Additional File 1. Reports of antimalarial medicine ...

[Pages:34]Additional File 1. Reports of antimalarial medicine quality in Africa ? updated from Newton et al. (2006a), Amin & Kokwaro (2007). Data on medicine stability are not included. If chemical analysis detected API outside reference range, with no wrong API detected, but packaging was not analysed the sample was regarded as poor quality (PQ) ? and could represent counterfeit (F), substandard (S) or degraded (D). C= convenience sample, r = convenience sample with some randomisation, R = random sample, CR = case report, S = seizure, WHO = World Health Organization, USP = United States Pharmacopeia. Additional reports kindly provided by Roger Bate.

Medicine

Country

Class Trade Name

Non-Artemisinins

Chloroquine

Angola

PQ

Chloroquine

Burkina Faso PQ

Chloroquine

Cameroon

F, PQ

Stated Manufacturer

Chloroquine

Cameroon

F

sulphate 136 mg

`Nivaquine'

Chloroquine

Cameroon

F, PQ

Chloroquine Chloroquine

Cameroon

F, PQ

Chad

GQ

Formulation Sampling Notes method

Reference

tab

CR

2/2 (100%) failed

Gaudiano et al.

dissolution assays

(2007)

tab

C

24/39 (61%) samples Tipke et al.

failed chemical assays (2008)

tab

C

6/32 (19%) failed

WHO (1995)

assays, 1/32 (3%)

`substitution' & 1/32

(3%) d?fauts de

fabrication'

tab

CR

In tampered bottles,

Basco et al.

contained 2.5-18mg

(1997)

chloroquine

phosphate/tablet

tab

C

6/11 (55%) of patients Basco (2004)

had taken chloroquine

with no API detected,

1/11 (9%) had taken

PQ chloroquine

tab

C

42/133 (32%)

Basco (2004)

counterfeit, 8/133 (6%)

PQ

tab

C

3/3 passed all tests

WHO (1995)

Chloroquine

Chloroquine Chloroquine

Chloroquine Chloroquine

Chloroquine Chloroquine Chloroquine Chloroquine

Chloroquine Chloroquine

Cote d'Ivoire F

`Nirupquin' `Syncom

tab

C

Formulations

(India)'

Gabon

GQ

Gabon

PQ

syrup

C

tab

C

Ghana

PQ

Ghana

PQ

syrup

C

tab

C

Guinea Guinea Kenya Kenya

Kenya Kenya

F

oral

CR

F

`Nivaquine' `Rh?ne Poulenc' syrup

CR

GQ

tab

C

PQ

tab &

C

injection

PQ

Syrup

C

PQ

tab

C

113.2% of stated API in 1/4 samples. 3/4 contained correct chloroquine content. A copy of Nivaquine of Aventis 0/8 failed chemical assays 5/17 (29%) failed content assays & 1/7 (14%) failed dissolution tests 1/20 (5%) failed content assays 12/18 (66.7%) failed content assays and 3/15 (20%) failed dissolution assays Made of aspirin

Legris (2005)

WHO (2003) WHO (2003) WHO (2003) WHO (2003) WHO (1995)

No API detected, syrup more viscous than the genuine product All 13 samples passed assays 4/29 (14%) tablet samples failed assays. The one injection sample passed 2/8 (25%) failed content assays 3/7 (42.8%) failed content assays & 2/7 (28.6%) failed dissolution assays

Barbereau (2006)

Kibwage et al. (1999) Thoithi et al. (2002)

WHO (2003)

WHO (2003)

Chloroquine Chloroquine Chloroquine

Chloroquine Chloroquine

Chloroquine

Chloroquine phosphate

Chloroquine sulphate Chloroquine Chloroquine Chloroquine Chloroquine

Madagascar S

Mali

PQ

Mali

PQ

Mozambique PQ Mozambique PQ

Nigeria

F, PQ

Nigeria

PQ

Nigeria

PQ

Nigeria

Nigeria

Nigeria

Abeokuta, Nigeria

F

F

`Nivaquine'

F

`Nivaquine'

F, S

tab

C

syrup

C

tab

C

Syrup

C

tab

C

oral

C

Caps

R

Syrups

Tab

Injection

Syrups

R

Tab

Capsules

CR

tab

S

syrup

S

C

2/8 (25%) d?fauts de fabrication'

