Off-label prescribing refers to the unapproved use, dosage, or formulation of a drug already approved by the FDA for another indication. It’s a legal and common practice—indeed, up to 20% of prescriptions are written for off-label uses. This practice occurs most frequently for children and older patients, as well as those with life-threatening or terminal conditions. Typical reasons to prescribe off label are often mundane, such as different doses or routes of administration. Some off-label uses, however, are pretty far out. Let’s take a look at the rationale behind seven surprising off-label uses for FDA-approved drugs. Naltrexone for kleptomania Naltrexone has been getting a lot of press lately in light of the opioid epidemic. It’s an opioid antagonist used to treat opioid and alcohol dependence. But did you know that it can also be used off label to treat impulse-control disorders, like problem gambling and compulsive hair pulling (trichotillomania)? In addition, results from one study demonstrated that the drug decreased urges to steal in those with kleptomania. “Opioid antagonists have been hypothesized to influence dopamine neurotransmission in the nucleus accumbens and linked motivational neurocircuitry, dampening stealing-related excitement and cravings,” the authors wrote. “Although modulation of drive and subsequent behavioral output by dopamine, endorphins, and gamma-aminobutyric acid has been hypothesized for impulse control disorders, the specific mechanisms underlying opioid receptor antagonism in kleptomania remain incompletely understood.” Methotrexate for autoimmune disorders Methotrexate is FDA approved as a chemotherapeutic agent for cancers, such as acute lymphocytic leukemia and non-Hodgkin's lymphoma, and is also indicated for treating rheumatoid arthritis and plaque psoriasis. Because methotrexate is a disease-modifying anti-rheumatic drug (DMARD), which suppresses the immune system, it has off-label uses for a number of autoimmune diseases and other closely related conditions, including scleroderma, sarcoidosis, alopecia areata, atopic dermatitis, psoriatic arthritis, and systemic lupus erythematosus. Hydroxyurea for patients with psoriasis and HIV Hydroxyurea is used to treat sickle cell disease. It works by boosting fetal hemoglobin levels and hindering sickling. But here’s a very specific, mind-bending use of hydroxyurea taken from a review article in Psoriasis Forum: “Hydroxyurea is a drug that has been long forgotten for the treatment of psoriasis. In addition to its anti-psoriatic effects, it has also been shown to have antiviral effects. This dual effect makes it a drug that dermatologists may want to consider when treating psoriasis in HIV-infected individuals… Dermatologists should consider hydroxyurea as a valid treatment option for psoriasis, especially in HIV-infected individuals where it may also have anti-HIV effects…Lastly, in this age of extremely expensive and frequently unaffordable medications, the fact that hydroxyurea is more affordable than acitretin, cyclosporine, and biologic agents, may prove helpful for many clinicians and patients alike even though its use is off-label.” Antifungals for eye infections Pop quiz: Which of these three antifungal agents is also indicated to treat superficial fungal infections in the eye: voriconazole, natamycin, or amphotericin B? The answer is… Natamycin! Natamycin is available as an eye drop formulation and is good at treating Aspergillus and Fusarium infections that affect the outer surface of the eye. The other two agents, voriconazole and amphotericin B, are heavy hitters used off-label to treat deeper eye infections, such as endophthalmitis. When systemic treatment will do, these agents are given by mouth or intravenously. But to be used as an ophthalmic agent—via direct injection into the eye or as topical eyedrops—they must usually be compounded. Memantine for OCD Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of dementia. By modulating NMDA receptor activity, this drug may restore the function of damaged nerve cells. Disrupted neurotransmission involving glutamate at the level of the cortico-striato-thalamocorticus likely also plays a role in the pathogenesis of obsessive-compulsive disorder (OCD). In a small, open-label trial, nearly 50% of patients with treatment-resistant OCD experienced improved symptoms after taking the medication for 12 weeks. Sildenafil for heart disease Sildenafil (Viagra) is a phosphodiesterase type 5 inhibitor that prevents cGMP breakdown, thus boosting vasodilation and erection. The vasodilatory effects of sildenafil also make for interesting off-label uses, including the treatment of heart disease and Raynaud phenomenon. Notably, the “little blue pill” is already approved for pulmonary arterial hypertension. Colchicine for pericardial disease Colchicine is commonly associated with gout treatment and is FDA-approved for this indication. Its anti-inflammatory effects are due to the inhibition of tubulin polymerization and phagocytosis migration. Guess what other inflammatory condition this drug can help with? Pericarditis. “The most common treatment for idiopathic and viral pericarditis in North America and Europe is NSAID therapy. Adjunctive colchicine can ameliorate the initial episode and is associated with approximately 50% lower recurrence rates,” wrote the authors of a review article in JAMA. “Colchicine should be combined with standard anti-inflammatory therapy to hasten the response to medical therapy and prevent recurrences in patients with nonbacterial causes.” On a final note, although prescribing off label is within the purview of the physician, and the US Congress has historically protected this practice, many lawsuits have been filed due to off-label prescribing. These cases usually revolve around the issue of failure to provide informed consent. Nevertheless, judges usually side with physicians in these cases in finding that physicians are not required to inform their patients of the regulatory status of a drug. Source
