Off-label

In 1998, the FDA approved fibrin sealant for three specific indications. These include hemostasis at the time of cardiac surgical operations [8] (Fig. 2) as well as at the time of operative procedures to treat splenic trauma. The application of the fibrin sealant which consists of normal biologic components in the body s clotting cascade creates a localized clot which further enhances inherent clotting ability. Although approved for these specific hemostatic indications only, fibrin sealant is useful as a hemostat in a wide variety of off-label clinical situations as well [9,10]. These include such applications as hemostasis for liver trauma or resection [11], vascular anastomoses [12], tonsillectomy [13], peripheral joint replacement [14], dental extractions [15], and bum debridement [16]. 

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. 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

Adalimumab is a TNF-a inhibitor initially approved for the treatment of rheumatoid arthritis in 2003. It is approved for treatment of psoriatic arthritis and off-label uses and clinical... 

Another important consideration for treatment of cancers is reimbursement by third-party payors for off-label use of chemotherapy agents because of the high expense. The American Association of Cancer Centers (www.accc-cancer.org) provides... 

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... 

Epoetin alfa can be considered, especially if cardiovascular status is compromised, but the response can be impaired in patients with anemia of chronic disease (off-label use). The initial dosage is 50 to 100 units/kg three times weekly. If Hb does not increase after 6 to 8 weeks, the dosage can be increased to 150 units/kg three times weekly. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

Additional ADRs linked to diet pills include psychosis myocardial ischemia drug interactions, such as the interaction of fenfluramine with imipramine, fenfluramine with amitriptyline or desipramine, or the toxic reaction between fluoxetine and phentermine and the release of serotonin while inhibiting its reuptake, contributing to hyperserotonin reactions. When the next craze takes hold of patients and their physicians, hopefully physicians and pharmacists will take a more vocal position and recommend restraint, xmtil some proof of efficacy and lack of toxicity is shown for new faddish off-label combinations. 

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.)... 

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