Drug Updates

New Drug Information

Belimumab (Benlysta) finally received Food and Drug Administration (FDA) approval on March 9, 2011, to treat patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy.¹ Belimumab is administered by intravenous infusion and is the first B-lymphocyte stimulator protein inhibitor to be approved by the FDA. The last SLE drugs to be FDA approved were hydroxychloroquine and corticosteroids.

Recent data reported on denosumab from the European Congress Osteoporosis and Osteoarthritis meeting in Valencia, Spain, showed that women treated for postmenopausal osteoporosis with denosumab had convincing bone mineral density (BMD) gains after five continuous years of treatment (7.0% total hip BMD versus 13.7% lumbar spine BMD).² The data were from the open-label extension (beyond three years) of the pivotal Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study, which is continuing out to 10 years. Currently 4,550 patients are receiving denosumab. Continued denosumab treatment has resulted in consistent BMD gains in the lumbar spine and total hip. The incidences of new osteoporotic fractures also have remained low for participants. For women who transitioned from placebo to denosumab, significant BMD increases (all P<0.0001 compared with extension baseline) were attained with a 4.1% increase in total hip BMD and a 7.9% increase in lumbar spine BMD. Adverse events occurred in approximately 83% of patients. Two subjects had osteonecrosis of the jaw that healed without further complications. No atypical femoral fractures were reported in either group.

The National Institute for Health and Clinical Excellence (NICE) has issued a final draft guidance for golimumab in treating psoriatic arthritis.^3,4 In the guidance, treatment is recommended for adults only with active and progressive psoriatic arthritis if it is used as described for other tumor necrosis factor (TNF) inhibitors and the manufacturer provides both the 100-mg dose and 50-mg dose at the same cost as the 50-mg dose.⁵ Practitioners need to use the Psoriatic Arthritis Response Criteria to make any treatment adjustments. NICE has not yet issued the final approval to the National Health Service.

Hydromorphone extended release (Exalgo) was approved by the FDA on March 1, 2011, to treat moderate-to-severe pain in opioid-tolerant patients requiring continuous, around-the-clock analgesia for an extended period of time, including those with low back pain.^6,7 Exalgo was formulated with the OROS osmotic drug delivery system to minimize drug peaks and troughs that occur when patients are dosed at more frequent intervals throughout the day. It was studied in doses of 8 mg to 64 mg once daily and will be available in 8-mg, 12-mg, and 16-mg dosage strengths. The most common adverse reactions in trials were constipation, nausea, vomiting, somnolence, headache, and dizziness, so clinicians also should prescribe a bowel regimen for patients and monitor them for central nervous system side effects. Breaking, chewing, dissolving, or crushing the tablets leads to rapid release and absorption of a potentially fatal hydromorphone dose, therefore this formulation is not abuse deterrent and has a high likelihood for abuse.

Zoster Vaccine Live (Zostavax), a live attenuated virus vaccine to prevent shingles, has now been approved for use in 50–59-year-olds as well as in older patients.^8,9 Use of the zoster vaccine in approximately 22,000 people aged 50–59 years in clinical trials reduced the risk of shingles development by approximately 70%. Redness, pain and swelling at the site of injection, and headache were the most common side effects. Live vaccines should not be given concurrently with TNF inhibitors and similar agents.

Pipeline Agents

Calcitonin, recombinant salmon oral, is being investigated for the treatment of postmenopausal osteoporosis. In a one-year, double-blind, double-dummy, placebo-controlled, phase III clinical trial, 565 women were randomized to receive either placebo nasal spray or synthetic salmon calcitonin nasal spray. At one year, the oral recombinant calcitonin product was statistically significantly noninferior in increasing bone mineral density compared with nasal calcitonin and placebo.¹⁰

Rilonacept (Arcalyst), a subcutaneous injection of interleukin (IL)-1 TRAP, which is already approved by the FDA to treat cryopyrin-associated periodic syndromes, is currently in phase III clinical trials to treat gout.¹¹ Rilonacept has met primary and secondary endpoints in a 16-week study in adult gout patients initiating allopurinol therapy. The primary endpoint was the number of gout flares during the study. Rilonacept is designed to attach to and neutralize IL-1 in the bloodstream before IL-1 can attach to cell-surface receptors and generate signals that trigger disease activity. Once attached to rilonacept, IL-1 cannot bind to the cell-surface receptors and is eventually eliminated from the body.

