Linelid Special Precautions

Administration details: Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO); however at doses used for antibacterial therapy, the drug has no antidepressant effect. Data on Linezolid interaction and safety in case of prescription to patients with concurrent diseases or taking concomitant drugs, which could put them at risk of MAO inhibiting, are limited. That's why under described conditions, use of Linezolid is not recommended. If only there is an opportunity of patient close monitoring.
Patients should be warned of necessity to refrain from intake of tyramine-enriched food. Every mL of solution contains 45.7 mg (13.7 g/300 mL) of glucose. It should be taken into account in patients with diabetes mellitus or other conditions characterized by impaired tolerance to glucose. Every mL of solution also contains 0.38 g (114 g/300 mL) of sodium. Reversible myelosuppression in some patients receiving Linezolid (anemia, thrombocytopenia, leukopenia and pancytopenia) was reported, intensity of which could depend on drug dose and therapy duration. In cases with known outcome, when Linezolid was discontinued, the affected hematologic parameters have risen toward pre-treatment levels. Risk of these effects' development could be associated with therapy duration. Thrombocytopenia could occur more frequently in patients with severe renal failure, regardless of dialysis. That's why complete blood cout should be monitored for patients with pre-existing anemia, granulocytopenia, thrombocytopenia; for those ones receiving drugs, able to decrease hemoglobin level or platelet count in peripheral blood or suppress their function; severe liver failure; increased risk of bleeding occurrence; previously identified myelosuppression; or receiving Linezolid for longer than 2 weeks. Linezolid (Linelid) should be prescribed to such patients only under possibility to monitor hemoglobin level, parameters of complete blood count and platelets. In case of considerable myelosuppression during course of therapy with Linezolid, the treatment should be discontinued, excluding cases when treatment prolongation was considered vital. In such situations, close monitoring of complete blood count parameters and implementation of strategy of relevant patients management are necessary.
In addition, it is recommended to monitor complete blood count parameters (including hemoglobin level, platelets, total and differential leukocyte count) in patients receiving Linezolid once a week regardless of baseline parameters of complete blood count.
In studies, higher grade of development of severe anemia was reported in patients who received Linezolid for a period longer than recommended 28 days. These patients required hemotransfusion more frequently. Cases of anemia that required hemotransfusion were reported during post-marketing observation. Most cases occurred in patients who received Linezolid for a period longer than recommended 28 days.
Development of lactic acidosis was reported at use of Linezolid. Patients receiving Linezolid in which repeated nausea or vomiting, unexplained acidosis or decrease in blood bicarbonate level, requiring urgent medical examination, were observed. Increased mortality rate was observed in patients who received Linezolid as compared to combination vancomycin/dicloxacillin/oxacillin during open-label, randomized clinical study in seriously ill patients with catheter-related infections caused by gram-positive causative agents.
Treatment regimens with the use of Linezolid (600 mg every 12 hours intravenously/orally) and vancomycin (1 g intravenously every 12 hours) or oxacillin (2 g intravenously every 6 hours)/dicloxacillin (500 mg orally every 6 hours) were compared at treatment duration from 7 to 28 days. Frequency of lethal outcomes in this study was 78/363 (21.5%) and 58/363 (16.0%) at the use of Linezolid and comparator drug, respectively. On the basis of results of logistic regression the expected relative risk is 1.426 [95% confidence interval 0.970, 2.098]. Although causal link was not defined, observed imbalance occurred more frequently in patients who received Linezolid, and in which before treatment initiation gram-negative causative agents or mixed gram-negative and gram-positive infection were identified, or causative agent was not identified.
Controlled clinical studies didn't include patients with diabetic foot, decubuti, ischemic injuries, severe burns or gangrene. So, Linezolid experience for treatment of these conditions is limited. In patients selected randomly for treatment with Linezolid, and in which before treatment initiation only gram-positive causative agents were identified, including subgroup of patients with gram-positive bacteremia, the same survival rate was observed as in patients of comparator group.
