protect it from light. The usual dose is 600mg every 12 hours ranging from 10 to 28 days with a minimum infusion time of 30 minutes.
In regards to long term stability of the medication during storage with or without the foil wrap, no studies are currently available (via personal communications with Pzifer).
How can we sell Linezolid?
When considering the selling of linezolid, the stance is similar to that expressed in the Cubicin ® article (March 2007). Yet, linezolid does have some advantages over Cubicin ® that would make the selling of linezolid more persuasive. Compared to Cubicin ®, linezolid does have FDA approval for its use in the pediatric population and is indicated for community and nosocomial pneumonia. Also with the availability of oral dosage forms of linezolid, the cost savings gained in administering the IV preparation in an outpatient setting then (if appropriate) switching the patient to an oral form is significant versus IV administration of linezolid at a hospital then discharging the patient on an oral formulation.
Who pays for Linezolid?
Virtually all private third-party payers will pay for this medication, though it typically requires prior authorization. T he availability of specific IV infusions, such as Zyvox ®, under Medicare will vary based on the individual drug formularies and plan benefit designs of the Part D plans. Medicare beneficiaries may need to pay out-of-pocket or find other sources of coverage for the supplies and administration services associated with home infusions under Part D, as plans will not cover the costs of these items and services. Thus it is beneficial to determine if the medication will be covered prior to admission with a home care company.
How is Linezolid Coded?
J2020 linezolid injection per 200 mg. Coverage is typically a max of 6 per day (total of 1200 mg daily).
What is the financial impact of Linezolid?
The average wholesale price (AWP) of a single 600 mg linezolid tablet is $56.31. Based on this pricing, a typical 10 day oral treatment regimen would cost over $1,000. The oral suspension price is $281.56 for 150 ml (100mg/5mL). The premixed IV solutions are $38.10 for the 100 ml (200mg) size and $76.19 for the 300 ml (600 mg) size. There is currently no AWP information on the 400 mg tablet strength.
What are the special considerations that pertain to Linezolid?
There is an emerging issue of developed bacterial resistance. Though it currently ranges less than 10 case reports, future use of linezolid (possibly many decades from now) may be hindered.
References
Zyvox ®. Prescribing information. Pzifer. March 2007
Sakoulas G, Moise-Broder PA, Schentag J, et al. J Clin Microbiology. 2004 June; 42(6): 2398–2402
Buck. Linezolid Use for Resistant Gram-positive Infections in Children. Pediatric Pharmacotherapy. 2003; 9(6)
The Pharmaceutical Journal. 2001; 266: 130
Sifton DW, ed. 2002 Drug Topics Red Book. 106 [th] ed. Montvale, NJ: Thomson Medical Economics, 2002: 600