Andere Anthracycline u. verwandte Substanzen

Farmorubicin® 10 mg HL/-20 mg HL/-50 mg HL Trockensubstanz und Lösungsmittel (hochlöslich)

1 Inj.-Fl. enth.: Epirubicin-HCl 10 mg/20 mg/50 mg.

Farmorubicin® 10 mg HL/20 mg HL/-50 mg HL; -Lösung 10 mg/-20 mg/-50 mg

Mamma-, Ovarial-, Magen-, Pankreas-, hormonrefraktäre Prostata-, Rektum- und kleinzellige Bronchialkarzinome, Non-Hodgkin-Lymphome und Weichteilsarkome.

Methyl-4-hydroxybenzoat 2 mg/4 mg/10 mg, Lactose.

Weit. Bestandteile: physiolog. NaCl-Lsg. 5 ml/10 ml/25 ml.

Farmorubicin® Lösung 10 mg/-20 mg/-50 mg (Fertiglösung)
Zus.: 1 Inj.Fl. enth.: Epirubicin-HCl 10 mg/20 mg/50 mg.
Weit. Bestandteile: Natriumchlorid, Salzsäure, Wasser f. Inj.-zwecke.

D 5, Z 3

Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that clinically significant drug interactions via these mechanisms are unlikely.

No dose adjustment is required when co-administering with probenecid in patients with normal renal function. Co-administration of probenecid, a potent inhibitor of the anionic pathway of renal tubular secretion, results in an approximate 2-fold increase in exposure to the active metabolite of oseltamivir.

Oseltamivir has no kinetic interaction with amoxicillin, which is eliminated via the same pathway, suggesting that oseltamivir interaction with this pathway is weak.

Clinically important drug interactions involving competition for renal tubular secretion are unlikely, due to the known safety margin for most of these substances, the elimination characteristics of the active metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. However, care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin (e.g., chlorpropamide, methotrexate, phenylbutazone).

No pharmacokinetic interactions between oseltamivir or its major metabolite have been observed when co-administering oseltamivir with paracetamol, acetyl-salicylic acid, cimetidine or with antacids (magnesium and aluminium hydroxides and calcium carbonates).

The overall safety profile of Tamiflu is based on data from 2107 adult and 1032 paediatric patients treated for influenza, and on data from 2914 adult and 99 paediatric patients receiving Tamiflu for the prophylaxis of influenza in clinical trials.

In adults, the most commonly reported adverse drug reactions (ADRs) were vomiting and nausea in the treatment studies, and nausea and headache in the prevention studies. The majority of these ADRs were reported on a single occasion on either the first or second treatment day and resolved spontaneously within 1-2 days. In children, the most commonly reported adverse drug reaction was vomiting.

The ADRs listed in the tables below fall into the following categories: 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). ADRs are added to the appropriate category in the tables according to the pooled analysis from clinical trials. Within each frequency grouping ADRs are presented in the order of decreasing seriousness.

Treatment and prevention of influenza in adults and adolescents:

Most Frequent Adverse Drug Reactions ( 1 % in the oseltamivir group) in Studies Investigating Tamiflu for Treatment and Prevention of Influenza in Adults and Adolescents or Through Post-Marketing Surveillance

^a These are events identified during post-marketing surveillance. They were also reported in the pooled clinical studies at the incidence presented in the table above.

^b Subjects who experienced nausea alone; excludes subjects who experienced nausea in association with vomiting.

^c The difference between the placebo and oseltamivir groups was statistically significant.

Treatment and prevention of influenza in children:

The table below shows the most frequently reported ADRs from paediatric clinical trials.

Most Frequent Adverse Drug Reactions ( 1 % in the oseltamivir group in the treatment studies and 10 % in the oseltamivir group in the prophylaxis study) in Children

^a The prevention study did not contain a placebo arm, i.e. was an uncontrolled study.

^b Unit dose = weight-based dosing (see section 4.2).

^c Patients experienced ear ache and ear pain.

In general, the adverse event profile in children with pre-existing bronchial asthma was qualitatively similar to that of otherwise healthy children.

Further post marketing surveillance data on selected serious adverse drug reactions:

Immune system disorders

Frequency not known: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Psychiatric disorders and nervous system disorders

Frequency not known: influenza can be associated with a variety of neurologic and behavioural symptoms which can include events such as hallucinations, delirium, and abnormal behaviour, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.

In patients with influenza who were receiving Tamiflu, there have been postmarketing reports of convulsions and delirium (including symptoms such as altered level of consciousness, confusion, abnormal behaviour, delusions, hallucinations, agitation, anxiety, nightmares), in a very few cases resulting in accidental injury or fatal outcomes. These events were reported primarily among paediatric and adolescent patients and often had an abrupt onset and rapid resolution. The contribution of Tamiflu to those events is unknown. Such neuropsychiatric events have also been reported in patients with influenza who were not taking Tamiflu.

Eye disorders

Frequency not known: visual disturbance.

Cardiac disorders

Frequency not known: cardiac arrhythmia.

Gastrointestinal disorders

Frequency not known: gastrointestinal bleedings and hemorrhagic colitis.

Hepato-biliary disorders

Frequency not known: hepato-biliary system disorders, including hepatitis and elevated liver enzymes in patients with influenza-like illness. These cases include fatal fulminant hepatitis/hepatic failure.

Skin and subcutaneous tissue disorders

Frequency not known: severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and angioneurotic oedema.

Additional information on special populations:

There were no clinically relevant differences in the safety population of the elderly subjects who received oseltamivir or placebo compared with the adult population aged up to 65 years.

The adverse event profile in adolescents and patients with chronic cardiac and/or respiratory disease was qualitatively similar to those of healthy young adults.

Pharmacia & Upjohn

22 May 2009