Transcript TB Procurement Training Guide

Selection of TB Medicines and
Supplies
Unit Objective
Understand basic principles of
selection of appropriate formulations
of essential tuberculosis medicines
QUAN 1
Pharmaceutical Management Cycle
Selection
Use
Management
Support
Procurement
Distribution
Policy and Legal Framework
Considerations for TB Drug Selection
• Epidemiological profile (category I II III MDR mix: morbidity,
drug resistance)
• Evidence-based medicine
• Bio-equivalence / Bio-availability
• National Treatment Guidelines / Regimens for first-line and
second-line therapies (patient treatment kits)
• Drug formulations (tablets, fixed-dose combination tablets
soluble tablets, powder in sachets)
• Marketing approval/registration
• Applied pharmaco-economics:
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the most cost effective TB treatment = DOTS
Costs of different drugs, availability, delivery times
Medicine Selection Process
• Review patterns of TB morbidity, drug resistance, and
populations affected
• Identify standard treatments in the TB program (e.g.
DOTS regimens)
• Develop a list of essential medicines and supplies to
standardize drug availability: specify medicine, generic
name, strength, dosage form and familiarity of health
worker at treatment centers
• Select specific 1st-line TB medicines
• Select specific 2nd-line medicines for drug-resistant TB
Advantages of Selecting Appropriate
Medicine Formulations
• Controls prescribing habits (prevention of MDR-TB,
controls limited resources)
• Facilitates better purchase prices: — fewer
number of products, economies of scale
• Simplifies management of supplies and stock
• Financial: short and long term savings and cost
control
• Improve treatment outcome
Selecting 1st-line Medicines (1)
WHO-recommended formulations: anti-tuberculosis drugs
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Separate drugs / Active ingredients
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Rifampicin *
(R) tablet / capsule, 150 mg, 300 mg
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Isoniazid
(H) tablet
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Pyrazinamide (Z) tablet
400 mg
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Ethambutol
100 mg, 400 mg
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Streptomycin (S) vial,
(E) tablet
100 mg, 300 mg
1 gr
* Only as (FDCs); single formulations under special
circumstances; develops resistance easily
Note: thioacetazone (T) is discouraged by WHO: risk of severe
toxicity, in HIV infected individuals
Selecting 1st-line Medicines (2)
WHO-recommended formulations: anti-tuberculosis drugs
Fixed-dose combinations of drugs (adult doses)
• 4-FDC RHZE tablet
• 3-FDC RHZ tablet
R150/H75/Z400/E275
R150/H75/Z400
• 2-FDC RH
tablet
• 2-FDC EH
tablet
R150/H75; (R300/H150);
R150/H150
E400/H150
Note: all in black are available from the GDF
http://www.stoptb.org/gdf/drugsupply/drugs_available.asp
Source: WHO. 2003. Treatment of Tuberculosis. Guidelines for National
Programmes Geneva: WHO.
Selecting 1st-line Medicines (3)
WHO-recommended formulations: anti-tuberculosis drugs
Fixed-dose combinations of drugs (pediatric treatment)
 3-FDC RHZ
 2-FDC RH
 2-FDC RH
R60/H30/Z150
R60/H30
R60/H60
(all are soluble tablets/granules)
Note: all will be available from the GDF shortly
http://www.stoptb.org/gdf/drugsupply/drugs_available.asp
Source: WHO. 2003. Treatment of Tuberculosis. Guidelines for National
Programmes Geneva: WHO.
Selecting 1st-line Medicines (4)
Using fixed-dose combinations (FDC)
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Advantages of FDCs
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simplifies dose calculations, procurement and supply
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provides patient with fewer tablets to swallow and provider to
administer
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reduces the risk of promoting drug-resistant TB / avoiding monotherapy
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H + R: 4 months continuation phase of treatment
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H + E: useful: can be self-administered during the second phase
but: may be less effective than H+R and extends treatment with
extra 2 months!
