Elements for a Public Summary

Transcription

1 VI.2 Elements for a Public Summary VI.2.1 Overview of disease epidemiology 400 mg film-coated tablets is a fluoroquinolone antibiotic with a broad spectrum of activity and bactericidal action. In the European Union (EU), film coated tablet are indicated for the treatment of acute bacterial sinusitis (ABS), acute exacerbation of chronic bronchitis (AECB), mild to moderate pelvic inflammatory disease (PID) and community acquired pneumonia (CAP) except severe cases. PhV Page 35/81

2 After cardiovascular disease, respiratory diseases rank second in terms of mortality, incidence, prevalence, and costs. The European prevalence of chronic obstructive pulmonary disease (COPD) ranges from <2% in France and the UK, to 9% in Spain. Moreover, a Europeanwide increase in the prevalence and mortality of COPD and other smoking-related diseases, particularly in women, is projected for the coming decades. Chronic bronchitis (CB), a component of COPD, usually associated with frequent exacerbations, is even more prevalent; as an example, 4.1% of the French population aged 25+ years develop this disease. Nonetheless, the prevalence of CB differs between countries. In a recent study of young European adults, the prevalence of CB in subjects aged years ranged from 0.7% in the UK to 9.7% in Spain, with the prevalence being directly associated with smoking prevalence. PID, the infection and inflammation of a woman s upper genital tract, is a frequent cause of infertility, ectopic pregnancy, and chronic pelvic pain among women of childbearing age. Surveillance data are sparse but suggest that PID is diagnosed in general practice in 1.7% of women aged years in the United Kingdom annually and in ~8% of US women and 15% of Swedish women in their lifetime, with 11 million US women treated annually. PID is thought to occur when microorganisms, frequently Chlamydia trachomatis or Neisseria gonorrhoeae, ascend from the lower genital tract and infect the uterus, fallopian tubes, and ovaries. However, PID has a multimicrobial etiology, and up to 70% of cases are nongonococcal and nonchlamydial. Anaerobic gram-negative rods, Mycoplasma genitalium, and bacterial vaginosis are also associated with PID. VI.2.2 Summary of treatment benefits The benefit risk balance of moxifloxacin containing medicinal products in oral formulations in the approved indications is favourable as second line indications. In acute bacterial sinusitis (ABS) and acute exacerbation of chronic bronchitis (AECB), moxifloxacin should only be used when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections or when these have failed to resolve the infection. In acquired pneumonia (CAP), it is to be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection. Serious safety concerns such as severe liver disorders, abnormal heart rhythms, severe diarrhoea and severe skin reactions will be specifically followed up by questionnaire if they occur during treatment with moxifloxacin. VI.2.3 Unknowns relating to treatment benefits The treatment benefits remain unknown for children and adolescents below the age of 18 years. VI.2.4 Summary of safety concerns Important identified risks Important identified risks Risk What is known Preventability Safety concern in lay language (medical term) If you experience allergic reactions, severe sudden aller- Brief summary in lay language In rare cases a severe, sudden allergic reaction (an an- Whether risk can be minimised or mitigated, and how the treatment and immediate PhV Page 36/81

3 gic reaction (Hypersensitivity, anaphylaxis) Serious bullous skin reactions Abnormal ECG changes, delayed conduction of electrical signals (Prolongation of QTc interval and potentially QTcprolongation related clinical conditions) Quinolone antibiotics, including [], may cause convulsions (Seizure) Tendon inflammation, tendon rupture (Tendinopathy) aphylactic reaction/shock) even with the first dose can be experienced following [] treatment. Symptoms include tightness in the chest, feeling dizzy, feeling sick or faint, or dizziness when standing up. In rare cases bullous skin reactions can be experienced following treatment with []. The physical findings of bullous drug eruptions vary greatly depending on the type of reaction. [] can change heart s ECG, especially in female and elderly. [], as quinolones does, can activate CNR problems in patient suffering from epilepsy or conditions makes likely to have convulsions [], may cause pain and inflammation of tendons, even within 48 hours of starting treatment and up to several months after discontinuing [] therapy. consultation with a doctor. the treatment and immediate consultation with a doctor. Yes. Drug should not be administered in patients born or with any condition with abnormal heart rhythm. Drug should not be administered in patient with salt imbalance in the blood (especially low levels of potassium or magnesium in the blood) or in patients with weak heart. In case that patient takes any medicine that decreases blood potassium level, doctor should be consulted before administration. As risk of heart problems may increase with increase of the dose, recommended dosage of should be followed. Monitoring of heart rhythm by ECG measure may be recommended during treatment Yes, by therapy discontinuation and treatment with appropriate drugs if needed. Yes, by immediate discontinuation of the treatment. At the first sign of any pain or inflammation [] treatment should be stopped and patient should rest the affected limb(s). PhV Page 37/81

