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

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* The product labeling of the protease inhibitor darunavir (Prezista) has been revised to include a warning of a possible association between use of the drug and development of hepatotoxicity.


* Liver function tests should be monitored carefully in patients taking the drug.


A new warning has been added to the labeling of the HIV-1 protease inhibitor darunavir (Prezista) indicating that use of the drug appears to be associated with hepatotoxicity. This revision was made after postmarketing case reports of adverse effects and clinical trial information were reviewed by the Food and Drug Administration and the manufacturer. It has not been established that darunavir itself, alone, causes hepatotoxicity. In fact, to ensure maximum bioavailability of the drug, it's often taken in combination with a low dose of ritonavir (Norvir), an inhibitor of the HIV-1 and HIV-2 proteases that has a known association with hepatotoxicity. Although most HIV antiretroviral drugs pose a risk of some degree of liver damage (as manifested in greatly elevated levels of liver enzymes), some of them, such as ritonavir, pose a comparatively greater risk. Nurses should be sure to discuss the risk of liver damage with patients who take the drug. Patients should report any symptoms to the prescriber that might indicate liver injury, such as nausea, abdominal pain, jaundice, dark urine, anorexia, and otherwise inexplicable fatigue. Nurses should monitor the results of liver function tests in patients taking darunavir and other HIV drugs and notify the prescriber when liver enzyme levels are higher than normal. Patients should also be informed of the importance of having follow-up blood work to monitor their liver function.


Center for Drug Evaluation and Research. FDA alert: darunavir ethanolate (marketed as Prezista) information. Rockville, MD: U.S. Food and Drug Administration; 2008 Mar 21.




* Certolizumab pegol (Cimzia), newly approved for use in Crohn's disease, is initially administered subcutaneously every two weeks, and then every four weeks.


* There is a higher risk of serious infection in patients taking the drug.


* Postmarketing studies will be conducted to determine the long-term safety of the drug.


Certolizumab pegol (Cimzia), a PEGylated anti-tumor necrosis factor-[alpha] therapy, has been approved for use in adults to alleviate the signs and symptoms of Crohn's disease and to maintain a clinical response in moderate-to-severe disease that has not responded adequately to conventional therapy. Typically produced in inflammatory conditions, tumor necrosis factor-[alpha] is overproduced in autoimmune disorders; therefore, inhibition of its activity reduces inflammation. PEGylation is a chemical process that augments a drug molecule to increase its half-life, thereby delaying its elimination. The benefit of PEGylation in pharmacologic therapy is that the desired therapeutic level of a drug is maintained with less frequent dosing-for example, certolizumab pegol is administered subcutaneously every two weeks during induction (the first three injections), and then every four weeks as maintenance treatment in the presence of a clinical response.


In a clinical trial involving patients with moderate-to-severe Crohn's disease, a slightly greater improvement in symptoms was achieved with certolizumab pegol, compared with placebo (35% and 27%, respectively), after six weeks. In patients who responded favorably to induction therapy with certolizumab pegol in another clinical trial, sustained response and remission were more common in those taking the drug than in those taking placebo after 26 weeks (48% and 29%, respectively).


Because certolizumab pegol suppresses the immune system, patients taking the drug are at risk for developing serious, possibly fatal, infections, including tuberculosis and opportunistic infection. In patients who are chronic carriers of the hepatitis B virus, there can be a heightened risk of a possibly fatal reactivation of the virus. Other drugs that inhibit tumor necrosis factor activity are known to have the potential to cause lymphomas or other malignancies, none of which were reported in the clinical trials of certolizumab pegol; postmarketing research will be conducted to confirm the safety of long-term use of the drug. Nurses should instruct patients in the subcutaneous administration of certolizumab pegol and advise them to be vigilant for symptoms of infection. Patients should also be instructed to thoroughly read the medication guide dispensed with each prescription because new information concerning the drug's safety will be included as it becomes available.


Sandborn WJ, et al. N Engl J Med 2007;357(3):228-38; Schreiber S, et al. N Engl J Med 2007;357(3):239-50; FDA approves Cimzia to treat Crohn's Disease. FDA News 2008 Apr 22.




* Tussionex Pennkinetic Extended-Release Suspension has been reported to cause severe, sometimes fatal, respiratory depression in patients who either have taken too much of the drug or are too young to take it at all.


* Prescribers are reminded to follow the product label indication specifying drug administration every 12 hours and to observe its contraindication in children younger than six years of age.


The Food and Drug Administration (FDA) has issued an alert to health care professionals concerning the safe and proper use of Tussionex Pennkinetic Extended-Release Suspension, a combination of hydrocodone polistirex and chlorpheniramine polistirex. The FDA released the alert after receiving case reports of severe and sometimes fatal respiratory depression resulting from improper use of the long-acting cough suppressant. The narcotic hydrocodone is a semisynthetic derivative of codeine that also suppresses cough (presumably by directly inhibiting the cough center) and depresses the respiratory drive-high doses of it can produce significant respiratory depression. Chlorpheniramine, an antihistamine that also has sedative properties, reduces edema in the respiratory mucosa.


Two problems are apparent in the case reports-first, as an extended-release product, Tussionex Pennkinetic Extended-Release Suspension is designed to be taken no more than once every 12 hours. Patients who suffered adverse effects either were given a prescription for its use at more frequent intervals or they themselves had chosen to take the drug more often. (There have also been reports of physicians prescribing higher doses or patients taking higher doses of their own accord.) Second, Tussionex Pennkinetic Extended-Release Suspension is not indicated for use in children younger than six years of age, yet some of the reported adverse effects have occurred in young children. Both misusages have resulted in life-threatening respiratory effects and death, sometimes in children younger than six.


Nurses should be sure to instruct patients not to take Tussionex Pennkinetic Extended-Release Suspension more often than once every 12 hours and, to prevent overdosage, to accurately measure doses with a dosing spoon, medication cup, or syringe, not with a household teaspoon or tablespoon. Patients and their families should also be instructed to watch for any labored, irregular, or periodic breathing; very slow breathing; very slow heart rate; severe sleepiness; or cold, clammy skin. If patients experience (or their families notice) any of these symptoms, the drug should be discontinued and the prescriber notified at once. Nurses who note that a child younger than six years of age has a prescription for this antitussive should consult the prescriber.


FDA issues alert on Tussionex, a long-acting prescription cough medicine containing hydrocodone. Agency gives new safety information on proper use of Tussionex as a cough suppressant. FDA News 2008 Mar 11.