1. Aschenbrenner, Diane S. MS, APRN, BC

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* The monoclonal antibody natalizumab (Tysabri), used to treat relapsing forms of multiple sclerosis, now is also approved for treating moderate-to-severe Crohn's disease in patients who cannot tolerate or have not responded to standard therapies.


* Because of the greater risks of progressive multifocal leukoencephalopathy and other serious events associated with use of the drug, patients must meet certain criteria and agree to comply with stringent monitoring requirements.


Formerly approved only for the treatment of relapsing forms of multiple sclerosis, the monoclonal antibody natalizumab (Tysabri) now is also approved for the treatment of moderate-to-severe Crohn's disease in patients evidencing inflammation who either respond inadequately to conventional therapy or cannot tolerate it. Natalizumab exerts an antiinflammatory therapeutic effect: it increases the number of circulating leukocytes by inhibiting their migration away from the vascular space. For both indications, the natalizumab product labeling bears a black box warning that use of the drug raises the risk of progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain that usually causes death or severe disability. Patients with Crohn's disease who are prescribed natalizumab must be enrolled in the Crohn's Disease-Tysabri Outreach Unified Commitment to Health (CD TOUCH), a special program that limits access to the drug to those who meet certain criteria (the absence of immune deficiency, for example) and who agree to comply with stringent monitoring requirements. Prescribers, pharmacies, and infusion centers at which natalizumab is administered must also enroll in the program, comply with its strict guidelines, and participate in a class on the drug's possible adverse effects and the serious risks associated with its use.


FDA approves Tysabri to treat moderate-to-severe Crohn's Disease [press release]. FDA News 2008 Jan 14.


Biogen Idec. Prescribing information: Tysabri [natalizumab] injection for intravenous use. 2008.




* The labeling of the Ortho Evra contraceptive transdermal patch has been further revised to include study data indicating that women who use it have higher circulating levels of estrogen and are therefore at greater risk for venous thromboembolism than women who use oral contraception.


The labeling of the Ortho Evra contraceptive transdermal patch (norelgestromin-ethinyl estradiol transdermal system) has been revised to include findings of an epidemiologic study demonstrating that women who use that contraceptive are at greater risk for developing venous thromboembolism than those who use oral birth control. The labeling of the drug had been revised in September 2006 to indicate the findings of two earlier studies: one study revealed a greater risk of venous thromboembolism with use of the product, and the other demonstrated that the risk was not heightened. Because the transdermal absorption of estrogen results in higher circulating levels of the hormone, the contraceptive patch may not be an appropriate form of birth control for patients at high risk for venous thromboembolism. Such a patient should consult her health care provider about possibly more suitable methods of contraception.


FDA approves update to label on birth control patch [press release]. FDA News 2008 Jan 18.


Ortho-McNeil Pharmaceutical. Prescribing information: Ortho Evra [norelgestromin/ethinyl estradiol] transdermal system. 2008.




* Health care practitioners are failing to recognize that patients with severe musculoskeletal pain could be suffering an adverse effect of a bisphosphonate.


* The FDA has issued an alert to encourage physicians and nurses to monitor patients for the possible adverse effect of bisphosphonates.


The Food and Drug Administration (FDA) has issued an alert indicating that patients with severe bone, joint, or muscle (musculoskeletal) pain while taking a bisphosphonate, such as such as alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), and zoledronic acid (Reclast, Zometa), could be experiencing an adverse effect of the drug. Because they increase bone density, the bisphosphonate drugs are often prescribed for the treatment and prevention of osteoporosis in women who have reached menopause. Other indications are Paget's disease of bone and hypercalcemia of malignancy. Although severe musculoskeletal pain has always been listed as an adverse effect in the labeling of the drugs, nurses and physicians might overlook the association. Such a failure to identify a symptom as an adverse drug effect results in delayed diagnosis, prolonged pain, and unnecessary use of analgesics. The adverse effect can appear days, months, or years after the initiation of bisphosphonate use.


The FDA alert serves as an important reminder. After obtaining a complete list of drugs that a patient is taking, the nurse should review all product labeling for the adverse effects identified. If it appears that the patient might be experiencing a serious adverse effect of a drug, the health care team should consider whether a modification in the therapy is warranted.


