Friday, September 22, 2023
This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.
October 3, 2007 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of the risks for angioedema, hypersensitivity reactions, peripheral edema, dizziness, and somnolence in patients receiving pregabalin therapy; the rare risk for serious skin reactions associated with use of ribavirin tablets; the potential for neuropsychiatric disorders in patients receiving treatment with interferon alfa-2b injection; and the risk for dental or periodontal disorders and fetal harm associated with interferon alfa-2b plus ribavirin.
On June 21, the FDA approved safety labeling revisions for pregabalin capsules ( Lyrica; Pfizer, Inc) to advise of the risks for angioedema, hypersensitivity reactions, peripheral edema, dizziness, and somnolence.
Postmarketing reports have identified a risk for angioedema during initial and chronic use of pregabalin. Symptoms included swelling of the face, mouth (tongue, lip, and gums), and neck (throat and larynx). Because some cases included life-threatening angioedema with respiratory compromise requiring emergency treatment, treatment should be discontinued immediately if these symptoms occur.
Caution is advised when prescribing pregabalin to patients with a history of angioedema and to those taking other medications, such as angiotensin-converting enzyme inhibitors, associated with this risk.
There also have been postmarketing reports of other hypersensitivity reactions shortly after initiating pregabalin therapy. Treatment should be immediately discontinued in patients who develop skin redness, blisters, hives, rash, dyspnea, or wheezing.
The FDA also warned that pregabalin may cause peripheral edema. In controlled clinical trials, this occurred in 6% of pregabalin-treated patients vs 2% of those receiving placebo; discontinuation rates were 0.5% and 0.2%, respectively.
Because of the risk for dizziness and somnolence observed in clinical studies (31% vs placebo, 9% and 22% vs 7%, respectively), patients should be warned that use of pregabalin may impair their ability to perform tasks such as driving or operating machinery.
Pregabalin is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. It also is approved as adjunctive therapy in adults with partial-onset seizures.
On June 19, the FDA approved safety labeling revisions for ribavirin tablets ( Copegus; Hoffmann-La Roche, Inc) to advise of the rare risk for serious skin reactions.
In addition to severe acute hypersensitivity reactions rarely observed during alpha-interferon/ribavirin therapy (eg, urticaria, angioedema, bronchoconstriction, and anaphylaxis), serious skin reactions have occurred.
These have included vesiculobullous eruptions, reactions in the spectrum of Stevens-Johnson syndrome (erythema multiforme major) with various degrees of skin or mucosal involvement, and exfoliative dermatitis (erythroderma). Discontinuation of therapy is advised for patients who develop signs or symptoms of these conditions.
Ribavirin is indicated with the alpha-interferon peginterferon alfa-2a ( Pegasys subcutaneous injection; Hoffman-La Roche, Inc) for the treatment of chronic hepatitis C virus infection in interferon-alfa–naive adults with compensated liver disease.
On July 13, the FDA approved revisions to the safety labeling for interferon alfa-2b powder for injection ( Intron A; Schering Corp) to warn of the risk for neuropsychiatric and dental and periodontal disorders, and to inform clinicians of a ribavirin pregnancy registry.
The FDA previously warned of the potential risk for depression (including suicidal ideation, suicidal attempts, and completed suicides) in patients treated with alpha-interferons such as interferon alfa-2b.
The agency now adds that aggressive behavior, sometimes directed toward others, has also been reported. Patients who develop psychiatric problems, including clinical depression, should be carefully monitored during therapy and for 6 months thereafter.
If psychiatric symptoms persist or worsen, or suicidal or aggressive behavior toward others is observed, use of interferon alfa-2b should be discontinued and psychiatric intervention instituted as necessary. The FDA notes that cases of encephalopathy have been observed, usually in elderly patients receiving high doses of interferon alfa-2b.
The FDA also warned that dental and periodontal disorders have been reported in patients receiving ribavirin and interferon combination therapy. Dry mouth can also have a damaging effect on teeth and mucous membranes during long-term treatment. Patients should be advised to brush their teeth thoroughly twice daily and have regular dental examinations. Those who experience vomiting should rinse their mouth thoroughly afterwards.
Use of interferon alfa-2a is contraindicated in pregnant women and their partners (category X). A Ribavirin Pregnancy Registry has been established to monitor maternal and fetal outcomes of pregnancies in women and women partners of male patients exposed to ribavirin during treatment and for 6 months thereafter. Clinicians are encouraged to report these cases by calling 1-800-593-2214.
Interferon alfa-2b alone or in combination with ribavirin is indicated for the treatment of chronic hepatitis C virus infection in interferon-alfa–naive adults with compensated liver disease; its use is contraindicated in patients with creatinine clearance rates of less than 50 mL/minute.
It also is approved for the treatment of AIDS-related Kaposi's sarcoma and hairy cell leukemia, as an adjunct to surgical treatment of malignant melanoma, with anthracycline-containing chemotherapy for the initial treatment of aggressive follicular non-Hodgkin's lymphoma, and for the intralesional treatment of certain patients with condylomata acuminate (genital warts).
http://www.fda.gov/medwatch/SAFETY/2007/Jun_PI/Lyrica_PI.pdf
http://www.fda.gov/medwatch/SAFETY/2007/Jun_PI/Copegus_PI.pdf
http://www.fda.gov/medwatch/safety/2007/Jul_PI/IntronA_PI.pdf
