Tezolin

Uses

Tedizolid is an oxazolidinone-class antibacterial drug used for adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tedizolid and other antibacterial drugs, Tedizolid should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria

Tezolin is also used to associated treatment for these conditions: Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

How Tezolin works

Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant Staphylococcus aureus, remain a threat. Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors.

Protein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit.

Early studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis. However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both linezolid and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component. The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in Escherichia coli), which renders the PTC non-productive for peptide bond formation. Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis.

Dosage

Tezolin dosage

Acute Bacterial Skin and Skin Structure Infection (ABSSSI):

• Intravenous: 200 mg Once daily 1 hour (Infusion Time) for6 days
• Oral: 200 mg Once daily for6 days

No dose adjustment is necessary when changing from intravenous to oral Tedizolid. If patients miss a dose, they should take it as soon as possible anytime up to 8 hours prior to their next scheduled dose. If less than 8 hours remain before the next dose, wait until their next scheduled dose.

Side Effects

The most common adverse reactions (>2%) are nausea, headache, diarrhea, vomiting, and dizziness

Toxicity

Toxicity information regarding tedizolid is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nausea, headache, dizziness, diarrhea, and vomiting. Symptomatic and supportive measures are recommended.

Precaution

Patients with neutropenia: The safety and efficacy of Tedizolid in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of Tedizolid was reduced in the absence of granulocytes. Consider alternative therapies in neutropenic patients.

Clostridium difficile-associated diarrhea: Evaluate if diarrhea occurs.

Interaction

Tedizolid (when administered orally) can increase the plasma concentrations of orally administered Breast Cancer Resistance Protein BCRP substrates. Monitor for adverse reactions related to the concomitant BCRP substrates if coadministration cannot be avoided

Food Interaction

• Take at the same time every day.
• Take with or without food.

Volume of Distribution

The volume of distribution for tedizolid following a single intravenous dose of 200 mg is between 67 and 80 L. In a study involving oral administration of 200 mg tedizolid to steady-state, the volume of distribution was 108 ± 21 L, while a single 600 mg oral dose resulted in an apparent volume of distribution of 113.3 ± 19.3 L. Tedizolid has been observed to penetrate the interstitial space of both adipose and skeletal muscle tissue and is also found in the epithelial lining fluid as well as in alveolar macrophages.

Elimination Route

Tedizolid reaches peak plasma concentrations within three hours for oral administration and within one hour following intravenous administration; the absolute oral bioavailability is approximately 91%. Food has no effect on absorption. When given once daily, either orally or intravenously, tedizolid reaches steady-state concentrations in approximately three days.

The C_max for tedizolid after a single dose/at steady-state is 2.0 ± 0.7/2.2 ± 0.6 mcg/mL for oral administration, and 2.3 ± 0.6/3.0 ± 0.7 mcg/mL for intravenous administration, respectively. Similarly, the T_max has a median (range) of 2.5 (1.0 - 8.0)/3.5 (1.0 - 6.0) hrs for the oral route and 1.1 (0.9 - 1.5)/1.2 (0.9 - 1.5) hrs when given intravenous. The AUC is 23.8 ± 6.8/25.6 ± 8.4 mcg*hr/mL for oral and 26.6 ± 5.2/29.2 ± 6.2 mcg*hr/mL for intravenous.

Half Life

Tedizolid has a half-life of approximately 12 hours.

Clearance

Tedizolid has an apparent oral clearance of 6.9 ± 1.7 L/hr for a single dose and 8.4 ± 2.1 L/hr at steady-state. The systemic clearance is 6.4 ± 1.2 L/hr for a single dose and 5.9 ± 1.4 L/hr at steady-state.

Elimination Route

When given as a single oral dose, approximately 82% of tedizolid is excreted via the feces and 18% in urine. The majority is found as the inactive sulphate conjugate, with only 3% recovered unchanged. Over 85% of the elimination occurs within 96 hours.

Pregnancy & Breastfeeding use

Pregnancy category C. There are no adequate and well-controlled studies of Tedizolid in pregnant women. Tedizolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Tedizolid is excreted in the breast milk of rats. It is not known whether tedizolid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tedizolid is administered to a nursing woman.

Contraindication

None

Special Warning

Pediatric Use: Safety and effectiveness in pediatric patients below the age of 18 have not been established.

Geriatric Use: Clinical studies of Tedizolid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. No overall differences in pharmacokinetics were observed between elderly subjects and younger subjects

Acute Overdose

In the event of overdosage, Tedizolid should be discontinued and general supportive treatment given. Hemodialysis does not result in meaningful removal of tedizolid from systemic circulation

Storage Condition

Tablets and injection should be stored at 20°C to 25°C

Innovators Monograph

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