Center for Drug Evaluation and Research. FDA alert: Information on bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa). Rockville, MD: U.S. Food and Drug Administration; 2008 Jan 7.




* Etravirine (Intelence), a new nonnucleoside reverse transcriptase inhibitor (NNRTI), has been approved to treat HIV-1 in adults who are not responding to other drug therapy.


* The drug is unique among NNRTIs because it has demonstrated efficacy in the presence of viral resistance to other NNRTIs.


* Etravirine should be administered as part of combination therapy.


* The most common adverse effects are rash and nausea, and as in other HIV drug therapy, adherence to the regimen is crucial.


Etravirine (Intelence), a new nonnucleoside reverse transcriptase inhibitor (NNRTI), has recently been approved for the treatment of HIV type 1 (HIV-1) in patients demonstrating virologic failure (manifested as an increase in the HIV viral load) while receiving other HIV drug therapy. In vitro studies of etravirine, which must be prescribed in combination with certain other antiretroviral drugs, have found it to be effective against HIV strains resistant to NNRTIs. This is unique because some mutations of HIV can produce resistance to all drugs in a class (especially the NNRTIs), rather than to only a specific drug.


The Food and Drug Administration's approval of etravirine, granted after a priority review, was prompted by 24-week data of two ongoing phase-3 clinical trials of identical design. (A drug receives a priority review if it is believed that its approval would represent "a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious or life-threatening disease.") Patients taking etravirine in combination with other HIV drugs in the clinical trials demonstrated a significant decrease in viral load and an increase in CD4+ cell counts, compared with patients taking placebo and a background regimen.


The most common adverse effects of etravirine are rash (usually not serious) and nausea. Rarely, severe and possibly life-threatening skin reactions, such as erythema multiforme and Stevens-Johnson syndrome, have occurred in study subjects. Treatment should be discontinued if a severe rash develops. Because the drug received a priority review, the effects of its use for longer than 24 weeks are not known, and nurses should monitor patients closely for signs of any adverse events.


As many HIV drugs are, etravirine is metabolized by the cytochrome P-450 (CYP) isoenzyme system, primarily by CYP3A4, CYP2C9, and CYP2C19, the first of which it induces and the latter two of which it inhibits. Because of that, there is the possibility of interaction with other drugs that are also metabolized by any of those isoenzymes or that either induce or inhibit them; there is also the possibility of an alteration of the therapeutic effect and adverse reaction profile of etravirine or of any concurrently administered drug. Before the initiation of therapy with etravirine, nurses should consult a database for information on all other drugs the patient is taking (including HIV drugs) to determine whether such an interaction could occur.


Taking the full prescribed dose of etravirine at regular intervals is critical, as it is with other HIV drugs. The nurse should instruct the patient to take the drug twice daily after meals: the type of food eaten doesn't matter. (The absorption of some other HIV drugs can be diminished by a high-fat meal.) The patient should swallow the tablets whole, but if that is not possible, they can be dispersed in a glass of water. The patient should be instructed to stir the dispersion well and drink it immediately. The glass should be refilled several times with water, which the patient should drink so that the entire dose of etravirine is received, ensuring its full therapeutic effectiveness. The patient should also be told that when a dose is missed by less than six hours, it should be taken as soon as possible after a meal, and the regular dosing schedule should be followed thereafter. On the other hand, when a dose is missed by more than six hours, it should be omitted and only the next dose should be taken according to the schedule--that is, the "doubling up" of doses should be avoided. Finally, because interruption of the drug therapy increases the risk of drug resistance, the nurse should instruct the patient to refill the prescription well before taking the last dose.


FDA approves new HIV drug after priority review [press release]. FDA News 2008 Jan 18.


Tibotec Therapeutics. Prescribing information: Intelence [etravirine]. Ortho Biotech Products. 2008.


Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research. Guidance for industry. Standards for the prompt review of efficacy supplements, including priority efficacy supplements. Rockville, MD: Food and Drug Administration; 1998 May. Procedural Guidance 4.