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Continued from last……
I outlined the manner in which Orthopedic was developed for Tarivid in Part I.
The second major breakthrough was use in Typhoid (Enteric Fever).
Enteric fever, which spreads through contaminated water and food, had been a major health problem in Pakistan. Some areas of interior Sindh and South Punjab were declared endemic areas. Every summer, hundreds of thousands of people suffered from typhoid epidemic. Long time back, there was no really effective treatment. This changed with the introduction of Chloramphenicol which worked wonderfully and helped to control the infection. After several years of use, it was found that the drug caused aplastic anemia which could be fatal. Gradually, the use was discouraged, and treatment was shifted to sulphamethoxazole + Trimethoprim combination, the famous Septran, and cephalosporins. These did provide remission of symptoms but did not eradicate the infection completely. This led to development of carriers. The carriers themselves suffered from relapse and recurrence every new season, and they also spread it to more people. The overall typhoid scene was pretty bad in Pakistan.
Tarivid did not have enough data on use in typhoid because it was developed in Japan and Europe where typhoid was virtually non-existent. The sensitivity of Salmonella spp. to Tarivid was excellent. Coupled with strong tissue penetration, it could give good results. This matter was discussed with selected consultants and they were requested to try the drug and see the results. The results were beyond anyone’s expectation. The patients became afebrile in 48-72 hours and became symptom free in 4-5 days. It was unthinkable at that time.
Use of Tarivid in enteric fever spread like nothing before. As more treatment cases were reported, another great fact came to surface. Tarivid treated carriers who had been having relapses for few years and stopped their suffering. It successfully treated difficult cases with the same effectiveness.
The doctors conceded that Tarivid provided fast, effective and complete treatment of enteric fever; that it eliminated the development of carriers and minimized the occurrence of complications. Tarivid enjoyed this status for several years.
In early 1990s, Ciprofloxacin was also launched. It had more or less similar profile as that of Tarivid. Bayer was the innovator company but Ciproxin could not get a foothold for quite some time, thanks to aggressive strategies of Hoechst. The first generic of ciprofloxacin “Novidat’ did better than the innovator and still leads.
Tarivid also started facing the onslaught of generic ofloxacin products, and despite valiant defense, they gradually chipped away business.
Meanwhile, Abbott introduced two fluoroquinolones; Enoxacin (Enoxabid) and Sparfloxacin (Sparaxin). Both did not do very well. Enoxabid was withdrawn while Sparaxin still sells in a limited number. Internationally, Abbott also introduced Temofloxacin. It was received very well, and Abbott was hoping to make it a blockbuster drug, but it had to be withdrawn early due to adverse effects.
Other fluoroquinolones introduced in Pakistan included Lomefloxacin from Searle; Gatifloxacin as generic though it came from BMS internationally; and Gemifloxacin generics. Lomefloxacin did not do well and stopped. Gatifloxacin was withdrawn on the direction of Ministry of Health Pakistan. Gemifloxacin sells but its use is patchy and small.
Then came Levofloxacin; Cravit from Hilton was pioneer, followed by Tavanic from Sanofi. It was developed to overcome the inherent weakness of quinolones, namely gram-positive respiratory infections. Levofloxacin did not take the market by storm, but it gradually consolidated its position in this segment and is a huge molecule now.
The last to enter was Moxifloxacin (Avelox – Bayer). Moxifloxacin was indicated only in respiratory infections. By this time, Levofloxacin had already broken barrier against use in RTIs. Moxifloxacin became instant hit particularly for serious RTIs.
The summary is that of the large number of fluoroquinolones brought to market, four molecules; ofloxacin, ciprofloxacin, levofloxacin and moxifloxacin, stood the test of time and became permanent members of treatment choices. The others fizzled out for various reasons.