Dosing & Uses
ADULT and PEDIATRIC
Dosage Forms & Strengths
tablet
- 600mg
Vancomycin-Resistant Enterococcal Infections
600 mg PO/IV q12hr for 14-28 days
Complicated Skin & Skin Structure Infections
600 mg PO/IV q12hr for 10-14 days
Uncomplicated Skin & Skin Structure Infections
400-600 mg PO q12hr for 10-14 days
Community-Acquired Pneumonia (Including Concurrent Bacteremia)
600 mg PO/IV q12hr for 10-14 days
Nosocomial Pneumonia
600 mg PO/IV q12hr for 10-14 days
Methicillin-Resistant Staphylococcal Infections
600 mg PO/IV q12hr
Methicillin-Susceptible Staphylococcus Aureus
600 mg PO/IV q12hr for 10-14 days
Dosing Considerations
Monitor: CBC count perWeek
PEDIATRIC
Complicated Skin & Skin Structure Infections
<12 years: 10 mg/kg PO/IV q8hr for 10-14 days
≥12 years: 600 mg PO/IV q12hr for 10-14 days
Uncomplicated Skin & Skin Structure Infections
<5 years: 10 mg/kg PO q8hr for 10-14 days
5-12 years: 10 mg/kg PO q12hr for 10-14 days
>12 years: 600 mg PO q12hr for 10-14 days
Pneumonia
<12 years: 10 mg/kg PO/IV q8hr for 10-14 days
≥12 years: 600 mg PO/IV q12hr for 10-14 days
Vancomycin-Resistant Enterococcal Infections
<12 years: 10 mg/kg PO/IV q8hr for 14-28 days
≥12 years: 600 mg PO/IV q12hr for 14-28 days
Dosing Considerations
Monitor: CBC count perWeek
Adverse Effects
>10%
Pediatrics
- Diarrhea (7.8-10.8%)
1-10%
Headache (5.7-8.8%)
Diarrhea (8.2-8.3%)
Nausea (5.1-6.6%)
Vomiting (2-4.3%)
Dizziness (1.8-2.6%)
Rash (1.1-2.3%)
Vaginal moniliasis (1.1-1.8%)
Taste alteration (1-1.8%)
Oral moniliasis (0.5-1.7%)
Abnormal LFTs (0.4-1.6%)
Fungal infection (0.3-1.5%)
Localized abdominal pain (1.2-1.3%)
Tongue discoloration (0.3-1.3%)
Generalized abdominal pain (0.9-1.2%)
Pediatrics
- Vomiting (2.9-9.4%)
- Headache (0.9-6.5%)
- Anemia (5.6%)
- Thrombocytopenia (4.7%)
- Nausea (1.9-3.7%)
- Generalized abdominal pain (0.9-2.4%)
- Localized abdominal pain (0.5-2.4%)
- Loose stools (1.6-2.3%)
- Eosinophilia (0.4-1.9%)
- Pruritus, other than application site (0.8-1.4%)
- Vertigo (1.2%)
<1%
Lactic acidosis
Myelosuppression
Peripheral neuropathy
Disorder of optic nerve
Serotonin syndrome
Postmarketing Reports
Superficial tooth discoloration
Superficial tongue discoloration
Myelosuppression including anemia, leukopenia, pancytopenia, and thrombocytopenia
Sideroblastic anemia
Anaphylaxis
Angioedema
Bullous skin disorders including severe cutaneous adverse reactions (SCAR) such as toxic epidermal necrolysis and Stevens-Johnson syndrome
Optic neuropathy
Hypersensitivity vasculitis
Hypoglycemia
Hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Warnings
Contraindications
Hypersensitivity
Within 14 days of taking MAO inhibitor
Cautions
Use caution in patients with pheochromocytoma, concurrent apraclonidine, brimonidine, uncontrolled hypertension, thyrotoxicosis, carcinoid syndrome, diabetes mellitus, or seizure disorders
Phenylalanine can be harmful to patients with phenylketonuria (PKU); oral suspension contains phenylalanine, a component of aspartame; each 5 mL of the 100 mg/5 mL oral suspension contains 20 mg of phenylalanine; before prescribing oral suspension to patient with PKU, consider combined daily amount of phenylalanine from all sources, including oral suspension; the other formulations do not contain phenylalanine
Not approved for gram-negative bacteria or for catheter-related infections; clinical study showed higher mortality rate with linezolid than with other antibiotics for these conditions
Evaluate for clostridium difficile if diarrhea occurs
Peripheral and optic neuropathy reported, especially in patients given extended courses of therapy >28 days
May cause hypoglycemia; monitor blood glucose levels
Lactic acidosis reported with use; immediately evaluate patients who develop recurrent unexplained acidosis with nausea and vomiting
Superinfection may develop
