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Zyvox (Linezolid) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Monoamine Oxidase Inhibition

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving ZYVOX may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Co-administration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase 1, 2 or 3 studies. Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed as described in the PRECAUTIONS, General Section.

Antibiotics: In healthy volunteers, coadministration of rifampin with linezolid resulted in a 21% decrease in linezolid Cmax and a 32% decrease in linezolid AUC (see CLINICAL PHARMACOLOGY, Drug-Drug Interactions). The clinical significance of this interaction is unknown.

OVERDOSAGE

In the event of overdosage, supportive care is advised, with maintenance of glomerular filtration. Hemodialysis may facilitate more rapid elimination of linezolid. In a Phase 1 clinical trial, approximately 30% of a dose of linezolid was removed during a 3-hour hemodialysis session beginning 3 hours after the dose of linezolid was administered. Data are not available for removal of linezolid with peritoneal dialysis or hemoperfusion. Clinical signs of acute toxicity in animals were decreased activity and ataxia in rats and vomiting and tremors in dogs treated with 3000 mg/kg/day and 2000 mg/kg/day, respectively.

CONTRAINDICATIONS

ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.

Monoamine Oxidase Inhibitors

Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g., phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product.

Potential Interactions Producing Elevation of Blood Pressure

Unless patients are monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g., pseudoephedrine), vasopressive agents (e.g., epinephrine, norepinephrine), dopaminergic agents (e.g., dopamine, dobutamine) (see PRECAUTIONS, Drug Interactions).

Potential Serotonergic Interactions

Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone (see PRECAUTIONS, General and Drug Interactions).

REFERENCES

  1. Gonzales RD, PC Schreckenberger, MB Graham, et al. Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. The Lancet 2001;357:1179.
  2. Herrero IA, NC Issa, R Patel. Nosocomial spread of linezolid-resistant, vancomycin-resistant Enterococcus faecium. The New England Journal of Medicine 2002;346:867–869.
  3. Tsiodras S, HS Gold, G Sakoulas, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. The Lancet 2001;358:207–208.
  4. Goldman DA, RA Weinstein, RP Wenzel, et al. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. The Journal of the American Medical Association 1996;275:234–240.
  5. Centers for Disease Control and Prevention. Guideline for hand hygiene in health-care settings: Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Morbidity and Mortality Weekly Report 2002;51 (RR-16).
  6. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January 2000.
  7. National Committee for Clinical Laboratory Standards. Twelfth Informational Supplement. Approved NCCLS Document M100-S12, Vol. 21, No. 1, NCCLS, Wayne, PA, January 2002.
  8. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests. Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January 2000.
  9. Walker SE et al. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. Journal of Clinical Psychopharmacology 1996;16(5):383–388.
  10. DaPrada M et al. On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. Journal of Neural Transmission 1988; [Supplement] 26:31–56.
  11. Fine MJ, Auble TE, Yealy DM, et al. A Prediction Rule to Identify Low-Risk Patients with Community-Acquired Pneumonia. The New England Journal of Medicine. 1997;336 (4):243–250.

Rx only

LAB-0139-18.0

July 2008

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