Todex

Dexamethasone:

• Pharmacological action
• Pharmacokinetics
• Why is Todex prescribed?
• Dosage and administration
• Todex (Dexamethasone) side effects, adverse reactions
• Todex contraindications
• Using during pregnancy and breastfeeding
• Todex (Dexamethasone) in case of emergency / overdose
• Todex (Dexamethasone) reviews

Pharmacological action

Todex is a glucocorticosteroid. This medication Inhibits the function of leukocytes and tissue macrophages. Todex (Dexamethasone) restricts the migration of leukocytes in the area of inflammation. This drug violates the ability of macrophages to phagocytosis and the formation of interleukin-1. Todex (Dexamethasone) decreases capillary permeability caused by histamine release. This medicine inhibits the activity of fibroblasts and collagen formation.

Todex (Dexamethasone) inhibits the activity of phospholipase A2, which leads to suppression of the synthesis of prostaglandins and leukotrienes.

With direct application to the vessels this drug has a vasoconstrictor effect.

Todex (Dexamethasone) has a pronounced dose-dependent effect on the metabolism of carbohydrates, proteins and fats.

In high doses Todex (Dexamethasone) may increase the excitability of brain tissue and contributes to lowering the threshold of convulsive readiness.

With systemic use of therapeutic activity of Todex (Dexamethasone) is due to anti-inflammatory, antiallergic, immunosuppressive and antiproliferative action.

For external and local use of therapeutic activity of Todex (Dexamethasone) is due to anti-inflammatory, antiallergic and antiexudative (due to vasoconstrictor effect) effect.

Pharmacokinetics

The plasma protein binding is 60-70%. This medication penetrates histohematic barriers. In a small amount it is excreted in breast milk. Todex (Dexamethasone) metabolized in a liver. T_1/2 is 2-3 hours. This drug is excreted by kidneys.

When Todex (Dexamethasone) applied topically in ophthalmology it absorbed through the cornea with intact epithelium in moisture anterior chamber. When inflammation of the tissues of the eye or mucosal damage and corneal absorption rate of Todex (Dexamethasone) significantly increased.

Why is Todex prescribed?

For oral administration: Biermer's disease; acute and subacute thyroiditis, hypothyroidism, progressive ophthalmopathy associated with thyrotoxicosis; bronchial asthma; rheumatoid arthritis in the acute phase; ulcerative colitis; connective tissue disease; autoimmune hemolytic anemia, thrombocytopenia, aplasia and hypoplasia of hematopoiesis, agranulocytosis, serum sickness; acute erythroderma, pemphigus (normal), acute eczema (early treatment); malignant tumor (as a palliative therapy); congenital adrenogenital syndrome; cerebral edema (usually after a preliminary parenteral corticosteroids).

For parenteral administration: shock of various origins; swelling of the brain (with brain tumors, head injury, neurosurgical intervention, brain hemorrhage, encephalitis, meningitis, radiation damage); asthmatic status; severe allergic reactions (angioedema, bronchospasm, dermatosis, acute anaphylactic reaction to medication, transfusion serum, pyrogenic reactions); acute hemolytic anemia, thrombocytopenia, acute lymphoblastic leukemia, agranulocytosis; serious infectious diseases (in combination with antibiotics); acute adrenal insufficiency, acute croup; arthropathy (scapulohumeral periarthritis, epicondylitis, styloiditis, bursitis, tenosynovitis, compression neuropathy, osteochondrosis, arthritis of various etiologies, osteoarthritis).

For use in ophthalmic practice: not purulent and allergic conjunctivitis, keratitis, keratoconjunctivitis without damaging the epithelium, iritis, iridocyclitis, blefaroconjuntivitis, blepharitis, episcleritis, scleritis, inflammation of injuries and eye surgeries, sympathetic ophthalmia.

Dosage and administration

The dosing regimen is individual. Orally for severe disease at the beginning of treatment it is prescribed to 10-15 mg / day, maintenance dose may be 2-4.5 mg / day or more. The daily dose divided into 2-3 doses. In small doses Todex is taken 1 time in the morning.

For parenteral administration this medication is administered IV slowly bolus or infusion (acute and urgent conditions); IM; it is possible also periarticular and intraarticular injection. During the day it can be administered from 4 to 20 mg of Todex (Dexamethasone) 3-4 times / day. The duration of parenteral administration is usually 3-4 days, then move on to maintenance therapy of oral form. In the acute period in various diseases and early treatment Todex (Dexamethasone) used in higher doses. Upon reaching the effect the dose is decreased within a few days before reaching the maintenance dose or until discontinuation of treatment.

When used in ophthalmology for acute conditions this drug instilled into conjunctival sac 1-2 drops every 1-2 hours, then with a decrease in inflammation after every 4-6 hours. The duration of treatment is from 1-2 days to several weeks depending on the clinical course of disease.

Todex (Dexamethasone) side effects, adverse reactions

Endocrine system: impaired glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (including moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children.

Metabolism: increased excretion of calcium, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypernatremia, hypokalemia.

CNS: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebellum, headache, convulsions.

Cardio-vascular system: arrhythmia, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic heart failure, ECG changes typical of hypokalemia, increased blood pressure, hypercoagulability, thrombosis. In patients with acute and subacute myocardial infarction - spread necrosis, slowing the formation of scar tissue that can lead to rupture of the heart muscle; with intracranial introduction - nosebleeds.

Digestive system: nausea, vomiting, pancreatitis, steroid gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccups; rarely - increased activity of hepatic transaminases and alkaline phosphatase.

Sensory organs: posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos.

Musculoskeletal system: growth retardation and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - a pathological bone fractures, aseptic necrosis of head of humerus and femur), rupture of tendons of muscles, steroid myopathy, reduced muscle mass (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymosis, skin thinning, hyper or hypopigmentation, steroid acne, stretch marks, susceptibility to the development of pyoderma and candidiasis.

Allergic reactions: generalized (including skin rash, itching, anaphylactic shock) and when applied topically.

Effects associated with immunosuppressive action: development or worsening of infection (the appearance of this side effect contribute jointly used immunosuppressive drugs, and vaccinations).

