PPracticalractical PharmacyPharmacy For Developing Countries NOTE TO OUR READERS: The goal of Practical Pharmacy is to provide accessible and accurate information on medicines issues for front-line health workers who may not have any pharmaceutical training. This issue of Practical Pharmacy would be best used as a supplement to your national Tuberculosis (TB) guidelines. It is extremely important for all people involved in TB care to have access to the national treatment guidelines. We therefore encourage you to get in contact with your National TB Program Centre for these resources. We are aware, however, that in some countries it may be diffi cult to obtain copies of these guidelines; in some cases they may not even be available at all. Aside from national guidelines, another “must have” is the WHO Treatment of Tuberculosis Guidelines for National Programs 2003 (see the reference section on the fi nal page). These guidelines provide a comprehensive information on all aspects of TB treatment. WWhathat iiss TTuberculosisuberculosis Treatment of TB is carried out according to your national guidelines. You should refer to the Tuberculosis (TB) infection is caused by QUICK TIP! national guidelines for specifi c details about bacteria – bacilli called Mycobacterium treatment regimens and procedures of your Tuberculosis. When a person with The common symptoms of active country. We have summarised the most TB infection coughs or sneezes, they TB disease are common treatment regimens [see page 3]. These release tiny particles containing TB persistent cough, regimens are based on the characteristics and bacilli into the air. A person who is bloody sputum, proven effi cacy of the medicines, although exposed to the bacilli becomes infected weight loss or loss regimens may deviate from this under some if they inhale the airborne bacilli into of appetite, fatigue, circumstances (e.g. known resistance, their lungs. fever, or night sweats. pregnancy, treatment of children), or according TB infection or non-active TB means to local guidelines. that TB bacilli are in the body, but the immune system Reminder: Commonly used abbreviations is keeping them under control. Active TB, on the other hand, develops when the immune system cannot Isoniazid H INH keep the TB bacilli under control and the bacilli begin Rifampicin to multiply rapidly. When the bacteria become active, (aka Rifampin) R RIF a person becomes ill with TB, and this can occur Pyrazinamide Z PZA Ethambutol E EMB when the person’s immunity goes down or is reduced. Streptomycin S SM Conditions that can reduce a person’s immunity include: HIV, malnutrition, advancing age, or some Standard adult treatment regimens start with an other diseases. initial (or intensive) phase of two months, normally consisting of Isoniazid, Rifampicin, Pyrazinamide and People who have TB infection (non-active TB disease) Ethambutol. [See table 1, page 2] During the initial phase, are NOT infectious. However, people with untreated TB bacilli are killed rapidly, infectious patients quickly active TB are infectious, and must be treated as soon become non-infectious (usually within 2 weeks) and as possible. symptoms improve. This is followed by a continuation phase of 4 to 6 months, normally consisting of Isoniazid and Rifampicin (although sometimes HHowow iiss TTuberculosisuberculosis ttreated?reated? Isoniazid and Ethambutol are used). During the According to the World health Organization (WHO), continuation phase, the medicines eliminate remaining the aims of TB treatment are: bacilli and prevent subsequent relapse. • to cure the patient of TB, • to prevent death from active TB or its Dosing frequency late effects, QUICK TIP! Treatment may be administered daily, fi ve-times If not treated, a • to prevent relapse of TB, per week (Monday to Friday), or three-times per person with active • to decrease transmission of TB to TB can infect on week (usually Monday, Wednesday and Friday). others, average 10 to 15 This is decided by each national TB program. It • to prevent the development of people every year. must be noted that twice-weekly regimens are acquired drug resistance. no longer recommended. continued on page 2... PracticalPractical PharmacyPharmacy Issue 18:18: MarchMarch 22008008 1 Table 1: Common treatment regimens Initial Phase Continuation Phase New Cases 2 months HRZE 4 months HR or 6 months HE Retreatment Cases 2 months HRZE S 1 month HRZE 5 months HRE Chronic Cases and Drug- According to your national guidelines resistant TB Retreatment QUICK TIP! If a patient has undergone a course of TB treatment, Directly Observed Treatment Providing a and is found to have TB infection either at the (DOT) is currently the most supportive and end of the course (failure), or at some time in the recommended adherence effi cient service in future (relapse), they will need to be considered method. DOT entails having your facility is one for retreatment. This is an important time for you a patient’s treatment fully of