FDA Safety Changes: Asmanex Twisthaler, Advair HFA, Avelox CME

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FDA Safety Changes: Asmanex Twisthaler, Advair HFA, Avelox CME

Medscape*

News Author: Yael Waknine

CME Author: Yael Waknine

..

http://www.medscape.com/viewarticle/577974

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.

July 24, 2008 — The US Food and Drug Administration (FDA) has

approved safety labeling revisions to emphasize certain warnings

associated with the use of mometasone furoate inhalation powder,

drug interactions that can increase the risk for cardiovascular

adverse events in patients receiving salmeterol xinafoate plus

fluticasone propionate inhalation therapy, and the risks for

photosensitivity and phototoxicity in patients receiving treatment

with quinolone antibiotics such as moxifloxacin HCl.

Mometasone Furoate Inhalation Powder (Asmanex Twisthaler) Warnings

Strengthened

On February 26, the FDA approved safety labeling revisions for

mometasone furoate inhalation powder (Asmanex Twisthaler; Schering-

Plough Corp) that place additional emphasis on warnings and

precautions associated with its use.

Because of the risk for local Candida albicans infection of the

mouth and pharynx (incidence in clinical studies, 6.5%), the FDA

advises that patients receiving mometasone therapy rinse their mouth

after each dose. If oropharyngeal candidiasis develops, systemic

antifungal therapy should be initiated while continuing treatment

with mometasone.

Inhaled corticosteroids such as mometasone should be used with

caution, if at all, in patients with active or quiescent

tuberculosis infection; untreated fungal, bacterial, viral, or

parasitic infection; or ocular herpes simplex, the FDA warned,

noting the potential for clinical worsening. In a similar fashion,

chickenpox or measles have been reported with increased severity and

some fatalities in susceptible patients. Prophylaxis with varicella

zoster immune globulin or pooled intramuscular immune globulin

prophylaxis should be considered for patients exposed to disease.

The FDA also warned of the risk for impaired adrenal function when

switching from oral steroids (eg, prednisone tablets) to inhaled

corticosteroids such as mometasone. Systemic agents should be slowly

tapered and patients carefully observed for signs and symptoms of

adrenal insufficiency such as fatigue, lassitude, weakness, nausea,

vomiting, and hypotension. Transfer from systemic therapy to

mometasone may also unmask previously suppressed allergic or other

immunologic conditions such as rhinitis, conjunctivitis,

eosinophilic conditions, eczema, and arthritis.

Decreases in bone mineral density (BMD) have been observed with long-

term use of inhaled corticosteroids, including mometasone. Although

the clinical significance of small changes in BMD on long-term

outcome remains unknown, caution and regular monitoring is advised

for patients with major risk factors for decreased bone mineral

content such as prolonged immobilization, family history of

osteoporosis, or chronic use of agents that can reduce bone mass

(eg, anticonvulsants).

The FDA also warned that use of orally inhaled corticosteroids, such

as mometasone, may cause a reduction in pediatric growth velocity.

Pediatric growth should be monitored routinely via methods such as

stadiometry, and treatment should be titrated to the lowest

effective dose.

Because glaucoma, increased intraocular pressure, and cataracts have

been reported in clinical trials of mometasone (incidence, 0.27%),

close monitoring is warranted in patients with vision changes or a

history of these conditions.

Mometasone inhalation powder is indicated for the maintenance

treatment of asthma as prophylactic therapy in patients aged 4 years

and older.

Drug Interactions With Salmeterol Xinafoate Component of Advair HFA

Linked to Cardiovascular Events

On March 20, the FDA approved safety labeling revisions for

fluticasone propionate plus salmeterol xinafoate inhalation aerosol

(Advair HFA, GlaxoKline) to warn of drug interactions with

salmeterol that may increase the risk for cardiovascular adverse

events.

Salmeterol is a long-acting â2-adrenergic agonist that is

extensively metabolized to á-hydroxysalmeterol (aliphatic oxidation)

by the cytochrome P450 3A4 (CYP3A4) isoenzyme. Concomitant use of

CYP3A4 inhibitors, such as ketoconazole, may therefore increase

salmeterol exposure and the risk for drug-related adverse events.

