Within pharmacovigilance, any adverse reactions that take place within a relatively shorter time from starting or stopping taking a particular medicinal product are somewhat less complex to detect. Often they are more readily suspected due to the closer temporal relationship. They are also often more readily associated with a higher degree of biological and pharmacological plausibility. By contrast, drug safety work for problems associated with a longer latency period can involve cases where the cause of the adverse reaction is far more complex to identify.
There are a number of factors which can contribute to this phenomenon. Medical records may be unavailable; and/or patients may not be able to accurately recall important details around how and when they took any medication. The relationship between the adverse medical event and the medicine responsible may be less likely to arouse suspicion from health care personnel, in the absence of a clear and logical pharmacological or biological relationship appearing between taking the drug and the reaction occurring. It could be that suspicions between adverse reactions and a particular medicinal product are only raised via epidemiological means.
Even Very Well Established Drugs Could Have The Potential To Cause Problems
There have been some cases where a very well established drug has been marketed for many years before its potential to cause an adverse reaction was detected. It is therefore essential that pharmaceutical companies and regulators continue to correctly monitor, evaluate, and process any reports associated with products long after they first entered the market, including after the patent has expired. For example, there may be many different manufacturers producing different versions of a well-established drug. Reports may be being received about reactions to just one particular version of the drug, or it could be that there are quality problems with particular batches from just one manufacturer that has provoked adverse reactions.
Some Examples Where Adverse Reactions Were Associated With Longer Latency Periods
There could be a latency period measured in years rather than months. Isoniazid has been estimated to have a latency period of approximately one year in relation to unpredictable immune-mediated hypersensitivity reactions. Practolol was a beta adrenergic receptor blocking agent withdrawn from sale in 1975 after it was found to provoke an oculomucocutaneous syndrome with an average latency period of four years.
Furthermore, certain therapeutic approaches may present a risk of an adverse reaction associated with a long latency period, or a delay in their detection. Examples here could include gene therapy and antiretroviral drugs. Long term follow up clinical trials are extremely important; controlled comparisons and certain epidemiological methodologies may prove useful.
An Example Of An Extremely Complex Problem – Patients Unaffected But Serious Problems For Their Children
Diethylstilbestrol (DES) was widely prescribed to prevent miscarriage during pregnancy in the USA from 1941. In 1970 suspicions were raised that the drug has caused problems not for the female patients who took it, but for their children. A series of reports of a rare vaginal cancer arose, affecting patients in an age group which was totally untypical for that cancer. Investigations lead to the findings that a number of serious adverse reactions were affecting some children of the original patients, including cases of fertility problems; malformation of the uterus and cervix; ectopic pregnancies and a higher incidence of spontaneous abortions and preterm births.
There are many more examples of cases where problems with a long latency period have proved difficult to detect. These include instances where there has been some mimicry of events which could occur during the usual clinical progression of the condition. There have been cases where a drug was strongly suspected yet then found not to cause a particular problem. Each and every drug should be monitored at every stage of its life cycle; pharmacovigilance work is absolutely essential even when a drug has been on the market for many years, even after a patent expires. Please note that this information is not any type of medical or other form of professional advice; enquiries or concerns about any of the medications discussed or any aspect of drug safety should only be directed to an appropriately qualified professional.