Treatment of epilepsy should begin with a single antiepileptic drug (AED), increasing its dosage gradually until seizures are controlled or adverse effects become intolerable. If seizures persist, specialists generally recommend trying at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs concurrently. When used for the appropriate seizure type, AEDs are roughly equivalent in efficacy. Drug choice is usually based on factors such as ease of use, adverse effects, drug interactions, presence of comorbidities, and cost.

Per capita spending on prescription drugs in the US is higher than in other industrialized nations, including Canada.

News about recent price increases for EpiPen and EpiPen Jr (Mylan) may have patients asking about other options for emergency treatment of anaphylaxis. Adrenaclick and its generic equivalent (epinephrine injection auto-injector) are the only other epinephrine auto-injectors currently available in the US. According to Impax (the manufacturer of both the brand and generic products), Adrenaclick is no longer being manufactured; the generic product will continue to be marketed after supplies of Adrenaclick are depleted. Auvi-Q (Sanofi), an epinephrine auto-injector that was approved by the FDA in 2013, was removed from the market in 2015 due to inconsistencies in delivery of epinephrine doses, including failure to deliver the drug.1

Adrenaclick and its generic equivalent are similar to EpiPen and EpiPen Jr in size and functionality, but they are not considered interchangeable with the EpiPen products due to differences in device design and instructions for use. One pack (two auto-injectors) of EpiPen or EpiPen Jr costs $608.60. One pack of Impax's generic auto-injectors costs $395.20.2

According to Mylan, generic versions of EpiPen and EpiPen Jr will soon become available at about half the cost of the brand-name products.

1. FDA. Updated: Sanofi US issues voluntary nationwide recall of all Auvi-Q due to potential inaccurate dosage delivery. Available at www.fda.gov. Accessed September 1, 2016.
2. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. August 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

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The FDA has authorized two manufacturers (Teva, Mylan) to market generic formulations of celecoxib (Celebrex – Pfizer), the only COX-2 selective inhibitor remaining on the US market. Celecoxib is less likely than nonselective NSAIDs to cause gastric ulcers or other GI toxicity,1 and unlike traditional NSAIDs, it does not have an antiplatelet effect.

Celecoxib is much less COX-2 selective than rofecoxib (Vioxx), which was removed from the US market because of an increased risk of cardiovascular events. One analysis of randomized clinical trials that included a total of about 26,000 patients taking celecoxib found no evidence of an increased risk of cardiovascular thrombotic events compared to nonselective NSAIDs or placebo.2 A review of controlled observational studies found an increased cardiovascular risk with celecoxib (RR 1.17) that was similar to the risk with ibuprofen (RR 1.18) and slightly higher than the risk with naproxen (RR 1.09).3 All NSAIDs can cause renal toxicity, especially in the elderly.4

1. PL McCormack. Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Drugs 2011; 71:2457.
2. WB White et al. Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol 2007; 99:91.
3. P McGettigan and D Henry. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med 2011; 8:e1001098.
4. RL Barkin et al. Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult? Drugs Aging 2010; 27:775.

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Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. When used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of drug is usually based on factors such as ease of use, adverse effects, interactions with other drugs, presence of comorbid conditions and cost.

The FDA has asked Impax Laboratories/Teva Pharmaceuticals to stop production and distribution of Budeprion XL 300 mg, a generic extended-release formulation of the antidepressant bupropion (Wellbutrin XL), because it has found that Budeprion XL 300 mg releases bupropion more rapidly than Wellbutrin XL 300 mg, the original brand name product. Patients switched from the brand name to the generic formulation have complained for years that the generic was less effective and caused more side effects than the original formulation. In 2007, ConsumerLab.com, an independent laboratory, conducted dissolution testing of Budeprion XL, which uses a matrix for slow release, and Wellbutrin XL, which uses a membrane. According to the test results, the Budeprion XL matrix released more bupropion in the first 4 hours than the Wellbutrin XL membrane did.1 The FDA decided to conduct its own studies of Budeprion XL 300 mg and arrived at a similar conclusion. The original approval of the generic formulation was based on pharmacokinetic tests conducted on 150-mg tablets of the Impax/Teva formulation, with results extrapolated to the 300-mg tablet.

Bupropion is often used as an alternative to a selective serotonin reuptake inhibitor (SSRI) or another antidepressant because it does not cause sexual dysfunction, sedation, or weight gain.2 It is also used as an aid in smoking cessation.3 It is contraindicated in patients at increased risk of seizures (including patients with a history of an eating disorder). Other 300-mg formulations of generic extended-release bupropion have not been associated with post-marketing complaints and continue to be available.

1. Wellbutrin versus generic bupropion. Med Lett Drugs Ther 2008; 50:54.

2. Drugs for depression and bipolar disorder. Treat Guidel Med Lett 2010; 8:35.

3. Drugs for tobacco dependence. Treat Guidel Med Lett 2008; 6:61.

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The equivalence of generic drugs to their brand-name precursors continues to be controversial. The last Medical Letter review of this subject (2002) concluded that well-documented therapeutic inequivalence between brand-name and FDA-approved generic drugs had not been reported. Is that still true? New data have become available for some drugs.

Bupropion (Wellbutrin - GlaxoSmithKline, and others) is a norepinephrine and dopamine reuptake inhibitor that has been a useful antidepressant because, unlike some other antidepressants, it does not cause sexual dysfunction, weight gain or sedation. Some patients who were switched from Wellbutrin to a generic alternative have reported worsening side effects and relapse of previously controlled depressive symptoms.1 Most of the complaints have come from patients switched from Wellbutrin XL 300 mg to the generic 300-mg formulation of extended-release bupropion marketed by Teva (Budeprion XL).2 In 2007, about 1 million prescriptions per month were dispensed for extended-release formulations of bupropion; about 40% of these were written for Budeprion XL 300 mg.

The FDA has determined that 3 generic formulations of levothyroxine are therapeutically equivalent to brand-name formulations. Some brand-name manufacturers have objected, and endocrine organizations have expressed their concern.
See levothyroxine addendum

When patents expire on brand-name drugs and generic formulations become available, patients and managed care organizations may express a preference for the lower-cost generics. Are they equivalent to the brand-name product?