4 Severe liver disorders (Hepatotoxicity) Diarrhea (including Severe diarrhea, containing blood and/or mucus) (Antibiotic associated diarrhea (including colitis) in hospital setting) Kidney problems (Renal failure) Problems with vision (Serious vision disorders) Depression, suicidal thoughts, mental health problems (Depression, suicidality, and psychosis) The risk of inflammation and rupture of tendons is increased in elderly or in patients taking corticosteroids. [] should not be administered if patient experienced previously problem with tendons related to quinolone antibiotics treatment. [] should not be administered in patient with severe liver disease or increased liver enzymes (transaminases) higher than 5 times the upper normal limit. [] may cause a rapid and severe inflammation of the liver which could lead to life-threatening liver failure Diarrhea can be developed whilst or after taking antibiotics including []. [] should be used with caution in elderly persons with renal disorders if they are unable to maintain adequate fluid intake. [] may cause double or blurred vision. Sudden, transient loss of vision may also be occurred. Quinolone antibiotics, including [] can cause mental health problems, when administered for the first time. In very rare cases depression or mental health problems have led to suicidal thoughts and selfendangering behaviour such as suicide attempts. Avoid any unnecessary exercise, as this might increase the risk of a tendon rupture the treatment. Doctor should be advised if patient suddenly feel unwell and/or are being sick and also if has yellowing of the whites of the eyes, dark urine, itching of the skin, a tendency to bleed or liver induced disease of the brain the treatment if diarrhea becomes severe or persistent or if stool contains blood or mucus. should not be administered with medicines that stop or slow down bowel movement. Yes, if drink plenty whilst taking [] Yes, by consulting immediately an eye specialist in case that patient s eyesight becomes impaired the drug PhV Page 38/81

5 Aneamia, low white blood cell count, low numbers of special white blood cells, decrease or increase of special blood cells necessary for blood clotting, increased specialised white blood cells, decreased blood clotting (Serious haematological disorders) Abnormal muscle fatigue leading to weakness and in serious cases paralysis (Exacerbation of myasthenia gravis) Low red blood cell count, low white blood cells count, low numbers of special white blood cells (neutrophils), decrease or increase of special blood cells necessary for blood clotting, increased specialised white blood cells (eosinophils), decreased blood clotting are adverse events been experienced in a frequency of up to 1 in 100 people In patients already suffering from abnormal muscle fatigue taking [] may worsen the symptoms of the disease. Yes. In case that patient takes medicines to thin his blood (oral anticoagulants such as warfarin), more frequently monitoring of the INR may be requested. If necessary, the oral anticoagulant dosage should be adjusted as appropriate. Yes, by immediate consulting of the doctor Important potential risks Important potential risks Risk Very slow heart rhythm (Bradycardia) Muscle reactions with muscle cell damage (Rhabdomyolysis, myositis, and myopathy) Troubles associated with the nervous system such as pain, burning, tingling, numbness and/or weakness in extremities (Peripheral neuropathy) What is known (Including reason why it is considered a potential risk) should be used with caution in patients with heart rhythms problems because can cause changes in the ECG. In addition, co administration of [] with other medicines that can lower blood potassium levels (e.g. some diuretics, some laxatives and enemas [high doses] or corticosteroids [anti-inflammatory drugs], amphotericin B) or cause a slow heart rate, can also increase the risk of serious heart rhythm disturbances. This adverse event is been reported following treatment with other quinolone antibiotics, but might possibly also occur during treatment with [] In rare cases troubles associated with the nervous system such as pain, burning, tingling, numbness and/or weakness in extremities have been reported. Therefore, doctor should be immediately informed about these symptoms in aim to decide on the discontinuation or not of the treatment Bacteria against [] is active (Selection of drug resistant isolates) [] is used in patients 18 years of age and older for treating the following bacterial infections caused by bacteria against which is active and only when usual antibiotics cannot be used or have not worked: Infection of the sinuses PhV Page 39/81

