Seena Zierler-Brown

Oral Varenicline for Smoking Cessation

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of varenicline and provide a review of relevant clinical data. Data Sources: A MEDLINE search (2001–December 2006) was conducted using the key words varenicline and nicotine replacement therapy for clinical trials limited to human subjects and published in English. Study Selection And Data Extraction: All available human trials of varenicline were selected for review. References cited in identified articles were used for additional citations. Data Synthesis: Varenicline selectively targets the α4β2 nicotine receptors in the brain that are responsible for cravings and withdrawal associated with nicotine use and dependence. Maximal plasma concentration occurs within 3–4 hours after administration and, after multiple doses, a steady-state concentration is reached within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is not affected by food or time of administration. It exhibits linear pharmacokinetics and tow plasma protein binding (≤20%) regardless of a patients age and renal status. It can be administered once daily. Dosage adjustments are not required in patients with hepatic insufficiency, but adjustments may be necessary in patients with severe renal insufficiency. Clinically significant drug–drug interactions have not been observed with varenicline or co-inhibitors of the human organic cation transporter, which mediates renal secretion of varenicline. Substrates such as warfarin, digoxin, cimetidine, metformin, bupropion, and transdermal nicotine do not alter pharmacokinetic parameters when coadministered with varenicline. In vitro studies have not demonstrated alterations in cytochrome P450 enzyme parameters. Vareniclines safety with coadministration of nicotine replacement products has not been well established. Conclusions: Varenicline is an effective oral agent for smoking cessation.

Online Resources for Assessing the Quality and Safety of Dietary Supplements

Vol. 43, No. 4 July/August 2003 Journal of the American Pharmacists Association (www.japha.org) 543 ent labeling, and proper manufacturing practices. Products that pass will be awarded the program’s certification mark. Along with USP, other nonprofit groups, such as Consumer Labs (CL), the National Nutritional Foods Association (NNFA), and NSF International, have established certification programs. A recent review of these initiatives is available at www.supplementquality.com/ testing/Quality_ seals.html. CL (www.consumerlabs. com) provides independent testing of health, wellness, and nutrition products and publishes the results online. To bear the CL Seal of Approval, a product must pass a voluntary certification program. While manufacturers must pay a fee to become certified, test samples are purchased independently from retailers, and blinded tests are conducted at academic or commercial laboratories selected for their analytic expertise. Both NNFA (www.nnfa. org/services/science/gmp.htm) and NSF International (www. nsf.org/dietary) have established GMP guidelines and standards for quality control and assurance, cleanliness, checking the identity and potency of ingredients, and testing of final products for potency, purity, and bioavailability. NNFA’s TrueLabel program is a dietary supplement label registration program required for all NNFA supplier members. Products must be registered in order to be displayed at the annual NNFA Marketplace trade show. Products are subject to random testing by independent laboratories, and companies whose products fail to comply with the association’s standards are excluded from membership. NNFA plans to publish lists of products that fail in its newsletters. Although NNFA’s GMP Certification Program is open only to NNFA members, any company can apply to have their products certified by NSF International. Both groups have similar standards, developed in collaboration with several other industry trade organizations. Lists of certified manufacturers, distributors, and products are available online at the organizations’ respective Web sites. The adoption and implementation of all these initiatives and programs would help ensure documented safety and efficacy, uniform testing standards, GMPs, and professional oversight for dietary supplements and herbal resources.