MYCOBUTIN

This medicine can be administered as a single, daily, oral dose at any time independently of meals. Posology Adults - prophylaxis of MAC infections in patients with HIV disease with CD4 counts lower than 75 cells/mcl: 300 mg (2 capsules) as a single agent.

- treatment of non-tuberculous mycobaterial disease: 450 - 600 mg (3 - 4 capsules) in combination regimens for up to 6 months after negative cultures are obtained. 5). - treatment of pulmonary tuberculosis: 150 - 450 mg (1 - 3 capsules) in combination regimens for at least 6 months.

In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, rifabutin should always be given in combination with other anti- mycobacterial drugs not belonging to the family of rifamycins. Paediatric population There are inadequate data to support the use of this medicine in children at the present time.

2 but no recommendation on a posology can be made. Elderly No specific recommendations for dosage alterations in the elderly are suggested.

The tolerability of rifabutin in multiple drug regimens, was assessed in both immunocompetent and immunocompromised patients, suffering from tuberculosis and non-tuberculous mycobacteriosis in long term studies with daily dosages up to 600 mg.

Bearing in mind that rifabutin was often given in these studies as part of a multidrug regimen it is not always possible to define with certainty a drug-event relationship. Treatment discontinuation was necessary only in a very few cases.

Adverse reactions identified through clinical trials or post-marketing surveillance by system organ class (SOC) are listed below in the following frequencies, 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’.

MedDRA System Organ Class Frequency Undesirable Effects Very common Leukopenia Common Anaemia Blood and lymphatic system disorders Uncommon Pancytopenia Agranulocytosis Lymphopenia Granulocytopenia Neutropenia White blood cell count decreased Neutrophil count decreased Thrombocytopenia Platelet count decreased Common RashImmune system disorders Uncommon Hypersensitivity Bronchospasm Eosinophilia Eye disorders Uncommon Uveitis Corneal deposits Common NauseaGastrointestinal disorders Uncommon Vomiting Hepatobiliary disorders Uncommon Jaundice Hepatic enzyme increased Skin and subcutaneous tissue disorders Uncommon Skin discolouration Common MyalgiaMusculoskeletal and connective tissue disorders Uncommon Arthralgia General disorders and administration site conditions Common Pyrexia Clostridioides difficile colitis is a mandated adverse reaction for the pharmacological class; this event was neither observed in the clinical trials nor in the spontaneous reporting for rifabutin.

Anaphylactic shock has occurred with other antibiotics of the same class. 4). Flu-like syndrome, chest pressure or pain with dyspnoea and rarely hepatitis and haemolysis have been reported. Anti-tuberculosis drug SCARs. 4). 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Before starting rifabutin prophylaxis, patients should be assessed to ensure that they do not have active disease caused by pulmonary tuberculosis or other mycobacteria. Prophylaxis against MAC infection may need to be continued throughout the patient's lifetime.

Rifabutin may impart a red-orange colour to the urine and possibly to skin and body secretions. Contact lenses, especially soft, may be permanently stained. Mild hepatic impairment does not require a dose modification. Rifabutin should be used with caution in cases of severe liver insufficiency.

Mild to moderate renal impairment does not require any dosage adjustment. Severe renal impairment (creatinine clearance below 30 ml/min) requires a dosage reduction of 50%. It is recommended that white blood cell and platelet counts and liver enzymes be monitored periodically during treatment.

Because of the possibility of occurrence of uveitis, patients should be carefully monitored when rifabutin is given in combination with clarithromycin (or other macrolides) and/or fluconazole (and related compounds). If such an event occurs, the patient should be referred to an ophthalmologist and, if considered necessary, rifabutin treatment should be suspended.

Uveitis associated with rifabutin must be distinguished from other ocular complications of HIV. HIV protease inhibitors act as substrates or inhibitors of CYP450 3A4 mediated metabolism. 5). Rifabutin is a CYP450 3A inducer. 5). For further recommendations, please refer to the most recent prescribing information of the antiretrovirals or contact the specific manufacturer.

Clostridioides difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including rifabutin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.

difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.

CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

8). If patients develop a skin rash they should be monitored closely and suspect drug(s) discontinued if lesions progress. Identifying the specific drug is difficult, as multiple anti-tuberculosis drugs are prescribed in association concurrently.

Specifically, for DRESS, a multi-system potential life-threatening SCAR, time to onset of the first symptoms may be prolonged. DRESS is a clinical diagnosis, and its clinical presentation remains the basis for decision making. , liver, bone marrow or kidney).

Excipients:

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

g. 1. 5). Due to insufficient clinical experience in pregnant and breast-feeding women, rifabutin should not be used in these patients.