FDA Safety Changes: Prinzide, Avinza, Epogen

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http://www.medscape.com/viewarticle/520899?sssdmh=dm1.176757 & src=nldne

FDA Safety Changes: Prinzide, Avinza, Epogen

News Author: Yael Waknine

Release Date: January 5, 2006; Valid for credit through January 5, 2007

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Jan. 5, 2006 — The U.S. Food and Drug Administration (FDA) approved in

October 2005 safety labeling revisions to advise that the lisinopril

component of lisinopril plus hydrochlorothiazide tablets has been associated

with rare incidences of head/neck angioedema and hepatic failure;

concomitant consumption of alcohol with morphine sulfate extended-release

capsules is associated with a risk for morphine overdose; and epoetin alfa

injection has been linked to a risk for pure red cell aplasia and severe

anemia caused by the development of neutralizing antibodies to

erythropoietin.

Lisinopril/HCTZ (Prinzide) Rarely Linked to Head/Neck Angioedema, Hepatic

Failure

On October 5, 2005, the FDA approved safety labeling revisions for

lisinopril plus hydrochlorothiazide (HCTZ) tablets (Prinzide, made by Merck

and Co, Inc) to warn that the lisinopril component has been associated with

rare incidences of head/neck angioedema and hepatic failure.

Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx

has been reported rarely in patients treated with angiotensin-converting

enzyme (ACE) inhibitors, such as lisinopril. This may occur at any time

during treatment and has occurred more frequently in black compared with

nonblack patients.

Immediate discontinuation of lisinopril/HCTZ therapy is advised in patients

presenting with angioedema; appropriate antihistamine/corticosteroid therapy

and monitoring should be provided until complete and sustained resolution of

all signs and symptoms has occurred.

The FDA notes that even patients presenting with swelling of the tongue only

(in the absence of respiratory distress) may require prolonged observation

because treatment may not be sufficient. Very rarely, airway obstruction due

to angioedema of the larynx or tongue has resulted in fatality.

Patients with involvement of the tongue, glottis, or larynx who are likely

to experience airway obstruction (especially those with a history of airway

surgery) should be treated with 0.3 to 0.5 mL subcutaneous 1:1000

epinephrine solution and/or other measures to ensure patency.

ACE inhibitor therapy also rarely has been associated with a syndrome that

initially presents as cholestatic jaundice or hepatitis and progresses to

fulminant hepatic necrosis and sometimes death. Although the mechanism of

this syndrome is not understood, ACE inhibitors should be discontinued in

patients who develop jaundice or marked elevations of hepatic enzymes.

Lisinopril plus HCTZ tablets are indicated for the treatment of

hypertension. The fixed-dose combinations are not indicated for initial

therapy.

Alcohol Interaction With Extended-Release Morphine Sulfate (Avinza) May Be

Lethal

On October 18, 2005, the FDA approved safety labeling revisions for morphine

sulfate extended-release capsules (Avinza, made by Ligand Pharmaceuticals,

Inc) to warn of the risk for morphine overdose in patients concomitantly

consuming alcohol.

The warning was based on data from FDA laboratory studies of a 30-mg dose in

900-mL buffer solutions containing 20% and 40% ethanol, showing the rapid

release of morphine to be alcohol concentration–dependent.

Although its clinical relevance has not been established, the accelerated

release of morphine observed in vitro may correlate with in vivo release and

absorption of a potentially fatal dose of morphine.

Patients receiving morphine therapy should be warned not to consume

alcoholic beverages or use prescription or over-the-counter medications

containing alcohol.

Morphine extended-release once-daily capsules are indicated for the relief

of moderate to severe pain requiring continuous, around-the-clock opioid

therapy for an extended period.

Epoetin Alfa (Epogen) Linked to Risks for Pure Red Cell Aplasia and Anemia

On October 26, 2005, the FDA approved safety labeling revisions for epoetin

alfa injection (Epogen, made by Amgen, Inc) to reflect postmarketing reports

of pure red cell aplasia (PRCA) and severe anemia, with or without other

cytopenias, associated with the development of neutralizing antibodies to

erythropoietin in patients receiving the product.

Although these events have occurred predominantly in patients with chronic

renal failure (CRF) receiving epoetin alfa by subcutaneous injection, any

patient who develops a sudden loss of response accompanied by severe anemia

and low reticulocyte counts should be evaluated for causative factors.

Causative etiologies to be considered include iron deficiency; underlying

infectious, inflammatory, or malignant processes; occult blood loss;

underlying hematologic diseases, such as thalassemia, refractory anemia, or

other myelodysplastic disorders; folic acid/vitamin B12 deficiencies;

hemolysis; aluminum intoxication; and osteitis fibrosa cystica.

In the absence of another etiology, patients should be evaluated for

evidence of PRCA and undergo serum testing for antibodies to erythropoietin.

Assays for binding and neutralizing antibodies may be requested from the

manufacturer by telephone at 1-800-AMGEN.

All treatment with epoetin alfa and other erythropoietic proteins should be

withheld in patients with suspected antibody-related anemia and permanently

discontinued on diagnostic confirmation. Because of the potential for

antibody cross-reactivity, switching patients from one therapy to another is

not recommended.

Epoetin alfa is indicated for the treatment of CRF-related anemia;

chemotherapy-related anemia in patients with nonmyeloid malignancies; and

anemia in zidovudine-treated HIV patients. It is also indicated to reduce

the risk for allogenic blood transfusion in surgery patients.

http://www.fda.gov/medwatch/safety/2005/oct05.htm

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