Source: Υπουργείο Υγείας (CY) Revision Year: 2018 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Rifasynt is contraindicated in patients who
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.
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 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 If signs of hepatocellular damage occur, rifampicin should be withdrawn.
Rifampicin should also be withdrawn if clinically significant changes in hepatic function occur.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 Rifasynt. 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 hyperbilirubinsemia 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.
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.
Because of the possibility of immunological reaction including anaphylaxis (see section 4.8) occurring with intermittent therapy (less than 2 to 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.
Rifasynt capsules may produce a reddish coloration of the urine, sweat, sputum and tears, and the patient should be forewarned of this. Soft contact lenses have been permanently stained.
All patients with abnormalities should have follow up examinations, including laboratory testing, if necessary.
Rifampicin is a potent inducer of certain cytochrome P-450 enzymes. Coadministration of rifampicin with other drugs that are also metabolised through these cytochrome P-450 enzymes may accelerate the metabolism and reduce the activity of these other drugs. Therefore, caution should be used when prescribing rifampicin with drugs metabolised by cytochrome P-450. To maintain optimum therapeutic blood levels, dosages of drugs metabolised by these enzymes may require adjustment when starting or stopping concomitantly administered rifampicin.
Examples of drugs metabolised by cytochrome P-450 enzymes are:
Patients on oral contraceptives should be advised to use alternative, non-hormonal methods of birth control during Rifasynt therapy. Also diabetes may become more difficult to control.
When rifampicin is given concomitantly with the combination saquinavir/ritonavir, the potential for hepatotoxicity is increased. Therefore, concomitant use of Rifasynt with saquinvir/ritonavir is contraindicated (see section 4.3).
When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.
Concurrent use of ketoconazole and rifampicin has resulted in decreased serum concentrations of both drugs.
Concurrent use of rifampicin and enalapril has resulted in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments should be made if indicated by the patient’s clinical condition.
Concomitant antacid administration may reduce the absorption of rifampicin. Daily doses of rifampicin should be given at least 1 hour before the ingestion of antacids.
When rifampicin is given concomitantly with either halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampicin andhalothane should be avoided. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.
If p-aminosalicylic acid and rifampicin are both included in the treatment regimen, they should be given not less than eight hours apart to ensure satisfactory blood levels.
Plasma concentrations of morphine may be reduced by rifampicin. The analgesic effect of morphine should be monitored and doses of morphine adjusted during and after treatment with rifampicin.
Therapeutic levels of rifampicin have been shown to inhibit standard microbiological assays for serum folate and Vitamin B12. Thus alternative assay methods should be considered. Transient elevation of BSP and serum bilirubin has been reported. Rifampicin may impair biliary excretion of contrast media used for visualization of the gallbladder, due to competition for biliary excretion. Therefore, these tests should be performed before the morning dose of rifampicin.
At very high doses in animals rifampicin has been shown to have teratogenic effects. There are no well controlled studies with rifampicin in pregnant women. Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin, alone or in combination with other antituberculosis drugs, on the human foetus is not known. Therefore, Rifasynt should be used in pregnant women or in women of child bearing potential only if the potential benefit justifies the potential risk to the foetus. When Rifasynt is administered during the last few weeks of pregnancy it may cause post-natal haemorrhages in the mother and infant for which treatment with Vitamin K1 may be indicated.
Rifampicin is excreted in breast milk, patients receiving rifampicin should not breast feed unless in the physician’s judgement the potential benefit to the patient outweighs the potential risk to the infant.
No studies on the effects on the ability to drive and use machines have been performed.
Reactions occurring with either daily or intermittent dosage regimens include:
Rare: Disseminated intravascular coagulation has also been rarely reported.
Very rare: Agranulocytosis has been reported very rarely reported.
Not known:
Not known:
Not known: Hepatitis can be caused by rifampicin and liver function tests should be monitored (see section 4.4).
Uncommon: Urticaria and more serious hypersensitivity cutaneous reactions have occurred but are uncommon.
Rare: Exfoliate dermatitis, pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, Lyell’s syndrome and vasculitis has been reported rarely.
Not known: Cutaneous reactions which are mild and self-limiting and do not appear to be hypersensitivity reactions. Typically they consist of flushing and itching with or without a rash.
Rare: Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.
Rare: Psychoses have been rarely reported.
Reactions usually occurring with intermittent dosage regimens and probably of immunological origin include:
Not known:
If serious complications arise, e.g. renal failure, thrombocytopenia or haemolytic anaemia, rifampicin should be stopped and never restarted.
Occasional disturbances of the menstrual cycle have been reported in women receiving long-term anti-tuberculosis therapy with regimens containing rifampicin.
Rifampicin may produce a reddish discolouration of the urine, sputum and tears. The patient should be forewarned of this.
Soft contact lenses may be permanently stained.
Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
None known.
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