Tofacitinib, an oral janus kinase inhibitor under investigation in phase III clinical trials to treat moderate-to-severe rheumatoid arthritis (RA), has been shown to significantly reduce the signs and symptoms of RA compared with placebo at six months and improve physical functioning at three months.¹² It is also being investigated to treat psoriasis, renal transplant patients, and inflammatory bowel disease.

Drug Shortages

The latest medication to face the problem of a drug shortage is the opioid combination product Embeda, which contains morphine sulfate/naltrexone hydrochloride.¹³ Numerous drug shortages are affecting medical treatment, and the problem only seems to be getting worse. Managing shortages and providing alternate therapies for patients can be challenging, time-consuming, and financially burdensome. Hospital and health-systems pharmacy departments have taken a leadership role to develop strategies and processes to decrease the burden of drug shortage problems by informing practitioners how to provide safe and effective patient care.^14,15 Some reasons for drug shortages are:

Raw/bulk material unavailability: Eighty percent of drug manufacturing raw materials come from abroad, so political unrest, natural disasters, or animal diseases that contaminate raw materials can affect availability.
Manufacturing difficulties/regulatory issues: Production may be delayed due to current good manufacturing practice noncompliance, old or unclean equipment/processes, company mergers, and other factors.
Voluntary recall: These are particularly problematic when one company is the sole manufacturer of a drug. Recalls usually only affect a particular medication lot number and are related to a lack of safety assurance or technical difficulties in product labelling.
Product formulation change/manufacturer change: One example of this is changing from chlorofluorocarbon metered-dose inhalers to more environmentally friendly ingredients.
Manufacturers’ business decisions/economics: Due to lack of financial return on investment, poor demand, or potential safety concerns, products are discontinued.
Industry consolidation/mergers: When manufacturers merge, they often narrow their product lines or disease focus. They may need to move to a new facility, which can limit drug availability until the new facility is functioning at capacity.
Restricted drug product distribution/allocation: Wholesalers may limit distribution of products that require postmarketing surveillance or risk evaluation mitigation strategies.
Unexpected increases in demand or shifts in clinical practice: When a drug receives a new indication, new guidelines are released, or a disease outbreak occurs, demand can shift. For example, in 2006 the flu vaccine was approved for use in children age six to 59 months, yet only one product was approved by the FDA for these young patients.
Natural disasters: Damaged manufacturing facilities due to tornados, tsunamis, earthquakes, and hurricanes can seriously affect drug product availability, particularly if they are the sole manufacturing source of an agent. The impact of these disasters can also escalate the need for certain drug classes to care for patients.

These are just some of the reasons for drug shortages. The FDA has limited authority in the area of drug discontinuation when the underlying reason is financial. Sometimes the FDA is notified by manufacturers if a product is going to be discontinued, but it usually cannot keep a manufacturer from stopping drug production. The exception to this is that the FDA may be able to prevent shortages of medically necessary drugs because there may be significant public health consequences if the drug were not available. The FDA’s definition of medically necessary is if a drug is used to treat or prevent a serious disease where no other available sources of that product exist or there are no other alternative drugs or therapies deemed an adequate substitute. The FDA can facilitate availability of alternate medications a number of different ways. For more information on how they do this, visit www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm235347.htm.¹⁶ For a full list of current drug shortages, visit the American Society of Health-System Pharmacists website at www.ashp.org/DrugShortages/Current.¹⁷ As for Embeda, it is anticipated that it will be back later this year after a stability requirement of the product is resolved.

Michele Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

New Drug Information

Pipeline Agents

Drug Shortages

References

Drug Updates: Information on New Approvals and Medication Safety

Drug UPDATES

Drug UPDATES

Persistent Symptomatic Hypocalcemia Due to Denosumab: A Case Review

New Drug Information

Pipeline Agents

Drug Shortages

References

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