the best aids to treatment adherence. to update the patient’s understanding of their TB observed by a treatment treatment, and to reassess and reinforce medication supporter. This ensures adherence. that every TB patient has the support of another concerned individual and guarantees better treatment The most common retreatment regimen is shown adherence. in the table above, and involves two months of an additional agent, the injectable aminoglycoside Streptomycin. However, some retreatment cases may have drug-resistant TB, so retreatment policies are entirely dependant on your national TB program and the laboratory resources that are available in your area. The best programs perform drug-susceptibility QUICK TIP! testing (DST), and this Empowerment of TB should be performed patients can also be before each patient begins assisted by encouraging Zellweger P. J. Library/ Image Health Lung Credit: a retreatment regimen. patients to interact with The treatment regimen one another, such as Supervision of drug intake at the TB hospital in Cotonou, Benin can later be adjusted through the daily visits “Because of the length of time the patient has to according to DST results to the health facility for DOT take treatment, completing TB treatment is a special and available second-line challenge and requires an unyielding sense of agents. commitment. This may be easy to sustain while the patient feels sick. However, after a few weeks of Adherence and DOT taking treatment, patients often feel better and see Adherence to TB no reason for continuing their treatment. It is thus treatment is not essential for health workers or treatment supporters easy due to the to be supportive and use the initial period to bond with heavy pill burden, the patient. This will enable them to build a strong the potential side- relationship in which the patient believes and trusts effects and the long advice given by the treatment supporter.” (Source: South African Guidelines) duration of treatment. Empowering the Reminder: DOT vs DOTS patients (and 1. DOT stands for Directly Observed Treatment, their families) with and is the strategy of having all of a TB patient’s information about TB medicine doses observed by a designated person is essential to allow (health care worker, or trained and supervised them to take positive community member) to help ensure adherence to control of their health therapy. and to give them Credit: Lung Health Image Library/Pierre Virot 2. DOTS stands for Directly Observed Treatment the best chance of Short-course refers to WHO’s comprehensive treatment success. A TB patient takes his medication “Internationally recommended policy package for From a public health TB control” to which countries are recommended point of view it is critical to stop both the spread of TB to adapt their TB programs (DOT is one element to others, and the development of drug resistance. of DOTS). PracticalPractical PharmacyPharmacy Issue 18:18: MarchMarch 22008008 2 TTuberculosisuberculosis MMedicinesedicines Table 2: Adult and children weight-based doses of fi rst-line medicines ONCE DAILY THREE TIMES WEEKLY Medication Potency Maximum Dose Dose and range Maximum Dose (common presentation) Dose and range (mg/kg) (mg) (mg/kg) (mg) Isoniazid (H) 5 10 High 300 600 (100, 300mg) (4-6) (8-12) Rifampicin (R) 10 10 High 600 600 (150, 300mg) (8-12) (8-12) Ethambutol (E) Adult: 15 Child: 20 30 Low 1600 2400 (100, 400mg) (15-20) (15-25) (25-35) Pyrazinamide (Z) 25 35 Low 2000 3000 (400mg) (20-30) (30-40) Streptomycin (S) 15 15 Low 1000 1000 (1g vial) (12-18) (12-18) Note: 1. Doses are based on WHO Guidelines (doses differ in some guidelines, but may be based on differently resourced settings) 2. Retreatment doses may be higher – refer to your national guidelines or WHO Drug-Resistant TB Guidelines • Pyridoxine (Vitamin B6) 10-30mg daily should always be given with isoniazid • WHO now discourages the use of thioacetazone because of the risk of side effects, especially for people living with HIV • For second-line medicines refer to the WHO Guidelines for the programmatic management of drug-resistant tuberculosis 2006 (available at http://www.who.int/tb/publications/en/ ) • No new TB medicines have been developed for the standard regimen since Credit: Lung Health Image Library/Pierre Virot Thiacetazone causes serious, sometimes the 1960s. This highlights the urgent need for medicines development for TB fatal, side effects in many HIV positive and other neglected diseases patients Fixed-Dose Combination tablets (FDCs) QUICK TIP! The use of FDCs makes TB treatment easier for both patients and healthcare workers. Soon after TB • For patients, FDCs reduce the number of tablets to take and help to minimise treatment is dosing errors, thereby improving adherence and reducing the chance of developing initiated, a patient’s resistance or side effects. health improves and • For healthcare workers, FDCs simplify dosing recommendations and weight-based their infectiousness declines.