Myelosuppression
- Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) reported in patients receiving this medication; in cases where outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels
- Thrombocytopenia reported more often in patients with severe renal impairment, whether or not on dialysis, and in patients with moderate to severe hepatic impairment
- Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, those with pre-existing myelosuppression, those with severe renal impairment or moderate to severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibacterial drug therapy
- Consider discontinuation of therapy in patients who develop or have worsening myelosuppression
Hyponatremia
- Postmarketing cases of hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) reported; in reported cases, the signs and symptoms included confusion, somnolence, generalized weakness, and in severe cases led to respiratory failure and even death
- Monitor serum sodium levels regularly in the elderly, in patients taking diuretics, and in other patients at risk of hyponatremia and/or SIADH while taking drug
- If signs and symptoms of hyponatremia and/or SIADH occur, discontinue therapy and institute appropriate supportive measures
Serotonin syndrome
- Avoid coadministration with serotonergic psychiatric drugs (eg, SSRIs, SNRIs, TCAs, MAOIs, bupropion, buspirone, serotonin 5-HT1 receptor agonists (triptans), and opioids, including meperidine) unless indicated for life-threatening or urgent infections (eg, vancomycin-resistant enterococcal infections, nosocomial pneumonia, complicated skin and skin structure infections such as methicillin-resistant S aureus), due to increased risk of serotonin syndrome; linezolid may increase serotonin CNS levels by MAO-A inhibition
- If linezolid must be administered to a patient currently taking a serotonergic drug, stop serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring (5 weeks if fluoxetine was taken), whichever comes first; serotonergic psychiatric medications should be stopped at least 2 weeks in advance of linezolid therapy; fluoxetine should be stopped at least 5 weeks in advance due to longer half-life
Pregnancy & Lactation
Pregnancy
Available data from published and postmarketing case reports with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
- When administered during organogenesis, linezolid did not cause malformations in mice, rats, or rabbits at maternal exposure levels approximately 6.5 times (mice), equivalent to (rats), or 0.06 times (rabbits) the clinical therapeutic exposure, based on AUCs; however, embryo-fetal lethality was observed in mice at 6.5 times the estimated human exposure
- When female rats were dosed during organogenesis through lactation, postnatal survival of pups was decreased at doses approximately equivalent to the estimated human exposure based on AUCs
Infertility
- Based on findings from studies in rats, drug may reversibly impair fertility in male patients
Lactation
Drug is present in breast milk; based on data from available published case reports, the daily dose that the infant would receive from breastmilk would be approximately 6% to 9% of the recommended therapeutic infant dose (10 mg/kg every 8 hours)
There is no information on effects of linezolid on breastfed infant; however, diarrhea and vomiting were the most common adverse reactions reported in clinical trials in infants receiving linezolid therapeutically
There is no information on effects of drug on milk production; consider developmental and health benefits of breastfeeding along with mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from underlying maternal condition
Advise lactating women to monitor a breastfed infant for diarrhea and vomiting
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.