Levviax

e. two 400 mg tablets once a day. The tablets should be swallowed whole with a sufficient amount of water. The tablets may be taken with or without food. 4). In patients of 18 years and older, according to the indication, the treatment regimen will be: - Community-acquired pneumonia: 800 mg once a day for 7 to 10 days, - Acute exacerbation of chronic bronchitis: 800 mg once a day for 5 days, - Acute sinusitis: 800 mg once a day for 5 days, - Tonsillitis/pharyngitis caused by Streptococcus pyogenes: 800 mg once a day for 5 days.

In patients of 12 to 18 years old, the treatment regimen will be: - Tonsillitis/pharyngitis caused by Streptococcus pyogenes: 800 mg once a day for 5 days.

In the elderly:

Medicinal Product no longer authorised3 No dosage adjustment is required in elderly patients based on age alone. 2).

Impaired renal function:

No dosage adjustment is necessary in patients with mild or moderate renal impairment. Levviax is not recommended as first choice in patients with severe renal impairment (creatinine clearance <30ml/min) or patients with both severe renal impairment and co-existing hepatic impairment, as an optimal dosage format (600 mg) is not available.

If telithromycin treatment is deemed necessary, these patients may be treated with alternating daily doses of 800 mg and 400 mg, starting with the 800 mg dose. 2).

Impaired hepatic function:

No dosage adjustment is necessary in patients with mild, moderate, or severe hepatic impairment, unless renal function is severely impaired, however the experience in patients with impaired hepatic function is limited. 2).

In 2461 patients treated by Levviax in phase III clinical trials, the following undesirable effects possibly or probably related to telithromycin have been reported. This is shown below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System organ class 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) Blood and the lymphatic system disorders Eosinophilia Nervous system disorders Dizziness, headache, disturbance of taste Vertigo somnolence, nervousness, insomnia, Transient loss of consciousness, paraesthesia Parosmia Eye disorders Blurred vision Diplopia Cardiovascular disorders Flush Palpitations Atrial arrhythmia, hypotension, bradycardia Gastro-intestinal disorders Diarrhoea Nausea, vomiting, gastrointestinal pain, flatulence Oral Candida infection, stomatitis anorexia, constipation, , Pseudomembranous colitis Hepato-biliary disorders Increase in liver enzymes (AST, ALT, alkaline phosphatase) Hepatitis Cholestatic jaundice Skin and subcutaneous tissue disorders Rash, urticaria, pruritus Eczema Erythema multiforme Musculoskeletal, connective tissue Muscle cramps Reproductive system disorders Vaginal Candida infection Visual disturbances (<1%) associated with the use of Levviax, including blurred vision, difficulty focusing and diplopia, were mostly mild to moderate.

They typically occurred within a few hours after the first or second dose, recurred upon subsequent dosing, lasted several hours and were fully reversible either during therapy or following the end of treatment. 7). In clinical trials the effect on QTc was small (mean of approximately 1 msec).

0% of cases, respectively. No patient in either group developed a ∆QTc >60 msec. There Medicinal Product no longer authorised8 were no reports of TdP or other serious ventricular arrhythmias or related syncope in the clinical program and no subgroups at risk were identified.

As with macrolides, due to a potential to increase QT interval, Levviax should be used with care in patients with coronary heart disease, a history of ventricular arrhythmias, uncorrected hypokalaemia and or hypomagnesaemia, bradycardia (<50 bpm), or during concomitant administration of Levviax with QT interval prolonging agents or potent CYP 3A4 inhibitors such as protease inhibitors and ketoconazole.

As with nearly all antibacterial agents, diarrhoea, particularly if severe, persistent and /or bloody, during or after treatment with Levviax may be caused by pseudomembranous colitis. If pseudomembranous colitis is suspected, the treatment must be stopped immediately and patients should be treated with supportive measures and/or specific therapy.

8). Alterations in hepatic enzymes have been commonly observed in clinical studies with telithromycin. 8). These hepatic reactions were observed during or immediately after treatment, and in most cases were reversible after discontinuation of telithromycin.

Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen. 2). Levviax may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation.

Visual disturbances included blurred vision, difficulty focusing, and diplopia. Most events were mild to moderate; however, severe cases have been reported. 8). 8). Consideration may be given to taking Levviax at bedtime, to reduce the potential impact of visual disturbances and loss of consciousness.

Levviax should not be used during and 2 weeks after treatment with CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s wort). 5). Levviax is an inhibitor of CYP3A4 and should only be used under specific circumstances during treatment with other medicinal products that are metabolised by CYP3A4.

4). Hypersensitivity to the active substance, to any of the macrolide antibacterial agents, or to any of the excipients. Levviax must not be used in patients with previous history of hepatitis and/or jaundice associated with the use of telithromycin.

5). Levviax should not be used concomitantly with simvastatin, atorvastatin and lovastastin. 5). Levviax is contraindicated in patients with a history of congenital or a family history of long QT syndrome (if not excluded by ECG) and in patients with known acquired QT interval prolongation.

In patients with severely impaired renal and/or hepatic function, concomitant administration of Levviax and strong CYP3A4 inhibitors, such as protease inhibitors or ketoconazole, is contraindicated.