In 2010, 21 drugs were approved by the Food and Drug Administration. Most hospitalists probably haven't run into them much yet, but Joseph Li, FACP, studied up and shared his findings with his peers during the Hospital Medicine 2011 session “Pharmacologic Advances of 2010.”
Dabigatran, the new drug most likely to be used by hospitalists, has already gotten significant attention (including in the March 2011 ACP Hospitalist) . “It's an anticoagulant that's indicated to reduce the risk of stroke in patients with afib,” said Dr. Li, who is director of hospital medicine at Beth Israel Deaconess Medical Center in Boston.
Trials showed the drug to be non-inferior to warfarin and, as an oral medication, potentially far more convenient, but there's been some debate about its cost-effectiveness, Dr. Li noted. He recommended that hospitalists investigate the cost of the medication at their own hospitals instead of relying on published estimates. “The total cost is actually lower than warfarin at our hospital,” he said. The issue will probably only get more confusing when two more dabigatran-like drugs, rivaroxaban and apixaban, hit the market soon.
Another drug with potential for hospitalist use is ceftaroline, an antibiotic approved for treatment of community-acquired pneumonia (CAP) and acute bacterial skin and skin structure infections. Two trials found that ceftaroline had similar effectiveness to ceftriaxone in curing CAP. The dosing is 600 mg as an intravenous infusion over an hour, given every 12 hours for adults 18 years old and over.
“Here's the one caution about ceftaroline that you should keep in the back of your mind…if you treat a patient with ceftaroline and you notice that their hematocrit is drifting down, you should think about doing a workup for drug-induced hemolytic anemia,” Dr. Li warned.
Currently, the drug has another, non-clinical problem: It's not included in the guidelines on which core measures are based. “You could actually do right by your patient and treat them with ceftaroline, but when they do the chart review for CMS core measures and see you didn't follow the guidelines, you could be noncompliant,” said Dr. Li.
Government (in the form of the FDA) is also affecting use of the new 13-valent pneumococcal conjugate vaccine. The vaccine was approved for use in children in 2010, as a replacement for the 7-valent conjugate vaccine. However, the FDA-approved choice for adults is still the 23-valent polysaccharide vaccine (Pneumovax).
The polysaccharide vaccine does cover more serotypes of pneumococcus, but “as it turns out, more is not better,” said Dr. Li. “Typically people get vaccinated with the polysaccharide vaccines and their titers go up, but then they have waning immunity over the next one to two years.” When patients are revaccinated, there is a smaller increase in titers than with the first vaccination.
Studies of the conjugate vaccine have shown more sustained response and led to its approval for children. “It really makes you wonder whether we're doing a service to our patients when they come in and get repeated doses of the [polysaccharide] pneumococcus vaccine,” said Dr. Li. “I think there's going to be a lot of discussion about what to do,” including possible additional review by the FDA later this year which could expand approval to adults, he added.
The other drugs approved in 2010 likely will not have as much direct application in inpatient practice, but hospitalists may still need to be aware of their names and attributes. “When you see the patients coming into the hospital on these drugs, even if you don't prescribe them, you have an idea what those drugs are,” Dr. Li said.
Hospitalists who work on infusion units (whose ranks are growing, Dr. Li noted) are particularly likely to encounter new therapies for rheumatoid arthritis and chronic gout. Tocilizumab, the arthritis drug, is indicated for patients who have not responded to tumor necrosis factor-alpha drugs.
“Before you give the patient this drug, you would want to have a checklist of things to monitor for. One of the things that should be on that checklist is that all patients, prior to receiving this drug, should be screened for latent TB [tuberculosis] infection,” said Dr. Li.
Pegloticase, the latest gout treatment, comes with more extensive warnings, including a FDA Risk Evaluation and Mitigation Strategy. In the trial that led to the drug's approval, 26% of patients had infusion reactions and 5% had anaphylaxis, with most reactions occurring within two hours of infusion. “These are going to be the patients who come in, get the infusion and sit around for a while to make sure they don't have a reaction,” noted Dr. Li.
