Sivextro (tedizolid phosphate)

Tedizolid phosphate is a prodrug that is inactive until metabolized in vivo to tedizolid (see Description); dosage of the drug is expressed in terms of the prodrug (i.e., tedizolid phosphate).

Dosage adjustments of tedizolid phosphate are not needed when switching from IV to oral administration.

Tedizolid phosphate is administered orally or by IV infusion.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

P-Gp Or Bcrp Inhibitors/Ubrogepant (> 50 Mg)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1)

CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) For patients on concurrent therapy with vimseltinib and ubrogepant: the manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) For patients on daraxonrasib, the manufacturer of daraxonrasib states that it should be taken at least 4 hours apart from P-gp substrates.(4)

DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, vadadustat, and zongertinib.(2,3,5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, danicopan, daraxonrasib, daridorexant, imlunestrant, neratinib, osimertinib, propafenone, quinidine, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, valbenazine, vimseltinib, and voclosporin.(2,3,5)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Oral Tedizolid/Selected Oral Bcrp Substrates

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Oral tedizolid may may inhibit Breast Cancer Resistance Protein (BCRP) in the intestine, which may result in increased absorption of orally administered BCRP substrates.(1-3)

CLINICAL EFFECTS: Concurrent use of oral tedizolid may result in elevated levels of and toxicity from orally administered BCRP substrates.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, consider interrupting therapy with orally administered BCRP substrates during therapy with oral tedizolid. If concurrent therapy is warranted, monitor patients for toxicity.(1-3)

DISCUSSION: Orally administered tedizolid (200 mg) increased the area-under-curve (AUC) and maximum concentration (Cmax) of rosuvastatin (10 mg) by 70% and 55%, respectively.(1-3) BCRP substrates include: imatinib, lapatinib, methotrexate, rosuvastatin, sulfasalazine, and topotecan.(1-3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

P-Gp Or Bcrp Inhibitors/Ubrogepant (<= 50 Mg)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1)

CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) For patients on concurrent therapy with vimseltinib and ubrogepant: The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) For patients on daraxonrasib, the manufacturer of daraxonrasib states that it should be taken at least 4 hours apart from P-gp substrates.(4)

DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, vadadustat, and zongertinib.(2,3,5,6) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, danicopan, daraxonrasib, daridorexant, imlunestrant, neratinib, osimertinib, propafenone, quinidine, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, valbenazine, vimseltinib, and voclosporin.(2,3,5,6)

The manufacturer states there are no contraindications to use of tedizolid phosphate.

There are no contraindication contraindications for this drug.

• Clostridioides difficile infection
• Pregnancy
• Serotonin syndrome

There are no moderate contraindications for this drug.

Adverse effects reported in 2% or more of patients receiving tedizolid phosphate include nausea, headache, diarrhea, vomiting, dizziness, and fatigue.

More Frequent

• Headache disorder

Less Frequent

• Abnormal hepatic function tests
• Hypersensitivity drug reaction
• Increased alanine transaminase
• Increased aspartate transaminase
• Thrombocytopenic disorder

Rare or Very Rare

• Anemia
• Clostridioides difficile infection
• Hypertension
• Leukopenia
• Neutropenic disorder
• Optic neuropathy
• Peripheral neuropathy

More Frequent

• Diarrhea
• Dizziness
• Injection site sequelae
• Nausea
• Phlebitis after infusion
• Vomiting

Less Frequent

• Asthenopia
• Blurred vision
• Facial nerve disorder
• Flushing
• Hypoesthesia
• Insomnia
• Oral candidiasis
• Palpitations
• Paresthesia
• Skin inflammation
• Tachycardia
• Urticaria
• Vision impairment
• Vitreous floater
• Vulvovaginal candidiasis

Rare or Very Rare

• Pruritus of skin

No enhanced messaging available.

Safety and efficacy of tedizolid phosphate have not been established in pediatric patients younger than 18 years of age.

Category C. (See Users Guide.)

There are no adequate and well-controlled studies of tedizolid in pregnant women, and the drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.

In embryofetal studies, tedizolid was shown to produce fetal developmental toxicities in mice, rats, and rabbits. In mice, reduced fetal weight and increased incidence of costal cartilage anomalies were observed at a dosage of 25 mg/kg daily (4 times the estimated human exposure level based on area under the plasma concentration-time curve (AUC)). In rats, decreased fetal weight and increased skeletal variations (e.g., reduced ossification of the sternebrae, vertebrae, and skull) were observed at a dosage of 15 mg/kg daily (6 times the estimated human exposure based on AUC) and were associated with maternal toxicity (reduced maternal body weight). In rabbits, reduced fetal weights, but no malformations or variations, were observed at dosages associated with maternal toxicity.

Tedizolid is distributed into milk in rats; it is not known whether the drug is distributed into human milk.

Tedizolid phosphate should be used with caution in nursing women.

Clinical studies did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults. Differences in tedizolid pharmacokinetics were not observed between geriatric and younger patients. Dosage adjustments are not needed in geriatric patients.