Drugs off-label use

On the other hand, the recent abuses and allegations of fraud that have occurred in manipulation of off-label drug use, resulting in the creation of the anti-kickback legislation and regulations, demonstrate that this is a complex matter that needs to be carefully controlled and adjusted to achieve the optimal balance between benefit and risk. 

Conroy S et al 2000 Survey of unlicenced and off label drug use in paediatric wards in European countries. British Medical Journal 320 79-82... 

Kimland E, Odlind V (2012) Off-label drug use in pediatric patients. Clin Pharmacol Ther 91 796-801... 

Thalidomide would fall into this category due to its inadequate testing but most commonly improper use refers to off-label use. Use of off-label pediatric medicines has been discussed earlier in this chapter. An example of off-label adult use is with Bromfenac (Duract), a nonsteroid anti-inflammatory drug. Duract was developed for short term therapy (<10 days) in 1997 butwith longer term, off-label, use elevated liver enzymes were evident and it was withdrawn approximately 1 year later. In its time on the market Duract generated approximately 90 million dollars in sales. 

It may be noted that in anesthetics, pediatrics and intensive care medicine in particular, drugs are used off-label almost routinely, and in practice it is doubtful that physicians in these specialties are even aware of these nuances in the IND regulations. Reimbursement systems in the USA will, however, often refuse to pay for drugs used off-label , and use this part of the regulations as their justification. 

The most extensive experience with tissue adhesive drug delivery exists in the fibrin sealant literature. This is clearly an off-label use of this agent as it is only currently approved for hemostasis in cardiac and splenic trauma surgery and for colon sealing at the time of colostomy closure. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

Drugs that work in the brain are considered appetite suppressants. Amphetamines are approved for use in treating other diseases their use as a weight loss drug is considered off label, or not approved. Doctors often prescribe drugs... 

Physicians are the prime recipients of this information, and their treatment of individual patients should be guided by it. (Guided is the correct word. The FDA cannot regulate individual physician practice. If information in the published literature supports use of a drug for conditions not described in the approved labeling, a physician has the right to prescribe for these off-label uses. One hopes there is evidence to support this indeed, medical professional societies often develop position papers when evidence becomes available to support such uses.)... 

Authorises manufacturers of new drugs to disseminate information on unapproved (off-label) uses of approved products under very limited conditions. 

As mentioned before, nifedipine was the first marketed dihydropyridine CCB. Initially, the drug indication was exclusively for angina, but the more recently developed extended release (ER) formulations are used off-label primarily for hypertension (Bayer, 2004). The extended-release tablets use a cellulose coat that extends their release time. The half-life of the ER formulation is reported as 7 h, whereas the immediate-release formulation has a half-life of 2 h (Bayer). 

Although the European Paediatric Regulation (14) has mandated pharmaceutical companies to address pediatric safety, many drugs are used off-label in children (15), with no formal safety testing in appropriately aged nonclinical species and there have been recent examples of adverse human effects (16). 

Horen B, Montastru JL, Lapeyre-Mestre M (2002) Adverse drug reactions and off-label use in paediatric outpatients. Br J Clin Pharmacol 54 665-670... 

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