The Story of Quinolones in Pakistan Part I – Blog Post by Asrar Qureshi

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Contrary to popular perception, Quinolones have been around for over forty years. Negram (nalidixic acid) was introduced by Sterling Winthrop, the company that also owned Panadol and the anabolic steroid Stanozolol. It was much before anabolic steroids were banned from sports and were discouraged for general population. Winthrop rolled back their operations from Pakistan and sold their these to Pharmatec. Later Panadol was acquired by GSK. Anyway, Negram was indicated for Urinary Tract Infections; simpler ones.

Years later, Abbott introduced another quinolone, Urixin (pipemidic acid). Urixin was also indicated only in UTI and was promoted heavily, Abbott style. Urixin caught up and became synonymous with UTI.

A few years further later, Merck Sharpe and Dohme (MSD) made a heavy launch of new generation quinolone, Noroxin (norfloxacin). It was the first of the fluoroquinolones. It was also indicated exclusively for UTIs but including complicated ones also. MSD had long experience of launching research products and they worked hard to sell the concept of norfloxacin; and won at that.

April 1987. Hoechst launched another fluoroquinolone, Tarivid (ofloxacin). Tarivid was a mega launch. Hoechst had been basking in the magnificent re-launch of their third-generation cephalosporin Claforan (cefotaxime). Tarivid was launched with great fervor. It had some unique features which helped to make it talk-of-the-town quickly. It was the most expensive antibiotic tablet ever introduced in Pakistan. It had a broad-spectrum profile and was indicated in a range of infections, unlike all earlier quinolones. It was received as the ultimate treatment for severe, intractable, chronic, complicated cases, though it was not promoted in this manner.

Tarivid lived up to its reputation in every way. Being part of ‘Tarivid Launch Task Force’ I witnessed the evolution of the mega brand first-hand. We followed every patient and collected doctors’ feedback for them. Tarivid proved extremely effective and ‘cured’ some very difficult and hopeless cases. The success stories came mainly from Urology, Gynecology and General Surgery. The notion became stronger that Tarivid worked better in Gram negative infections, as compared to Gram positive ones. Tarivid was not heavily used in Respiratory infections for this reason. For the same reason, Orthopedic surgeons also did not start it immediately as the common causative pathogen was considered to be Gram positive Staphylococcus.

The development of two indications, Bone Infections and Enteric Fever, is a story worth-knowing and understanding. It was a combination of creativity, out-of-box thinking, knowledge-mining, customer-focus and persistence.

We talk about Bone & Joints infections first.

Tarivid had three distinct advantages at the time of launch.

1.     It had extremely high sensitivity for a number of pathogens which was depicted in very low MICs (Minimum Inhibitory Concentration). It meant that very low concentration of drug was needed in the tissues to eradicate infections.

2.     It had very high penetration in all body tissues. Low requirement and high availability of drug in the tissues made it effective even in difficult-to-treat infections.

3.     Being a new drug, it did not display any resistance pattern against most common pathogen.

First, there were couple of focus groups with the leading orthopedic surgeons of the country. These discussions crystallized the positioning of Tarivid in orthopedics. Then small-scale seeding trials were arranged which showed promising results. Tarivid entered orthopedic surgery. The real breakthrough however came when Tarivid was mixed with bone cement to make beads which were put in the bone to treat chronic, recalcitrant bone infections.

Orthopedic surgeons faced difficulty when they had to treat chronic osteomyelitis. The tissues became dead and had poor circulation due to which the antibiotic did not achieve enough concentration to eradicate bacteria. In such cases, the surgeon would mix the antibiotic powder with bone cement, make a string of beads and leave it in the infected tissue. Of course, debridement of dead tissue was done before leaving the beads. The antibiotic kept leaching into the tissue and provided sustained concentration to eradicate bacteria. Prior to Tarivid, cephalosporins were used for this purpose. Tarivid showed outstanding results.

When a certain amount of clinical experience was gathered, a mini-conference of orthopedic surgeons was organized. Most renowned surgeons from all over the country and shared their experiences. It was a very inspiring show for us as well.

Tarivid proved to be an excellent choice in orthopedic infections and the specialty became a major business segment.

To be Continued......