Local reactions: when Todex (Dexamethasone) administered parenteral - tissue necrosis.

For external use: rarely - itching, redness, burning, dryness, folliculitis, acne, hypopigmentation, perioral dermatitis, allergic dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria. With prolonged use or application to large areas of skin may develop systemic side effects characteristic of SCS.

Todex contraindications

For short-term use for health reasons - increased sensitivity to Todex (Dexamethasone).

For intra-articular injection and injection directly into the lesion: previous arthroplasty, abnormal bleeding (endogenous or caused by the use of anticoagulants), intra-articular fracture, infection (sepsis) inflammation in the joints and periarticular infections (including in history), as well as general infectious disease, pronounced juxta-articular osteoporosis, no signs of inflammation in the joints ("dry" joint, such as osteoarthritis without synovitis), severe bone destruction and deformity of the joint (a sharp narrowing of joint space, ankylosis), instability of the joint as a result of arthritis, aseptic necrosis of the epiphyses of bones forming the joint.

For external use: bacterial, viral, fungal skin diseases, tuberculosis, skin, cutaneous manifestations of syphilis, skin tumors, post-vaccination period, violation of the integrity of the skin (ulcers, wounds), children's age (up to 2 years, with itching in the anal area - up to 12 years), rosacea, acne vulgaris, perioral dermatitis.

For use in ophthalmology: bacterial, viral, fungal eye diseases, tuberculosis eye damage, tampering with the ocular epithelium, acute form of purulent eye infection in the absence of specific therapy, diseases of the cornea, combined with defects in the epithelium, trachoma, glaucoma.

Using during pregnancy and breastfeeding

During pregnancy and lactating Todex (Dexamethasone) is used taking into account the expected therapeutic effect and adverse effect on the fetus. Long-term therapy during pregnancy does not exclude the possibility of violations of fetal growth. In the case of the end of pregnancy there is a danger of atrophy of the adrenal cortex of the fetus, which may require replacement therapy in the newborn.

Category effects on the fetus by FDA - C.

Todex (Dexamethasone) in case of emergency / overdose

Symptoms: increased side effects.

Treatment: the development of adverse reactions - symptomatic therapy, the Itsenko-Cushing syndrome - the prescription of aminoglutethimide.

Tobramycin:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Tobramycin (toe-bra-mye-sin) inhalation solution, usp
• Todex (Tobramycin) reviews

DESCRIPTION

Todex (Tobramycin) inhalation solution, USP is a Todex (Tobramycin) solution for inhalation. It is a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution with the pH and salinity adjusted specifically for administration by a compressed air driven reusable nebulizer. The chemical formula for Todex (Tobramycin), USP is C₁₈H₃₇N₅O₉ and the molecular weight is 467.52. Todex (Tobramycin), USP is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine. The structural formula for Todex (Tobramycin), USP is:

Each single-use 5 mL ampule contains 300 mg Todex (Tobramycin), USP and 11.25 mg sodium chloride in sterile water for injection. Sulfuric acid and sodium hydroxide are added to adjust the pH to 6.0. Nitrogen is used for sparging. All ingredients meet USP requirements. The formulation contains no preservatives.

Todex (Tobramycin), USP is a solution for inhalation. It is a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution with the pH and salinity adjusted specifically for administration by a compressed air driven reusable nebulizer. The chemical formula for Todex (Tobramycin), USP is C₁₈H₃₇N₅O₉ and the molecular weight is 467.52. Todex (Tobramycin), USP is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine. The structural formula for Todex (Tobramycin), USP is:

Each single-use 5 mL ampule contains 300 mg Todex (Tobramycin), USP and 11.25 mg sodium chloride in sterile water for injection. Sulfuric acid and sodium hydroxide are added to adjust the pH to 6.0. Nitrogen is used for sparging. All ingredients meet USP requirements. The formulation contains no preservatives.

Formulation

CLINICAL PHARMACOLOGY

Todex (Tobramycin) inhalation solution is specifically formulated for administration by inhalation. When inhaled, Todex (Tobramycin) is concentrated in the airways.

Pharmacokinetics

Todex (Tobramycin) inhalation solution contains Todex (Tobramycin), a cationic polar molecule that does not readily cross epithelial membranes.⁽¹⁾ The bioavailability of Todex (Tobramycin) inhalation solution may vary because of individual differences in nebulizer performance and airway pathology.⁽²⁾ Following administration of Todex (Tobramycin) inhalation solution, Todex (Tobramycin) remains concentrated primarily in the airways.

Sputum Concentrations: Ten minutes after inhalation of the first 300-mg dose of Todex (Tobramycin) inhalation solution, the average concentration of Todex (Tobramycin) was 1237 mcg/g (ranging from 35 to 7417 mcg/g) in sputum. Todex (Tobramycin) does not accumulate in sputum; after 20 weeks of therapy with the Todex (Tobramycin) inhalation solution regimen, the average concentration of Todex (Tobramycin) at ten minutes after inhalation was 1154 mcg/g (ranging from 39 to 8085 mcg/g) in sputum. High variability of Todex (Tobramycin) concentration in sputum was observed. Two hours after inhalation, sputum concentrations declined to approximately 14% of Todex (Tobramycin) levels at ten minutes after inhalation.

Serum Concentrations: The average serum concentration of Todex (Tobramycin) one hour after inhalation of a single 300-mg dose of Todex (Tobramycin) inhalation solution by cystic fibrosis patients was 0.95 mcg/mL. After 20 weeks of therapy on the Todex (Tobramycin) inhalation solution regimen, the average serum Todex (Tobramycin) concentration one hour after dosing was 1.05 mcg/mL.

Elimination: The elimination half-life of Todex (Tobramycin) from serum is approximately 2 hours after intravenous (IV) administration. Assuming Todex (Tobramycin) absorbed following inhalation behaves similarly to Todex (Tobramycin) following IV administration, systemically absorbed Todex (Tobramycin) is eliminated principally by glomerular filtration. Unabsorbed Todex (Tobramycin), following Todex (Tobramycin) inhalation solution administration, is probably eliminated primarily in expectorated sputum.