Linezolid has no clinical activity against gram-negative causative agents, so its use for infections caused by these microorganisms, is not indicated. In case when presence of concomitant gram-negative infection is established or suspected, the use of specific antimicrobial therapy against gram-negative microorganisms is indicated. Linezolid should be used with caution in patients with high risk of life-threatening systemic infections, particularly infections caused by installed central venous catheter in patients of intensive care unit. The use of Linezolid for treatment of patients with septic infection caused by installed venous catheters was not approved. Linezolid (Linelid) should be used with caution in patients with severe renal failure, and only in the cases when expected drug benefit is higher that potential risk.
In patients with severe liver injury the use of Linezolid (Linelid) is recommended only in the cases when expected drug benefit is higher that potential risk.
Cases of pseudomembranous colitis were reported with the use of almost all antibacterial agents, including Linezolid; its severity could vary from insignificant to life-threatening. Diarrhea associated with Clostridium difficile was reported at the use of almost all antibacterial agents, including Linezolid; its severity could vary from insignificant diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal colon microflora that leads to excessive growth of C. difficile. C. difficile produces toxins A and B, causing diarrhea development. Hypertoxin produced by strains of C. difficile leads to increase in morbidity and lethality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Diarrhea associated with C. difficile should be suspected in all patients with diarrhea, occurred after use of antibiotics. Medical history should be collected with caution, as cases of C. difficile-asociated diarrhea could develop in more than 2 months after administration of antibacterial agents.
Peripheral and optic neuropathy were reported in patients receiving Linezolid, more often at drug use for a period longer than recommended 28 days. In case of optic neuropathy that had progressed to loss of vision, patients had received the drug for a period longer than recommended treatment duration.
In case of occurrence of such symptoms as visual impairment, change in colour perception, blurring of vision or visual field defects, immediate ophthalmological examination is recommended. Visual function should be monitored in all patients receiving Linezolid for a long-term period (3 months or more), and in all patients complaining of occurrence of new eye disorders regardless of duration of therapy with Linezolid. In case of development of peripheral and optic neuropathy, advisability of further use of Linezolid associated potential risk should be considered.
Seizures were rarely reported among patients receiving Linezolid. In most cases, there were seizures or factors of seizure occurrence risk in history of patients.
There were spontaneous reports of serotonin syndrome, related to concomitant administration of Linezolid and serotonergic drugs, including antidepressant drug, in particular, selective serotonin reuptake inhibitors (SSRIs). When concomitant administration of Linezolid and serotonergic drugs is clinically necessary, a patient should be under close medical supervision for early detection of signs and symptoms of serotonin syndrome, such as cognitive dysfunction, hyperpyrexia, hyperreflexia and loss of coordination. In case of occurrence of these signs and symptoms, a physician should consider necessity of discontinuation of the use of one of two or both these drugs. After serotonergic drug rechallenge, these symptoms could disappear.
In adult male rats, Linezolid reversibly reduces fertility and causes abnormal sperm morphology at exposure levels approximately similar to those in human. Possible drug effects on human reproductive system are unknown.
Effect on ability to drive and operate other machines: Linezolid effect on ability to drive and use machines was not systemically evaluated.
Use in Children: Drug is used since the first days of life.
n adolescents (ranging in age from 12 to 17 years) pharmacokinetics of Linezolid is similar to that in adults, when the drug is used at dose of 600 mg. Therefore, in adolescents receiving the drug at dose of 600 mg every 12 hours on daily basis, the same exposure would be observed as in adults at administration of the drug at the same dose.
In age from 1 week to 12 years: drug administration at dose of 10 mg/kg every 8 hours on daily basis ensures exposure, which is close to that one achieved in adults in case of drug administration at dose of 600 mg twice a day.
In neonates of less than one week of age: Linezolid systemic clearance (on the basis per 1 kg of body weight) rapidly increases during the first week of life. Therefore, in neonates receiving the drug at dose of 10 mg/kg every 8 hours on daily basis, higher systemic drug exposure on the first postnatal day is observed. However, excessive drug body accumulation is expected at such a dosage during the first week of infant life (due to rapidly increased drug clearance during first 7 days of life).