Transcript Selection of TB medicines and supplies

Selection of TB Medicines &
Supplies
PSM Workshop to Develop GFATM PSM plans for HIV, TB and Malaria
20-24 February 2006 Nairobi
Objective
Understand basic principles of
selection of appropriate formulation
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 mix: morbidity,
drug resistance)
• Evidence-based medicine
• Bio-equivalence / Bio-Availability
• Applied pharmaco-economics
• Standard treatment guidelines for first-line and
second-line therapies (inclusion of fixed-dose
combination [FDC]; kits)
• Marketing approval/registration
Medicine Selection Process
• Review patterns of TB morbidity, drug resistance, and
populations affected
• Identify standard treatments for TB program patients (e.g.
DOTS regimens)
• Develop a list of essential medicines and supplies to
standardize availability—specify medicine, generic name,
strength, dosage form and capability 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 (MDR, limited resources)
• Facilitates better purchase prices: —fewer number of
products, economies of scale
• Simplifies management of supplies and stock
• Financial: short and long term
• Improve treatment outcome
Selecting 1st-line Medicines (1)
WHO-recommended formulations: anti-tuberculosis drugs
•
Separate drugs

Rifampicin *(R) tablet / capsule, 150 mg, 300 mg

Isoniazid (H) tablet
100 mg, 300 mg

Pyrazinamide (Z) tablet
400 mg

Ethambutol (E) tablet
100 mg, 400 mg

Streptomycin (S) vial
1 gr
* Under special circumstances only; 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
R150/H75/Z400/E275
• 3-FDC
RHE
tablet
R150/H75/E275
• 2-FDC
RH
tablet
R150/H75; R300/H150;
R150/H150
• 2-FDC
EH
tablet
E400/H150
Note: all 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 doses)
 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)
•
Advantages of FDCs

simplifies dose calculations, procurement and supply

provides patient with fewer tablets to swallow and provider to
administer

reduces the risk of promoting drug-resistant TB/ avoiding monotherapy

H + R: reduces the risk of mono-therapy with bactericidal drugs

H + E: useful: can be self-administered during the second phase
but: may be less effective than H+R extends treatment with extra 2
months!
Selecting 1st-line Medicines (5)
• Cautions when using FDCs



Need demonstration of bioavailability
(particularly for rifampicin) by independent
labs
Need coordination and training for initial
switch-over and follow-on monitoring of
treatment practices
Use of FDCs still requires 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
 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 medicines are always available)
Disadvantages of Kits
 Need more storage space in warehouse, depot and
health facility (patient full treatment for 6-8 months)
1st line TB Medicines
• Can also be procured through Direct
Procurement service of GDF
• Offers total package of Q.A. medicines for
competitive prices plus monitoring visits
• Separate Presentation on D.P. service of GDF
can be organised for those interested
Selecting 2nd-line Medicines (1)
• WHO-recommended for MDR TB









Capreomycin
Cycloserine
Para-aminosalicylic acid
Ethionamide
Amikacin
Kanamycin
Ciprofloxacin
Ofloxacin
Levofloxacin
Selecting 2nd-line Medicines (2)
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 drug-resistance patterns
• Note: international recommendations and
standard guidelines developed through
Green Light Committee (GLC)
Characteristics of 2nd-line Medicines
• Limited supply
Number
of suppliers


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Capreomycin 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 expiry
• Using 2nd-line medicines incorrectly may
seriously increase resistance to a “lastresort” treatment
2nd line Medicines for MDR TB
• For GFATM Grantees CAN ONLY BE
PROCURED after Green Light Committee
(GLC) approval
• Offers several advantages but certain
conditions are applied
• Separate Presentation on GLC can be
organised for those interested
Ancillary Medicines for 2nd line treatment:
Managing Adverse Effects
Categories of Adverse Reactions
•
•
•
•
•
Minor side effects
Toxic reactions
Hypersensitivity reactions
Idiosyncratic reactions
Reactions not classified in any of the
above
Ancillary Medicines: Examples
• Analgesics for headaches: aspirin,
paracetamol
• Antiemetics: promethazine, metoclopramide
• Antiulcer: antacids, ranitidine
• Anti-fungal agents: fluconazole or clotrimazole
• Antidiarrheals: loperamide
• Antidepressants: amitriptyline, fluoxetine
• Anticonvulsants: 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
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 (noninformative 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