Microbiology

Todex (Tobramycin) is an aminoglycoside antibiotic produced by Streptomyces tenebrarius.⁽¹⁾ It acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death.⁽³⁾

Todex (Tobramycin) has in vitro activity against a wide range of gram-negative organisms including Pseudomonas aeruginosa. It is bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Susceptibility Testing

A single sputum sample from a cystic fibrosis patient may contain multiple morphotypes of Pseudomonas aeruginosa and each morphotype may have a different level of in vitro susceptibility to Todex (Tobramycin). Treatment for 6 months with Todex (Tobramycin) inhalation solution in two clinical studies did not affect the susceptibility of the majority of P. aeruginosa isolates tested; however, increased minimum inhibitory concentrations (MICs) were noted in some patients. The clinical significance of this information has not been clearly established in the treatment of P. aeruginosa in cystic fibrosis patients. For additional information regarding the effects of Todex (Tobramycin) inhalation solution on P. aeruginosa MIC values and bacterial sputum density, please refer to the CLINICAL STUDIES section.

The in vitro antimicrobial susceptibility test methods used for parenteral Todex (Tobramycin) therapy can be used to monitor the susceptibility of P. aeruginosa isolated from cystic fibrosis patients. If decreased susceptibility is noted, the results should be reported to the clinician.

Susceptibility breakpoints established for parenteral administration of Todex (Tobramycin) do not apply to aerosolized administration of Todex (Tobramycin) inhalation solution. The relationship between in vitro susceptibility test results and clinical outcome with Todex (Tobramycin) inhalation solution therapy is not clear.

INDICATIONS AND USAGE

Todex (Tobramycin) inhalation solution, USP 300 mg/5 mL is indicated for the management of cystic fibrosis patients with P. aeruginosa.

Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV₁) <25% or >75% predicted, or patients colonized with Burkholderia cepacia (see CLINICAL STUDIES ).

CONTRAINDICATIONS

Todex (Tobramycin) inhalation solution, USP is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

WARNINGS

Caution should be exercised when prescribing Todex inhalation solution to patients with known or suspected renal, auditory, vestibular, or neuromuscular dysfunction. Patients receiving concomitant parenteral aminoglycoside therapy should be monitored as clinically appropriate.

Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use Todex (Tobramycin) inhalation solution during pregnancy, or become pregnant while taking Todex (Tobramycin) inhalation solution should be apprised of the potential hazard to the fetus.

Ototoxicity

Ototoxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with Todex (Tobramycin) inhalation solution therapy during clinical studies. However, transient tinnitus occurred in eight Todex (Tobramycin) inhalation solution-treated patients versus no placebo patients in the clinical studies. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution (see ADVERSE REACTIONS ). Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.

In postmarketing experience, patients receiving Todex (Tobramycin) inhalation solution 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.

Nephrotoxicity

Nephrotoxicity was not seen during Todex inhalation solution clinical studies but has been associated with aminoglycosides as a class. If nephrotoxicity occurs in a patient receiving Todex (Tobramycin) inhalation solution, Todex (Tobramycin) therapy should be discontinued until serum concentrations fall below 2 mg/mL.

Muscular Disorders

Todex (Tobramycin) inhalation solution should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.

Bronchospasm

Bronchospasm has been reported with inhalation of Todex (Tobramycin) inhalation solution. In clinical studies of Todex (Tobramycin) inhalation solution, changes in FEV₁ measured after the inhaled dose were similar in the Todex (Tobramycin) inhalation solution and placebo groups. Bronchospasm should be treated as medically appropriate.

PRECAUTIONS

Information for Patients

NOTE: In addition to information provided below, a Patient Medication Guide providing instructions for proper use of Todex inhalation solution is contained inside the package.

Safety Information

Todex (Tobramycin) inhalation solution is in a class of antibiotics that have caused hearing loss, dizziness, kidney damage, and harm to a fetus. Ringing in the ears and hoarseness were two symptoms that were seen in more patients taking Todex (Tobramycin) inhalation solution than placebo in research studies. Patients with cystic fibrosis can have many symptoms. Some of these symptoms may be related to your medications. If you have new or worsening symptoms, you should tell your doctor.

Hearing: You should tell your doctor if you have ringing in the ears, dizziness, or any changes in hearing.

Kidney Damage: Inform your doctor if you have any history of kidney problems.

Pregnancy: If you want to become pregnant or are pregnant while on Todex (Tobramycin) inhalation solution, you should talk with your doctor about the possibility of Todex (Tobramycin) inhalation solution causing any harm.

Nursing Mothers: If you are nursing a baby, you should talk with your doctor before using Todex (Tobramycin) inhalation solution.

Todex (Tobramycin) Inhalation Solution Packaging

Todex (Tobramycin) inhalation solution comes in a single dose, ready-to-use ampule containing 300 mg Todex (Tobramycin). Each foil pouch contains 4 ampules, for 2 days of Todex (Tobramycin) inhalation solution therapy.

Dosage

The 300 mg dose of Todex (Tobramycin) inhalation solution is the same for patients regardless of age or weight. Todex (Tobramycin) inhalation solution has not been studied in patients less than 6 years old. Doses should be inhaled as close to 12 hours apart as possible and not less than 6 hours apart.

You should not mix Todex (Tobramycin) inhalation solution with dornase alfa (PULMOZYME^®, Genentech) in the nebulizer.

If you are taking several medications, the recommended order is as follows: bronchodilator first, followed by chest physiotherapy, then other inhaled medications and, finally, Todex (Tobramycin) inhalation solution.

Treatment Schedule

You should take Todex (Tobramycin) inhalation solution in repeated cycles of 28 days on drug followed by 28 days off drug. You should take Todex (Tobramycin) inhalation solution twice a day during the 28-day period on drug.

How To Administer Todex (Tobramycin) Inhalation Solution for Inhalation

THIS INFORMATION IS NOT INTENDED TO REPLACE CONSULTATION WITH YOUR PHYSICIAN AND CF CARE TEAM ABOUT PROPERLY TAKING MEDICATION OR USING INHALATION EQUIPMENT.

