RAXONE Film-coated tablet Ref.[9792] Active ingredients: Idebenone

Monitoring

Patients should be regularly monitored according to local clinical practice.

Hepatic or renal impairment

No data are available in these populations. Therefore, caution should be exercised when prescribing Raxone to patients with hepatic or renal impairment.

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.

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 were administered together. After repeated administration C_max 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.

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.

Raxone has no or negligible influence on the ability to drive and use machines.

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 postmarketing 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).

Infections and Infestations

Very common: Nasopharyngitis

Not known: Bronchitis

Blood and lymphatic system disorders

Not known: Agranulocytosis, anaemia, leukocytopenia, thrombocytopenia, neutropenia

Metabolism and nutrition disorders

Not known: Blood cholesterol increased, blood triglycerides increased

Nervous system disorders

Not known: Seizure, delirium, hallucinations, agitation, dyskinesia, hyperkinesia, poriomania, dizziness, headache, restlessness, stupor

Respiratory, thoracic and mediastinal disorders

Very common: Cough

Gastrointestinal disorders

Common: Diarrhoea

Not known: Nausea, vomiting, anorexia, dyspepsia

Hepatobiliary disorders

Not known: Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, gammalutamyltransferase increased, blood bilirubin increased, hepatitis

Skin and subcutaneous tissue disorders

Not known: Rash, pruritus

Musculoskeletal and connective tissue disorders

Common: Back pain

Not known: Pain in extremity

Renal and urinary disorders

Not known: Azotaemia, chromaturia

General disorders and administration site conditions

Not known: Malaise

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.