Advair HFA (combination), Serevent Diskus

Name: Advair HFA (combination), Serevent Diskus

Advair HFA (combination), Serevent Diskus Pharmacokinetics

Absorption

Bioavailability

Most of an orally inhaled drug actually is swallowed.1 2 38 39 188 Bronchodilating action of orally inhaled sympathomimetic agents is believed to result from a local action of the portion of dose that reaches the bronchial tree.1 2 38 39 188

Low or undetectable systemic concentrations occur after inhalation of the recommended dosage and are not predictive of therapeutic effects.1 39 188

Onset

Time to onset of effective bronchodilation 60 minutes with salmeterol oral inhalation powder.188 Initial improvement in asthma control may occur within 30 minutes following oral inhalation of salmeterol in fixed combination with fluticasone propionate. Maximum benefit may not be achieved for 1 week or longer after initiating treatment with salmeterol in fixed combination with fluticasone propionate.221 257

Maximum improvement in FEV1 generally occurs within 3 hours after administration of salmeterol oral inhalation powder.188

Duration

Clinically important improvements are maintained for up to 12 hours in most patients receiving salmeterol oral inhalation powder.188 In the prevention of exercise-induced bronchospasm in adolescents and adults, salmeterol oral inhalation powder provides protection for up to 9 hours and up to 12 hours in children 4–11 years of age.188

Distribution

Extent

Crosses the blood-brain barrier in trace amounts.13 38

Not known whether the drug and/or its metabolites cross the placenta.154

Distributed into milk in rats;38 188 not known whether is distributed into human milk.253

Plasma Protein Binding

94–98%.25 154

Elimination

Metabolism

Extensively metabolized in the liver by hydroxylation.1 2 25 38

Elimination Route

Eliminated in feces (60%) and urine (25%), 1 2 25 38 188 principally as metabolites.1 2 38 154 188

Half-life

About 5.5 hours (oral administration).1 25 188

Special Populations

Pharmacokinetics not studied in patients with hepatic impairment; however, increased plasma concentrations may occur since drug is predominantly cleared by hepatic metabolism.188 (See Hepatic Impairment under Cautions.)

Stability

Storage

Oral Inhalation

Powder

Salmeterol Serevent Diskus alone or in fixed combination with fluticasone Advair Diskus: 20–25°C in a dry place away from direct heat and sunlight.188 221 253

Discard Serevent Diskus 6 weeks after removal from foil pouch or when every blister used (when the dose counter reads “0”), whichever comes first.188

Discard Advair Diskus 1 month after removal from foil pouch or when every blister used, whichever comes first.254 255

Aerosol

Fixed combination with fluticasone: 25°C (may be exposed to 15–30°C) with mouthpiece down.257 258

Contents under pressure; do not puncture, use or store near heat or open flame, or place into fire or incinerator.257 258 Exposure to temperatures >49°C may cause canister to burst.257 Discard when dose counter reads “000.”257

Other Comments

Administration advice:
-For oral inhalation only.
-This drug should not be used more often or at doses higher than recommended.
-If a dose is missed, skip that dose and take the next dose at the usual time. Do not take 2
doses at one time.
-Consult the manufacturer product information for instructions on how to use the inhaler.

Storage requirements:
-Store in a dry place away from direct heat or sunlight.
-Store inside the unopened moisture-protective foil pouch and only removed from the pouch immediately before initial use.

General:
-This drug should only be used with a long-term asthma control medicine, such as an inhaled corticosteroid; it should not be used as the only asthma medicine.
-Patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids should not use this drug.

Limitation of use:
-This drug is not indicated for the relief of acute bronchospasm.

Monitoring:
-Cardiac monitoring is recommended in cases of overdosage.

Patient advice:
-Patients should seek immediate attention if their condition deteriorates.
-Dose or frequency should not be increased without consulting the prescribing physician.
-Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
-Concomitant asthma therapy should not be stopped or reduced without medical advice.
-Other LABA should not be used when using this drug.

Salmeterol Breastfeeding Warnings

Caution is recommended. Benefit should outweigh risk. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.

Studies of HFA-134a revealed no effects on the reproductive performance and lactation of adult or two successive generations of rats or on the fetal development of rats or rabbits. Plasma levels of this drug after inhaled therapeutic doses are negligible and therefore levels in milk should be correspondingly low.

Salmeterol Levels and Effects while Breastfeeding

Summary of Use during Lactation

Although no published data exist on the use of salmeterol by mouth or inhaler during lactation, data from the related drug, terbutaline, indicate that very little is expected to be excreted into breastmilk.[1] The authors of several reviews agree that use of inhaled bronchodilators is acceptable during breastfeeding because of the low bioavailability and maternal serum levels after use.[2][3][4][5]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Formoterol

References

1. Lindberg C, Boreus LO, de Chateau P et al. Transfer of terbutaline into breast milk. Eur J Resp Dis. 1984;65 (Suppl 134):87-91. PMID: 6586490

2. McDonald CF, Burdon JGW. Asthma in pregnancy and lactation. A position paper for the Thoracic Society of Australia and New Zealand. Med J Aust. 1996;165:485-8. PMID: 8937369

3. Ellsworth A. Pharmacotherapy of asthma while breastfeeding. J Hum Lact. 1994;10:39-41. PMID: 7619245

4. Nelson-Piercy C. Asthma in pregnancy. Thorax. 2001;56:325-8. PMID: 11254828

5. Taddio A, Ito S. Drugs and breast-feeding. In: Koren G, ed. Maternal-fetal toxicology. A clinician's guide. 3rd ed. New York: Marcel Dekker, 2001:177-32.

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