Todex (Tobramycin) inhalation solution is specifically formulated for inhalation using a PARI LC PLUS Reusable Nebulizer and a DeVilbiss^® Pulmo-Aide^® air compressor. Todex (Tobramycin) inhalation solution can be taken at home, school, or at work. The following are instructions on how to use the DeVilbiss Pulmo-Aide air compressor and PARI LC PLUS Reusable Nebulizer to administer Todex (Tobramycin) Inhalation Solution for Inhalation.

You will need the following supplies:

- Todex (Tobramycin) inhalation solution plastic ampule (vial)

- DeVilbiss Pulmo-Aide air compressor

- PARI LC PLUS Reusable Nebulizer

- Tubing to connect the nebulizer and compressor

- Clean paper or cloth towels

- Nose clips (optional)

It is important that your nebulizer and compressor function properly before starting your Todex (Tobramycin) inhalation solution therapy.

Note: Please refer to the manufacturers’ care and use instructions for important information.

Preparing Your Todex (Tobramycin) Inhalation Solution for Inhalation

1. Wash your hands thoroughly with soap and water.

2a. Todex (Tobramycin) inhalation solution is packaged with 4 ampules per foil pouch.

2b. Separate one ampule by gently pulling apart at the bottom tabs. Store all remaining ampules in the refrigerator as directed.

3. Lay out the contents of a PARI LC PLUS Reusable Nebulizer package on a clean, dry paper or cloth towel. You should have the following parts:

- Nebulizer Top and Bottom (Nebulizer Cup) Assembly

- Inspiratory Valve Cap

- Mouthpiece with Valve

- Tubing

4. Remove the Nebulizer Top from the Nebulizer Cup by twisting the Nebulizer Top counter-clockwise, and then lifting off. Place the Nebulizer Top on the clean paper or cloth towel. Stand the Nebulizer Cup upright on the towel.

5. Connect one end of the tubing to the compressor air outlet. The tubing should fit snugly. Plug in your compressor to an electrical outlet.

6. Open the Todex (Tobramycin) inhalation solution ampule by holding the bottom tab with one hand and twisting off the top of the ampule with the other hand. Be careful not to squeeze the ampule until you are ready to empty its contents into the Nebulizer Cup.

7. Squeeze all the contents of the ampule into the Nebulizer Cup.

8. Replace the Nebulizer Top. Note: In order to insert the Nebulizer Top into the

Nebulizer Cup, the semi-circle halfway down the stem of the Nebulizer Top should face the Nebulizer Outlet.

9. Attach the Mouthpiece to the Nebulizer Outlet. Then firmly push the Inspiratory Valve Cap in place on the Nebulizer Top. Note: the Inspiratory Valve Cap will fit snugly.

10. Connect the free end of the tubing from the compressor to the Air Intake on the bottom of the nebulizer, making sure to keep the nebulizer upright. Press the tubing on the Air Intake firmly.

Todex (Tobramycin) Inhalation Solution Treatment

1. Turn on the compressor.

2. Check for a steady mist from the Mouthpiece. If there is no mist, check all tubing connections and confirm that the compressor is working properly.

3. Sit or stand in an upright position that will allow you to breathe normally.

4. Place Mouthpiece between your teeth and on top of your tongue and breathe normally only through your mouth. Nose clips may help you breathe through your mouth and not through your nose. Do not block airflow with your tongue.

5. Continue treatment until all your Todex (Tobramycin) inhalation solution is gone, and there is no longer any mist being produced. You may hear a sputtering sound when the Nebulizer Cup is empty. The entire Todex (Tobramycin) inhalation solution treatment should take approximately 15 minutes to complete. Note: if you are interrupted, need to cough or rest during your Todex (Tobramycin) inhalation solution treatment, turn off the compressor to save your medication. Turn the compressor back on when you are ready to resume your therapy.

6. Follow the nebulizer cleaning and disinfecting instructions after completing therapy.

Cleaning Your Nebulizer

To reduce the risk of infection, illness or injury from contamination, you must thoroughly clean all parts of the nebulizer as instructed after each treatment. Never use a nebulizer with a clogged nozzle. If the nozzle is clogged, no aerosol mist is produced, which will alter the effectiveness of the treatment. Replace the nebulizer if clogging occurs.

1. Remove tubing from nebulizer and disassemble nebulizer parts.

2. Wash all parts (except tubing) with warm water and liquid dish soap.

3. Rinse thoroughly with warm water and shake out water.

4. Air dry or hand dry nebulizer parts on a clean, lint-free cloth. Reassemble nebulizer when dry, and store.

5. You can also wash all parts of the nebulizer in a dishwasher (except tubing). Place the nebulizer parts in a dishwasher basket, then place on the top rack of the dishwasher.

Remove and dry the parts when the cycle is complete.

Disinfecting Your Nebulizer

Your nebulizer is for your use only - Do not share your nebulizer with other people. You must regularly disinfect the nebulizer. Failure to do so could lead to serious or fatal illness.

Clean the nebulizer as described above. Every other treatment day, disinfect the nebulizer parts (except tubing) by boiling them in water for a full 10 minutes. Dry parts on a clean, lint-free cloth.

Care and Use of Your Pulmo-Aide Compressor

Follow the manufacturer’s instructions for care and use of your compressor.

Filter Change:

1. DeVilbiss Compressor filters should be changed every six months or sooner if filter turns completely gray in color.

Compressor Cleaning:

1. With power switch in the “Off” position, unplug power cord from wall outlet.

2. Wipe outside of the compressor cabinet with a clean, damp cloth every few days to keep dust free.

Caution: Do not submerge in water; doing so will result in compressor damage.

Storage Instructions

You should store Todex (Tobramycin) inhalation solution ampules in a refrigerator (2°C to 8°C or 36°F to 46°F). However, when you don’t have a refrigerator available (e.g., transporting your Todex (Tobramycin) inhalation solution), you may store the foil pouches (opened or unopened) at room temperature (up to 25°C/77°F) for up to 28 days.

Avoid exposing Todex (Tobramycin) inhalation solution ampules to intense light.

