RIFADIN

Posology The daily dose of Rifadin, calculated from the patient’s body weight, should preferably be taken at least 30 minutes before a meal or 2 hours after a meal to ensure rapid and complete absorption. Tuberculosis Rifadin should be given with other effective anti-tuberculosis drugs to prevent the possible emergence of rifampicin-resistant strains of Mycobacteria.

Adults:

The recommended single daily dose in tuberculosis is 8 – 12 mg/kg.

Usual Daily dose:

Patients weighing less than 50 kg – 450 mg. Patients weighing 50 kg or more – 600 mg.

Children:

In children, oral doses of 10 – 20 mg/kg body weight daily are recommended, although a total daily dose should not usually exceed 600 mg. Leprosy 600 mg doses of rifampicin should be given once per month. Alternatively, a daily regimen may be used.

The recommended single daily dose is 10 mg/kg.

Usual daily dose:

Patients weighing less than 50 kg – 450 mg. Patients weighing 50 kg or more – 600 mg. In the treatment of leprosy, rifampicin should always be used in conjunction with at least one other anti-leprosy drug, Brucellosis, Legionnaires Disease or serious staphylococcal infections Adults: The recommended daily dose is 600 – 1200 mg given in 2 - 4 divided doses, together with another appropriate antibiotic to prevent the emergence of resistant strains of the infecting organisms.

Prophylaxis of meningococcal meningitis Adults: 600 mg twice daily for 2 days. Children (1 – 12 years): 10 mg/kg twice daily for 2 days. Children (3 months – 1 year): 5 mg/kg twice daily for 2 days.

Prophylaxis of Haemophilus influenzae Adults and children:

For members of households exposed to H. influenzae B disease when the household contains a child 4 years of age or younger, it is recommended that all members (including the child) receive rifampicin 20 mg/kg once daily (maximum daily dose 600 mg) for 4 days.

Index cases should be treated prior to discharge from hospital. Neonates (1 month): 10 mg/kg daily for 4 days.

Impaired liver function:

A daily dose of 8 mg/kg should not be exceeded in patients with impaired liver function.

Use in the elderly:

In elderly patients, the renal excretion of rifampicin is decreased proportionally with physiological decrease of renal function; due to compensatory increase of liver excretion, the terminal half-life in serum is similar to that of younger patients.

However, as increased blood levels have been noted in one study of rifampicin in elderly patients, caution should be exercised in using rifampicin in such patients, especially if there is evidence of impaired liver function. Method of administration For oral administration

The following CIOMS frequency rating is used, when applicable:

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); Not known (cannot be estimated from available data).

Reactions occurring with either daily or intermittent dosage regimens include:

System organ class Frequency Preferred Term Infections and Not known Pseudomembranous colitis infestations Influenza Common Thrombocytopenia with or without purpura, usually associated with intermittent therapy, but is reversible if drug is discontinued as soon as purpura occurs.

2% (53/573) (data between October 2007 and March 2010) and higher frequency is reported as 25% (19/76) (data between 2000 and 2010). 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.

Rifampicin should be given under the supervision of a respiratory or other suitably qualified physician. Cautions should be taken in case of renal impairment if dose > 600 mg/day. All tuberculosis patients should have pre-treatment measurements of liver function.

Adults treated for tuberculosis with rifampicin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate). Baseline tests are unnecessary in children unless a complicating condition is known or clinically suspected.

All patients with abnormalities should have follow up examinations, including laboratory testing, if necessary. Patients with impaired liver function should only be given rifampicin in cases of necessity, and then with caution and under close medical supervision.

In these patients, lower doses of rifampicin are recommended and careful monitoring of liver function, especially serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) should initially be carried out prior to therapy, weekly for two weeks, then every two weeks for the next six weeks.

If signs of hepatocellular damage occur, rifampicin should be withdrawn. Rifampicin should also be withdrawn if clinically significant changes in hepatic function occur. The need for other forms of antituberculosis therapy and a different regimen should be considered.

Urgent advice should be obtained from a specialist in the management of tuberculosis. If rifampicin is re-introduced after liver function has returned to normal, liver function should be monitored daily. In patients with impaired liver function, elderly patients, malnourished patients, and possibly, children under two years of age, caution is particularly recommended when instituting therapeutic regimens in which isoniazid is to be used concurrently with Rifadin.

If the patient has no evidence of pre-existing liver disease and normal pre- treatment liver function, liver function tests need only be repeated if fever, vomiting, jaundice or other deterioration in the patient’s condition occur.

Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions. In some patients hyperbilirubinaemia can occur in the early days of treatment. This results from competition between rifampicin and bilirubin for hepatic excretion.

An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patient’s clinical condition.

Cases of drug-induced liver injury, including fatal cases (especially when used in combination with other anti-tuberculosis drugs), have been reported in patients treated with rifampicin with an onset of a few days to a few months following treatment initiation.

Signs and symptoms include elevated serum hepatic enzymes, cholestatic jaundice, hepatitis, hepatotoxicity, hepatocellular injury, and mixed liver injury. Most patients recovered on discontinuation of rifampicin treatment; nevertheless, progression to acute liver failure requiring liver transplantation can occur.

The mechanism of rifampicin-induced liver injury is not clearly elucidated, but data indicate either an immuno-allergic mechanism or direct toxicity of metabolic products. Patients should be instructed to contact their physician in case symptoms suggestive of liver injury occur.

In such patients rifampicin should be discontinued and liver function should be assessed. Rifampicin should not be re-introduced in patients with an episode of hepatic injury during treatment with rifampicin for which no other cause of liver injury has been determined.

8) occurring with intermittent therapy (less than 2 - 3 times per week) patients should be closely monitored. Patients should be cautioned against interrupting treatment. Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D.

Isolated reports have associated porphyria exacerbation with rifampicin administration. Cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uremic syndrome (HUS), including fatal cases, have been reported with Rifadin capsules use.

If laboratory or clinical findings associated with TMA occur in a patient receiving Rifadin capsules, treatment should be discontinued and thorough evaluation for TMA performed, including platelet levels, renal function, serum lactate dehydrogenase (LDH) and a blood film for schistocytes (erythrocyte fragmentation).

ADAMTS13 activity and anti- ADAMTS13-antibody determination should be completed. If anti-ADAMTS13- antibody is elevated in conjunction with low ADAMTS13 activity, treatment with Rifadin capsules should not be resumed and patients should be treated accordingly (consider plasma exchange).

8). It is important to note that early manifestations of hypersensitivity, such as fever, lymphadenopathy or biological abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be advised to consult immediately their physician.

Rifadin capsules should be discontinued if an alternative aetiology for the signs and symptoms cannot be established. Paradoxical drug reaction After initial improvement of tuberculosis under therapy with Rifadin capsules, the symptoms may worsen again.

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