6 Sudden worsening of long term inflammation of the airways Infection of the lungs (pneumonia) acquired outside the hospital (except severe cases) Mild to moderate infections of the female upper genital tract (pelvic inflammatory disease), including infections of the fallopian tubes and infections of the uterus mucous membrane. [] is not sufficient on it s own for treating this kind of infection. Therefore, another antibiotic in addition to [] should be prescribed by the doctor for the treatment of infections of the female upper genital tract. If there is no improvement in symptoms after 3 days of treatment, doctor should be consulted again. If the following bacterial infections have shown improvement during initial treatment with [] solution for infusion, [] tablets may also be prescribed by your doctor to complete the course of therapy: Infection of the lungs (pneumonia) acquired outside the hospital, Infections of the skin and soft tissue. [] tablets should not be used to initiate therapy for any type of infections of the skin and soft tissue or in severe infections of the lungs. Important missing information Important missing information Risk usage together with QTc-prolonging drugs or in patients with concurrent risk factors for QTc prolongation Use of moxifloxacin in children and growing adolescents What is known An additive effect on QT interval prolongation of moxifloxacin and other medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. Therefore, co-administration of moxifloxacin with any of the following medicinal products is contraindicated: - anti-arrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide) - anti-arrhythmics class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) - antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride) - tricyclic antidepressive agents - certain antimicrobial agents (saquinavir, sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine) - certain antihistaminics (terfenadine, astemizole, mizolastine) - others (cisapride, vincamine IV, bepridil, diphemanil). is contraindicated in children and adolescents (< 18 years). Efficacy and safety of moxifloxacin in children and adolescents have not been established. PhV Page 40/81

7 Arthropathy (in paediatric patients) Quinolones are known to cause lesions in the cartilage of the major diarthrodial joints in immature animals. The lowest oral dose of moxifloxacin causing joint toxicity in juvenile dogs was four times the maximum recommended therapeutic dose of 400 mg (assuming a 50 kg bodyweight) on a mg/kg basis, with plasma concentrations two to three times higher than those at the maximum therapeutic dose. Due to adverse effects on the cartilage in juvenile animals the use of moxifloxacin in children and adolescents < 18 years is contraindicated VI.2.5 Summary of risk minimisation measures by safety concern This medicine has no additional risk minimisation measures. VI.2.6 Planned post authorisation development plan No post-authorisation safety or efficacy studies are ongoing or are planned to be conducted for moxifloxacin. VI.2.7 Summary of changes to the Risk Management Plan over time Major changes to the Risk Management Plan over time Version Date Safety Concerns Comment MAY- NA Initial version SEP Hypersensitivity, anaphylaxis 2. Prolongation of QTc interval and potentially QTc-prolongation related clinical conditions 3. Seizure 4. Tendinopathy 5. Hepatotoxicity 6. Antibiotic associated diarrhea (including colitis) in hospital setting 7. Renal failure 8. Serious vision disorders 9. Serious bullous skin reactions (not in version 1.0) 10. Depression, suicidality, and psychosis 11. Serious haematological disorders 12. Exacerbation of myasthenia gravis 13. Bradycardia 14. Rhabdomyolysis, myositis, and myopathy 15. Peripheral neuropathy 16. Selection of drug resistant isolates 17. usage together with QTc- Updated with recommendations received in the assessment of RMP version 1.0. Updates to: Section V.1 Section VI.2.1 Section VI.2.2 Section VI 2.4 PhV Page 41/81

8 Version Date Safety Concerns Comment prolonging drugs or in patients with concurrent risk factors for QTc prolongation 18. Use of moxifloxacin in children and growing adolescents 19. Arthropathy (in paediatric patients) PhV Page 42/81