Unrefrigerated Todex (Tobramycin) inhalation solution, which is normally slightly yellow, may darken with age; however, the color change does not indicate any change in the quality of the product.

You should not use Todex (Tobramycin) inhalation solution if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days. You should not use Todex (Tobramycin) inhalation solution beyond the expiration date stamped on the ampule.

Additional Information

Nebulizer: 1-800-327-8632

Compressor: 1-800-338-1988

Todex (Tobramycin) Inhalation Solution: 1-877-835-5472

Laboratory Tests

Audiograms

Clinical studies of Todex (Tobramycin) inhalation solution did not identify hearing loss using audiometric tests which evaluated hearing up to 8000 Hz. Physicians should consider an audiogram for patients who show any evidence of auditory dysfunction, or who are at increased risk for auditory dysfunction. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution.

Serum Concentrations

In patients with normal renal function treated with Todex (Tobramycin) inhalation solution, serum Todex (Tobramycin) concentrations are approximately 1 mcg/mL 1 hour after dose administration and do not require routine monitoring. Serum concentrations of Todex (Tobramycin) in patients with renal dysfunction or patients treated with concomitant parenteral Todex (Tobramycin) should be monitored at the discretion of the treating physician.

The serum concentration of Todex (Tobramycin) should only be monitored through venipuncture and not finger prick blood sampling. Contamination of the skin of the fingers with Todex (Tobramycin) may lead to falsely increased measurements of serum levels of the drug. This contamination cannot be completely avoided by hand washing before testing.

Renal Function

The clinical studies of Todex (Tobramycin) inhalation solution did not reveal any imbalance in the percentage of patients in the Todex (Tobramycin) inhalation solution and placebo groups who experienced at least a 50% rise in serum creatinine from baseline (see ADVERSE REACTIONS ). Laboratory tests of urine and renal function should be conducted at the discretion of the treating physician.

Drug Interactions

In clinical studies of Todex (Tobramycin) inhalation solution, patients taking Todex (Tobramycin) inhalation solution concomitantly with dornase alfa (PULMOZYME, Genentech), ß-agonists, inhaled corticosteroids, other anti-pseudomonal antibiotics, or parenteral aminoglycosides demonstrated adverse experience profiles similar to the study population as a whole.

Concurrent and/or sequential use of Todex (Tobramycin) inhalation solution with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided. Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. Todex (Tobramycin) inhalation solution should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and Todex (Tobramycin) inhalation solution has not been evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A two-year rat inhalation toxicology study to assess carcinogenic potential of Todex (Tobramycin) inhalation solution has been completed. Rats were exposed to Todex (Tobramycin) inhalation solution for up to 1.5 hours per day for 95 weeks. The clinical formulation of the drug was used for this carcinogenicity study. Serum levels of Todex (Tobramycin) of up to 35 mcg/mL were measured in rats, in contrast to the average 1 mcg/mL levels observed in cystic fibrosis patients in clinical trials. There was no drug-related increase in the incidence of any variety of tumor.

Additionally, Todex (Tobramycin) inhalation solution has been evaluated for genotoxicity in a battery of in vitro and in vivo tests. The Ames bacterial reversion test, conducted with 5 tester strains, failed to show a significant increase in revertants with or without metabolic activation in all strains. Todex (Tobramycin) was negative in the mouse lymphoma forward mutation assay, did not induce chromosomal aberrations in Chinese hamster ovary cells, and was negative in the mouse micronucleus test.

Subcutaneous administration of up to 100 mg/kg of Todex (Tobramycin) did not affect mating behavior or cause impairment of fertility in male or female rats.

Pregnancy

Teratogenic Effects – Pregnancy Category D

(See WARNINGS )

No reproduction toxicology studies have been conducted with Todex (Tobramycin) inhalation solution. However, subcutaneous administration of Todex (Tobramycin) at doses of 100 or 20 mg/kg/day during organogenesis was not teratogenic in rats or rabbits, respectively. Doses of Todex (Tobramycin) ≥40 mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of teratogenicity. Aminoglycosides can cause fetal harm (e.g., congenital deafness) when administered to a pregnant woman. Ototoxicity was not evaluated in offspring during nonclinical reproduction toxicity studies with Todex (Tobramycin). If Todex (Tobramycin) inhalation solution is used during pregnancy, or if the patient becomes pregnant while taking Todex (Tobramycin) inhalation solution, the patient should be apprised of the potential hazard to the fetus.

Nursing Mothers

It is not known if Todex (Tobramycin) inhalation solution will reach sufficient concentrations after administration by inhalation to be excreted in human breast milk. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate nursing or discontinue Todex (Tobramycin) inhalation solution.

Pediatric Use

The safety and efficacy of Todex (Tobramycin) inhalation solution have not been studied in pediatric patients under 6 years of age.

Geriatric Use

Clinical studies of Todex (Tobramycin) inhalation solution did not include patients aged 65 years and over. Todex (Tobramycin) is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function (see WARNINGS – Nephrotoxicity ; PRECAUTIONS – Serum Concentrations ).

ADVERSE REACTIONS

Todex (Tobramycin) inhalation solution was generally well tolerated during two clinical studies in 258 cystic fibrosis patients ranging in age from 6 to 48 years. Patients received Todex (Tobramycin) inhalation solution in alternating periods of 28 days on and 28 days off drug in addition to their standard cystic fibrosis therapy for a total of 24 weeks.

Voice alteration and tinnitus were the only adverse experiences reported by significantly more Todex (Tobramycin) inhalation solution-treated patients. Thirty-three patients (13%) treated with Todex (Tobramycin) inhalation solution complained of voice alteration compared to 17 (7%) placebo patients. Voice alteration was more common in the on-drug periods.

Eight patients from the Todex (Tobramycin) inhalation solution group (3%) reported tinnitus compared to no placebo patients. All episodes were transient, resolved without discontinuation of the Todex (Tobramycin) inhalation solution treatment regimen, and were not associated with loss of hearing in audiograms. Tinnitus is one of the sentinel symptoms of cochlear toxicity, and patients with this symptom should be carefully monitored for high frequency hearing loss. The numbers of patients reporting vestibular adverse experiences such as dizziness were similar in the Todex (Tobramycin) inhalation solution and placebo groups.

