Guidelines for chemotherapy of tuberculosis in Taiwan 馬偕紀念醫院 一般內科及感染科 主治醫師 曾祥洸

Infectious Disease Society of Taiwan The Society of Tuberculosis, Taiwan Medical Foundation in Memory of Dr. Deh-Lin Cheng (J Microbiol Immunol Infect 2004;37: ) Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education CY Lee’s Research Foundation for Pediatric Infectious Diseases and Vaccines

Three principles for the guidelines 1. From the viewpoint of primary care physician 2. Antimicrobial agents recommended already marketed in Taiwan 3. Base on academic principles rather than the regulation of the Bureau of National Health Insurance

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) New Case

Pulmonary tuberculosis Drugs of choice for New case 1. Standard regimen: (total 6 months) INH+RIF+EMB+PZA for 2 months, Then INH+RIF+EMB for 4 months 2. Fixed-dose combinations: (total 6 months) Rifater+EMB for 2 months Then Rifinah+EMB for 4 months cavitations on initial chest X ray and/or positive cultures at completion of initial 2 months’ treatment,  extend treatment to total 9 months.

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) Retreatment

Pulmonary tuberculosis Drugs of choice for Retreatment (total 8 months) 1. Relapse 2. Default 3. Failure INH+RIF+EMB+PZA+IA for 3 months, Then INH+RIF+EMB for 5 months IA: Injectable aminoglycosides include streptomycin, kanamycin, and amikacin, and should be administered in the initial 2 months of treatment

Retreatment 1. Relapse is defined as a patient who develops active tuberculosis (by culture, clinical or radiological deterioration) after completion of anti-tuberculous therapy. 2. Default is defined as interruptions in therapy of longer than 2 months. 3. Failure is defined as continued or recurrent positive cultures after 4 months of treatment in patients with assured adherence to the prescribed anti-tuberculous regimen.

Pulmonary tuberculosis Culture and susceptibility testing should be done immediately and regimen should be tailored to susceptibility testing results. Referral to specialists in Infectious diseases, chest medicine or experts on tuberculosis is recommended.

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) Drugs Resistance and Drugs Intolerance

Drug resistance to INH RIF+EMB+PZA for 6 months RIF+EMB+PZA +IA for 6 months

Drug intolerance to INH RIF+EMB+PZA for 6 months

Drug resistance to RIF INH+EMB+PZA for 9-12 months INH+EMB+PZA +IA +/- FQ for 9 months Fluroquinolones include ofloxacin, ciprofloxacin and levofloxacin.

Drug intolerance to RIF INH+EMB+PZA for 9-12 months INH+EMB+PZA +IA +/- FQ for 9 months Fluroquinolones include ofloxacin, ciprofloxacin and levofloxacin.

Drug resistance to EMB INH+RIF+PZA for 2 months, then INH+RIF for 4 months (total 6 months) --

Drug intolerance to EMB INH+RIF+PZA for 2 months, then INH+RIF for 4 months (total 6 months) --

Drug resistance to INH, RIF (MDR-TB): EMB +PZA +IA +FQ +TBN ( 本院無 ) (prothionamide) for months * -- * Treatment duration is a total of 18 months after sputum conversion.

Drug resistance to INH, RIF, EMB (MDR-TB): PZA +IA +FQ +TBN ( 本院無 ) (prothionamide) +PSA ( 本院無 ) for months * -- * Treatment duration is a total of 18 months after sputum conversion.

Drug intolerance to PZA INH+RIF+EMB for 9 months --

Drug intolerance to INH, RIF : EMB +PZA +IA +FQ +TBN ( 本院無 ) (prothionamide) for months * -- * Treatment duration is a total of 18 months after sputum conversion.

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) 3 Special situations

Liver function impairment and/or liver cirrhosis RIF+EMB+PZA for 6 months Or INH+RIF+EMB for 9 months RIF+EMB+IA+FQ for months Or EMB+TBN ( 本院無 ) (prothionamide) +IA+FQ for months

Renal function impairment is defined as Ccr<30mL/min or ESRD INH+RIF+ EMB*+PZA* for 2 months then INH+RIF+ EMB* for 4 months (total 6 months) INH+RIF+EMB+PZA for 2 months then INH+RIF+EMB for 4 months * * Intermittent dosing (total 6 months)

Pregnancy or breastfeeding INH+RIF+EMB+PZA for 2 months then INH+RIF+EMB for 4 months (total 6 months) INH+RIF+EMB for 9 months

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) Dosage of antituberculous agents (for adult only)

Dosage of antituberculous agents (for adult only) INH (100 mg) RIF (150; 300 mg) EMB (400 mg) EMB* PZA (250 mg) PZA* 5 mg/kg BW qd (maximum 300mg) 10 mg/kg BW qd (maximum 600mg) mg/kg BW qd mg/kg BW qod mg/kg BW qd (maximum 2 g) mg/kg BW qd

Intermittent dosing (3 times weekly) after hemodialysis INH (100mg) RIF (150; 300 mg) EMB (400 mg) PZA (250 mg) 900mg 600mg mg/kg BW mg/kg BW

Dosage of antituberculous agents (for adult only) Streptomycin (1g) amikacin (250mg) kanamycin ( 本院無 ) Ciprofloxacin (250mg) Levofloxacin (100mg) Ofloxacin ( 本院無 ) 15 mg/kg BW qd mg bid 500mg qd 400mg bid

Dosage of antituberculous agents (for adult only) TBN ( 本院無 ) PAS ( 本院無 ) mg/kg BW, divided to bid-tid (maximum 1 g) 200 mg/kg BW, divided to bid-qid

Dosage of antituberculous agents (for adult only) Rifater (INH 80 +RIF 120 +PZA 250) Rifinah-300 ( 本院無 ) (INH 150 +RIF 300 ) Rifinah-150 ( 本院無 ) (INH 100 +RIF 150 ) 1 tab/10kg BW qd (maximum 5 tab) 2 tab qd, if BW > 50 kg BW 3 tab qd, if BW < 50 kg BW

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) Extrapulmonary tuberculosis

Pleurisy, Lymphadenitis, Peritonitis (intestinal disease), Pericarditis, Genito-urinary tract disease INH+RIF+EMB+PZA for 2 months then INH+RIF+EMB for 4 months (total 6 months) --

Bone and joint diseases, pleural empyema INH+RIF+EMB+PZA for 2 months then INH+RIF+EMB for 7 months (total 9 months) --

Meningitis, CNS disease INH+RIF+EMB+PZA for 2 months then INH+RIF+EMB for 10 months (total 12 months) --

Steroids Prednisolone < 1 mg/kg BW qd or equivalent for a minimum of 3 weeks Recommended in Pericarditis Meningitis CNS disease

Topics not included 1. TB - HIV coinfection 2. Drug-drug interaction 3. Other antituberculosis drugs (rifabutin, cycloserine) 4. Treatment of the pediatric population

Guidelines for chemotherapy of tuberculosis in Taiwan (J Microbiol Immunol Infect 2004;37: ) Thanks for yours attention!