Raxone

HOS-097183 · has-adverse-reaction-information · PDF-Seite 4

Summary of the safety profile The most commonly reported adverse reactions to idebenone are mild to moderate diarrhoea (usually not requiring the discontinuation of the treatment), nasopharyngitis, cough and back pain. Tabulated list of adverse reactions The following adverse reactions emerging from clinical trials in LHON patients or reported post- marketing in other indications are tabulated below. Frequency groupings are defined to the following convention: very common (≥1/10), common (≥1/100 to <1/10), not known (cannot be estimated from the available data). System Organ Class Preferred Term Frequency Infections and Nasopharyngitis Very common Infestations Bronchitis Not known Blood and lymphatic Agranulocytosis, anaemia, leukocytopenia, Not known system disorders thrombocytopenia, neutropenia Metabolism and nutrition Blood cholesterol increased, blood Not known disorders triglycerides increased 4  System Organ Class Preferred Term Frequency Nervous system disorders Seizure, delirium, hallucinations, agitation, dyskinesia, hyperkinesia, poriomania, Not known dizziness, headache, restlessness, stupor Respiratory, thoracic and Cough Very common mediastinal disorders Gastrointestinal disorders Diarrhoea Common Nausea, vomiting, anorexia, dyspepsia Not known Hepatobiliary disorders Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood Not known lactate dehydrogenase increased, gamma- glutamyltransferase increased, blood bilirubin increased, hepatitis Skin and subcutaneous Rash, pruritus Not known tissue disorders Musculoskeletal and Back pain Common connective tissue Pain in extremity

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097179 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-097178 · has-indication-information · PDF-Seite 2

Raxone is indicated for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON) (see section 5.1).

HOS-097181 · has-interaction-information · PDF-Seite 3

Data from in vitro studies have demonstrated that idebenone and its metabolite QS10 do not exert systemic inhibition of cytochrome P450 isoforms CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 at clinically relevant concentrations of idebenone or QS10. In addition, no induction of CYP1A2, CYP2B6 or CYP3A4 was observed. In vivo idebenone is a mild inhibitor of CYP3A4. Data from a drug-drug interaction study in 32 healthy volunteers indicate that on the first day of oral administration of 300 mg idebenone t.i.d., the metabolism of midazolam, a CYP3A4 substrate, was not modified when both medicinal products 3 were administered together. After repeated administration Cmax and AUC of midazolam were increased by 28% and 34%, respectively, when midazolam was administered in combination with 300 mg idebenone t.i.d. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving idebenone. Idebenone may inhibit P-glycoprotein (P-gp) with possible exposure increases of, e.g., dabigatran etexilate, digoxin or aliskiren. These medicines should be administered with caution in patients receiving idebenone. Idebenone is not a substrate for P-gp in vitro.

HOS-097182 · has-pregnancy-information · PDF-Seite 4

Pregnancy The safety of idebenone in pregnant women has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Idebenone should only be administered to pregnant women or women of child-bearing potential likely to become pregnant if it is considered that the benefit of the therapeutic effect outweighs any potential risk. Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of idebenone in milk (for details see 5.3). A risk to the suckling child cannot be excluded. . A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Raxone therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data concerning the effect of exposure to idebenone on human fertility.

HOS-097180 · has-warning-information · PDF-Seite 3

Monitoring Patients should be regularly monitored according to local clinical practice. Hepatic or renal impairment Caution should be exercised when prescribing Raxone to patients with hepatic or renal impairment. Adverse events have been reported in patients with hepatic impairment, which have resulted in temporary interruption or discontinuation of treatment. Chromaturia The metabolites of idebenone are coloured and may cause chromaturia, i.e. a reddish-brown discoloration of the urine. This effect is harmless, not associated with haematuria, and does not require any adaptation of dose or discontinuation of treatment. Caution should be exercised to ensure that the chromaturia does not mask changes of colour due to other reasons (e.g. renal or blood disorders). Lactose Raxone contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take Raxone. Sunset yellow Raxone contains sunset yellow (E110) which may cause allergic reactions.