What is the role of triple therapy in Asia?

From the Guidelines

Triple therapy in Asia is not recommended due to the increased risk of adverse effects and drug interactions, as well as the availability of more effective and safer treatment options. The use of triple therapy, including boceprevir or telaprevir, in the treatment of hepatitis C has been associated with improved sustained virologic response (SVR) rates, but also with increased adverse effects, such as dysgeusia, anemia, and neutropenia 1. However, more recent studies have shown that newer treatment options, such as direct-acting antivirals (DAAs), are more effective and have a better safety profile compared to triple therapy 1.

In the context of hepatitis C treatment in Asia, the use of DAAs is recommended due to their high efficacy and safety profile. The treatment regimen should be tailored based on the patient's genotype, treatment history, and other factors, such as the presence of cirrhosis or other comorbidities.

Some key points to consider when treating hepatitis C in Asia include:

• The use of DAAs, such as sofosbuvir or ledipasvir, in combination with other agents, such as ribavirin or peginterferon alpha, is recommended for the treatment of genotype 1 and 4 infections 1.
• The treatment regimen should be individualized based on the patient's treatment history, genotype, and other factors, such as the presence of cirrhosis or other comorbidities.
• Patients should be advised to take medications as prescribed, complete the full course, and undergo post-treatment testing to confirm SVR, typically using viral load testing at least 12 weeks after therapy completion.

It is essential to note that the treatment of hepatitis C is rapidly evolving, and newer treatment options are becoming available. Therefore, it is crucial to stay up-to-date with the latest guidelines and treatment recommendations to provide the best possible care for patients with hepatitis C in Asia.

From the FDA Drug Label

A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low

The use of triple therapy in Asia is not directly addressed in the provided drug labels. However, the labels do provide information on the recommended treatment regimens for tuberculosis, which include a combination of rifampin, isoniazid, and pyrazinamide, with the option to add a fourth drug such as streptomycin or ethambutol in certain cases 2, 2. The labels also mention that the need for a fourth drug should be reassessed when the results of susceptibility testing are known, and that community rates of INH resistance should be considered when determining the initial treatment regimen 2, 2, 3.

• Key points:
  • Triple therapy is not explicitly mentioned in the context of Asia.
  • The recommended treatment regimens for tuberculosis involve a combination of rifampin, isoniazid, and pyrazinamide, with the option to add a fourth drug.
  • The need for a fourth drug should be reassessed based on susceptibility testing and community rates of INH resistance.

From the Research

Triple Therapy in Asia

• The World Health Organization (WHO) has declared Tuberculosis (TB) a global emergency in 1993, with a prevalence of TB and Human Immunodeficiency Virus (HIV) co-infection worldwide of 0.18% and about 8% TB cases having HIV infection 4.
• Effective chemotherapy has been available for treatment of TB for over 50 years now, with the essential anti-tuberculosis (ATT) drugs being Isoniazid (H), Rifampicin (R), Ethambutol (E), Pyrazinamide (Z) and Streptomycin (S) 4.
• The API TB Consensus Guidelines 2006 recommend a short course chemotherapy (SCC) regimen of 2EHRZ, 4HR given daily or thrice weekly for the treatment of TB, including for adults and children, pregnant and lactating females, and cases associated with diabetes mellitus and HIV infection 4.
• The use of triple therapy, which typically consists of a combination of two or three antituberculosis medications, has been shown to be effective in the treatment of TB, with studies demonstrating bactericidal synergism between certain drug combinations, such as streptomycin and isoniazid 5.
• However, the treatment of TB can be complex, particularly in cases of multidrug-resistant TB (MDR-TB), which requires specialized care and the use of second-line drugs, such as ethionamide, cycloserine, viomycin, and para-amino salicylic acid (PAS) 4.
• In Asia, the treatment of TB is often guided by national guidelines, such as the Revised National TB Control Programme in India, which recommends the use of directly observed therapy short course (DOTS) and fixed-dose combinations (FDCs) of antituberculosis drugs 4.

Determinants of Antituberculosis Drug Pharmacokinetics

• Studies have identified several factors that can affect the pharmacokinetics of antituberculosis drugs, including human immunodeficiency virus (HIV) infection, formulation factors, patient sex and age, and previous antituberculosis treatment 6.
• For example, HIV infection has been shown to be associated with reduced concentrations of rifampin and ethambutol, while female patients have been found to have increased concentrations of rifampin and isoniazid, but reduced concentrations of ethambutol 6.
• These findings highlight the importance of considering individual patient factors when selecting and dosing antituberculosis drugs, in order to optimize treatment outcomes and minimize the risk of adverse effects.

Bactericidal Activity of Antituberculosis Drugs

• Studies have demonstrated the bactericidal activity of antituberculosis drugs, both alone and in combination, against Mycobacterium tuberculosis 5.
• The results of these studies have shown that certain drug combinations, such as streptomycin and isoniazid, exhibit synergistic bactericidal activity, while others, such as rifampin and ethambutol, may exhibit antagonistic effects 5.
• These findings have important implications for the selection and use of antituberculosis drugs in clinical practice, and highlight the need for further research into the optimal treatment regimens for TB.