FDA Safety Changes: Pexeva, Vfend, Suprane

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FDA Safety Changes: Pexeva, Vfend, Suprane

Abkhazia - Los Angeles,CA*

Written by Ramaz Mitaishvili

Saturday, 29 December 2007

News Author: Yael Waknine

CME Author: Yael Waknine

http://www.abkhazia.com/content/view/1105/74/

The US Food and Drug Administration (FDA) has approved safety

labeling revisions to advise of the risk for serotonin syndrome in

patients receiving concomitant treatment with paroxetine mesylate

and triptans, drug interactions between voriconazole and efavirenz

requiring dose adjustments for both drugs when used concomitantly,

and the risk for respiratory adverse events associated with use of

desflurane in certain pediatric settings.

Concomitant Use of Paroxetine Mesylate (Pexeva) and Triptans Linked

to Risk for Serotonin Syndrome On December 9, 2006, the FDA approved

safety labeling revisions for paroxetine mesylate (Pexeva tablets,

made by Synthon Pharmaceuticals, Ltd) to advise of the potential

increased risk for serotonin syndrome in patients receiving

concomitant treatment with other serotonergic drugs (including 5-

hydroxytryptamine-receptor agonists [triptans]) or drugs that impair

serotonin metabolism (including monoamine oxidase inhibitors

[MAOIs]).

Concurrent treatment with paroxetine and MAOIs is therefore

contraindicated. Concomitant use of other selective serotonin

reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake

inhibitors (SNRIs), or the serotonin precursor tryptophan is not

recommended. Caution is advised when using paroxetine in combination

with other drugs or agents that can affect serotonergic

neurotransmitter systems, such as the antibiotic linezolid (a

reversible nonselective MAOI), lithium, tramadol, St. 's Wort,

and triptans.

According to the FDA, rare postmarketing cases of serotonin syndrome

have been reported with use of SSRIs and triptans. Associated

symptoms may include changes in mental status (eg, agitation,

hallucinations, and coma), autonomic instability (eg, tachycardia,

labile blood pressure, and hyperthermia), neuromuscular aberrations

(eg, hyperreflexia and incoordination), and/or gastrointestinal

tract symptoms, such as nausea, vomiting, and diarrhea.

Paroxetine-treated patients in whom concomitant triptan therapy is

clinically warranted should be carefully monitored, particularly

during initiation of therapy, dose increases, or the addition of

another serotonergic drug.

Triptans are used to treat migraines. The drug class includes

naratriptan HCl (Amerge, made by GlaxoKline), almotriptan

malate (Axert, made by Ortho-McNeil Pharmaceutical, Inc),

frovatriptan succinate (Frova, made by Endo Pharmaceuticals),

sumatriptan/sumatriptan succinate (Imitrex, made by

GlaxoKline), rizatriptan benzoate (Maxalt and Maxalt-MLT, made

by Merck and Co, Inc), eletriptan HBr (Relpax, made by Pfizer, Inc),

and zolmitriptan (Zomig and Zomig ZMT, made by AstraZeneca

Pharmaceuticals LP).

Paroxetine mesylate is indicated for the treatment of major

depressive, obsessive-compulsive, panic, and generalized anxiety

disorders. Although the risk for suicidal behavior/thoughts

(suicidality) warrants monitoring of all patients regardless of the

condition being treated, it is of particular importance in patients

with a history of suicidality, those exhibiting a significant degree

of suicidal ideation prior to treatment, and young adults.

FDA Warns of 2-Way Drug Interaction Between Voriconazole (Vfend) and

Efavirenz

On December 1, 2006, the FDA approved safety labeling revisions for

voriconazole (Vfend injection, tablets, and oral suspension, made by

Pfizer, Inc) to advise of a 2-way drug interaction with

coadministered efavirenz (Sustiva tablets and capsules, made by

Bristol-Myers Squibb).

Standard doses of voriconazole are contraindicated with efavirenz

because efavirenz significantly decreases voriconazole plasma

concentrations while voriconazole significantly increases efavirenz

plasma concentrations.

The warning was based on data from a pharmacokinetic study of

healthy subjects, showing that systemic exposure of voriconazole

(400 mg given orally every 12 hours for 1 day followed by 200 mg

every 12 hours for 8 days) was significantly decreased (mean area

under the curve [AUC], 61%; Cmax, 77%) when given concurrently with

efavirenz (400 mg every 12 hours for 9 days). The AUC and Cmax for

efavirenz increased by an average of 38% and 44%, respectively.

Concomitant therapy therefore requires dosage adjustments for both

agents. Voriconazole maintenance dosing should be increased from 200

to 400 mg and given every 12 hours. The once-daily dose of efavirenz

should be decreased from 600 to 300 mg using the capsule formulation.

Voriconazole is indicated for the treatment of fungal infections,

including invasive aspergillosis, candidemia in nonneutropenic

patients, esophageal candidiasis, and serious infections intolerant

of or refractory to other therapy. It is marketed as 50- and 200-mg

tablets and reconstituted as 40-mg/mL oral suspension and 200-mg

vials.

