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TB Drugs – First & second line, drug names, regimens

More than twenty drugs have been developed for the treatment of TB. Most of them were developed some years ago. The drugs are used in differing combinations in different circumstances. For example some TB drugs are only used for the treatment of new patients who are very unlikely to have resistance to any of the TB drugs. There are other drugs that are only used for the treatment of drug resistant TB.1“Treatment of Tuberculosis guidelines”, WHO, Geneva, 2010, 85 www.who.int/tb/en/ There are now starting to be some new TB drugs, but there is not very much known about them, and they are still undergoing testing.

TB drugs – the basic drugs

The five basic or “first line” TB drugs are:2“Treatment of Tuberculosis Guidelines”, WHO, Geneva, 2010, 30 www.who.int/tb/

  • Isoniazid (H/Inh)
  • Rifampicin (R/Rif) (In the United States rifampicin is called rifampin)
  • Pyrazinamide (Z/Pza)
  • Ethambutol (E/Emb)
  • and Streptomycin (S/Stm)

These are the TB drugs that generally have the greatest activity against TB bacteria. These drugs are particularly used for someone with active TB disease who has not had TB drug treatment before. All the other TB drugs are generally referred to as second line or reserve TB drugs.

TB drug names

myambutol, a drug used to treat TB

myambutol, a drug used to treat TB

All the drug names have abbreviations which are either one, two or three letters.3Alimuddin Zumia, “Advances in the development of new tuberculosis drugs and treatment regimens”, Nature Reviews Drug Discovery, 2013 http://www.nature.com/nrd/journal/v12/n5/box/nrd4001_BX3.html There are also trade or brand names, which is the name by which a drug is known when it is being sold in a particular country and is made by a particular manufacturer.

For example ethambutol is known in India by a variety of trade names which include Abitol (made by Alpic Remedies), Actuate (made by Biocin Genetics) and Albutol (Alkem Laboratories).4“Tuberculosis – Drugs for its Treatment”, http://www.medindia.net/drugs/medical-condition/tuberculosis.htm In other countries the trade name will be different. For example, ethambutol is sometimes referred to as Myambutol. Isoniazid is sometimes called AKT4 (Lupin Laboratories).

The United States uses abbreviations and names that are not internationally recognised. For example, rifampicin is called rifampin and abbreviated RIF. In the United States only, streptomycin is no longer considered a first line drug.5“Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management

TB drug treatment for new patients

Patients who have not had any TB treatment before, or they have had less than one month of anti TB drugs, are considered to be new patients. New patients are presumed to have drug susceptible TB (i.e. TB which is not resistant to any of the drugs) unless there is a high level of isoniazid resistance in new patients in the area. The other people who may have drug resistant TB are people who have developed active TB disease after they have been in contact with a patient who is known to have drug resistant TB.

For new patients the World Health Organisation (WHO) recommends that they should have six months of TB drug treatment. This should consist of a two month “intensive” treatment phase followed by a four month “continuation” phase.

For the two month “intensive” TB drug treatment phase they should receive:

  • Isoniazid (H/Inh)
  • with rifampicin (R/Rif)
  • and pyrazinamide (Z/Pza)
  • and ethambutol (E/Emb)

followed by

  • Isoniazid (H/Inh)
  • with rifampicin (R/Rif)

for the “continuation” TB drug treatment phase.

It is essential to take several TB drugs together. If only one TB drug is taken on its own, then the patient will very quickly become resistant to that drug.

TB drugs © WHO

TB drugs © WHO

It is recommended that patients take the TB drugs every day for the six months, although taking them three times a week is possible in some circumstances. It is extremely important that all the recommended TB drugs are taken for the entire time. The amount of any drug that a patient needs to take depends on the patient’s weight.

If only one or two of the TB drugs are taken, or the treatment is interrupted or stopped early, then the treatment probably won’t work. This is because the TB bacteria that a patient has, develops resistance to the TB drugs. Not only is the patient then still ill, but to be cured they then have to take drugs for the treatment of drug resistant TB.

TB drugs for the treatment of drug resistant TB

Recommendations before May 2016

Before May 2016 the TB drugs which were used as treatment for drug resistant TB were those listed below. They were grouped according their effectiveness, experience of use, and drug class, as shown below.

All the TB drugs in Group or class 1 are “first line” drugs. Another “first line” drug is streptomycin which is with the other injectable agents in Group 2. All the drugs in Groups 2 to 5, apart from streptomycin, were referred to as “second line” or reserve TB drugs.6“Treatment of Tuberculosis Guidelines”, WHO, Geneva, 2010, 84 www.who.int/tb/

The first four groups of TB drugs listed below were those that were mainly used for the treatment of drug resistant TB. The fifth group of TB drugs were some drugs that were unknown in how effective they were in the treatment of TB. They could however be tried when there was no other option. They were sometimes used in the treatment of totally drug resistant TB.

