Academic journal article Bulletin of the World Health Organization

The Rationale for Recommending Fixed-Dose Combination Tablets for Treatment of Tuberculosis

Academic journal article Bulletin of the World Health Organization

The Rationale for Recommending Fixed-Dose Combination Tablets for Treatment of Tuberculosis

Article excerpt

Bulletin of the World Health Organization, 2001, 79: 61-68.

Voir page 66 le resume en francais. En la pagina 67 figura un resumen en espanol.

Introduction

Tuberculosis has been a scourge of mankind for thousands of years (1) and remains one of the largest health problems in the world today, with an estimated 8 million new cases and at least 2 million deaths every year (2). This burden is increased by human immunodeficiency virus (HIV) infection, which impairs the immune system and allows large numbers of people already infected with tuberculosis to progress to active disease. In many African countries, where more than 60% of those infected with HIV reside, this has led to an exponential increase in tuberculosis cases over recent years (3-9). The emergence of multidrug-resistant cases of tuberculosis also poses a major challenge to control of the disease worldwide (10) and tuberculosis experts and health policy-makers have urged a global response (11).

Effective treatment of tuberculosis patients with short-course multidrug chemotherapy is the cornerstone of the modern approach to the control of the disease. To emphasize this principle, WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD), together with their partners, recommend the use of fixed-dose combination (FDC) formulations of the essential anti-tuberculosis drugs as one further step to ensure adequate treatment of patients (12, 13).

This article presents the justification for the change in treatment policy from single-drug formulations to FDCs and discusses the major challenges and possible solutions in this process.

Treatment options for tuberculosis

FDCs versus single drug formulations

Multidrug therapy is necessary to cure tuberculosis patients and to prevent the selection of drug-resistant mutants, which may arise during the course of treatment. The major advantages of using FDCs to treat tuberculosis are simplified treatment and drug management, and the reduced probability of monotherapy (12-16). By preventing monotherapy, it is expected that FDCs can limit the risk of emergence of drug-resistant tuberculosis, although this contention remains to be validated.

Simplifying treatment

One of the constraints in the conventional treatment of tuberculosis is that patients have to take a large number of tablets, usually 9-16 per day for 2 months (initial phase of treatment), followed by 3-9 tablets daily for 4-6 months (continuation phase). Using FDCs, the number of tablets to be taken can be reduced to as few as three or four per day for the whole course of the treatment (Table 1). Having fewer pills to swallow makes treatment easier, and minimizes the probability of splitting the doses or of taking only some of the drugs in the regimen. In a study conducted in Hong Kong (17), only 1% of 312 patients who received FDCs complained about the quantity of drugs to be ingested or about difficulty with swallowing, compared with 5% of 308 patients receiving the single drug preparations. Complaints relating to adverse effects were similar in the two groups. Use of FDCs may therefore improve the patient's compliance with treatment and limit prescription mistakes by simplifying the calculation of dosages. Where national guidelines are not readily available, and the treatment of tuberculosis is largely left in the hands of the private sector, the use of inadequate regimens may be more commonplace (18). In such a situation, FDCs might be a better option than use of single-drug formulations.

Table 1. Example of the number of tablets to be taken daily in the initial phase of anti-tuberculosis treatment by a 50-kg patient either as single drugs or as a fixed-dose combination of four drugs

Single drug          No. of        Fixed-dose combination    No. of
 tablets             tablets                                 tablets

Rifampicin (R)
 150 mg                 3          RHZE (150 mg + 75 mg +       3
                                      400 mg + 275 mg)
Isoniazid (H)
 300 mg [(100
 mg). … 
Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.