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On drug therapy in Africa: the safety

of poverty

Bello S.O

Department of Pharmacology

College of Health Sciences

Usmanu Danfodiyo University

Sokoto, Nigeria

E-Mail: bellooricha@hotmail.com

Tel: 2348066024503
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Abstract

Africans have limited access to the latest innovations in medicine, especially therapeutic

agents. This is often considered a disadvantage but it may be the opposite. The early

phase of introduction of drugs in the market involve rigorous phase 4 clinical trials that

may expose devastating adverse effects. On the other hand, cheaper alternatives are

usually more available and often have extensive treatment experiences that have profiled

their safety or adverse effects with known risk scores. The default poor access to

innovative mediations in Africa may have prevented certain disasters. This paper

expounds this argument using the examples of Rofecoxib (Vioxx) , Montelukast and

Rosiglitazone.
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Introduction

Contemporary treatment in Africa usually lags behind that of the developing world by

decade (s) (ref.). This has been a source of concern to the W.H.O and National Health

authorities. The common reason for the lag is cost (ref). Innovative therapies usually cost

5-8 times the alternative medication during the life of the patent, are not affordable to

most Africans and are, therefore, not usually available at the local Pharmacy shops(ref).

This scenario is often considered generally undesirable, especially when clinical trials are

conducted. To prevent unethical exploitation of resource poor settings in clinical trials

and as an undeniable reasonable policy targets, balancing global health is desirable. In

this regards attempts are being focused on providing free generic medications or allowing

cheaper non generic versions of innovative therapies. The point for caution is that 90% of

health needs are in resource poor settings. This means that if a new drug was immediately

affordable , about 9 times more patient would have taken the medication at any given

point in time. Resource poor Africa is particularly more vulnerable and would have

consumed the most number of doses. Early phase clinical trials are usually done in

limited number of normal persons (usually less than 500) who are frequently and
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predominantly non Negroid. Early clinical trial may, therefore, not be very valid in

Africa. Meanwhile, post marketing survey of drugs (so called phase 4 trials) is

continuous and involves millions of individuals. An adverse event with an inherent risk

of , say, 0.1% will not show during pre-marketing clinical trials but may well involve

1million events in 1 billion post marketing exposures (one person may take repeated

doses of drug ). This is a likely situation in disease burden Africa. Furthermore, post

marketing survey and adverse event notification are poor in Africa and most events go

unnoticed. In many cases, poverty may have saved Africans from certain disasters

Rofecoxib

Rofecoxib (Vioxx) is a selective cyclo-oxyginase (COX) 2 inhibitor and was marketed

by Merck Pharmaceutical as a magic bullet drug that spared the constitutively expressed

COX- 1 enzyme, which is extremely important for gastric cytoprotection, while acting as

a potent blocker of the inducible COX-2 enzyme involved in most chronic tissue

inflammations. This drug was rapidly market even before the science behind the COX-2

enzyme was fully elucidated mainly due to defective science and effective marketing

(ref). It was rapidly prescribed for many diseases, even premenstrual acne (ref), dental

pain (ref) and post operative analgesia (ref). Fortunately, it was too costly for sub-

Saharan Africa and only few individuals in this region could afford the drug. The rest

were probably saved by poverty because a tell-tale heart population based surveillance

pointed to a clear and strong association with mycardiac infarction. Merck had to pay
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$5bn in claims and Rofecoxib was withdrawn (ref). Even in northwestern Nigeria,

anecdotal evidence suggests the Rofecoxib was prescribed to the elites. No data was

generated about the cost of this drug to the lives of Africans while it lasted. Meanwhile,

traditional non selective COX inhibitors have been used extensively in Africa, even at

primary level clinics, without evidence of disastrous consequences from limited

anecdotal, observational and few randomized trials (ref). Taken together, these limited

studies provide reasonable evidence of their relative safety.

Montelukast

Montelukast is a leukotriene inhibitor that modulates an important effector of atopic

asthma (ref). It has been marketed as the new age anti-asthmatic that avoids the draw

backs of corticosteroids and betamimetics while maintaining superior efficacy. It has

been used extensively for patients in the developed world but is rarely and option in

resource poor countries due to cost and availability. The so called hygiene hypothesis

which suggests that asthma should be lower in environment where infection is

widespread due to early establishment of protective type 1, cytotoxic, immune response

has been shown to be defective because atopic asthma is still rampant in resource poor

countries (ref). This has lead to proposal for non-generic Montelukast (ref) targeted at

sub-Saharan Africa (ref). Recently, a high rate of suicide has been reported in patients on

Montelukast and United States FDA has issued a warning to this effect (ref). Poverty has
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probably saved patients in Africa from Montelukast. The concerns over traditional anti-

asthmatics, especially the long term control medication of the steroid group, have not

been shown to occur looking at the limited studies in Africa (ref). Even non aerosol

steroids have not revealed the theoretical fear of immune compromise, growth stunting

and induction of type-2 diabetes (ref). Traditional anti-asthmatics probably represent

more robust options when compared to relatively new Montelukast that is still in early

phase 4 trials.

Rosiglitazone (Avanida)

Rosiglitazone is a thiazolidinedione that has been approved for type 2 diabetes. Due to

the current pandemic of obesity and type 2 diabetes, non-generic formulations have been

allowed. It is now easily available in sub-Saharan Africa and is available in Sokoto,

northwestern Nigeria. Its usage statistic in Africa is not available neither is there any

adverse event survey. A potentially significant increase in heart attack and heart related

deaths have been reported (ref) and an FDA (USA) study has been started to confirm this

(ref). Has Rosiglitazone cost lives in Africa? We may never know the answer. Metformin

is a biguanide oral anti-hyperglycemic agent with wide treatment experiences. After

billions of dosages, lactic acidosis is the main adverse effect and is fortunately an

extremely rare effect in Africans (ref). Life might have been lost from switching from

such a well known drug to new Rosiglitazone with untested adverse effect profile.

Conclusion
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One of the basic principles of therapeutics is conservatism. Conservative drug

prescription may well deny a patient of the current best treatment option and may be

decried where complementary pharmoco-vigilance is well established. This is not the

case in Africa and many resource poor countries. Considering that phase 4 clinical trials

carry real risks of adverse effects that are not quantified, conservative drug prescription

may have saved lives and may be the best options when the available alternatives are

sufficiently effective.

Reference

Charatan F. 94% of patients suing Merck over Rofecoxib agree to company's offer. BMJ.

2008 Mar 15;336(7644):580-1

Charatan FMerck to pay $5bn in rofecoxib claims. BMJ. 2007 Nov 17;335(7628):1011

Mayer TVMerck's Careful Study of Vioxx. Am J Cardiol. 2008 Apr 1;101(7):1068-9

Tehrani R, Dharmalingam MManagement of premenstrual acne with Cox-2 inhibitors: a

placebo controlled study. Indian J Dermatol Venereol Leprol. 2004 Nov-Dec;70(6):345-8

Desjardins PJ, Black PM, Daniels SE, Bird SR, Petruschke RA, Chang DJ, Smugar SS,

Tershakovec AM. A double-blind randomized controlled trial of rofecoxib and multidose

oxycodone/acetaminophen in dental impaction pain. J Oral Maxillofac Surg. 2007

Aug;65(8):1624-32
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Newcomb W, Lincourt A, Hope W, Schmelzer T, Sing R, Kercher K, Heniford

BTProspective, double-blinded, randomized, placebo-controlled comparison of local

anesthetic and nonsteroidal anti-inflammatory drugs for postoperative pain management

after laparoscopic surgery. Am Surg. 2007 Jun;73(6):618-24