4/6 (66.7%) failed content assays 9/19 (47.3%) failed content assays and 1/19 (5.2%) failed dissolution tests 3/12 (25%) failed content assays 3/15 (20%) failed content assays & 1/15 (6.7%) failed dissolution tests 2/32 (8%) no API detected, 8/32 failed BP assays but chloroquine detected 9/20 (70%), 20/20 (100%), 17/18 (94%), 14/15 (93%) outside British Pharmacopeia limits 8/11 (73%), 15/19 (93%), 0/1 outside British Pharmacopeia limits Chlorpheniramine sold as chloroquine

Fake labels seized

WHO (1995) WHO (2003) WHO (2003)

WHO (2003) WHO (2003)

Shakoor et al. (1997)

Taylor et al. (2001)

Taylor et al. (2001)

Erhun et al. (2001) Edike (2003)

Fake labels seized

Edike (2003)

3/50 (6%) no API detected, 16/50 (32%) substandard

Idowu et al. (2006)

Chloroquine

Nigeria

PQ

Chloroquine

Nigeria

F, PQ

Chloroquine

Chloroquine phosphate 250mg

Senegal

PQ

Sierra Leone F

Chloroquine

Sudan

S

Chloroquine

Sudan

PQ

Chloroquine

Sudan

PQ

Chloroquine

Sudan

GQ

tab, syrup and C injection

tab

C

tab

C

`The Wallis

tab

CR

Laboratory, 11

Camford Rd.,

Luton' UK

tab

Bio

tab

CR

syrup

CR

injection

CR

`Over 85% of (14) tablet samples complied' with content assays and 21% failed friability test. Over 90% of (13) syrups failed content analysis (API too high) and 23% failed microbial growth test. All 5 injections failed content analysis. All tablets passed dissolution/disintegrati on tests 2/56 failed chemical assays, 1/56 no API detected 35% failed USP monograph tests Made of aspirin

Aina et al. (2007)

Onwujekwe et al. (2009) Smine et al. (2002) Sesay (1988)

1/5 had significantly lower bioavailability than the other 4/5 8% tablets failed chemical % API analysis and 8% failed dissolution tests Some syrups and suspension failed visual inspection All passed visual inspection and content analysis

Mahmoud et al. (1994)

Alfadl et al. (2006)

Alfadl et al. (2006)

Alfadl et al. (2006)

Chloroquine

Tanzania

PQ

tab

C

phosphate 250mg

and chloroquine

sulphate 100mg

Chloroquine

Tanzania

GQ `Dawaquine' `DAWA, Dar es

tab

Bio

phosphate 150 mg

and `Kabi- Salaam, Tanzania

base

Vitrum'

and

preparation Kabi-Vitrum,

Stockholm'

Chloroquine

Tanzania

GQ 7 brands

tab

C

phosphate 250mg

Chloroquine

Tanzania

S

Sugar coated `Dawa

tab

CR

`Dawaquin' Pharmaceuticals,

Nairobi'

Chloroquine

Tanzania

PQ 9 brands

tab

C

Chloroquine Chloroquine Chloroquine Chloroquine

Uganda

PQ

Uganda

PQ

Zimbabwe

PQ

Zimbabwe

PQ

tab and

C

injection

tab and

C

injection

syrup

C

tab

C

1/3 failed content assay Anthony &

at 92% API. All passed Temu-Justin

dissolution.

(1999)

Passed bioequivalence Nsimba et al.

testing

(2001)

Passed content and dissolution tests

99% API but low bioavailability

Risha et al. (2002)

Rimoy et al. (2002)

All 9 passed content assay but 1/9 failed dissolution testing. The failed sample was sugar coated Tablets 22/40 (55%) and injection 30/48 (63%) failed assay for chloroquine content Tablets 18/47 (39%) and injection 23/45 (51%) failed assay for chloroquine content 2/15 (13.3%) failed content assays

8/14 (57.1%) failed content assays and 1/14 (7.1%) failed dissolution tests

Abdi et al. (1995)

Ogwal-Okeng et al. (1998)

Ogwal-Okeng et al. (2003)

WHO (2003) WHO (2003)