Selecting 1st-line Medicines (5)
• Cautions when using FDCs
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Need demonstration of bioavailability (particularly for
rifampicin) by independent labs
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Need planning, coordination and training for initial
switch-over and follow-on monitoring of treatment
practices
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Use of FDCs still require stocking of limited quantities
of separate medicines for patients who experience
adverse reactions (about 2%--WHO)
Selecting 1st-line Medicines (6)
Advantages of using patient kits (full treatment for one
patient for 6-8 months)
 Solidly promotes rational drug use, DOTS expansion and
recording and reporting system
 Simplifies drug management
– quantification of needs (1 patient = 1 kit)
– stock management and distribution
– provider adherence to treatment standards
– patient acceptability of treatment (ownership of kit and all
required medicines are always available)
Disadvantages of Kits
 Need more storage space in warehouse, depot and health
facility
 Not suitable for large clinics: >100 patients p.d.
Selecting 2nd-line Medicines (1)
Requirements
• Only do so after the country has a documented
outbreak of multi-drug resistant (MDR) TB
• Qualified specialists should make decisions for
selecting 2nd-line medicines for the country, based
on demonstrated drug-resistance patterns
• Note: international recommendations and
standard guidelines are still being developed
Selecting 2nd-line Medicines (1)
• WHO-recommended for MDR TB
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Capreomycin
Cycloserine
Para-aminosalicylic acid
Ethionamide
Amikacin
Kanamycin
Ciprofloxacin
Ofloxacin
Levofloxacin
Characteristics of 2nd-line Medicines
• Limited supply
Number of suppliers
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Capremycin 1 g. vial
Cylcoserine 250 mg tablet
Ethionamide 250 mg tablet
Kanamycin/amikacin 1 g. vial
Para-aminosalicylic acid 4 g. sachet
Ofloxacin/ciprofloxacin 200/250 mg tablet
few
few
many
many
few
few
• More medicines are needed for longer periods of time
(up to 24 months)
• More expensive—can be 100 to 1000 times as
expensive as 1st-line TB medicines
• Not as effective
• More toxic
Criteria for Selecting 2nd line Medicines
• Possible regimens
 Use only standardized protocol
– Individualize if standardized fails
 Use empiric protocols,
– if fails then individualized
(Note: Comparative effectiveness has not been
determined for any of the regimens)
• Registration in the country
• Acquisition costs and longest possible expiry date
Cautions for 2nd-line Medicines
• Should not keep drugs in reserve—some have
only 18 months shelf life
• Using 2nd-line medicines incorrectly may
seriously increase resistance to our “lastresort” TB treatment
Ancillary Medicines for 2nd line treatment:
Managing Adverse Effects
Categories of Adverse Reactions
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Minor side effects
Toxic reactions
Hypersensitivity reactions
Idiosyncratic reactions
Reactions not classified in any of the above
Ancillary Medicines: Examples
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Analgesics for headaches: aspirin, paracetamol
Anti-emetics: promethazine, metoclopramide
Anti-ulcer: anti-acids, ranitidine
Anti-fungal agents: fluconazole or clotrimazole
Anti-diarrheals: loperamide
Anti-depressants: amitriptyline, fluoxetine
Anti-convulsants: diazepam, phenytoin
Inhaled beclomethasone for bronchospasms
Epinephrine for systemic hypersensitivity reactions
TB Supplies - Examples
• Water for injection
• Needles and syringes
• Disinfectants, soaps,
towels, and tissues
• Gloves and face masks
• Sputum cups
• Forms and labels
• ZN stains and other
chemicals
• Microscopes
• Resuscitation equipment
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Slides
Filter and lens paper
Applicator
Miscellaneous equipment
for microscopy
Culture media, Petri plates
Autoclave, incubator,
sterilizer
BCG, PPD
X-ray machine, film
developer and fixer
Management Challenges (1)
• Authority to select TB medicines ?
 NTP manager
 NDRA
 Essential drug committee
 National Pharmacy Board
 Private sector
Selection: Management Challenges (2)
• Lack of quality TB drugs registered in the country
• Pressure from manufacturers and suppliers
• Branded versus generic drugs (non-informative
brand names)
• Local biases: schools of thought, personal
interests
• Lack of skills to use selected drugs (e.g., FDC)
• Unjustified selection of second-line drugs