DrugindexOnline^{2nd edition}

Pronouncation: (IH-pruh-TROE-pee-umm BROE-mide/al-BYOO-ter-ahl SULL-fate)
Class: Anticholinergic

Trade Names:
Combivent
- Aerosol 18 mcg ipratropium bromide and 103 mcg albuterol sulfate per actuation (equiv. to 90 mcg albuterol base)

Trade Names:
DuoNeb
- Inhalation solution 0.5 mg ipratropium bromide and 3 mg albuterol sulfate (equiv. to 2.5 mg albuterol base)

Mechanism of Action

Pharmacology

Albuterol

Produces bronchodilation by relaxing bronchial smooth muscle through beta ₂ -receptor stimulation.

Ipratropium

Antagonizes action of acetylcholine on bronchial smooth muscle in lungs, causing bronchodilation.

Indications and Usage

Treatment of bronchospasm associated with COPD in patients requiring more than 1 bronchodilator.

Contraindications

History of hypersensitivity to soya lecithin or related food (eg, soybean, peanuts) ( Combivent only) or to atropine and its derivatives.

Dosage and Administration

Combivent
Adults

Inhalation 2 inhalations 4 times daily (max, 12 inhalations per 24 h).

DuoNeb
Adults

Inhalation One 3 mL vial 4 times daily via nebulization with up to 2 additional 3 mL doses daily, if needed.

General Advice

Inhalation aerosol

• For oral inhalation only. Avoid spraying into nose or eyes.
• Shake well before each use.
• Have patient exhale deeply through the mouth, place inhaler between lips, and take a slow, deep breath while inhaler is being activated. Have patient hold breath for 5 to 10 sec and then breathe out slowly. Wait 5 min before administering the second dose. A spacing device (eg, Aerochamber ) may be used to enhance delivery of medication. Have patient rinse mouth after inhalations are complete.

Inhalation solution

• Administer only via nebulizer. Not for injection or oral use.
• Medication requires no dilution before administration and is added directly into nebulizer reservoir.
• Discard solution if not colorless.
• Discard any unused solution.
• Do not mix with other nebulized medications unless ordered by health care provider.

Storage/Stability

Inhalation aerosol

Store inhalation aerosol at ambient room temperature (59° to 86°F). Protect from excessive humidity. Store pressurized canister with nozzle end down, away from heat or open flame. Do not puncture or discard pressurized canister in incinerator.

Inhalation solution

Store unused vials in protective foil pouch in refrigerator (36° to 46°F) or room temperature (less than 77°F). Protect vials from light.

Drug Interactions

Anticholinergic agents

Possible additive anticholinergic effects.

Beta-adrenergic agonists

Risk of adverse CV effects may be increased.

Beta-receptor blocking agents

These agents and albuterol may inhibit the effect of each other.

Digoxin

Albuterol component may decrease serum digoxin concentrations and therapeutic effects.

Diuretics

Albuterol component may exaggerate ECG and/or hypokalemia from non-potassium-sparing diuretics.

MAOIs, tricyclic antidepressants

Concomitant use of these agents or use within 2 wk of stopping such agents may potentiate the CV effects of albuterol.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, arrhythmia, palpitation, tachycardia, angina, hypotension (less than 2%).

CNS

Headache (6%); fatigue, dizziness, nervousness, tremor, paresthesia, insomnia (less than 2%); drowsiness, stimulation, coordination difficulty, weakness (postmarketing).

Dermatologic

Alopecia (postmarketing).

EENT

Pharyngitis (4%); dysphonia (less than 2%); worsening of narrow-angle glaucoma, acute eye pain, blurred vision, nasal congestion, drying of secretions, mucosal ulcers (postmarketing).

GI

Nausea (2%); diarrhea, dry mouth, dyspepsia, vomiting, taste perversion (less than 2%); GI distress, constipation (postmarketing).

Genitourinary

UTI, dysuria (less than 2%); urinary difficulty (postmarketing).

Musculoskeletal

Arthralgia (less than 2%).

Respiratory

Bronchitis (12%); upper respiratory tract infection (11%); lung disease (6%); dyspnea (5%); coughing (4%); respiratory disorders (3%); sinusitis (2%); rhinitis, pneumonia (1%); paradoxical bronchospasm, wheezing, exacerbation of COPD symptoms (postmarketing).

Miscellaneous

Pain, chest pain (3%); influenza, leg cramps (1%); allergic type reactions (including skin rash, angioedema of tongue, lips, and face, laryngospasm, anaphylaxis), edema, increased sputum (less than 2%); heartburn, itching, flushing (postmarketing).

Precautions

Monitor Respiratory status Monitor patient's respiratory status during each treatment. If bronchospasm worsens during or shortly after a treatment, discontinue the treatment and notify health care provider immediately.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

Immediate hypersensitivity reactions may occur.

Anticholinergic effects

Use with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction.

CV effects

Toxic symptoms may occur in patients with CV disorders. Use with caution in patients with coronary insufficiency, arrhythmias, or hypertension.

CNS effects

CNS stimulation may occur; use cautiously in patients with history of seizures or hyperthyroidism.

Diabetes

Dosage adjustment of insulin may be required.

Excessive use

Death may occur with excessive use of inhaled sympathomimetic drugs in patients with asthma.

Hypokalemia

Transient decreases in potassium levels may occur.

Paradoxical bronchospasm

Life-threatening bronchospasms can occur, usually with the first use of a new container.

Overdosage

Symptoms

Tremor, palpitations, tachycardia, elevated BP, angina.

Patient Information

• Advise patient to continue taking other medications for same condition as prescribed by health care provider.
• Advise patient using inhalation solution for nebulizer to read the patient's instructions for use before starting therapy and again with each refill.
• Ensure that patient using inhalation solution can prepare, use, and clean the nebulizer without difficulty.
• Review proper administration technique for patient using inhalation aerosol. Have patient demonstrate technique to ensure effective use of the MDI.
• Advise patient using inhalation aerosol to test-spray 3 times before using the first time or if the aerosol has not been used for more than 24 h.
• Advise patient to discard the aerosol canister when the labeled number of doses has been used.
• Instruct patient not to exceed prescribed dose. Advise patient to inform health care provider if symptoms do not improve or worsen, if treatments are needed more often than usual, or if the medication appears to become less effective.
• Instruct patient not to stop the medication once symptoms have been controlled. Continued daily use is necessary to control symptoms.
• Advise patient to carry medical identification (eg, card, bracelet) indicating COPD.