Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs: 2. PROGRAMMATIC AND MANAGERIAL REQUIREMENTS FOR FDCS: 2.4 Justification for dosage forms and dosage schedules

Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs
(2002; 81 pages)

Table des matières

ACKNOWLEDGEMENTS
LIST OF ACRONYMS AND ABBREVIATIONS
PREFACE
KEY POINTS
1. INTRODUCTION
	1.1 Aim and objectives
	1.2 What you can find in this guide
	1.3 Background and rationale
2. PROGRAMMATIC AND MANAGERIAL REQUIREMENTS FOR FDCS
	2.1 DOTS strategy
		2.1.1 Challenges in TB control
		2.1.2 Why switch to FDCs?
		2.1.3 FDCs and adverse effects
		2.1.4 Directly observed treatment and FDCs
	2.2 FDC formulations in the WHO Model List of Essential Medicines
	2.3 Treatment regimens using FDCs
	2.4 Justification for dosage forms and dosage schedules
3. FDC DRUG MANAGEMENT
	3.1 Product selection
	3.2 Procurement
		3.2.1 Quantification of drug needs
		3.2.2 Procurement methods and selection of suppliers
		3.2.3 Procurement and quality assurance
		3.2.4 Minimum product specifications, packaging and labelling requirements to be specified in the contract
	3.3 Distribution and storage
	3.4 Rational use of anti-TB medicines
	3.5 Drug problem reporting system
	3.6 Monitoring and evaluation
	3.7 Summary checklist for good anti-TB drug management
4. ENSURING THE QUALITY OF FDC DRUGS
	4.1 Building a quality assurance system for the national TB programme
		4.1.1 Quality assurance where there is an operational drug regulatory authority
		4.1.2 Quality assurance where there is no national drug regulatory authority or no operational drug registration system
	4.2 Bio-availability and bio-equivalence (interchangeability) data
	4.3 Laboratory testing
	4.4 The WHO Certification Scheme
	4.5 Facilitating the drug registration process
5. HOW TO INTRODUCE AND CHANGE OVER TO A REGIMEN WITH 4-DRUG FDCS/2-DRUG FDCS: PLANNING AND IMPLEMENTING A "SCENARIO"
	5.1 The challenge
	5.2 Planning
	5.3 The process
		5.3.1 Decision-making phase
		5.3.2 Preparation
		5.3.3 Initial implementation
		5.3.4 Full implementation
Annex 1. Glossary and use of terms
Annex 2. WHO Certification Scheme - Model Certificate of a Pharmaceutical Product¹
Annex 3. WHO Certification Scheme - Model Batch Certificate of a Pharmaceutical Product
Annex 4. Example of an order form for anti-TB drugs for treatment facilities
Annex 5. Steps in the quantification of anti-TB drugs using consumption-based information
Annex 6. Suggested reading
Request for feedback on the guide

2.4 Justification for dosage forms and dosage schedules

The therapeutic range within which the 4-drug FDC (RHZE) recommended by WHO is effective and not toxic is illustrated in Figures 2-5 below. The charts demonstrate that, for the anti-TB drugs included in the FDC tablet, varying the dosage schedule according to body weight ensures that the dose remains within the therapeutic margin.

Figures 2-5: Dose distributions of the four FDC drugs
(rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, ethambutol 275 mg) recommended by WHO (by body weight cut-off points of 30-37 kg, 38-54 kg, 55-70 kg, 71 kg and above).

Figure 2: Rifampicin dosage

Figure 3: Isoniazid dosage

Note: The body weight range is adequately covered by all drugs in the 4-drug FDC formulation, i.e. the doses in mg per kg body weight do not breach the minimum or maximum cut-off points.

Figure 4: Pyrazinamide dosage

Figure 5: Ethambutol dosage