By William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco.  

The hepatitis C wars have escalated with the approval of a new four-drug oral combination to treat hepatitis C virus (HCV) genotype 1 infection. The combination contains three new drugs — ombitasvir, paritaprevir and dasabuvir — as well as the previously approved ritonavir, a CYP3A inhibitor, to boost the levels of paritaprevir. The drug is approved for use in patients with HCV infections, including those with cirrhosis. It can be used with or without ribavirin, but it is not recommended in those with decompensated cirrhosis. The combination was evaluated in six clinical trials of more than 2300 patients with HCV infection with and without cirrhosis, showing 91-100% sustained viral response (SVR) rate after 12 weeks of treatment. The new combination is marketed by AbbVie Inc as Viekira Pak. The approval comes 2 months after the approval of Gilead’s combination HCV drug, Harvoni, which boasts similar SVR rates. Harvoni is also an all-oral regimen for 12 weeks, and like VIekira Pak, is an interferon-free regimen. It appears that AbbVie and Gilead may be locked in a price war, with both drugs costing from $85,000 to $95,000 per treatment course. Health plans and PBMs are already maneuvering for best pricing. In late December, Express Scripts announced an exclusive contract with AbbVie to make Viekira Pak, their drug of choice, for HCV genotype 1 patients.

The popular pain reliever tramadol is associated with hypoglycemia, according to a new study from the United Kingdom. In a nested case-control analysis conducted in the United Kingdom, tramadol was compared to codeine for non-cancer pain between 1998 and 2012. Cases of hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up, in a study that included more than 330,000 patients. Compared to codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.09-2.10), particularly in the first 30 days of use (OR, 2.61; 95% CI, 1.61-4.23). This was confirmed in both cohort and case-crossover analyses. The authors conclude that initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization (JAMA Int Med, published online Dec 8, 2014, doi:10.1001/jamainternmed.2014.6512). This study is important because the use of tramadol has increased in the past few years. The drug is a weak opioid analgesic that was only recently placed in schedule IV. Tramadol has been viewed by some physicians as an option to hydrocodone, which was moved from schedule III to the more restrictive schedule II in August. Tramadol has been reported to cause hypoglycemia in those with no known risk factors in up to 40% of cases.

Use caution when prescribing clarithromycin with all statins. That according to an observational study from Canada. Clarithromycin has been shown to increase the toxicity of statins metabolized by CYP3A4, but even statins that are not metabolized by CYP3A4 are implicated in a new study. These include rosuvastatin (Crestor), fluvastatin (Lescol) and pravastatin (Pravachol). The study looked at Canadian health care databases and compared the use of clarithromycin (which also not only inhibits CYP3A4, but also inhibits liver enzymes that help metabolize all statins) with azithromycin (which does inhibit statin metabolism). Compared to use with azithromycin, use of clarithromycin, plus one of the three statins, increased the risk of hospitalization for kidney injury (relative risk [RR], 1.65; CI, 1.31-2.09), admission with hyperkalemia (RR, 2.17; CI, 1.22-3.86), rhabdomyolysis (RR, 2.27; CI, 0.86-5.96), and all-cause mortality (RR, 1.43; CI, 1.15-1.76). The incidence of these outcomes was small, with an absolute increase of less than 1%, still statistically significant (CMAJ published online December 22, 2014, doi:10.1503/cmaj.140950). The FDA has recommended use of non-CYP3A4 metabolized statins as safer alternative when taken with a CYP3A4 inhibitor, but as this study points out, all statins may cause risk.


  This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. For questions and comments, please e-mail: leslie.hamlin