By Dr Samah M Shehata Assistant professor of
By Dr. Samah M. Shehata Assistant professor of Chest Diseases
TB Disease Treatment Regimens for Specific Situations
l Pregnant women l Breast-feeding women l Infants and children l Renal insufficiency/end-stage renal disease l Hepatic disease l Drug-resistant TB disease
Pregnant Women
l Untreated TB disease represents a greater hazard to a pregnant woman and her fetus than does its treatment. l The initial treatment regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they do not appear to have teratogenic effects. l Streptomycin is the only anti-TB drug documented to have harmful effects on the human fetus (congenital deafness) and should not be used.
l Although detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and is recommended by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). l If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months.
Breast-feeding l Breast-feeding should not be discouraged for women being treated with first-line anti-TB drugs, because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn. l Pyridoxine (vitamin B 6) supplementation (25 mg/day) is recommended for all women taking INH who are either pregnant or breast-feeding.
Infants and Children
l Infants and children with TB disease should be treated with the regimens recommended for adults, l with the exception that EMB is not used routinely in children. For children whose clarity or sharpness of vision cannot be monitored.
Renal Insufficiency and End-stage Renal Disease
l Renal insufficiency complicates the management of tuberculosis because some antituberculous medications are cleared by the kidneys. l Management may be further complicated by the removal of some antituberculous agents via hemodialysis. l Thus, some alteration in dosing antituberculous medications is commonly necessary in patients with renal insufficiency and end-stage renal disease (ESRD) receiving hemodialysis.
– RIF and INH are metabolized by the liver, so conventional dosing may be used in the setting of renal insufficiency. – PZA is also metabolized by the liver but its metabolites (pyrazinoic acid) may accumulate in patients with renal insufficiency. – EMB is about 80% cleared by the kidneys and may accumulate in patients with renal insufficiency. – Streptomycin dose must be adjusted because the kidneys excrete all of these drugs. – Fluoroquinolones undergo some degree of renal clearance that varies from drug to drug. For example, levofloxacin undergoes greater renal clearance than moxifloxacin. l A longer interval between doses with three times a week administration is recommended for last four drugs and this is better than decreasing the dose as peak serum concentrations may be too low.
Dosing recommendations in Renal Insufficiency(creatinine clearance <30 ml/min) and End-stage Renal Disease(receiving hemodialysis) Drug Recommended dose and frequency INH 300 mg once daily , or 900 mg 3 times/week (as) RIF 600 mg once daily , or 600 mg 3 times/week (as) EMB 15 -25 mg/kg/dose 3 times/week (not daily) PZA 25 -35 mg/kg/dose 3 times/week (not daily) Levofloxacin 750 -1000 mg /dose 3 times/week (not daily) Streptomycin 15 mg/kg/dose 2 -3 times/week (not daily)
l Antituberculous drugs should be given after hemodialysis to avoid any loss of the drugs during hemodialysis, and to facilitate DOT.
Hepatic Disease
The treatment of tuberculosis in patients with advanced liver disease is problematic for : l The likelihood of drug-induced hepatitis may be greater. l The implications of drug-induced hepatitis for patients with marginal hepatic reserve are potentially serious, even life-threatening. l Thus, clinicians may consider regimens with fewer potentially hepatotoxic agents in patients with advanced liver disease, and expert consultation is advisable in treating such patients.
Possible treatment regimens in liver disease include the following. 1 -Treatment without INH. l Initial Phase regimen of RIF, PZA, and EMB followed by a continuation phase of RIF, EMB, and PZA. l Although this regimen has two potentially hepatotoxic medications, it has the advantage of retaining the 6 -month duration. 2 -Treatment without PZA. l Although the frequency of PZA-induced hepatitis is slightly less than occurs with INH or RIF, the liver injury induced by this drug may be severe and prolonged. l Therefore, one might elect to employ a regimen with an initial phase of INH, RIF, and EMB for 2 months followed by a continuation phase of INH and RIF for 7 months, for a total of 9 months.
3 -Regimens with only one potentially hepatotoxic drug (without INH and PZA) l Generally, RIF should be retained. l Additional agents in such regimens could include EMB, SM, and Fluoroquinolone. l The duration of treatment with such regimens should be 12– 18 months, depending on the extent of the disease and the response. 4 -Regimens with no potentially hepatotoxic drugs. l In the setting of severe unstable liver disease, a regimen with no hepatotoxic agents might be necessary. Such a regimen might include EMB, SM, Fluoroquinolone, and another Second-line oral drug. l Expert opinion suggests that a regimen of this sort should be given for 18– 24 months. l
Ø IT MDR-TB is resistant to both INH and rifampin Ø We can select five anti-TB drugs in the stage of extensive, these drugs include: - aminoglycosides(amikacin, kanamycin, capremycin), cycloserine, EMB, Quinolones (levofloxacin, ofloxacin), PZA, ethionamide. Ø The whole therapy lasts at least 18 months.
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