Celutis200 mg

Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Celutis is an FDA-approved, established treatment for acute bacterial skin and skin structure infections (ABSSSI) in adults and adolescents (12 years of age and older), caused by susceptible Gram-positive organisms. Documented susceptible organisms include Staphylococcus aureus (including methicillin-resistant strains, MRSA, and methicillin-susceptible strains, MSSA), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group (including S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis. Celutis is useful when infection is known or suspected to involve MRSA, or when oral step-down therapy from an intravenous antibiotic is desired.

Not Established for Other Infections

Celutis is not approved for, and should not be used to treat, other types of infection such as community-acquired pneumonia, bloodstream infections, or infections caused by Gram-negative bacteria; clinical trials of Celutis for indications outside ABSSSI have not established a favorable benefit-risk profile, and off-label use of Celutis for such infections is not recommended outside specialist guidance.

Each Tedizolid Phosphate tablet for oral use contains Tedizolid Phosphate 200 mg (equivalent to 200 mg of tedizolid). Each single-use vial for intravenous infusion contains Tedizolid Phosphate 200 mg as a sterile, lyophilized powder for reconstitution, equivalent to 200 mg of tedizolid.

Celutis is an antibiotic belonging to the oxazolidinone class of medicines. Celutis is a prodrug that is rapidly converted in the body to its active form, tedizolid, which stops susceptible bacteria from producing the proteins they need to grow and multiply. Celutis is used to treat acute bacterial skin and skin structure infections (ABSSSI) caused by certain Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Celutis is available as an oral tablet and as a powder for intravenous infusion, and treatment with Celutis is given as a fixed, short course under the direction of a qualified healthcare professional.

Antibiotic (Oxazolidinone class)

Tedizolid Phosphate is a water-soluble prodrug that is rapidly and almost completely converted to its microbiologically active moiety, tedizolid, by endogenous phosphatases following oral or intravenous administration. Orally administered Tedizolid Phosphate has high absolute bioavailability (approximately 91%), and peak plasma concentrations of tedizolid are reached in about 3 hours; administration with food does not require a dose change, although peak concentration is somewhat delayed and reduced. Tedizolid is widely distributed into tissues (including skin and soft tissue) and is approximately 70–90% bound to plasma proteins. Unlike many antibiotics, tedizolid is metabolized mainly by sulfation (not significantly by cytochrome P450 enzymes) and is eliminated predominantly in feces, with a smaller amount excreted in urine; the terminal elimination half-life of tedizolid is approximately 12 hours, supporting once-daily dosing of Tedizolid Phosphate. Tedizolid Phosphate/tedizolid exhibits concentration-independent, time-above-MIC-related bactericidal or bacteriostatic activity depending on the organism, and demonstrates in vitro activity against Gram-positive organisms including strains resistant to other antibiotic classes.

• Celutis tablets may be taken by mouth with or without food.
• Celutis for injection must be reconstituted and then further diluted before use, and given only as an intravenous infusion over 1 hour; do not give Celutis as an intravenous push or bolus injection.
• Celutis may be started intravenously and switched to the oral tablet (or vice versa) when clinically appropriate, without a dose change, because both forms of Celutis produce equivalent drug exposure.
• Complete the full 6-day course of Celutis exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, even if symptoms improve early.

• Serotonergic drugs (SSRIs, SNRIs, triptans, MAO inhibitors, and similar agents): tedizolid, the active moiety of Celutis, has weak, reversible monoamine oxidase (MAO) inhibitory activity in vitro, considerably less than linezolid. A clinically significant interaction has not been established in studies to date, but as a conservative precaution, caution is advised when Celutis is combined with serotonergic medicines because of a theoretical risk of serotonin syndrome; patients should be monitored for symptoms such as agitation, confusion, rapid heart rate, or muscle rigidity.
• Tyramine-rich foods (aged cheese, cured meats, tap beer, soy products): because of the weak MAO-inhibiting activity described above, conservative caution regarding large amounts of tyramine-rich foods is reasonable during treatment with Celutis, although a clinically significant tyramine reaction, unlike with linezolid, has not been demonstrated for Celutis at the recommended dose and short treatment duration.
• Rifampin and other P-glycoprotein inducers: co-administration with rifampin has been shown to reduce tedizolid plasma concentrations; concurrent use of Celutis with strong P-glycoprotein inducers is generally not recommended, as it may reduce the effectiveness of Celutis.

Common Side Effects

• Nausea
• Headache
• Diarrhea
• Vomiting
• Dizziness

Serious Side Effects (Seek Medical Attention)

• Unusual bruising or bleeding, tiredness, pallor, or signs of infection such as fever, which may indicate myelosuppression (low blood cell counts) — see Precautions and Warnings for details
• Numbness, tingling, burning pain in the hands or feet, or changes in vision, which may indicate peripheral or optic neuropathy, generally reported with more prolonged oxazolidinone-class treatment than the approved 6-day course of Celutis
• Severe or persistent watery or bloody diarrhea, which may indicate Clostridioides difficile-associated diarrhea or colitis
• Signs of a severe allergic reaction, such as rash, hives, swelling of the face, lips, or throat, or difficulty breathing

Pregnancy

There are no adequate and well-controlled studies of Celutis in pregnant women. Animal reproduction studies have shown adverse effects on embryo-fetal development at exposures relevant to the clinical dose of Celutis. Celutis should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; a pregnant woman should consult her physician before using Celutis.

Breastfeeding

It is not known whether Celutis or tedizolid passes into human breast milk, or what effect this may have on a breastfeeding infant. A decision should be made, in consultation with a physician, whether to discontinue breastfeeding or to discontinue/avoid Celutis, taking into account the importance of the medicine to the mother and the potential for infant exposure.