Nine (3%) patients in the Todex (Tobramycin) inhalation solution group and nine (3%) patients in the placebo group had increases in serum creatinine of at least 50% over baseline. In all nine patients in the Todex (Tobramycin) inhalation solution group, creatinine decreased at the next visit.

Table 1 lists the percent of patients with treatment-emergent adverse experiences (spontaneously reported and solicited) that occurred in >5% of Todex (Tobramycin) inhalation solution patients during the two Phase III studies.

Adverse drug reactions (<5%) occurring more frequently with Todex (Tobramycin) inhalation solution in the placebo-controlled studies and assessed as drug-related in ≥1% of patients:

Ear and labyrinth disorders

Tinnitus (3.1%, vs 0% for placebo)

Musculoskeletal and connective tissue disorders

Myalgia (4.7%, vs 2.7% for placebo)

Infections and infestations

Laryngitis (4.3%, vs 3.1% for placebo)

Adverse drug reactions derived from spontaneous reports

The following adverse reactions have been identified during postapproval use of Todex (Tobramycin) inhalation solution. 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.

Ear and labyrinth disorders

Hearing loss (see WARNINGS – Ototoxicity )

Skin and subcutaneous tissue disorders

Hypersensitivity, pruritus, urticaria, rash

Nervous system disorders

Aphonia, dysgeusia

Respiratory, thoracic, and mediastinal disorders

Bronchospasm (see WARNINGS – Bronchospasm ), oropharyngeal pain

Metabolism and Nutrition Disorders

Decreased appetite

OVERDOSAGE

Signs and symptoms of acute toxicity from overdosage of intravenous (IV) Todex (Tobramycin) might include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment. Administration by inhalation results in low systemic bioavailability of Todex (Tobramycin). Todex (Tobramycin) is not significantly absorbed following oral administration. Todex (Tobramycin) serum concentrations may be helpful in monitoring overdosage.

In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered.

DOSAGE AND ADMINISTRATION

The recommended dosage for both adults and pediatric patients 6 years of age and older is 1 single-use ampule (300 mg) administered BID for 28 days. Dosage is not adjusted by weight. All patients should be administered 300 mg BID. The doses should be taken as close to 12 hours apart as possible; they should not be taken less than 6 hours apart.

Todex (Tobramycin) inhalation solution, USP is inhaled while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breathe through the mouth.

Todex (Tobramycin) inhalation solution, USP is administered BID in alternating periods of 28 days. After 28 days of therapy, patients should stop Todex (Tobramycin) inhalation solution, USP therapy for the next 28 days, and then resume therapy for the next 28 day on/28 day off cycle.

Todex (Tobramycin) inhalation solution, USP is supplied as a single-use ampule and is administered by inhalation, using a hand-held PARI LC PLUS Reusable Nebulizer with a DeVilbiss Pulmo-Aide compressor. Todex (Tobramycin) inhalation solution, USP is not for subcutaneous, intravenous or intrathecal administration.

Usage

Todex (Tobramycin) inhalation solution, USP is administered by inhalation over an approximately 15-minute period, using a hand-held PARI LC PLUS Reusable Nebulizer with a DeVilbiss Pulmo-Aide compressor. Todex (Tobramycin) inhalation solution, USP should not be diluted or mixed with dornase alfa (PULMOZYME, Genentech) or other medications in the nebulizer.

During clinical studies, patients on multiple therapies were instructed to take them first, followed by Todex (Tobramycin) inhalation solution, USP.

HOW SUPPLIED

Todex inhalation solution, USP 300 mg is supplied in 5 mL single-use ampules.

It is available as follows:

5 mL single-dose ampule packaged in cartons containing 56 ampules

(14 pouches, each containing 4 ampules) NDC 65162-914-46

Storage

Todex (Tobramycin) inhalation solution, USP should be stored under refrigeration at 2º to 8ºC (36º to 46ºF). Upon removal from the refrigerator, or if refrigeration is unavailable, Todex (Tobramycin) inhalation solution, USP pouches (opened or unopened) may be stored at room temperature (up to 25ºC/77ºF) for up to 28 days. Todex (Tobramycin) inhalation solution, USP should not be used beyond the expiration date stamped on the ampule when stored under refrigeration (2º to 8ºC/36º to 46ºF) or beyond 28 days when stored at room temperature (25ºC/77ºF).

Todex (Tobramycin) inhalation solution, USP ampules should not be exposed to intense light. The solution in the ampule is slightly yellow, but may darken with age if not stored in the refrigerator; however, the color change does not indicate any change in the quality of the product as long as it is stored within the recommended storage conditions.

Clinical Studies

Two identically designed, double-blind, randomized, placebo-controlled, parallel group, 24-week clinical studies (Study 1 and Study 2) at a total of 69 cystic fibrosis centers in the United States were conducted in cystic fibrosis patients with P. aeruginosa. Subjects who were less than 6 years of age, had a baseline creatinine of >2 mg/dL, or had Burkholderia cepacia isolated from sputum were excluded. All subjects had baseline FEV₁ % predicted between 25% and 75%. In these clinical studies, 258 patients received Todex (Tobramycin) inhalation solution therapy on an outpatient basis using a hand-held PARI LC PLUS Reusable Nebulizer with a DeVilbiss Pulmo-Aide compressor.

All patients received either Todex (Tobramycin) inhalation solution or placebo (saline with 1.25 mg quinine for flavoring) in addition to standard treatment recommended for cystic fibrosis patients, which included oral and parenteral anti-pseudomonal therapy, β2-agonists, cromolyn, inhaled steroids, and airway clearance techniques. In addition, approximately 77% of patients were concurrently treated with dornase alfa (PULMOZYME, Genentech).

