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UAP [ United Lab ]
MIMS Class : Antiasthmatic & COPD Preparations

See related Duavent Metered-dose inhaler information

Contents 
   Ipratropium Br 500 mcg, salbutamol sulfate 2.5
mg. 


  Ipratropium Br 21 mcg, salbutamol sulfate 120 mcg
Indications Management of reversible bronchospasm associated with obstructive
airway diseases (eg, bronchial asthma).

For patients with chronic obstructive pulmonary disease (COPD) on a

regular inhaled bronchodilator who continue to have evidence of
bronchospasm and who require a second bronchodilator.
Dosage @
 Each pulmoneb of ipratropium bromide-salbutamol contains
2500 mcg (2.5 mg) of salbutamol base (with each drop containing 50
mcg).

`


    `  
Ñ

  
 1 pulmoneb (2.5 mL) is sufficient for
prompt symptom relief in many cases; 2 pulmonebs (5 mL) may be
required in severe cases where an attack has not been relieved by 1
pulmoneb.


Ñ

1 pulmoneb (2.5 mL) every 6-8 hrs daily.

   3 drops/kg/dose, maximum dose 2500 mcg (2.5
mg) of salbutamol every 6-8 hrs.



  The solution is intended only for inhalation with
suitable nebulizing devices and should not be taken orally.

Prepare the nebulizer for use. Remove the pulmoneb from the labeled
strip by twisting and pulling. Hold the pulmoneb upright and twist off the
cap, transfer the contents to the reservoir of the nebulizer. (Note: In most
studies, a volume fill of 4 mL in the nebulizer chamber, using sterile
normal saline as diluent, is recommended to ensure high aerosol output,
small respirable particle size and acceptably short treatment time.)

Use the nebulizer as instructed by the manufacturer. After use, discard

any remaining solution and thoroughly clean the nebulizer.

Other Information: Since the solution contains no preservatives, it is

important to use the content soon after opening. A new pulmoneb should
be used for each administration to avoid microbial contamination.
Discard partly used, opened or damaged pulmoneb. Do not mix the
inhalation solution with other drugs in the same nebulizer.

m 
 
  `
     2 actuations
every 6 hrs.

Patients may have additional inhalations as required but should not

exceed 12 actuations in 24 hrs.

Directions for Use:

1. Before using the inhaler for the 1st time, or if it has not been used for a
week or longer, shake it well and then "test fire" by releasing 1 actuation
into the air. Avoid spraying in the eyes.

2. Shake the inhaler well before each use.

3. Remove the mouthpiece cover, and check if it is clean.

4. Hold the inhaler between the index and thumb. Breathe out deeply
through the mouth and immediately place the mouthpiece in the mouth
between the teeth and close lips around it.

5. Tilt head slightly backwards. Keep the eyes closed because ocular
undesirable effects (ie, temporary blurring of vision, precipitation or
worsening of narrow-angle glaucoma, eye pain) may result after contact
of the aerosol with the eyes.

6. Start breathing in slowly and deeply through the mouth. Press down
the canister while breathing in to release 1 dose while continuing to
breathe in steady and deeply.

7. Remove the inhaler from the mouth and hold breath for 10 seconds, or
for as long as comfortable. Breathe out slowly.

8. For the 2nd dose, wait for at least 1 min and repeat steps 4-7.

9. After use, replace the mouthpiece cover.

Cleaning Instructions: Clean inhaler at least once a week.

 1. Gently pull the metal canister out of the inhaler's adapter. Remove the
mouthpiece cover.

2. Rinse the adapter and the mouthpiece cover in warm water. Do not put
the metal canister in water.

3. Shake well to remove excess water.

4. Leave to dry in warm place. Avoid excess heat.

5. Replace the canister and mouthpiece cover correctly.

Overdosage —   Metered-Dose Inhaler: Signs and symptoms of overdose are
associated with salbutamol since ipratropium bromide is not well
absorbed after oral inhalation. These include extensions of salbutamol's
common undesirable effects (eg, angina, hypertension or hypotension,
arrhythmias, palpitation, tachycardia, nervousness, dizziness, tremor,
headache, sleeplessness or insomnia, dry mouth and nausea).
Hypokalemia has also been reported; thus, plasma potassium
concentrations should be monitored.

Ñ

 Discontinue the use of Duavent and institute appropriate
symptomatic therapy in cases of overdosage. Administration of a ȕ-
adrenergic blocking agent may be appropriate, but use with caution if the
patient is asthmatic. There is no adequate evidence to support the use of
dialysis in the treatment of salbutamol overdose.
Contraindications Hypersensitivity to soya lecithin or related food products eg, soybeans or
peanuts; and to any component of Duavent or to atropine and its
derivatives. Hypertrophic obstructive cardiomyopathy or
tachyarrhythmia.
Warnings Pulmoneb: Ipratropium bromide-salbutamol combination can produce
paradoxical bronchospasm that can be life-threatening. If it occurs,
discontinue the preparation immediately and institute alternative therapy.
It should be recognized that paradoxical bronchospasm, when associated
with inhaled formulations, frequently occurs with the first use of a new
pulmoneb.

