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TB Treatment for Children – Drugs, dosages & FDCs

TB treatment for children is fundamentally the same as for adults, with a combination of TB drugs needing to be taken for a number of months. TB treatment for children consists of an intensive phase followed by a continuation phase. The purpose of the intensive phase is to rapidly eliminate the majority of the TB bacteria, and this phase uses a greater number of TB drugs than the continuation phase whose aim is to eradicate any remaining dormant bacteria.

When started promptly the outcome of TB treatment in children is generally good, even in those children that are very young and who have compromised immune systems.

Achieving successful TB treatment for children

Achieving successful treatment of TB in children depends on a number of different factors including:1“Out of the Dark: Meeting the Needs of Children with Tuberculosis”, MSF Access to Essential Medicines October 2011 www.msfaccess.org/

  • The child must be promptly diagnosed
  • TB treatment must be started promptly
  • The correct TB drugs must be provided
  • The dosage of the TB drugs must be adjusted according to the child’s weight
  • Support must be provided to ensure that the TB drugs are taken correctly
  • There must be a continuous supply of quality assured TB drugs.

TB drugs for children

Children being treated for TB in hospital in South Africa ©WHO/TBP/Gary Hampton

During 2009 and 2010 the WHO carried out a major review of the evidence concerning the correct dosages of TB drugs for use in children. They published this new guidance in 2010.2“Rapid Advice Treatment of tuberculosis in children” WHO 2010 http://apps.who.int/

The 2010 WHO TB drug dosage guidance for children

The major recommendations of the WHO drug dosage guidance for children were that:

1) The dosages of the following four TB drugs should be:

  • Isoniazid(H) 10mg/kg (range 10-15 mg/kg); maximum dose 300 mg/day
  • Rifampicin(R) 15mg/kg (range 10-20 mg/kg); maximum dose 600 mg/day
  • Pyrazinamide(Z) 35mg/kg (30-40) mg/kg)
  • Ethambutol(E) 20mg/kg (15-25 mg/kg)

As children approach a body weight of 25kg, adult dosages can be used.

2) In some settings, for example where the prevalence of HIV is high, or where resistance to Isoniazid is high, or both, children should be treated with a four drug regime (HRZE) for 2 months, followed by a 2 drug regime (HR) for four months at the above dosages.

Child friendly formulations of TB drugs & FDCs

Young children who are unable, or unwilling to swallow large number of tablets each day need child friendly formulations to treat their TB. Ideally these should be in solid fixed dose combination (FDC) forms that are then dispersible in liquids, and can easily provide for dosing across different weight groups.

TB-FDC-treatment

FDC dispersible TB treatment consisting of Rifampicin 60mg and Isoniozid 60mg © Sandoz

FDCs are when several drugs are combined together with a specific dosage of each drug included in one tablet. FDCs are used not only for TB but also for the management of HIV and Malaria.

A major advantage of FDCs is that they improve patient adherence as fewer tablets need to be taken and a single drug cannot be taken on its own. At the same time there appears to be no loss of effectiveness. Although there is still some discussion about the benefit of FDCs for the treatment of TB in adults, there would appear to be little dispute about the benefit of FDCs for the treatment of TB in children.

When the new guidance about dosages was released in 2010, many of the currently available FDCs no longer fitted with the recommended doses. This meant that providing treatment for children became a much more complex process.  The use of FDCs had to be combined with additional single tablets or divided tablets of individual drugs, in order to achieve the new recommended dose for a child’s weight.

“This leads to a situation where, attempting to arrive at a suitable dose of a TB drug for a young child, the clinic staff [in a peripheral clinic] may take a kitchen knife to halve an adult tablet and then perhaps, will have to halve it again. This must lead to inaccuracies and the possibility of under dosing affecting efficacy and over-dosing that could precipitate toxicity. In the early twenty first century this is no longer an acceptable situation”

Professor Peter Donald, University of Stellenbosch and Tygerberg Children’s Hospital, South Africa3Starke, J “Tuberculosis in Children”, Semin Respir Crit Care Med, 2004;25(3

WHO did provide some interim dosing instructions for how children could be treated to achieve the new recommended doses of the drugs, but it was all extremely complicated.4“Dosing instructions for the use of currently available fixed-dose combination TB medicines for children” WHO 2009 apps.who.int/medicinedocs/en/m/abstract/ They did also provide some additional general advice concerning children receiving treatment for TB. This included:

  • Children receiving treatment for TB must be weighed at least every month
  • Treatment doses should be adjusted as soon as a child changes weight bands
  • Tablet strengths must be carefully checked, especially tablets containing 60mg rifampicin & 30mg isoniazid, and 60mg rifampicin & 60mg isoniazid to avoid toxicity
  • Children weighing more than 30 kg should be treated according to the current adult treatment guidelines.