In each study, Todex (Tobramycin) inhalation solution-treated patients experienced significant improvement in pulmonary function. Improvement was demonstrated in the Todex (Tobramycin) inhalation solution group in Study 1 by an average increase in FEV₁ % predicted of about 11% relative to baseline (Week 0) during 24 weeks compared to no average change in placebo patients. In Study 2, Todex (Tobramycin) inhalation solution-treated patients had an average increase of about 7% compared to an average decrease of about 1% in placebo patients. Figure 1 shows the average relative change in FEV₁% predicted over 24 weeks for both studies.

Figure 1: Relative Change From Baseline in FEV₁% Predicted

In each study, Todex (Tobramycin) inhalation solution therapy resulted in a significant reduction in the number of P. aeruginosa colony forming units (CFUs) in sputum during the on-drug periods. Sputum bacterial density returned to baseline during the off-drug periods. Reductions in sputum bacterial density were smaller in each successive cycle.

Figure 2: Absolute Change From Baseline in Log₁₀ CFUs

Patients treated with Todex (Tobramycin) inhalation solution were hospitalized for an average of 5.1 days compared to 8.1 days for placebo patients. Patients treated with Todex (Tobramycin) inhalation solution required an average of 9.6 days of parenteral anti-pseudomonal antibiotic treatment compared to 14.1 days for placebo patients. During the 6 months of treatment, 40% of Todex (Tobramycin) inhalation solution patients and 53% of placebo patients were treated with parenteral anti-pseudomonal antibiotics.

The relationship between in vitro susceptibility test results and clinical outcome with Todex (Tobramycin) inhalation solution therapy is not clear. However, 4 Todex (Tobramycin) inhalation solution patients who began the clinical trial with P. aeruginosa isolates having MIC values ≥128 mcg/mL did not experience an improvement in FEV₁ or a decrease in sputum bacterial density.

Treatment with Todex (Tobramycin) inhalation solution did not affect the susceptibility of the majority of P. aeruginosa isolates during the 6-month studies. However, some P. aeruginosa isolates did exhibit increased Todex (Tobramycin) MICs. The percentage of patients with P. aeruginosa isolates with Todex (Tobramycin) MICs ≥16 mcg/mL was 13% at the beginning, and 23% at the end of 6 months of the Todex (Tobramycin) inhalation solution regimen.

Figure 1 Figure 2

REFERENCES

1. Neu HC. Todex (Tobramycin): an overview. [Review]. J Infect Dis 1976; Suppl 134:S3-19.

2. Weber A, Smith A, Williams-Warren J et al. Nebulizer delivery of Todex (Tobramycin) to the lower respiratory tract. Pediatr Pulmonol 1994; 17 (5):331-9.

3. Bryan LE. Aminoglycoside resistance. Bryan LE, Ed. Antimicrobial drug resistance. Orlando, FL: Academic Press, 1984: 241-77.

Distributed by:

Amneal Pharmaceuticals

Glasgow, KY 42141

Rev. 10-2015-01

Todex (toe-bra-MYE-sin) Inhalation Solution, USP

Nebulizer Solution - For Inhalation Use Only

Information for Patients

Safety Information

Todex (Tobramycin) inhalation solution is in a class of antibiotics that have caused hearing loss, dizziness, kidney damage and harm to a fetus. Ringing in the ears and hoarseness were two symptoms that were seen in more patients taking Todex (Tobramycin) inhalation solution than placebo in research studies. Patients with cystic fibrosis can have many symptoms. Some of these symptoms may be related to your medications. If you have new or worsening symptoms, you should tell your doctor.

Hearing: You should tell your doctor if you have ringing in the ears, dizziness, or any changes in hearing.

Kidney Damage: Inform your doctor if you have any history of kidney problems.

Pregnancy: If you want to become pregnant or are pregnant while on Todex (Tobramycin) inhalation solution, you should talk with your doctor about the possibility of Todex (Tobramycin) inhalation solution causing any harm.

Nursing Mothers: If you are nursing a baby, you should talk with your doctor before using Todex (Tobramycin) inhalation solution.

Todex (Tobramycin) Inhalation Solution Packaging

Todex (Tobramycin) inhalation solution comes in a single dose, ready-to-use ampule containing 300 mg Todex (Tobramycin). Each foil pouch contains 4 ampules, for 2 days of Todex (Tobramycin) inhalation solution therapy.

Dosage

The 300 mg dose of Todex (Tobramycin) inhalation solution is the same for patients regardless of age or weight. Todex (Tobramycin) inhalation solution has not been studied in patients less than 6 years old. Doses should be inhaled as close to 12 hours apart as possible and not less than six hours apart. You should not mix Todex (Tobramycin) inhalation solution with dornase alfa (PULMOZYME^®, Genentech) in the nebulizer.

If you are taking several medications, the recommended order is as follows: bronchodilator first, followed by chest physiotherapy, then other inhaled medications and, finally, Todex (Tobramycin) inhalation solution.

Treatment Schedule

You should take Todex (Tobramycin) inhalation solution in repeated cycles of 28 days on drug followed by 28 days off drug. You should take Todex (Tobramycin) inhalation solution twice a day during the 28-day period on drug.

How To Administer Todex (Tobramycin) Inhalation Solution for Inhalation

THIS INFORMATION IS NOT INTENDED TO REPLACE CONSULTATION WITH YOUR PHYSICIAN AND CF CARE TEAM ABOUT PROPERLY TAKING MEDICATION OR USING INHALATION EQUIPMENT.

Todex (Tobramycin) inhalation solution is specifically formulated for inhalation using a PARI LC PLUS Reusable Nebulizer and a DeVilbiss^® Pulmo-Aide^® air compressor. Todex (Tobramycin) inhalation solution can be taken at home, school, or at work. The following are instructions on how to use the DeVilbiss^® Pulmo-Aide^® air compressor and PARI LC PLUS Reusable Nebulizer to administer Todex (Tobramycin) Inhalation Solution for Inhalation.

You will need the following supplies:

- Todex (Tobramycin) inhalation solution plastic ampule (vial)

- DeVilbiss^® Pulmo-Aide^® air compressor

- PARI LC PLUS Reusable Nebulizer

- Tubing to connect the nebulizer and compressor

- Clean paper or cloth towels

- Nose clips (optional)

It is important that your nebulizer and compressor function properly before starting your Todex (Tobramycin) inhalation solution therapy.