Salbutamol sulfate contained in the formulation, like other ȕ-adrenergic

agonists, can produce a clinically significant cardiovascular effect in
some patients as measured by pulse rate, blood pressure and/or other
symptoms. Such effects are uncommon after administration of the
combination at recommended doses.

Metered-Dose Inhaler: If a previously effective dose fails to provide the

usual relief, symptoms become worse, or the usual duration of action is
reduced, consult a physician for medicinal advice as this would require
 reassessment of therapy.

Excessive use of sympathomimetic oral inhalations has been associated

with fatalities in asthmatic patients. The exact cause of death in unknown
but cardiac arrest following severe, acute asthmatic crisis and hypoxia is
suspected.

Paradoxical bronchospasm, a potentially life-threatening event,

frequently occurs with the 1st use of a new canister. If it occurs,
discontinue the use of Duavent immediately.

Therapy with salbutamol and other ȕ2-agonists may produce decrease in

plasma potassium concentration possibly through intracellular shunting
resulting in cardiovascular undesirable effects.

Immediately hypersensitivity reactions including urticaria, angioedema,

rash, bronchospasm, anaphylaxis and oropharyngeal edema may occur
rarely after administration of Duavent.
Special Precautions Patients should avoid spraying the aerosol into the eyes since this may
result in precipitation or worsening of narrow-angle glaucoma, eye pain
or discomfort, temporary blurring of vision, visual halos or colored
images in association of red eyes from conjunctival and corneal
congestion. Consult a physician if any combination of these symptoms
develops. Use with caution in patients with the following conditions:
Prostatic hypertrophy or bladder-neck obstruction; convulsive disorders,
hyperthyroidism or diabetes mellitus and in patients who are unusually
responsive to sympathomimetic amines (ȕ-adrenergic agents may also
produce significant hypokalemia in some patients, possibly through
intracellular shunting, which has the potential to produce adverse
cardiovascular effects. The decrease in serum potassium is usually
transient, not requiring supplementation.); hepatic or renal disease, since
use of Duavent in these patients has not been studied.

2
 
 !

  Safety and efficacy of Duavent during
pregnancy has not yet been established. The inhibitory effect of Duavent
on uterine contraction should be taken into account.

It is not known whether the components (ipratropium bromide and

salbutamol sulfate) of the FDC are excreted in human milk. Although
lipid-insoluble quaternary bases pass into breast milk, it is unlikely that
ipratropium bromide would reach the infant to an important extent,
especially when taken as a nebulized solution. Because of the potential
for tumorigenicity shown for salbutamol sulfate in some animals, a
decision should be made whether to discontinue nursing or discontinue
the drug, taking into account the importance of the drug to the mother.
 Labor and Delivery: Since ȕ2-agonists may interfere with uterine
contraction, Duavent should be used in labor only if the potential benefit
justifies the potential risk.

2
 The safety and efficacy of the FDC in patients <18
years have not been established.
Adverse Drug Pulmoneb: The following adverse effects were reported by •2% in
Reactions patients with COPD in a 12-week controlled clinical trial on ipratropium
bromide-salbutamol sulfate combination (N=358):

Body as a Whole (General Disorders): Headache, pain, influenza, chest

pain.

Gastrointestinal: Nausea.

Respiratory: Bronchitis, dyspnea, coughing, pneumonia, bronchospasm,

pharyngitis, sinusitis, rhinitis.

Additional adverse reactions, reported in <2% of patients include edema,

fatigue, hypertension, dizziness, nervousness, paresthesia, tremor,
dysphonia, insomnia, diarrhea, dry mouth, dyspepsia, vomiting,
arrhythmia, palpitation, tachycardia, arthralgia, angina, increased
sputum, taste perversion and urinary tract infection/dysuria. Allergic-
type reactions eg, skin rash, angioedema of the tongue, lips and face,
urticaria, laryngospasm and anaphylactic reaction have also been
reported.

Metered-Dose Inhaler: The most frequently reported undesirable effects

of ipratropium bromide-salbutamol combination include bronchitis,
dyspnea, cough, lower respiratory tract disorders, pneumonia,
bronchospasm, upper respiratory tract disorders, sinusitis, pharyngitis,
rhinitis, influenza, nasal congestion, wheezing, central nervous system
stimulation, tremor, nervousness, dizziness, headache, sleeplessness or
insomnia, tachycardia, palpitation, angina, pain, weakness, nausea,
vomiting, diarrhea, dyspepsia, dry mouth, dysphonia, increased sputum,
unusual taste/taste perversion and urinary tract infection/dysuria.

