FDA Safety Changes: Cialis, Sonata, Lunesta CME
FDA Safety Changes: Cialis, Sonata, Lunesta
News Author: Yael Waknine
CME Author: Yael Waknine
Disclosures
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Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians; Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians |
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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.
April 30, 2008 — In December 2007 and January 2008, the US Food and Drug Administration (FDA) approved safety labeling revisions to advise of the risks for drug interactions with once-daily tadalafil therapy, concerns regarding once-daily tadalafil use in patients with renal or hepatic impairment, and the risks for abnormal thinking and behavioral changes in patients receiving zeleplon or eszopiclone for the treatment of insomnia.
Once-Daily Tadalafil (Cialis) Linked to Drug Interactions
On January 7, 2008, the FDA approved safety labeling revisions for tadalafil tablets (Cialis; Eli Lilly and Co) to warn of the potential for drug interactions associated with use of a once-daily dose for the treatment of erectile dysfunction. The recommended starting dose for this regimen is 2.5 mg taken once daily without regard to food.
Although dose increases to 5 mg are allowed based on efficacy and tolerability, healthcare clinicians should be aware that the continuous tadalafil levels produced by the once-daily regimen may lead to drug interactions with other medications and alcohol.
Because tadalafil is metabolized predominantly by the cytochrome P450 isoenzyme 3A4 (CYP3A4), the once-daily dose should not exceed 2.5 mg in patients receiving concomitant therapy with potent CYP3A4 inhibitors such as ritonavir, ketoconazole, and itraconazole. For those using tadalafil on an as-needed basis, dosing should not exceed 5 mg taken every 72 hours.
Alcohol and phosphodiesterase type 5 inhibitors, such as tadalafil, are both mild vasodilators, and their concomitant use may have an additive effect on lowering blood pressure. Patients should be informed that substantial consumption of alcohol (eg, ≥ 5 units) in combination with tadalafil can increase the risk for orthostatic signs and symptoms, including increased heart rate, decreased standing blood pressure, dizziness, and headache.
Once-daily use of tadalafil is not recommended for patients with severe renal insufficiency because of increased drug exposure, limited clinical experience, and the lack of ability to influence clearance by dialysis. For these patients, as-needed use should not exceed 5 mg every 72 hours.
According to the FDA, no dose adjustments to the once-daily regimen are required for patients with mild or moderate renal insufficiency. This is also true of as-needed dosing in mild renal impairment; patients with moderate impairment should take a starting dose of 5 mg as needed, not to exceed 10 mg in 48 hours.
Caution is advised when using once-daily tadalafil therapy in patients with mild to moderate hepatic impairment; the dose should not exceed 10 mg for those taking tadalafil on an as-needed basis. Lack of clinical data precludes recommending its use in patients with severe liver dysfunction.
Zaleplon (Sonata) and Eszopiclone (Lunesta) Linked to Risk for "Sleep-Driving"
On December 12, 2007, and January 29, 2008, the FDA approved safety labeling revisions for zaleplon capsules (Sonata; King Pharmaceuticals, Inc) and eszopiclone tablets (Lunesta; Sepracor, Inc), respectively, to warn of the risks for abnormal thinking and behavioral changes associated with use of these and other sedative-hypnotic drugs.
Because sleep disturbances may indicate a physical or psychiatric disorder, patients with insomnia that does not remit after 7 to 10 days of therapy should be evaluated for the presence of a primary illness.
Worsening of insomnia or the emergence of new thinking or behavioral abnormalities during treatment can likewise indicate an underlying physical or psychiatric disorder. Use of sedative-hypnotics in primarily depressed patients has been linked to worsening depression, including suicidal thoughts and actions and completed suicide.
Complex behaviors have been reported in treatment-naive and treatment-experienced patients who are not fully awake after taking sedative-hypnotics such as zaleplon and eszopiclone. These behaviors are associated with amnesia and include "sleep-driving" (driving while not fully awake after taking a sedative-hypnotic), preparing or eating meals, telephone calls, and having sexual intercourse.
Although these behaviors can occur with normal doses of a sedative-hypnotic, the likelihood of performing activities while asleep increases with excessive doses and concomitant use of alcohol or other central nervous system depressants.
Because of the risk to the patient and to the community, strong consideration should be given to discontinuing therapy in patients who report "sleep-driving" episodes.
All newly emergent behaviors should be evaluated, although it may not be possible to discern whether they are of spontaneous origin, drug-induced, or the result of an underlying disorder. Because of the risk for withdrawal symptoms, treatment should not be abruptly withdrawn, and rapid dose decreases should be avoided. Some events related to sedative or hypnotic use appear to be dose related, necessitating use of the lowest effective dose, particularly in elderly people.
The FDA also warned that rare cases of angioedema involving the tongue, glottis, or larynx have been reported in patients taking the first or subsequent doses of sedative-hypnotics. In some cases, these symptoms were accompanied by dyspnea, throat closing, or nausea and vomiting that suggested anaphylaxis and required emergency care. Because airway obstruction can cause death, patients in whom angioedema develops after taking zaleplon or eszopiclone should not be rechallenged with a sedative-hypnotic.
Eszopiclone and Zaleplon are indicated for the treatment of insomnia.
Cialis Prescribing Information
Sonata Prescribing Information
Lunesta Prescribing Information
Pearls for Practice
- The recommended starting dose for once-daily tadalafil is 2.5 mg, which may be increased to 5 mg if needed. The dose should be limited to 2.5 mg for patients receiving concomitant therapy with potent cytochrome P450 isoenzyme 3A4 inhibitors. Substantial consumption of alcohol (≥ 5 units) can increase the risk for orthostatic signs and symptoms.
- Once-daily use of tadalafil is not recommended in severe renal insufficiency or severe liver dysfunction. No dose adjustments are required for mild or moderate renal impairment, and caution is advised in mild to moderate hepatic impairment.
- Eszopiclone and zaleplon as well as other sedative-hypnotics have been linked to "sleep-driving" and other complex behaviors in treatment-naive and treatment-experienced patients. These events can occur at normal doses but are more likely to occur with excessive doses or concomitant use of alcohol and other central nervous system depressants. Patients in whom angioedema of the tongue, glottis, or larynx develops should not be rechallenged with a sedative-hypnotic.