Amodiaquine Amodiaquine Amodiaquine Amodiaquine

Amodiaquine

Burkina Faso GQ

Ghana

PQ

Kenya

GQ

Kenya

GQ

Kenya

PQ

Amodiaquine

Kenya

PQ

Amodiaquine

Nigeria

PQ

Amodiaquine

Senegal

GQ

tab

C

tab

C

tab

C

tab and

C

suspension

tab

R

syrup

tab

C

tab

C

tab

C

Amodiaquine

Tanzania

S

`Emoquin' `Made in Kenya' tab

C

Amodiaquine Amodiaquine Amodiaquine Amodiaquine

Tanzania

PQ

Tanzania

PQ

Uganda

PQ

Nigeria

PQ

tab

C

tab

C

tab

C

tabs

R

0/6 samples failed chemical assays

2/6 (33%) failed TLC and/or dissolution tests One sample of one passed assays One sample each of tablets and suspension passed 11/29 (38%) tablet samples & 7/23 (30%) syrups failed content and/or dissolution tests 4/8 (50%) failed TLC and/or dissolution tests 1/4 (25%) failed TLC and/or dissolution tests `all of the amodiaquine samples passed the monograph tests' 2 (both `Emoquin')/15 (13%) failed dissolution tests 6/100 failed chemical tests

2/2 (100%) failed TLC and/or dissolution tests 5/9 (56%) failed TLC and/or dissolution tests 1/5 failed dissolution tests

Tipke et al. (2008) Bate et al. (2008) Kibwage et al. (1999) Thoithi et al. (2002)

Amin et al. (2005)

Bate et al. (2008) Bate et al. (2008) Smine et al. (2002)

Minzi et al. (2003)

Kaur et al. (2008) Bate et al. (2008) Bate et al. (2008) Odunfa et al. (2009)

Primaquine phosphate

Namibia

PQ

Halofantrine

Halofantrine Halofantrine Halofantrine

Ghana,

F

Nigeria,

Sierra Leone

Nigeria

F

Nigeria

F

Tanzania

F

`Halfan'

`Halfan' `Halfan' `Halfan'

`GSK'

Quinine Quinine Quinine

Quinine Quinine

Angola

PQ

Burkina Faso PQ

Burundi

F

Cameroon

F

Cameroon

F

tab

CR

syrup

CR

tab

CR

tab

CR

tab

CR

tab

CR

tab

C

tab

CR

tab and

C

injection

tab

C

Peace Corp volunteer contracted P. vivax during prophylaxis with primaquine containing 12mg/tablet, as opposed to genuine 26.3mg

Kron (1996)

No API detected, contained sulfamethazine or sulfisomidine

Fake labels seized Smuggled amongst imported clothes and boots. 2005, Counterfeiters extended shelf life of expired halofantrine by 2 years

Wolff et al. (2003), Anon (2003a), Cockburn et al. (2005) Edike (2003) Oyeniran (2007)

NdomondoSigonda (2005)

1/2 failed dissolution tests 3/9 samples failed chemical assays 1/3 (30%) failed content assay. Contained chloroquine 1/24 (4%) no quinine detected (tablet) 2/4 (50%) of patients who had taken `quinine' had taken fakes containing chloroquine

Gaudiano et al. (2007) Tipke et al. (2008) Gaudiano et al. (2007)

WHO (1995)

Basco (2004)

Quinine

Quinine Quinine 300mg Quinine

Cameroon

F, PQ

Chad

GQ

DR Congo

PQ

DR Congo

PQ

Quinine sulphate Ghana

F

Quinine

Kenya

PQ

Quinine Quinine sulphate

Madagascar S

Nigeria

F

Quinine

Nigeria

GQ

hydrochloride

tab

C

tab and

C

injection

tab

CR

tab

CR

?

S

Raw material, C tabs, syrup & injection

tab or

C

injection

tab

Bio

injection

R

7/70 (10%) contained no API; 45/70 (64%) probably PQ 6/6 passed all tests

Basco (2004) WHO (1995)

88.6% quinine present

1/10 (10%) failed uniformity of mass assay, 3/10 (30%) failed dissolution tests and 1/10 (10%) failed content assay. Total failures were 4/10 (40%) Stated to be counterfeit

? raw material failed, 2/2 tablets, 1/1 syrups and 1/1 injections passed 1/11 (9%) `d?fauts de fabrication' sugar-coated tablets with no quinine detected. Two other oral preparations passed bioequivalence testing 10/10 passed British Pharmacopeia limits

Gaudiano et al. (2006) Gaudiano et al. (2007)

Ghana News Agency (2010) Thoithi et al. (2002)

WHO (1995) Sowunmi et al. (1994)

Taylor et al. (2001)

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