Note: Please refer to the manufacturers’ care and use instructions for important information.

Preparing Your Todex (Tobramycin) Inhalation Solution for Inhalation

1. Wash your hands thoroughly with soap and water.

2a. Todex (Tobramycin) inhalation solution is packaged with 4 ampules per foil pouch.

2b. Separate one ampule by gently pulling apart at the bottom tabs. Store all remaining ampules in the refrigerator as directed.

3. Lay out the contents of a PARI LC PLUS Reusable Nebulizer package on a clean, dry paper or cloth towel. You should have the following parts:

- Nebulizer Top and Bottom

(Nebulizer Cup) Assembly

- Inspiratory Valve Cap

- Mouthpiece with Valve

- Tubing

4. Remove the Nebulizer Top from the Nebulizer Cup by twisting the Nebulizer Top counter-clockwise, and then lifting. Place the Nebulizer Top on the clean paper or cloth towel. Stand the Nebulizer Cup upright on the towel.

5. Connect one end of the tubing to the compressor air outlet. The tubing should fit snugly. Plug in your compressor to an electrical outlet.

6. Open the Todex (Tobramycin) inhalation solution ampule by holding the bottom tab with one hand and twisting off the top of the ampule with the other hand. Be careful not to squeeze the ampule until you are ready to empty its contents into the Nebulizer Cup.

7. Squeeze all the contents of the ampule into the Nebulizer Cup.

8. Replace the Nebulizer Top. Note: In order to insert the Nebulizer Top into the Nebulizer Cup, the semi-circle halfway down the stem of the Nebulizer Top should face the Nebulizer Outlet. Turn the Nebulizer Top clockwise until securely fastened to the Nebulizer Cup.

9. Attach the Mouthpiece to the Nebulizer Outlet. Then firmly push the Inspiratory Valve Cap in place on the Nebulizer Top. Note: The Inspiratory Valve Cap will fit snugly.

10. Connect the free end of the tubing to the Air Intake on the bottom of the nebulizer, making sure to keep the nebulizer upright. Press the tubing on the Air Intake firmly.

Todex (Tobramycin) Inhalation Solution Treatment

1. Turn on the compressor.

2. Check for a steady mist from the Mouthpiece. If there is no mist, check all tubing connections and confirm that the compressor is working properly.

3. Sit or stand in an upright position that will allow you to breathe normally.

4. Place Mouthpiece between your teeth and on top of your tongue and breathe normally only through your mouth. Nose clips may help you breathe through your mouth and not through your nose. Do not block airflow with your tongue.

5. Continue treatment until all of your Todex (Tobramycin) inhalation solution is gone, and there is no longer any mist being produced. You may hear a sputtering sound when the Nebulizer Cup is empty. The entire Todex (Tobramycin) inhalation solution treatment should take approximately 15 minutes to complete. Note: If you are interrupted, need to cough or rest during your Todex (Tobramycin) inhalation solution treatment, turn off the compressor to save your medication. Turn the compressor back on when you are ready to resume your therapy.

6. Follow the nebulizer cleaning and disinfecting instructions after completing therapy.

Cleaning Your Nebulizer

To reduce the risk of infection, illness or injury from contamination, you must thoroughly clean all parts of the nebulizer as instructed after each treatment. Never use a nebulizer with a clogged nozzle. If the nozzle is clogged, no aerosol mist is produced which will alter the effectiveness of the treatment. Replace the nebulizer if clogging occurs.

1. Remove tubing from nebulizer and disassemble nebulizer parts.

2. Wash all parts (except tubing) with warm water and liquid dish soap.

3. Rinse thoroughly with warm water and shake out water.

4. Air dry or hand dry nebulizer parts on a clean, lint-free cloth. Reassemble nebulizer when dry, and store.

5. You can also wash all parts of the nebulizer in a dishwasher (except tubing). Place the nebulizer parts in a dishwasher basket, then place on the top rack of the dishwasher. Remove and dry the parts when the cycle is complete.

Disinfecting Your Nebulizer

Your nebulizer is for your use only - Do not share your nebulizer with other people. You must regularly disinfect the nebulizer. Failure to do so could lead to serious or fatal illness.

Clean the nebulizer as described above. Every other treatment day, disinfect the nebulizer parts (except tubing) by boiling them in water for a full 10 minutes. Dry parts on a clean, lint-free cloth.

Care and Use of Your Pulmo-Aide^® Compressor

Follow the manufacturer’s instructions for care and use of your compressor.

Filter Change:

1. DeVilbiss^® Compressor filters should be changed every six months or sooner if filter turns completely gray in color.

Compressor Cleaning:

1. With power switch in the “Off” position, unplug power cord from wall outlet.

2. Wipe outside of the compressor cabinet with a clean, damp cloth every few days to keep dust free.

Caution: Do not submerge in water; doing so will result in compressor damage.

Storage Instructions

You should store Todex (Tobramycin) inhalation solution ampules in a refrigerator (2° to 8°C or 36° to 46°F). However, when you don’t have a refrigerator available (e.g., transporting your Todex (Tobramycin) inhalation solution), you may store the foil pouches (opened or unopened) at room temperature (up to 25°C/77°F) for up to 28 days.

Avoid exposing Todex (Tobramycin) inhalation solution ampules to intense light.

Unrefrigerated Todex (Tobramycin) inhalation solution, which is normally slightly yellow, may darken with age; however, the color change does not indicate any change in the quality of the product.

You should not use Todex (Tobramycin) inhalation solution if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days. You should not use Todex (Tobramycin) inhalation solution beyond the expiration date stamped on the ampule.

Additional Information

Nebulizer: 1-800-327-8632

Compressor: 1-800-338-1988

Todex (Tobramycin) Inhalation Solution: 1-877-835-5472

Distributed by:

Amneal Pharmaceuticals

Glasgow, KY 42141

Rev. 03-2015-00

Printed in USA

Pic 1 Pic 2 Pic 3 Pic 4 Pic 5 Pic 6 Pic 7 Pic 8 Pic 9 Pic 10 Pic 11 300 mg/5 mL Ampules pouch carton