Rifampicin leprosy

Rifampicin has also shown antiviral activity but at levels 500—1000 times greater than required for antibacterial activity (130,140—142). Rifampicin shows promise in the treatment of leprosy (130,143). A large number of rifampicinlike derivatives are potent inhibitors of reverse transcriptase (123,144-148). 

Dapsone (diaminodiphenylsulphone Fig. 5.16F) is used specifically in the treatment of leprosy. However, because resistance to dapsone is unfortunately now well known, it is recommended that dapsone be used in conjunction with rifampicin and clofazimine. 

Clofazimine is a substituted iminophenazine that was first proposed for treating leprosy in 1962 however, it entered into medical practice toward the end of the 1980s. The mechanisms of its action is not definitively known, although there is the assumption that it can inhibit the formation of matrixes with DNA, which leads to a delay in the growth of mycobacteria. Clofazimine exhibits a bactericidal effect between that of dapsone and rifampicin. Synonym of this drug is lamprene. 

Rifampicin, a semisynthetic derivative of the antimicrobial agent rifamycin B obtained from Strep-tomyces mediterranei, is bactericidal for intra- and extracellular bacteria. Bacterial RNA synthesis is inhibited by binding to the beta-subunit of DNA-dependent RNA polymerase. Human polymerases are not affected. It has activity against gram-positive and gram-negative cocci, chlamydia as well as mycobacteria. It is used in combination with dapsone for leprosy. 

Agents used for the management of leprosy are dap-sone, rifampicin, clofazimine and recently thalido-... 

The rifamycins, a class of antibacterials isolated from Streptomyces mediterranei, contain a macrocyclic ring bridging across two nonadjacent positions on an aromatic system. Rifampicin (9.96), a semisynthetic derivative of rifamycin, is a drug of choice in the treatment of tuberculosis as well as leprosy, either alone or in combination with other drugs. Rifampicin is much safer than other antituberculotics since it inhibits DNA-directed RNA polymerase in bacteria but not in mammals. Another rifamycin, rifabutin (9.97), is a spiroimidazopiperidyl derivative of the rifamycin. 

PABA) incorporation into folic acid (inhibition of folate synthesis). In large proportion of Mycobacterium leprae infections e.g. in lepromatous leprosy, resistance can develop, so combination of dapsone, rifampicin and clofazimine is used in initial therapy. 

Clofazimine is phenazine dye and used as alternative to dapsone in dapsone intolerant/resistant cases and in combination with dapsone and rifampicin in the multidrug treatment of leprosy. It s probable mechanism of action is its involvement in DNA binding, it may interfere with template function of DNA. 

It is bactericidal and highly effective in leprosy. A single monthly dose of 600 mg may be used in combination with other antileprosy drugs to avoid any probable risk of rifampicin resistant M. leprae. 

Choice of antimicrobial follows automatically from the clinical diagnosis because the causative organism is always the same, and is virtually always sensitive to the same drug, e.g. meningococcal septicaemia (benzylpenicillin), some haemolytic streptococcal infections, e.g. scarlet fever, erysipelas (benzylpenicillin), typhus (tetracycline), leprosy (dapsone with rifampicin). 

Alycobocteriiim leprae (leprosy) Actinomycetes dapsone + rifampicin clofazimine ethionamide or cycloserine... 

Rifampicin has bactericidal activity against the tubercle bacillus, comparable to that of isoniazid. It is also used in leprosy. 

It acts by inhibiting RNA synthesis, bacteria being sensitive to this effect at much lower concentrations than mammalian cells it is particularly effective against mycobacteria that lie semidormant within cells. Rifampicin has a wide range of antimicrobial activity. Other uses include leprosy, severe Legionnaires disease (with erythromycin or ciprofloxacin), the chemoprophylaxis of meningococcal meningitis, and severe staphylococcal infection (with flucloxacillin or vancomycin). 

When thionamides are used in combination with rifam-picin, hepatotoxicity is more common and severe (18,19). There was a 13% incidence of hepatotoxicity in patients with multibaciUary leprosy treated with dap-sone, rifampicin, and protionamide 10 mg/kg/day, and a 17% incidence in 110 patients treated with dapsone, rifampicin, and protionamide 5 mg/kg/day however, although the lower dose of protionamide did not reduce the incidence of hepatotoxicity, it did reduce its severity (20). Protionamide does not affect the pharmacokinetics of rifampicin (21). 

Mathur A, Venkatesan K, Girdhar BK, Bharadwaj VP, Girdhar A, Bagga AK. A study of drug interactions in leprosy—1. Effect of simultaneous administration of prothionamide on metabolic disposition of rifampicin and dapsone. Lepr Rev 1986 57(l) 33-7. 