In a drug interaction study of 20 healthy subjects, coadministration

of ketoconazole (400 mg once daily) with salmeterol (50 µg twice

daily) for 7 days yielded a 16-fold increase in salmeterol total

exposure (area under the curve), with a 1.4-fold increase in peak

blood levels.

Three participants were withdrawn from the study because of â2-

adrenergic agonist adverse events; 2 subjects had prolonged QTc

intervals, and 1 experienced palpitations and sinus tachycardia.

Although there was no statistically significant effect on mean QTc,

coadministration of salmeterol and ketoconazole was associated with

more frequent increases in QTc duration vs salmeterol and placebo

administration.

Because of the potential increased risk for cardiovascular adverse

events, concomitant use of salmeterol with strong CYP3A4 inhibitors

(eg, ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir,

itraconazole, nefazodone, nelfinavir, saquinavir, or telithromycin)

is not recommended.

Salmeterol plus fluticasone inhalation aerosol is indicated for the

long-term, twice-daily maintenance treatment of asthma in patients

aged 12 years and older.

Quinolones, Including Moxifloxacin HCl (Avelox), Linked to Risk for

Phototoxicity

On February 15, the FDA approved safety labeling revisions for

moxifloxacin HCl tablets and moxifloxacin in sodium chloride

injection (Avelox, Bayer Pharmaceuticals Corp) to warn of the risk

for photosensitivity and phototoxicity associated with quinolone

antibiotics.

In addition to moderate to severe photosensitivity, the agency has

received postmarketing reports of phototoxicity reactions that can

manifest as exaggerated sunburn reactions such as burning, erythema,

exudation, vesicles, blistering, and edema that involve areas

exposed to light (eg, the face, " V " area of the neck, extensor

surfaces of the forearms, and dorsa of the hands). These reactions

can be associated with the use of quinolones after sun or

ultraviolet light exposure.

Excessive exposure to these sources of light should therefore be

avoided, and treatment should be discontinued if photosensitivity or

phototoxicity occurs.

Patients should be advised to minimize or avoid exposure to natural

or artificial sunlight (eg, tanning beds or ultraviolet A/B light

treatment) while taking quinolones. Those who need to be outdoors

during therapy should wear loose-fitting clothes that protect skin

from sun exposure and adopt other sun protection measures such as

sunscreen if possible.

Moxifloxacin is a broad-spectrum fluoroquinolone antimicrobial agent

indicated for use in adults to treat infections caused by

susceptible strains of designated microorganisms. Indications

include acute bacterial sinusitis, acute bacterial exacerbation of

chronic bronchitis, community-acquired pneumonia, uncomplicated and

complicated skin or skin structure infections, and complicated

intraabdominal infections.

Asmanex Twisthaler Prescribing Information

Advair Prescribing Information

Avelox Prescribing Information

Pearls for Practice

Use of orally inhaled corticosteroids, such as mometasone furoate,

is linked to risks for oropharyngeal candidiasis, worsening of

preexisting infections, decreased bone mineral density, and

reductions in pediatric growth velocity. Patients switching from

systemic therapy should be observed for signs of adrenal

insufficiency; previously suppressed allergic conditions may be

unmasked.

Because of the potential increased risk for cardiovascular adverse

events, concomitant use of salmeterol xinafoate with strong

cytochrome P450 3A4 isoenzyme inhibitors (eg, ketoconazole,

ritonavir, atazanavir, clarithromycin, indinavir, itraconazole,

nefazodone, nelfinavir, saquinavir, or telithromycin) is not

recommended.

Phototoxicity reactions have been reported with use of quinolone

antibiotics such as moxifloxacin HCl. These reactions can manifest

as exaggerated sunburn that involves areas exposed to light and can

be associated with the use of quinolones after sun or ultraviolet

light exposure. Excessive exposure to these sources of light should

therefore be avoided and treatment discontinued if

photosensitivity/phototoxicity occurs.