At the same time WHO made some recommendations for some new FDCs that would be particularly helpful in providing TB treatment for children, but discussion about exactly what was needed continued. Finally in 2012 some consensus was reached on the FDCs required for children.5“Update of Report Out of the Dark: Meeting the Needs of Children with Tuberculosis”, MSF Access to Essential Medicines November 2012 www.msfaccess.org/content/out-dark-meeting-needs-of-children-with-TB 6“TB drugs for children”, Treatment Action Group www.treatmentactiongroup.org/tagline/2013/spring/tb-drugs-children

New FDCs for Children

In 2015 the TB Alliance announced that in early 2016 some new TB drugs for children would be available. 7“Child friendly TB drugs on the way”, www.sbs.com.au/news/article/2015/09/01/child-friendly-tb-drugs-way

“Children with the disease will no longer have to take crushed tablets intended for adult sufferers, meaning that they will get the proper dosage”.

This was further discussed at the annual World Conference on Lung Health in December 2015, where it was said that:8“New Tuberculosis Treatment Aimed at Children”, www.voanews.com

“For the first time, we have appropriate treatment for the million children who have tuberculosis, with a formulation of drug that is easy for kids to take, that tastes good and that will hopefully make the disease much easier to treat”.

Countries can now access the new formulations through the Global Drug Facility.9“New fixed-dose combinations for the treatment of TB in children Factsheet”, www.tballiance.org

The new formulations now available are:
For the intensive phase of TB treatment
Rifampicin 75mg + Isoniazid 50mg + Pyrazinamide 150mg.
For the continuation phase
Rifampicin 75mg + Isoniazid 50mg.

The dosages of first line anti TB medicines should be those given above, which were first recommended in 2010. So with the new FDCs the following is the number of daily tablets needed to reach the proper dosing based on the child’s weight.

Tablets for TB dosing in children

Tablets for TB dosing in children
Weight band Number of tablets Intensive phase RHZ 75/50/150 Number of tablets Continuation phase RH 75/50
4-7kg 1 1
8-11kg 2 2
12-15kg 3 3
16-24kg 4 4
25+kg Adult doses recommended

Ethambutol should be added in the intensive phase for children with extensive disease or living in settings where the prevalence of HIV or of isoniazid is high.

Progress on scale-up of new Childhood TB Medicines

By September 2016 more than 155,000 treatment courses had been ordered. This is enough to meet the needs of 43% of children who are diagnosed with TB. Eighteen countries have adopted the new medicines.10“Progress on Global Scale-up of Childhood TB Medicines”, TB Alliance, www.tballiance.org The government in Kenya announced that all children with TB would be able to have the new drugs free of charge. They would however, still need to pay for the X-ray that is needed to diagnose TB.11“Kenya Rolls Out New Child-friendly TB Drugs”,  VOA,  http://www.voanews.com/a/kenya-rolls-out-new-child-friendly-tb-drug/3527071.html

References

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1. “Out of the Dark: Meeting the Needs of Children with Tuberculosis”, MSF Access to Essential Medicines October 2011 www.msfaccess.org/
2. “Rapid Advice Treatment of tuberculosis in children” WHO 2010 http://apps.who.int/
3. Starke, J “Tuberculosis in Children”, Semin Respir Crit Care Med, 2004;25(3
4. “Dosing instructions for the use of currently available fixed-dose combination TB medicines for children” WHO 2009 apps.who.int/medicinedocs/en/m/abstract/
5. “Update of Report Out of the Dark: Meeting the Needs of Children with Tuberculosis”, MSF Access to Essential Medicines November 2012 www.msfaccess.org/content/out-dark-meeting-needs-of-children-with-TB
6. “TB drugs for children”, Treatment Action Group www.treatmentactiongroup.org/tagline/2013/spring/tb-drugs-children
7. “Child friendly TB drugs on the way”, www.sbs.com.au/news/article/2015/09/01/child-friendly-tb-drugs-way
8. “New Tuberculosis Treatment Aimed at Children”, www.voanews.com
9. “New fixed-dose combinations for the treatment of TB in children Factsheet”, www.tballiance.org
10. “Progress on Global Scale-up of Childhood TB Medicines”, TB Alliance, www.tballiance.org
11. “Kenya Rolls Out New Child-friendly TB Drugs”,  VOA,  http://www.voanews.com/a/kenya-rolls-out-new-child-friendly-tb-drug/3527071.html