Cases of skin rash, angioedema of the tongue, lips and face, urticaria,
laryngospasm, oropharyngeal edema, anaphylactic reactions and
paradoxical bronchospasm have also been reported.

The following adverse effects have been noted after oral inhalation of
ipratropium bromide: Precipitation or worsening of narrow-angle
glaucoma, blurred vision, acute eye pain, drowsiness, coordination
difficulty, hypotension, exacerbation of respiratory symptoms, fatigue,
paresthesia, pruritis, flushing, alopecia, irritation, drying of secretions,
 GI distress, mucosal ulcers and urinary retention/difficulty.

The following adverse effects have been observed after administration of

inhaled salbutamol: Edema, hypertension or hypotension, arrhythmias
(including atrial fibrillation, supraventricular tachycardia and
extrasystoles), heartburn, sweating and rarely muscle cramos. Potentially
serious hypokalemia has been reported.
Click to view ADR Monitoring Website
Drug Interactions Anticholinergic Agents: Although ipratropium bromide is minimally
absorbed into the systemic circulation, there is some potential for an
additive interaction with concomitantly used anticholinergic medications.

Beta-Adrenergic Agents: Co-administration with other sympathomimetic

agents may increase risk of adverse cardiovascular events.

Beta-Receptor Blocking Agents: Salbutamol and a ȕ-receptor blocking

agent inhibit each other's effect.

Diuretics: The ECG changes and/or hypokalemia which may result from
the administration of non-potassium-sparing diuretics (eg, loop or
thiazide diuretics) can be acutely worsened by ȕ-agonists, especially
when the recommended dose of the ȕ-agonist is exceeded.

Monoamine Oxidase Inhibitors (MAOI) or Tricyclic Antidepressant

(TCAs): Concomitant administration with these agents may potentiate
salbutamol's effect on the cardiovascular system.
View more drug interactions for Duavent
Pregnancy Category
(US FDA)




: Either studies in animals have revealed adverse effects on
the foetus (teratogenic or embryocidal or other) and there are no
controlled studies in women or studies in women and animals are not
available. Drugs should be given only if the potential benefit justifies
the potential risk to the foetus.
Storage Store at temperatures not exceeding 30°C. Protect from direct sunlight or
heat. Do not freeze or refrigerate.

Pulmoneb: Do not use if the solution is discolored.

Metered-Dose Inhaler: Exposure to temperatures >48°C (120°F) may

cause bursting. Do not break, puncture or burn the canister even when
apparently empty.
Description Pulmoneb: Each 2.5 mL pulmoneb contains ipratropium bromide
anhydrous 500 mcg and salbutamol sulfate 2.5 mg.
 Metered-Dose Inhaler: Each actuation delivers ipratropium bromide BP
monohydrate 21 mcg (equivalent to 20 mcg ipratropiun bromide
anhydrous) and salbutamol sulfate 120 mcg (equivalent to 100 mcg
salbutamol BP).

Duavent 20 mcg/100 mcg/actuation metered-dose inhaler is a milky

white homogenous suspension filled in aluminum container in propellant
gases with suitable surface active agent. The aluminum container is fitted
with a metering valve and a plastic oral actuator.
Mechanism of 


   Ipratropium bromide: Ipratropium bromide is a
Action quaternary ammonium compound with anticholinergic
(parasympatholytic) properties. Similar to atropine, it is a nonselective
competitive antagonist of muscarinic receptors present in airways and
other organs. Ipratropium bromide relaxes smooth muscles of bronchi
and bronchioles by blocking acetylcholine-induced stimulation of guanyl
cyclase, thus reducing formation of cyclic guanosine monophosphate
(cGMP), a mediator of bronchoconstriction. Ipratropium generally
exhibits greater antimuscarinic activity of bronchial smooth muscle than
on secretory (eg, salivary, gastric) glands.

Ipratropium bromide is a potent bronchodilator, particularly in large

bronchial airways; however, some evidence suggests that it also has
bronchodilator activity in small airways. Bronchodilation results from
relaxation of smooth muscles of the bronchial tree. The extent of
bronchodilation produced by ipratropium appears to be determined by
the level of cholinergic parasympathetic bronchomotor tone and by
inhibition of bronchoconstriction resulting from neural reflex activation
of cholinergic pathways.

Salbutamol: Salbutamol stimulates adenyl cyclase, the enzyme which

catalyzes the formation of cyclic-3', 5'-adenosine monophosphate
(cAMP) from adenosine triphosphate (ATP). The cAMP thus formed
mediates the cellular response eg, bronchial smooth muscle relaxation. 
  and  pharmacologic studies have demonstrated that
salbutamol has a preferential effect on ȕ-adrenergic receptors that are
especially found in respiratory tract compared with isoproterenol.
Salbutamol has been shown in most controlled studies to have more
effect on respiratory tract, in the form of bronchial smooth muscle
relaxation, than isoproterenol at comparable doses while producing fewer
cardiovascular effects.

