Quinsair · 4.1 Therapeutic indications · 1

HOS-216594 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The most frequently reported adverse reactions were cough/productive cough (54%), dysgeusia (30%) and fatigue/asthenia (25%). Tabulated list of adverse reactions reported with Quinsair The adverse reactions with at least a reasonable possibility of a causal relationship with Quinsair are presented according to the MedDRA System Organ Classification. The adverse drug reactions are ranked by frequency with the most frequent reactions first. The frequency categories are defined using the following convention: 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); and not known (cannot be estimated from the available data). 8 System organ class Very common Common Uncommon Infections and Vulvovaginal mycotic Oral fungal infection infestations infection Blood and lymphatic Anaemia*, system disorders Neutropenia* Immune system Hypersensitivity* disorders Metabolism and Anorexia* nutrition disorders Psychiatric Insomnia* Anxiety*, disorders1 Depression* Nervous system Dysgeusia Headache, Hyposmia*, disorders1 Dizziness* Somnolence*, Peripheral neuropathy Eye disorders1 Visual disturbance* Ear and labyrinth Tinnitus* Hearing loss* disorders1 Cardiac disorders** Tachycardia* Respiratory, thoracic Cough/productive Dysphonia Bronchospasm***, and mediastinal cough, Bronchial disorders Dyspnoea, hyper-reactivity, Changes in bronchial Obstructive airways

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216590 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance, other quinolones or to any of the excipients listed in section 6.1; • History of tendon disorders related to fluoroquinolone administration; • Epilepsy; • Pregnancy; • Breast-feeding.

HOS-216589 · has-indication-information · PDF-Seite 2

Quinsair is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in adult patients with cystic fibrosis (CF, see section 5.1). Consideration should be given to official guidance on the appropriate use of antibacterial medicinal products.

HOS-216592 · has-interaction-information · PDF-Seite 7

Effect of other medicinal products on levofloxacin Levofloxacin is primarily excreted unchanged in the urine and metabolism is minimal (see section 5.2). Interactions with CYP inhibitors or inducers are thus not expected. Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. However, a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other substances which lower the seizure threshold. Levofloxacin concentrations were about 13% higher in the presence of fenbufen than when administered alone. Probenecid and cimetidine The renal clearance of levofloxacin was reduced by cimetidine (24%) and probenecid (34%). This is because both active substances are capable of blocking the renal tubular secretion of levofloxacin. However, at the tested doses in the study, the statistically significant kinetic differences are unlikely to be of clinical relevance. Caution should be exercised when levofloxacin is coadministered with active substances that affect the tubular renal secretion such as probenecid and cimetidine, especially in patients with renal impairment. Other relevant information Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with the following active substances: calcium carbonate, digoxin, glibenclamide and ranitidine. Effect of levofloxacin on other medicinal products CYP1A2 substrates In a pharmacokinetic interaction study, levofloxacin did not affect the pharmacokinetics of theophylline (which is a probe substrate for CYP1A2) indicating that levofloxacin is not a CYP1A2 inhibitor. CYP2C9 substrates An in vitro study indicated a low potential for interaction between levofloxacin and CYP2C9 substrates. Interactions mediated by effects on transporters In vitro studies demonstrated that inhibition of the key transporters associated with drug disposition in the kidney (organic anion-transporting polypeptide-1B1 (OATP1B1), OATP1B3, organic anion transporter-1 (OAT1), OAT3 and organic cationic transporter-2 (OCT2)) at exposures following inhalation of 240 mg levofloxacin twice daily is low. Furthermore, clinical data do not suggest interaction with P-glycoprotein (P-gp) substrates such as digoxin. Ci

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216593 · has-pregnancy-information · PDF-Seite 8

Pregnancy There is a limited amount of data from the use of levofloxacin in pregnant women. Animal studies with levofloxacin do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). However, in the absence of human data and findings in non-clinical studies suggesting a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, use of Quinsair is contraindicated during pregnancy (see sections 4.3 and 5.3). Breast-feeding There is insufficient information on the excretion of levofloxacin/metabolites in human milk; however, other fluoroquinolones are excreted in breast milk. In the absence of human data and findings in non-clinical studies suggesting a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, use of Quinsair is contraindicated in breast-feeding women (see sections 4.3 and 5.3). Fertility Levofloxacin caused no impairment of fertility or reproductive performance in rats (see section 5.3).

HOS-216591 · has-warning-information · PDF-Seite 3

The use of levofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with levofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3). Hypersensitivity reactions Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. including angioedema and anaphylactic shock). Severe bullous reactions Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with systemic administration of levofloxacin (see section 4.8). Hepatobiliary disorders Cases of hepatic necrosis up to fatal hepatic failure have been reported with systemically administered levofloxacin, primarily in patients with severe underlying diseases (e.g. sepsis, see section 4.8). 3 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. QT interval prolongation Caution should be taken when using fluoroquinolones, including levofloxacin, in patients with known risk factors for prolongation of the QT interval (see sections 4.5, 4.8 and 4.9) such as, for example: • Congenital long QT syndrome. • Concomitant use of active substances that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics). • Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia). • Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia). Elderly patients and women may be more sensitive to QTc-prolonging medicinal products. Therefore, caution should be taken when using fluoroquinolones, including levofloxacin, in these populations. Patients predisposed to seizures Quinolones may lower the seizure threshold and may trigger seizures (see section 4.8). Levofloxacin is contraindicated in patients with a history of epilepsy (see section 4.3) and, as with other quinolones, should be used with extreme caution in patients predisposed to seizures or on concomitant treatment with active substances that lower the cerebral seizure threshold, such as theophylline (see section 4.5). Psychotic reaction

Auszug; vollständigen Abschnitt im Original lesen.