Efavirenz is a nonnucleoside reverse transcriptase inhibitor

indicated for use in combination with other antiretroviral agents

for the treatment of HIV-1 infection. It is available in 50-, 100-,

and 200-mg capsules and 600-mg tablets.

Desflurane (Suprane) Linked to Respiratory Adverse Events in Certain

Pediatric Settings

On December 15, 2006, the FDA approved safety labeling revisions for

desflurane volatile liquid for inhalation (Suprane, made by Baxter

Healthcare Corp) to advise of the risk for respiratory adverse

events associated with its use in certain pediatric settings.

The FDA warns that desflurane is not recommended for induction of

general anesthesia via a mask in children because of the high

incidence of moderate to severe respiratory adverse reactions,

including laryngospasm (50%), coughing (72%), breath-holding (68%),

increased secretions, (21%), and oxyhemoglobin desaturation (pulse

oximetry [spO2] of <90%, 26%) reported in clinical studies.

Also, desflurane is not approved for maintenance of anesthesia in

nonintubated children because of the increased risk for respiratory

adverse events relative to isoflurane observed in a clinical safety

trial of 300 pediatric patients aged 2 to 16 years (mean, 7.4 years)

who received desflurane via a face mask or laryngeal mask airway

after induction with intravenous propofol or inhaled sevoflurane.

Study results showed that the overall rate of respiratory adverse

events in the desflurane group was 39% and most commonly included

coughing (26%), laryngospasm (13%), and secretions (12%); 5% of

pediatric patients experienced severe laryngospasm (associated with

SpO2 < 90% for > 15 seconds or requiring succinylcholine). The

incidence rate for severe laryngospasm was higher in children aged 2

to 6 years (9%) than in those aged 7 to 11 years or 12 to 16 years

(1% and 1%, respectively).

Removal of the laryngeal mask airway under deep anesthesia (minimum

alveolar concentration [MAC] range, 0.6 - 2.3; mean, 1.12 MAC) was

linked to further increases in the rate of respiratory adverse

events compared with awake removal or removal under deep anesthesia

with isoflurane. The frequency and severity of nonrespiratory

adverse events were comparable between the 2 groups.

Desflurane is indicated as an inhalation agent for induction and/or

maintenance anesthesia in adults undergoing inpatient or outpatient

surgery. Although it is not recommended for anesthetic induction in

pediatric patients because of the high risk for moderate to severe

upper airway adverse events, it may be used for anesthesia

maintenance in infants and children following induction with other

agents and tracheal intubation.

The US Food and Drug Administration (FDA) is warning consumers and

healthcare professionals of the risk for obtaining counterfeit drugs

when purchasing prescription medications online, according to a news

release. The alert was based on information regarding 24 apparently

related Web sites that appear on the pharmacycall365.com home page

under the " Our Websites " heading, according to an alert sent

yesterday from MedWatch, the FDA's safety information and adverse

event reporting program.

On 3 recent occasions, the FDA was informed that counterfeit

versions of orlistat 120-mg capsules (Xenical; Hoffmann-La Roche,

Inc) were being supplied by 2 of the Web sites. None of the capsules

contained orlistat; one contained sibutramine (Meridia; Abbott

Laboratories, Inc) and the others were filled with talc and starch.

The latter were provided in blister packs stamped with a valid Roche

lot number but displaying an expiration date of April 2007 rather

than March 2005. The counterfeit products cannot be differentiated

on sight alone as they closely resemble legitimate products (photos

are available at

http://www.fda.gov/bbs/topics/news/photos/xenical.html).

The Web sites involved in distributing the counterfeit orlistat

capsules were Brandpills.com and PillsPharm.com, which appear on the

same pharmacycall365.com page that is home to 22 other Web sites, 4

of which previously have been linked to shipments of counterfeit

oseltamivir phosphate (Tamiflu; Roche Laboratories, Inc) and

tadalafil (Cialis, Lilly ICOS, LLC).

These include AllPills.net, Pharmacy-4U.net, DirectMedsMall.com,

Emediline.com, RX-ed.com, RXePharm.com, Pharmacea.org,

MensHealthDrugs.net, BigXplus.net, MediClub.md, InterTab.de,

Pillenpharm.com, Bigger-X.com, PillsLand.com, EZMEDZ.com,

UnitedMedicals.com, est-Medz.com, USAPillsrx.net, USAMedz.com,

BluePills-Rx.com, Genericpharmacy.us, and I-Kusuri.jp.

According to the FDA, the Web sites appear to operate from outside

the United States. Consumers should therefore be wary if the company

cannot be contacted by phone, if their prices appear to be extremely

low, or if no prescription is required. Additional information

regarding the purchase of prescription drugs over the Internet may

be obtained online at www.fda.gov/buyonline/.

Healthcare professionals are encouraged to report potentially

counterfeit drugs to the FDA's MedWatch reporting program by phone

at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at

http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane,

Rockville, MD 20852-9787.