Groups of TB drugs
Group 1 : First Line Oral Agents
pyrazinamide (Z/Pza)
ethambutol (E/Emb)
rifabutin (Rfb)
Groups 2 – 5 Second line drugs (apart from streptomycin)
Group 2 : Second line Injectable Agents Group 3 : Fluoroquinolones Group 4 : Oral Bacteriostatic Second Line Agents Group 5 : Agents with an unclear role in the treatment of drug resistant TB
kanamycin (KM) levofloxacin (Lfx) para-aminosalicylic acid (Pas) clofazimine (Cfz)
amikacin (Amk) moxifloxacin (Mfx) cycloserine (Dcs) linezolid (Lzd)
capreomycin(Cm) ofloxacin (Ofx) terizidone (Trd) amoxicillin/clavulanate (Amx/Civ)
streptomycin (S/Stm) thionamide thioacetazone
protionamide (Pto) imipenem/cilastatin (lpm/Cin)
high dose isoniazid (Hh)
clarithromycin (Clr)

Change of recommendations in May 2016

In May 2016 the WHO changed their recommendations on the use of drugs for the treatment of drug resistant TB.7“WHO treatment guidelines for drug-resistant tuberculosis (2016 update)”, http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/resources/en/ This was partly because of the Bangladesh regimen, which appeared to show that a shorter regimen could be just as successful as a longer regimen.8Van Deun, A et. al. “Short, highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis”, Am J Respir Crit Care Med 2010; 182:684-692 http://www.atsjournals.org/doi/full/10.1164/rccm.201001-0077OC There had also been a number of other studies which had shown a similar result. There had however been no randomized control trial, but the WHO had decided that the treatment of MDR-TB was too important for there not to be new recommendations.

This regrouping is intended to guide the design of conventional regimens. For shorter regimens lasting 9-12 months the composition is usually standardised.

TB drugs used to treat rifampicin resistant and multi drug resistant TB after May 2016
Group A : Fluoroquinolones Group B : Second line injectable agents Group C : Other core second line Agents Group D : Add-on agents (not part of the core MDR-TB regimen)
Levofloxacin (Lfx) Amikacin (Am) Ethionamide/Prothionamide (Eto/Pto) D1 Pyrazinamide
Moxifloxacin (Mfx) Capreomycin (Cm) Cycloserine / Terizidone (Cs Trd) D1 Ethambutol (E)
Gatifloxacin (Gfx) Kanamycin (Km) Linezolid (Lzd) D1 High-dose isoniazid (Hh)
(Streptomycin) Clofazimine (Cfz) D2 Bedaquiline (Bdq)
D2 Delamanid (Dlm)
D3 p-aminosalicylic acid PAS)
D3 lmipenem-cilastatin (lpm)
D3 Meropenem (Mpm)
D3 Amoxicillin-clavulanate (Amx-Clv)
D3 (Thioacetazone) (T)

Drug regimens

A regimen means a course of treatment. For TB this means a combination of drugs. Drug regimens are described in a standard manner. The drugs are listed by their single letter abbreviations. The order is the order that is roughly the order that they were introduced into clinical practice. The number of months that the drug should be given for is denoted by a prefix. A subscript denotes intermittent dosing, and no subscript means daily dosing. Most regimens have an initial high intensity phase followed by a continuation phase. The high intensity phase is described first and is followed by the continuation phase. A slash separates the two phases.

So 2HREZ/4HR3 means isoniazid, rifampicin, ethambutol and pyyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week.9“Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management

Read more

You can read more about the treatment of drug resistant TB.

References

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1. “Treatment of Tuberculosis guidelines”, WHO, Geneva, 2010, 85 www.who.int/tb/en/
2. “Treatment of Tuberculosis Guidelines”, WHO, Geneva, 2010, 30 www.who.int/tb/
3. Alimuddin Zumia, “Advances in the development of new tuberculosis drugs and treatment regimens”, Nature Reviews Drug Discovery, 2013 http://www.nature.com/nrd/journal/v12/n5/box/nrd4001_BX3.html
4. “Tuberculosis – Drugs for its Treatment”, http://www.medindia.net/drugs/medical-condition/tuberculosis.htm
5. “Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management
6. “Treatment of Tuberculosis Guidelines”, WHO, Geneva, 2010, 84 www.who.int/tb/
7. “WHO treatment guidelines for drug-resistant tuberculosis (2016 update)”, http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/resources/en/
8. Van Deun, A et. al. “Short, highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis”, Am J Respir Crit Care Med 2010; 182:684-692 http://www.atsjournals.org/doi/full/10.1164/rccm.201001-0077OC
9. “Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management