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

More than twenty drugs are currently used for the treatment of TB and almost all 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/

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
  • Rifampicin (In the United States rifampicin is called rifampin)
  • Pyrazinamide
  • Ethambutol
  • and Streptomycin

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 often referred to as Myambutol.

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

The drugs for the treatment of drug resistant TB, are more expensive, have more side effects, and have to be taken for longer. The current TB drugs which are used for the treatment of drug resistant TB,  are 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, are 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 are those that are mainly used for the treatment of drug resistant TB. The fifth group of TB drugs are some drugs that are unknown in how effective they are in the treatment of TB. They can however be tried when there is no other option. An example is using them in the treatment of totally drug resistant TB.

There are also now two new TB drugs which are bedaquiline and delamanid. They can be used for the treatment of drug resistant TB when there are no other alternatives. It is extremely important that these two drugs should not be used on their own. They must also not be used with other drugs that the patient might already be resistant too. If this was done the patient could become resistant to bedaquiline and/or delamanid as well. This type of TB could then be passed on to other patients.

TB drugs used to treat drug resistant TB according to group (class)

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

Very few trials have been carried out of the drugs in Group 5 to see how effective they actually are in the treatment of drug resistant TB. For example, the drug linezolid is an antibiotic usually used to treat severe bacterial infections. The first trial has just been carried out of this drug looking at the use of it in treating XDR-TB. It was a small trial but it did show that the drug was effective when added to patients current treatments, although most of the patients experienced side effects.7Steenhuysen, J. “Drug showed promise in clearing drug-resistant tuberculosis”, Reuters, 17 October 2012 www.reuters.com/article/2012/ There is much more about TB drug trials, and about new TB drugs.

Further information about how the anti TB drugs are used to treat drug resistant TB, and about the role of drug susceptibility testing, can be found on the treatment of drug resistant TB page.

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.8“Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management

The cost of TB drugs

In low and middle income countries the cost of drugs per patient amounts to less than US$40.  In upper middle income countries the cost is around US$50. This is the cost of treatment with first line anti TB drugs. The unit cost for second line anti TB drugs is much greater than for first line drugs.9“Global Tuberculosis Control 2012”, WHO, Geneva, 2012, www.who.int/tb/publications/global_report/

Read more

You can read more about TB treatment failure, and also about treatment monitoring.

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. Steenhuysen, J. “Drug showed promise in clearing drug-resistant tuberculosis”, Reuters, 17 October 2012 www.reuters.com/article/2012/
8. “Tuberculosis management”, https://en.wikipedia.org/wiki/Tuberculosis_management
9. “Global Tuberculosis Control 2012”, WHO, Geneva, 2012, www.who.int/tb/publications/global_report/