• Myelosuppression: decreases in blood cell counts (such as neutrophils, hemoglobin, or platelets) have been reported with oxazolidinone-class antibiotics, including Celutis. The shorter, fixed 6-day course of Celutis is associated with a lower risk than longer courses of other oxazolidinones, but the risk is not eliminated, particularly if treatment is extended beyond the approved duration; complete blood counts should be monitored if clinically indicated, especially in patients receiving repeated or prolonged courses.
• Peripheral and optic neuropathy: peripheral and optic neuropathy have been reported with other drugs in the oxazolidinone class, generally with treatment durations longer than the 6 days approved for Celutis; the safety of Celutis beyond 6 days has not been established, and Celutis should not be used for longer than prescribed. Patients should report any new numbness, tingling, pain in the hands or feet, or visual changes.
• Serotonergic and tyramine interactions: see the Drug Interactions section for conservative precautions regarding serotonergic medicines and tyramine-rich foods during treatment with Celutis.
• Clostridioides difficile-associated diarrhea (CDAD): as with almost any antibiotic, Celutis can disturb normal gut bacteria and allow overgrowth of C. difficile, ranging from mild diarrhea to severe colitis; seek medical advice for persistent or severe diarrhea, even weeks after completing Celutis.
• Hypersensitivity reactions: discontinue Celutis immediately and seek urgent medical care if signs of a severe allergic reaction occur.
• Development of drug-resistant bacteria: using Celutis in the absence of a proven or strongly suspected susceptible bacterial infection is unlikely to provide benefit and increases the risk of the development of antibiotic-resistant bacteria; use Celutis only as prescribed by your physician, and take exactly as prescribed — do not stop, extend, skip doses, or share this medicine with others without medical advice.

There is limited clinical experience with overdose of Celutis, and no specific antidote is known. In the event of a suspected overdose of Celutis, seek immediate medical attention or contact a poison control center; management is expected to be supportive and symptomatic, including monitoring of vital signs and blood counts as clinically indicated. It is not known whether tedizolid is significantly removed by hemodialysis, so this should not be relied upon as a treatment for overdose.

Store Celutis tablets and vials for injection at room temperature (below 30°C), away from excessive heat, light, and moisture, in the original packaging. After reconstitution and dilution, the intravenous solution of Celutis should be used according to the timeframe stated in the product literature and should not be frozen. Keep Celutis out of the reach and sight of children, and do not use beyond the expiry date.

Renal Impairment

No dose adjustment of Celutis is required in patients with mild, moderate, or severe renal impairment, including those requiring hemodialysis, based on pharmacokinetic studies.

Hepatic Impairment

No dose adjustment of Celutis is required for patients with mild to moderate hepatic impairment. Celutis has not been studied in severe hepatic impairment; use with caution in this group.

Elderly

Clinical studies of Celutis did not identify differences in safety or effectiveness between elderly and younger adult patients, and no dose adjustment based on age alone is required; as with any antibiotic, elderly patients should be monitored for the general precautions described above.

Pediatric Patients

See Pediatric Uses below for details on the age and weight groups in which Celutis is approved.

Pregnant and Breastfeeding Women

See the Pregnancy and Lactation section above for detailed guidance on the use of Celutis in this population.

Celutis is approved for a fixed course of 6 days of treatment for acute bacterial skin and skin structure infections (ABSSSI), whether given orally, intravenously, or as a switch between the two. The safety and efficacy of Celutis beyond 6 days of treatment have not been established, and prolonging treatment with Celutis may increase the risk of myelosuppression and other adverse effects associated with the oxazolidinone class. Patients should complete the full prescribed course of Celutis and should not stop early, extend, or repeat treatment with Celutis without medical advice.

Celutis for injection is supplied as a single-use vial of lyophilized powder that must be reconstituted before use. Reconstitute each vial with 4 mL of Sterile Water for Injection to yield a solution containing approximately 50 mg/mL of Celutis; gently swirl (do not shake) until fully dissolved. Withdraw the appropriate volume of reconstituted Celutis and further dilute it in a 250 mL intravenous bag of a compatible diluent (such as 0.9% Sodium Chloride Injection or 5% Dextrose Injection) to prepare the final infusion solution. Inspect the reconstituted and diluted solution visually for particulate matter and discoloration before administration, and infuse over 1 hour. Discard any unused portion; the vial is for single use only. Reconstitution and dilution of Celutis should be performed by, or under the direct supervision of, trained healthcare personnel using aseptic technique.

Oxazolidinone antibacterial

Tedizolid Phosphate is a prodrug that is converted in vivo to tedizolid, the active antibacterial moiety. Tedizolid binds to the 23S ribosomal RNA of the 50S bacterial ribosomal subunit, at a site that overlaps the binding site of other protein synthesis inhibitors, and thereby prevents formation of the 70S ribosomal initiation complex that is essential for bacterial protein synthesis. By blocking this early step in protein synthesis, Tedizolid Phosphate/tedizolid inhibits bacterial growth and replication; this mechanism is generally bacteriostatic against most susceptible organisms.

Celutis is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adolescents 12 years of age and older who weigh at least 35 kg, using the same fixed dose as adults: 200 mg of Celutis once daily for 6 days, given orally or intravenously. The safety and efficacy of Celutis in children younger than 12 years of age, or in adolescents weighing less than 35 kg, have not been established, and Celutis is not recommended for use in these groups outside specialist guidance. As with adults, the general precautions regarding myelosuppression and neuropathy with prolonged use apply to adolescent patients receiving Celutis.