Pegloticase should be given with pre-medication antihistamines and corticosteroids, and it can increase gout flares at first. “This drug doesn't sound like it's too easy to use. There are a lot of risks,” said Dr. Li.
Costs and benefits will also need to be weighed for new oncology drugs. Sipuleucel-T is exciting because it's a novel patient-specific vaccine for hormone-refractory prostate cancer, but its extension of survival by about four months doesn't come cheap. “The cost is about $31,000 per infusion, so with three infusions, the cost is $93,000. That's about $23,000 per month for survival,” Dr. Li said. Other new drugs for late-stage cancer include eribulin for metastatic breast cancer and cabazitaxel for hormone-refractory prostate cancer.
More likely to be widely used are new drugs for type 2 diabetes and osteoporosis. Liraglutide is a glucagon-like peptide-1 analogue, indicated for use in addition to other anti-diabetic agents. “This drug reduced the mean A1c by 0.8 to 1.4 percentage points compared to placebo,” said Dr. Li. It also was associated with a lower risk of hypoglycemia than sulfonylureas, caused weight loss similar to metformin, and required no adjustment based on renal function.
“But there are some potentially serious safety concerns,” said Dr. Li, noting that animal studies found an increased risk of thyroid tumors and human trials found more cases of pancreatitis in patients taking the drug. “If you're a hospitalist and you see a patient coming in through the emergency department having some nausea and vomiting, it could be a harbinger of pancreatitis with this drug,” he suggested.
The new osteoporosis drug, denosumab, comes with two different brand names. Prolia is approved for post-menopausal women with osteoporosis. It's given subcutaneously every six months and significantly reduced vertebral fractures compared to placebo in trials. Xgeva is for patients with bone metastases from solid tumors. Dr. Li predicts that the latter formulation may be used in place of long-acting bisphosphonates, while the former will be a second-line treatment.
Another first-of-its-class entry is tesamorelin, indicated for HIV patients with lipodystrophy. “It acts on the pituitary cells in the brain to stimulate production of endogenous growth hormone,” said Dr. Li. Trials showed that the drug decreased visceral adipose tissue and triglycerides. “We do know of course that visceral fat is associated with cardiovascular risk factors, but what we don't know is if tesamorelin will reduce cardiovascular events,” Dr. Li cautioned. If the drug is found to improve cardiovascular outcomes, the next question will be whether it should be used in non-HIV patients, he noted.
2010 was a big year for multiple sclerosis (MS) medications. Dalfampridine is a novel potassium-channel blocker approved to improve walking in patients with MS. “Unfortunately, while it does improve symptoms, it does not alter the progression of this disease,” said Dr. Li. Progression is delayed by the other new MS drug, fingolimod, which is also noteworthy for being an oral medication. It's the first, but definitely not the last, according to Dr. Li. “There's a bunch of oral MS drugs getting ready to come out in the next couple years,” he said.
Speaking of next year, Dr. Li also ran through the names and indications of all the medications that have already been approved in 2011: azilsartan for hypertension, ipilimumab for metastatic melanoma, belimumab for lupus, roflumilast for COPD, vilazodone for depression, vandetanib for medullary thyroid and cancer, and spinosad for head lice.
There were also a few 2010 drugs that Dr. Li didn't have time to discuss in-depth: aztreonam for cystic fibrosis, a new meningococcal vaccine, carglumic acid for hyperammonemia, ondansetron soluble film for nausea and vomiting, and extended-release versions of hydromorphone and naltrexone. A few new combination drugs also hit the market last year: aliskiren plus amlodipine and olmesartan plus amlodipine, both for hypertension; dutasteride plus tamsulosin for benign prostate hyperplasia; mometasone plus formoterol for asthma; and finally, naproxen plus esomeprazole, a nonsteroidal anti-inflammatory combined with a proton-pump inhibitor.