Drug Information Request/Response Form
Requester: Dr. Hamour
Location: PGRH
Telephone:
Fax: 250-563-8285
e-mail:
Patient specific:  No Yes - Patient’s initials:
Resident:
Jennifer Day
Preceptor: Jenn Hawkes
ASAP 
Today 
1-2 Days  No Rush 
Source of Request
Health Professional:  Physician  Nurse  Pharmacist  Other ________
 Patient
Background Information
(age, sex, weight, disease states, medications, lab values, allergies
etc.):
Non-patient specific
Ultimate Question:
In a patient who requires tobramycin inhalation therapy, is it possible to
use the injection formulation in a nebulizer?
Type of Request
 Administration
__Adverse effect
__Alternative therapy
__Biopharmaceutics
__Compatibility/stability
__Copy of article
__Cost
 Dosage/Route
Confidential
__Formulation
__Geriatrics
__ID/availability
__ Interaction
__Law/regulation
__Lecture
__Library
__Monograph/ Ingredients
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__Patient information
__Pediatrics
__Pharmacokinetics
__Pharmacology
__Pregnancy/lactation
__Therapeutics
__Toxicity / poisoning
__Other
3/7/2016
Response (use additional paper if needed):
The only product that has been approved for use in a nebulizer is TOBI,
tobramycin for inhalation. (1) Although the CPS monograph for tobramycin
injection has no clear indication for use in a nebulizer, UpToDate lists its
aerosolized use in Cystic Fibrosis (CF) as unlabeled, stating that although it can
be used, the preservatives in the injectable formulation may cause
bronchospasm. (1,2) This risk of bronchoconstriction may be decreased by
pre-treating with salbutamol and it has been noted that although patients
reported increased cough, dsypnea, wheezing and non-cardiac chest pain,
the symptoms did not limit therapy. (3) Inhaled intravenous formulation of
tobramycin is also reported to cause bronchial obstruction, independent of dose,
but this passed after 10 minutes of continued inhalation. (3)
After a brief search of the Health Canada MedEffect Canada Adverse Drug
Reaction Database, three reports of pulmonary complaints were linked to
tobramycin for injection used for inhalation but several (5+) cases of
bronchospasm were listed for TOBI, from 1980-present. Of the three reports with
the injection formulation, only one case was life threatening but the details
surrounding the case are unclear. (5)
According to a manufacturer of tobramycin for injection, Sandoz, the phenol
and the sodium bisulfite are the two main constituents which cause the
bronchospasms and the company can not recommend its use with a nebulizer as
it has not been approved by Health Canada. Another manufacturer, SteriMax,
can also not recommend their injection formulation to be used by the inhalation
route for the same reason. (9) However, tobramycin for intravenous use has
been used in CF patients off-label for inhalation for “decades” in Canada and
Europe. (4,7)
Ingredients:
TOBI, Tobramycin for Inhalation (Novartis): each ampule of sterile, clear, slightly
yellow, nonpyrogenic, aqueous solution, with a pH (6.0) and salinity specifically
adjusted for administration by a compressed air driven reusable nebulizer,
contains: tobramycin solution 300 mg (as sulfate). Nonmedicinal ingredients:
nitrogen, sodium chloride, sodium hydroxide, sterile water for injection and
sulfuric acid.
Multidose, 40 mg/mL Tobramycin for Injection (Sandoz): each mL contains:
tobramycin 40 mg. Nonmedicinal ingredients: disodium edetate 0.1 mg, phenol 5
mg (as preservative), sodium bisulfite 3.2 mg, sulfuric acid and/or sodium
hydroxide to adjust pH, and water for injection. Discard unused portion 28 days
after initial use. Store between 15 and 30°C. Protect from light.
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Single use, 40 mg/mL (2mL) Tobramycin for Injection (Sandoz): each mL
contains: tobramycin 40 mg. Nonmedicinal ingredients: disodium edetate 0.1 mg,
sodium bisulfite 3.2 mg, sulfuric acid and/or sodium hydroxide to adjust pH, and
water for injection. Preservative-free. Discard unused portion.
Multidose, 40mg/mL (30mL) Tobramycin for Injection (SteriMax): each multidose
vial contains: tobramycin sulphate equivalent to 1.2 g tobramycin. Nonmedicinal
ingredients: sulfuric acid and/or sodium hydroxide may have been added during
manufacturing to adjust pH. Store between 15 and 30°C. Protect from light. (1)
The usual regimens for both products are as follows:

TOBI 300 mg inhaled BID for 28 days, then off for 28 days

Tobramycin for injection 80 mg inhaled BID continuously
In a head to head, cross over study (see attached), there was no difference in
efficacy between the two regimens, but patients preferred the TOBI product over
the injection formulation. This preference was thought to be due to the inhalation
break the TOBI regimen offers. (6) There is a significant cost difference between
the two products as well, with TOBI costing upwards of $2,400/month and
tobramycin for injection sitting at roughly $650/month. (7) In addition, the single
use vials are partial benefits through PharmaCare once the patient reaches their
deductible. (8)
Bottom Line:
In conclusion, it may be suitable to use the tobramycin for injection in a
nebulizer, but this faces the risk of possible pulmonary side-effects, such as
bronchospasms. This would be an off-label use of this formulation as well, one
not supported by the manufacturer. If this approach is to be used, it may be best
to use the single use vials as they only contain sodium bisulfite and not phenol or
the SteriMax product as it contains neither ingredients. It also appears important
to pre-dose with salbutamol and to ensure the patient receives the proper dose –
tobramycin 80 mg inhaled BID continuously with no break in therapy.
References Used (Correct citations) and Search Strategy:
1) Compendium of Pharmaceuticals and Specialities [online] TOBI
monograph, Tobramycin injection monograph. [cited 2009 Nov 20]
Available from: URL: http://www.e-therapeutics.ca/cps.
2) UpToDate [online] Tobramycin monograph. [cited 2009 Nov 20]. Available
from: URL:
http://utdol.com/online/content/topic.do?topicKey=drug_l_z/263855&select
edTitle=1%7E86&source=search_result
3) Aronson, JK, editor. Meyler’s side effects of drugs.15th ed. Amsterdam:
Elsevier BV; 2006.
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4) Emily, representative from Sandoz Manufacturer, personal
communication, December 15, 2009.
5) Health Canada: MedEffect Canada – Adverse Drug Reaction Database
[Online]. 2009 Nov 11 [cited 2009 Nov 20] Available from: URL:
http://webprod3.hc-sc.gc.ca/arquery-rechercheei/nextsuivant.do?lang=eng&page=12
6) Nikolaizik WH, Vietzke D, Ratjen F. A pilot study to compare tobramycin
80 mg injectable preparation with 300 mg solution for inhalation in cystic
fibrosis patients. Can Respir J 2008 July/Aug; 15 (5): 259-262.
7) Asmus MJ, Milavetz G, Tice AL, Teresi ME. In vitro characteristics of
tobramycin aerosol from ultrasonic and jet nebulisers. Pharmacotherapy
[serial online] 2001; [cited 2009 Nov 20] 21 (5): [5 screens]. Available
from: URL: http://www.medscape.com/viewarticle/409713
8) Representative from PharmaCare, personal communication, December
16, 2009.
9) Paul, representative from SteriMax Manufacturer, personal
communication, December 18, 2009.
Signed copy in binder
Time taken to respond: Two weeks
Evaluation: Pass □
Fail
□
Date: __________
Signed by Primary Preceptor
Date: ___________
Signed by Resident
Date: ___________
Signed by Residency Coordinator
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