SIVEXTRO

Posology Adults, as well as adolescents and children weighing at least 35 kg The recommended dosage of tedizolid phosphate is 200 mg once daily for 6 days. Tedizolid phosphate tablets or powder for concentrate for solution for infusion may be used as initial therapy.

Patients who commence treatment on the parenteral formulation may be switched to the oral presentation when clinically indicated. Adolescents and children weighing less than 35 kg The recommended intravenous dosage of tedizolid phosphate is presented in Table 1.

In these patients, tedizolid phosphate is administered twice daily for 6 days, as an IV infusion over 1 hour.

Table 1:

Intravenous dosage of tedizolid phosphate for paediatric patients weighing less than 35 kg Weight Band (kg) Dosage Frequency 1 to less than 3 6 mg Twice daily 3 to less than 6 12 mg Twice daily 6 to less than 10 20 mg Twice daily 10 to less than 14 30 mg Twice daily 14 to less than 20 40 mg Twice daily 20 to less than 35 60 mg Twice daily If a dose is missed it should be given to the patient as soon as possible anytime up to 8 hours prior to the next scheduled dose.

If less than 8 hours remains before the next dose, then the physician should wait until the next scheduled dose. A double dose should not be given to compensate for a missed dose. 2). The clinical experience in patients ≥75 years is limited.

2). 2). Paediatric population Tedizolid phosphate is available as 200 mg tablets for adolescents and children weighing at least 35 kg. Method of administration Sivextro must be administered by intravenous infusion over a 60-minute period.

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3%), and were generally mild to moderate in severity. The safety profile was similar when comparing patients receiving intravenous tedizolid phosphate alone to patients who received oral administration alone, except for a higher reported rate of gastrointestinal disorders associated with oral administration.

Safety was additionally evaluated in a randomised, double-blind, multicenter study conducted in China, the Philippines, Taiwan, and the US, which included a total 292 adult patients treated with tedizolid phosphate 200 mg administered IV and/or oral once daily for 6 days, and 297 patients treated with linezolid 600 mg administered IV and/or oral every 12 hours for 10 days for ABSSSI.

7%) in tedizolid phosphate treated subjects than in the linezolid control group (0%), particularly among Asian patients. These findings suggest a higher frequency of infusion related reactions (phlebitis) than was observed in previous clinical studies with tedizolid phosphate.

Tabulated list of adverse reactions The following adverse reactions have been identified in two comparative pivotal Phase 3 studies and one post-authorisation study in adults treated with Sivextro (Table 2). Increased ALT, increased AST and liver function tests abnormal were the only adverse drug reactions reported in one comparative Phase 3 study in patients 12 to < 18 years of age.

Adverse reactions are classified by preferred term and System Organ Class, and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Table 2:

Adverse reactions by body system and frequency reported in clinical trials and/or post-marketing use System organ class Frequency Adverse reactions Infections and infestations Uncommon: Vulvovaginal mycotic infection, fungal infection, vulvovaginal candidiasis, abscess, Clostridioides difficile colitis, dermatophytosis, oral candidiasis, respiratory tract infection Uncommon: LymphadenopathyBlood and lymphatic system disorders Not known*: Thrombocytopenia* Immune system disorders Uncommon: Drug hypersensitivity Metabolism and nutrition disorders Uncommon: Dehydration, diabetes mellitus inadequate control, hyperkalaemia Psychiatric disorders Uncommon: Insomnia, sleep disorder, anxiety, nightmare Common: Headache, dizzinessNervous system disorders Uncommon: Somnolence, dysgeusia, tremor, paraesthesia, hypoaesthesia Eye disorders Uncommon: Vision blurred, vitreous floaters Cardiac disorders Uncommon: Bradycardia Vascular disorders Uncommon: Flushing, hot flush Respiratory, thoracic and mediastinal disorders Uncommon: Cough, nasal dryness, pulmonary congestion Common: Nausea, diarrhoea, vomitingGastrointestinal disorders Uncommon: Abdominal pain, constipation, abdominal discomfort, dry mouth, dyspepsia, abdominal pain upper, flatulence, gastro-oesophageal reflux disease, haematochezia, retching Common: Pruritus generalisedSkin and subcutaneous tissue disorders Uncommon: Hyperhidrosis, pruritus, rash, urticaria, alopecia, rash erythematous, rash generalised, acne, pruritus allergic, rash maculo-papular, rash papular, rash pruritic Musculoskeletal and connective tissue disorders Uncommon: Arthralgia, muscle spasms, back pain, limb discomfort, neck pain Renal and urinary disorders Uncommon: Urine odour abnormal Reproductive system and breast disorders Uncommon: Vulvovaginal pruritus System organ class Frequency Adverse reactions Common: Fatigue, infusion site reactions (phlebitis)General disorders and administration site conditions Uncommon: Chills, infusion site pain, irritability, pyrexia, infusion related reaction, peripheral oedema Investigations Uncommon: Grip strength decreased, transaminases increased, white blood cell count decreased * Based on post-marketing reports.

Patients with neutropenia The safety and efficacy of tedizolid phosphate in patients with neutropenia (neutrophil counts < 1 000 cells/mm3) have not been investigated. In an animal model of infection, the antibacterial activity of tedizolid was reduced in the absence of granulocytes.

The clinical relevance of this finding is unknown. 1). Mitochondrial dysfunction Tedizolid inhibits mitochondrial protein synthesis. Adverse reactions such as lactic acidosis, anaemia and neuropathy (optic and peripheral) may occur as a result of this inhibition.

These events have been observed with another member of the oxazolidinone class when administered over a duration exceeding that recommended for tedizolid phosphate. Myelosuppression Thrombocytopenia, decreased haemoglobin and decreased neutrophils have been observed during treatment with tedizolid phosphate.

Anaemia, leucopenia and pancytopenia have been reported in patients treated with another member of the oxazolidinone class and the risk of these effects appeared to be related to the duration of treatment. Most cases of thrombocytopenia occurred with treatment lasting longer than the recommended duration.

There may be an association with thrombocytopenia in patients with renal insufficiency. Patients who develop myelosuppression should be monitored and the benefit-risk should be re-evaluated. If treatment is continued, close monitoring of blood counts and appropriate management strategies should be implemented.

Peripheral neuropathy and optic nerve disorders Peripheral neuropathy, as well as optic neuropathy sometimes progressing to loss of vision, have been reported in patients treated with another member of the oxazolidinone class with treatment durations exceeding that recommended for tedizolid phosphate.

Neuropathy (optic and peripheral) has not been reported in patients treated with tedizolid phosphate at the recommended treatment duration of 6 days. All patients should be advised to report symptoms of visual impairment, such as changes in visual acuity, changes in colour vision, blurred vision, or visual field defect.

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