Rationale of Combination: Ipratropium bromide-salbutamol fixed-dose

combination (FDC) maximizes the response to treatment in patients with
bronchial asthma and chronic obstructive pulmonary disease (COPD) by
increasing bronchodilation through 2 distinctly different mechanisms ie,
anticholinergic (parasympatholytic) and ȕ2-agonist (sympathomimetic)
effects. Simultaneous administration of both an anticholinergic
(ipratropium bromide) and a ȕ2-sympathomimetic (salbutamol sulfate)
produces a greater bronchodilator effect than when either drug is used
alone.




  Pulmoneb: Two 3-month double-blind, randomized,
parallel, multicenter clinical trials were done in a total of 1067 patients
with stable COPD comparing ipratropium bromide-salbutamol
combination with each individual component. Pulmonary function test
(PFT) response rates were analyzed using 12% and 15% increases in
FEV, compared with baseline values and were measured in various
treatment groups on days 1, 29, 57 and 85 in these trials. Regardless of
whether a 12% or a 15% increase in FEV was used to define a positive
response, the ipratropium bromide-salbutamol combination was superior
to the individual agents (p<0.05; all comparisons within 30 min). A
•15% increase in FEV was seen in >80% of patients who received the
ipratropium and salbutamol sulfate combination administered as a single
inhalation aerosol.

Studies demonstrate that each component of the FDC contributed to the

improvement of pulmonary function produced by the combination
especially during the 1st 4-5 hrs after the dosing, and that the ipratropium
bromide-salbutamol inhalation was significantly more effective than
ipratropium bromide or salbutamol administered alone.

In a crossover pharmacokinetic study in 12 healthy male volunteers

comparing the pattern of absorption and excretion of 2 inhalations of the
ipratropium bromide-salbutamol FDC to the 2 active components
individually, the co-administration of ipratropium bromide from a single
inhalation preparation did not significantly alter the systemic absorption
of either component. Ipratropium bromide levels remained below
detectable limits (<100 pg/mL). Peak salbutamol level obtained within 3
hrs post-administration was 492±132 pg/mL. Following this single
administration 27.1±5.7% of the estimated mouthpiece dose was
excreted unchanged in the 24-hr urine. From pharmacokinetic
perspective, the synergistic efficacy of the FDC is likely to be due to a
local effect on the muscarinic and ȕ2-adrenergic receptors in the lung.

Ipratropium bromide is minimally bound (0-9%  ) to plasma

albumin and Į1-acid glycoprotein. It is partially metabolized to inactive
ester hydrolysis products.

Salbutamol is extensively metabolized in the liver, mainly to salbutamol

4'-O-sulfate which has little or no ȕ-adrenergic stimulating effect and no
ȕ-adrenergic blocking effect. Unlike isoproterenol, salbutamol is not
 metabolized by the enzyme catechol-O-methyl transferase and is not a
substrate for catecholamine cellular uptake processes.

Metered-Dose Inhaler: After oral inhalation of ipatropium bromide-

salbutamol sulfate combination in patients with COPD, the onset of
bronchodilation is evident within 15 min, with peak effect in 1 hr.
Bronchodilation persists for 4-5 hrs with the combination compared with
4 hrs with ipratropium bromide alone and 3 hrs for salbutamol alone.
Ipratropium's peak plasma concentration remains below detectable limits
(<100 pg/mL) white maximum salbutamol concentration is 492 pg/mL
occurring within 3 hrs after administration; 27.1% of the estimated
mouthpiece dose of ipratropium-salbutamol combination is excreted in
urine as unchanged drug within 24 hrs.

Ipratropium is 0-9% bound to lasma albumin and Į1-acid glycoproteins

 . It is partially metabolized to N-isopropylnortropium
methobromide, an inactive ester hydrolysis product.

Salbutamol is metabolized in the liver, being converted to salbutamol 4'-

-sulafet which has little or no ȕ-adrenergic stimulating effect and no ȕ-
adrenergic blocking effect.

Animal studies show that salbutamol can cross the blood-brain barrier
and the placenta. It may be secreted in breast milk, but the concentrations
are not known.
MIMS Class Antiasthmatic & COPD Preparations
ATC Classification R03AK04 - Salbutamol and other drugs for obstructive airway diseases ;
Belongs to the class of adrenergics and other inhalants used in the
treatment of obstructive airway diseases.
Poison Schedule Rx
Presentation/Packing Pulmoneb 2.5 mL x 20's. Metered-dose inhaler 200 dose
?