# RE: E-DRUG: 4-drug fixed dose combinations for TB **URL:** \ **Category:** e-drug\ **Created:** [September 2, 1999, 3:58pm UTC](https://talk.edrugplus.org/t/re-e-drug-4-drug-fixed-dose-combinations-for-tb/5925 "1999-09-02T15:58:01Z")\ **Posts on this page:** 1\ **Page:** 1
**Author:** ![richardl1951](https://avatars.discourse-cdn.com/v4/letter/r/b3f665/32.png) [@richardl1951](https://talk.edrugplus.org/u/richardl1951)\ **Post date:** [September 2, 1999, 3:58pm UTC](https://talk.edrugplus.org/t/re-e-drug-4-drug-fixed-dose-combinations-for-tb/5925/1 "1999-09-02T15:58:01Z")
E-DRUG: 4-drug fixed dose combinations for TB (2) ------------------------------------------------- With regard to the 4 drug fixed dose combinations for TB, I have become convinced by the excellent work being done by staff at WHO, Bernard Fourie in South Africa and Gordan Ellard in London of the correctness of this approach. The advantages are very clear. These include a simpler dosage schedule which will improve compliance. This is not a matter of changing to once a day schedules. This is the same whether for FDC's or single doses. It is the difference between 3 or 4 tabs from a single bottle compared to 10 or 12 tablets from four different bottles. It will make health worker DOTS supervision much easier! It will prevent resistance; rifampicin or isoniazid is never alone in the blood creating resistance. This is for me the major advantage that outweighs any negatives. I am extremely alarmed at the reports I hear and read from Russia and the Baltic states as well as from Peru where MDRTB is emerging. Treating this condition is very difficult (2 years therapy with only 75% cure rates at best at a cost at present of US$2-6,000 per year). In some situations patients may be tempted to sell their rifampicin capsules to individuals who want to treat or "prevent" STDs. This is a recipe for MDRTB. There are other benefits such as simplifying drug storage and handling, having only 1 expiry date (single products may have different expiry dates) and having lower packing, storage and shipping costs With regard to the CONS mentioned by Wilbert, cost is an issue but I think it will be a short term issue. We only have to look at what happened with the two drug Rifampicin Isoniazid combination. It started off more expensive but within a few years the combination was cheaper than the single product according to the MSH price indicator guide. At the moment there are a limited number of suppliers but once the new WHO policy is implemented by WHO, IUATLD and the World Bank as well as National TB programs, I feel sure that a number of high quality producers will start producing driving the price down. IDA will be one of these suppliers. The quality issue is a real issue and it relates to the bio availability of rifampicin and this is an issue for single product as well as combination product. Testing of bioavailability is expensive but WHO have come up with an abbreviated protocol which can be used and this is a cost that should be borne by the producer. It is reasonable to demand from the company that they document the bioavailability of their product. One related problem to this is that small scale manufacturers who are producing the other oral TB drugs (not rifampicin) may not be able to produce the combination product and they are likely to resist it's introduction. But so long as there are a few good quality producers in the market the price is likely to come down. The allergy argument holds true for combination or single product systems. The patient in the intensive phase takes four drugs whether these are in combination or separately. If there is an allergic reaction the patient is changed to different regimen which hopefully will not have the drug causing the reaction. The rate of reaction is no higher with FDC's than with single formulations nor should it be. The tablet will be heavy but balanced against the other advantages I think this is a minor problem. WHO has produced a very good report on this issue and if E-Druggers or TB-Netters are interested I would suggest that you ask Bjorn Blomberg [blombergb@who.ch] for a copy of the report and a copy of the submission being prepared for the Essential Drug List review committee which will be meeting in November. I would encourage E-Druggers and TB-Netters to get up to speed on this issue as it is likely to be one of the most important issues faced in 2000. TB kills over 3 million people a year, in many environments it is getting worse and while DOTS has been great in improving cure rates, the danger of MDRTB exploding lurks in the background unless we can ensure that no patient receives monotherapy. For some countries TB drugs are the ones on which they spend the most of their money. So there will be a lot of interest in this topic from commercial interests. Richard Laing Associate Professor of International Health Boston University School of Public Health 715 Albany St, T4W, Boston MA 02118 USA Tel 617 414-1444 Fax 617 638-4476 E-mail richardl@bu.edu [thanks, Richard, for the very detailed response. I hope the developing countries are going to be convinced. So far in Southern Africa only South Africa has introduced the 4-drug combination. Two countries are considering it, the rest are (not yet?) interested. There are 2 suppliers currently in South Africa. Let's hope their prices will indeed go down in coming years. One worry is that South Africa uses a 'light' version whereas WHO recommends a 'heavy' 4-drug combination. The lack of consensus among the TB specialists will probably mean that the prices will stay higher than needed, as drug companies have to test quality of 2 different strengths. Maybe African countries could start with harmonising weight bands? WB] -- Send mail for the `E-Drug' conference to `e-drug@usa.healthnet.org'. Mail administrative requests to `majordomo@usa.healthnet.org'. For additional assistance, send mail to: `owner-e-drug@usa.healthnet.org'.