April 30, 2017
Recommended Topic Related To:


"The U.S. Food and Drug Administration today approved Anoro Ellipta (umeclidinium and vilanterol inhalation powder) for the once-daily, long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease ("...



Side Effects


Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of drugs cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to BETHKIS in two placebo-controlled studies in 305 cystic fibrosis patients. Patients receiving BETHKIS ranged in age from 6 to 31 years.

In Study 1, an eight week study, 29 patients received BETHKIS versus 30 patients who received placebo for a total of four weeks on drug and four weeks off drug. All patients were ≤ 30 years of age (mean age 12.6 years) and 46% were females. 52.5% of patients were 6 to 12 years of age while 30.5% of patients were 13-17 years old. Only 16.5% of patients were adults ( > 17 years old). Eighty percent (80%) of patients were chronically colonized with Pseudomonas aeruginosa while 20.3% of patients were initially or intermittently colonized with Pseudomonas aeruginosa during the study.

More patients in the placebo group discontinued/dropped out of Study 1 than in the BETHKIS group (23% [7/30] vs 3.4% [1/29], respectively). Five patients in the placebo group compared to none in the BETHKIS group discontinued/dropped out because of treatment-emergent adverse events (TEAEs) such as pulmonary exacerbations and respiratory disorders.

In Study 2, a 24 week study, 161 patients received BETHKIS versus 85 patients who received placebo in alternating four week on-off cycles for three cycles. All patients were ≤ 46 years of age (mean age 14.8 years) and 45% were females. 41% of patients were 612 years old while 29% of patients were 13-17 years old. Only 30% were adults ( > 17 years). Eighty-seven percent (87%) of patients were chronically colonized with P. aeruginosa. Only 13% were either initially or intermittently colonized with P. aeruginosa during the study.

More patients in the placebo group discontinued/dropped out of Study 2 than in the BETHKIS group (9.4% [8/85] vs 4.3% [7/161], respectively). Of these, 3 patients in the BETHKIS group (1.9%) compared to 2 patients in the placebo group (2.4%) withdrew due to a TEAE. The most common TEAEs causing patients to discontinue from the study drug are respiratory, thoracic, and mediastinal disorders.

The most common adverse experiences reported were respiratory disorders, consistent with the underlying disease in the patient population being evaluated and these were similarly distributed between both BETHKIS- and placebo-treated patients. The following adverse reactions were reported in at least 5% of Bethkis-treated patients and at rates ≥ 2% more common compared to the placebo-treated patients: decreased forced expiratory volume, rales, red blood cell sedimentation rate increased, and dysphonia (Table 1).

Table 1: Patients with Selected Treatment-Emergent Adverse Reactions Occurring in ≥ 2% of BETHKIS Patients

Adverse Reactions BETHKIS
N=190 (%)
N=115 (%)
Forced expiratory volume decreased 59 (31%) 33 (29%)
Rales 36 (19%) 18 (16%)
Red blood cell sedimentation rate increased 16 (8%) 6 (5%)
Dysphonia 11 (6%) 2 (2%)
Wheezing 10 (5%) 4 (4%)
Epistaxis 6 (3%) 0
Pharyngolaryngeal pain 5 (3%) 2 (2%)
Bronchitis 5 (3%) 1 (1%)
Tonsillitis 4 (2%) 0
Diarrhea 3 (2%) 1 (1%)
Eosinophilia 3 (2%) 0
Immunoglobulins increased 3 (2%) 0

Postmarketing Experience

In postmarketing experience, some patients receiving inhaled tobramycin have reported hearing loss. Some of these reports occurred in patients with previous or concomitant treatment with systemic aminoglycosides. Patients with hearing loss frequently reported tinnitus (see WARNINGS AND PRECAUTIONS, Ototoxicity).

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Read the Bethkis (tobramycin inhalation solution) Side Effects Center for a complete guide to possible side effects


Drugs With Neurotoxic Or Ototoxic Potential

Concurrent and/or sequential use of BETHKIS with other drugs with neurotoxic or ototoxic potential should be avoided.

Ethacrynic Acid, Furosemide, Urea, Or Mannitol

Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. Therefore, BETHKIS should not be administered concomitantly with ethacrynic acid, furosemide, urea, or mannitol.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 11/29/2016

Side Effects

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Women's Health

Find out what women really need.