A flu-like illness, with fever, headache, malaise, and bone pain, can occur shortly after the administration of rifampicin, and was observed in a man who had taken rifampicin 600 mg monthly for multibacillary leprosy (10). However, the reaction usually occurs with higher doses given weekly or twice weekly. The usual procedure is to reduce the dose or increase the frequency of treatment. Antipyretic drugs can be used to provide symptomatic relief. 

A 46-year-old woman died of severe disseminated intravascular coagulation after her third monthly dose of rifampicin, given with daily dapsone for the treatment of leprosy (41). 

Hepatotoxicity of combined therapy for leprosy has been reported in 39 patients treated with dapsone, pro-tionamide, and rifampicin. There were similar findings in 50 patients treated with dapsone, clofazimine, rifampicin, and protionamide. Deaths probably related to the drngs occurred in both groups after 3-4 months of treatment... 

There is no evidence that rifampicin causes clinically significant deleterious effects on the immune system in humans (78), whereas it can cause immunosuppression in animals (79). Rifampicin partially suppresses cutaneous hypersensitivity to tuberculin and T cell function (80). In 33 patients with leprosy treated with a rifampicin drug combination, a flu-like illness or antibodies to rifampicin-conjugated proteins were not observed (81). 

The interaction of rifampicin with dapsone has been reviewed (105). In seven patients with leprosy, rifampicin shortened the half-hfe of dapsone by 50% (116). 

Ji BH, Chen JK, Wang CM, Xia GA. Hepatotoxicity of combined therapy with rifampicin and daily prothiona-mide for leprosy. Lepr Rev 1984 55(3) 283-9. 

Kar HK, Roy RG. Reversible acute renal failure due to monthly administration of rifampicin in a leprosy patient. Indian J Lepr 1984 56(4) 835-9. 

Krishna DR, Appa Rao AVN, Ramanakar TV, Prabhakar MC. Pharmacokinetic interaction between dap-sone and rifampicin (rifampin) in leprosy patients. Drug Dev Ind Pharm 1986 12 443-9. 

The occurence of drug interactions involving clofazimine have also been investigated. Most of the studies show that clofazimine does not exert any effect on dapsone excretion in leprosy patients (Balakrishnan and Seshadri, 1981 Zuidema et al., 1986). Clofazimine has been shown to significantly reduce the absorption of simultaneously administered rifampicin, resulting in delayed time to reach peak serum concentration and increased t j. No significant changes were seen in Cmax or AUC (Mehta et al., 1986). 

A study in untreated patients with leprosy showed that the pharmacokinetics of a single 600-mg dose of rifampicin were not markedly changed by 1 g of metamizole sodium (dipyrone), but peak serum rifampicin levels occurred sooner (at 3 instead of 4 hours) and were about 50% higher. ... 

The interaction between dapsone and rifampicin is established but of uncertain clinical importance. Concurrent use should be well monitored to confirm that treatment is effective. It may be necessary to raise the dosage of dapsone. It has been pointed out that there is the risk of treatment failures for Pneumocystis pneumonia as well as for leprosy. Also be alert for any evidence of methaemoglobinaemia. 

Pieters FAJM, Woonink F, Zuidema J. Influence of once-monthly rifampicin and daily clofazimine on the pharmacokinetics of dapsone in leprosy patients in Nigeria. EurJ CUn Pharmacol (1988) 34,73-6. 

A study in 7 patients with leprosy given single doses of dapsone 100 mg and rifampici n 600 mg, alone or together, found that while the pharmacokinetics of rifampicin were not significantly changed, the half-life of the dapsone was roughly halved and the AUC was reduced hy about 20%. ... 

Jaundice, liver damage and deaths have occurred in other leprosy patients given rifampicin and protionamide or ethionamide. Protionamide does not affect the pharmacokinetics of either dapsone or rifampicin. ... 

Clofazimine 100 mg daily, given to 15 patients with leprosy taking ri-fampiein 600 mg daily and dapsone 100 mg daily, had no effect on the pharmaeokineties of rifampiein. A single-dose study similarly found that the bioavailability of elofazimine remained unaltered when rifampicin was given, although a reduction in the rate of absorption was seen4 No special precautions would seem to be necessary on concurrent use. 

Venkatesan K, Mathur Girdhar BK, Bharadwaj VP. The effect of clofazimine on the pharmacokinetics of rifampicin and dapsone in leprosy. JAntimicrob Chemother (1986) 18, 715-18. 

Mehta J, Gandhi IS, Sane SB, Wamburkar MN. Effect of clofazimine and dapsone on rifampicin (Lositril) pharmacokinetics inmultibacillary andpaucibacillary leprosy cases. Indian JLepr( 9S5)57, 297-310. 

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