Atrovent (Ipratropium Bromide Monohydrate) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Adverse reaction information concerning ATROVENT (ipratropium bromide) Inhalation Aerosol is derived from 90 day controlled clinical trials (N=254), other controlled clinical trials using recommended doses of ATROVENT Inhalation Aerosol (N=377) and an uncontrolled study (N=1924). Additional information is derived from the post-marketing experience and the published literature.

Adverse reactions occurring in greater than one percent of patients in the 90 day controlled clinical trials appear in Table 1.

Table 1 Adverse Reactions Occurring in >1% of COPD Patients

	Percent of Patients
	Ipratropium Bromide	Metaproterenol Sulfate
	N = 254	N= 249
Reaction
Cardiovascular
Palpitations	1.8	1.6
Central Nervous System
Nervousness	3.1	6.8
Dizziness	2.4	2.8
Headache	2.4	2.0
Dermatological
Rash	1.2	0.4
Gastrointestinal
Nausea	2.8	1.2
Gastrointestinal    distress	2.4	2.8
Vomiting	0	1.2
Musculoskeletal
Tremor	0	2.4
Ophthalmological
Blurred vision	1.2	0.8
Oro-Otolaryngeal
Dry mouth	2.4	0.8
Irritation from    aerosol	1.6	1.6
Respiratory
Cough	5.9	1.2
Exacerbation   of symptoms	2.4	3.6

Additional adverse reactions reported in less than one percent of the patients considered possibly due to ATROVENT Inhalation Aerosol include urinary difficulty, fatigue, insomnia and hoarseness.

The large uncontrolled, open-label study included seriously ill patients. About 7% of patients treated discontinued the program because of adverse events.

Of the 2301 patients treated in the large uncontrolled study and in clinical trials other than the 90 day studies, the most common adverse reactions reported were: dryness of the oropharynx, about 5 in 100; cough, exacerbation of symptoms and irritation from aerosol, each about 3 in 100; headache, about 2 in 100; nausea, dizziness, blurred vision/difficulty in accommodation, and drying of secretions, each about 1 in 100. Less frequently reported adverse reactions that were possibly due to ATROVENT (ipratropium bromide) Inhalation Aerosol include tachycardia, paresthesia, drowsiness, coordination difficulty, itching, hives, flushing, alopecia, constipation, tremor, and mucosal ulcers.

Cases of precipitation or worsening of narrow-angle glaucoma, acute eye pain, and hypotension, have been reported.

In a 5-year placebo-controlled trial, hospitalizations for supraventricular tachycardia and atrial fibrillation occurred with an incidence rate of 0.5% in patients receiving ATROVENT Inhalation Aerosol.

Post-Marketing Experience

Allergic-type reactions such as skin rash, angioedema of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reaction have been reported, with positive rechallenge in some cases. Many of the patients had a history of allergies to other drugs and/or foods, including soybean. (See CONTRAINDICATIONS).

Additionally, urinary retention, mydriasis, and bronchospasm, including paradoxical bronchospasm, have been reported during the post-marketing period.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ATROVENT

Possible Atrovent side effects / adverse reactions in 68 year old male

Reported by a physician on 2007-02-16

Patient: 68 year old male

Reactions: Rhabdomyolysis, Hepatorenal Failure, Renal Failure Acute

Adverse event resulted in: life threatening event

Suspect drug(s):
Atrovent
    Administration route: Oral
    Start date: 2006-07-01
    End date: 2006-12-18

Corvitol
    Administration route: Oral
    Start date: 2006-07-01
    End date: 2006-12-18

Rulid
    Administration route: Oral
    Indication: Leukocytosis
    Start date: 2006-12-17
    End date: 2006-12-18

Other drugs received by patient: Lusopress; Diroton; Agapurin Retard; Anopyrin

Possible Atrovent side effects / adverse reactions in 61 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2007-02-22

Patient: 61 year old male

Reactions: Ocular Hyperaemia, Skin Necrosis, Lacrimation Increased, Mucous Membrane Disorder, Rash Maculo-Papular, Eye Pruritus

Adverse event resulted in: hospitalization

Suspect drug(s):
Atrovent
    Dosage: 0.5 mg/2ml 3 times daily
    Start date: 2007-01-11
    End date: 2007-01-19

Bricanyl
    Dosage: 5 mg/2 ml 3 times daily
    Start date: 2007-01-11
    End date: 2007-01-19

Cancidas
    Indication: Pyrexia
    Start date: 2007-01-12
    End date: 2007-01-19

Gentamicin Sulfate
    Indication: Pyrexia
    Start date: 2007-01-11
    End date: 2007-01-15

Rifamycine Chibret
    Dosage: unknown
    Start date: 2007-01-12
    End date: 2007-01-19

Targocid
    Indication: Pyrexia
    Start date: 2007-01-11
    End date: 2007-01-12

Targocid
    Dosage: unknown
    Start date: 2007-01-18
    End date: 2007-01-22

Tazocilline
    Dosage: 4 g piperacillin/500 mg tazobactam 3 times daily
    Indication: Pyrexia
    Start date: 2007-01-11
    End date: 2007-01-14

Tazocilline
    Dosage: unknown
    Start date: 2007-01-18
    End date: 2007-01-19

Other drugs received by patient: Cellcept; Valganciclovir HCL; Bactrim DS; Celluvisc; Ropinirole HCL; Doxazosin Mesylate; Actonel

Possible Atrovent side effects / adverse reactions in 61 year old male

Reported by a physician from France on 2007-02-22

Patient: 61 year old male

Reactions: Rash Maculo-Papular

Adverse event resulted in: hospitalization

Suspect drug(s):
Atrovent

Other drugs received by patient: Gentamicine Panpharma; Targocid; Cancidas; Tazocilline; Bricanyl; Rovalcyte; Bactrim DS; Cellcept; Adartrel; Zoxan LP; Actonel; Rifamycine; Vfend