Kitabis Pak inhalation

Do not mix tobramycin solution with dornase alfa (Pulmozyme) in the nebulizer.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• urea;

• a diuretic or "water pill"--furosemide, Lasix, ethacrynic acid, and others; or

• other medicine that may harm your kidneys, hearing, or nervous system--antibiotics, antiviral medicine, chemotherapy, medicine for bowel disorders, medicine to prevent organ transplant rejection, injectable osteoporosis medication, and some pain or arthritis medicines (including aspirin, Tylenol, Advil, and Aleve).

This list is not complete. Other drugs may interact with tobramycin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Hoarseness and changes in voice may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: signs of hearing damage (such as ringing/roaring sounds in the ears, hearing loss, dizziness), signs of kidney problems (such as change in the amount of urine).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, wheezing/unusual trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Overdose is unlikely with tobramycin that is inhaled or swallowed. However, if someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

Do not share this medication with others.

Laboratory and/or medical tests (such as breathing tests, hearing tests, kidney function, tobramycin levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Missed Dose

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage

Store ampules in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Ampules may also be stored at room temperature up to 77 degrees F (25 degrees C) for up to 28 days. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired, or no longer needed, or if it has been stored at room temperature for more than 28 days. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.Information last revised December 2016. Copyright(c) 2016 First Databank, Inc.

Applies to tobramycin: inhalation capsule, inhalation solution

Other dosage forms:

• injection powder for solution, injection solution

Along with its needed effects, tobramycin (the active ingredient contained in Kitabis Pak) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tobramycin:

• Bloody nose
• difficulty with breathing
• discoloration of sputum
• fever
• runny nose
• sneezing
• stuffy nose
• voice changes

• Black, tarry stools
• chest pain
• chills
• continuing ringing or buzzing or other unexplained noise in the ears
• hearing loss
• painful or difficult urination
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• tightness in the chest
• unusual bleeding or bruising
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking tobramycin:

• Blue lips, fingernails, or skin
• dizziness or lightheadedness
• drowsiness
• feeling of constant movement of self or surroundings
• irregular, fast or slow, or shallow breathing
• sensation of spinning

Some side effects of tobramycin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• general feeling of discomfort or illness
• hoarseness

• Bloody nose
• change or loss of taste
• diarrhea
• rash

Applies to tobramycin: compounding powder, inhalation capsule, inhalation solution, injectable powder for injection, injectable solution, intravenous solution

Nervous system

Very common (10% or more):
-TOBI(R): Headache (12%)
-TOBI(R) Podhaler(TM): Headache (11.4%), hypoacusis (10%)

Common (1% to 10%):
-TOBI(R): Tinnitus (up to 3.1%)
-TOBI(R) Podhaler(TM): Tinnitus (1.9%), deafness including unilateral deafness (reported as mild to moderate hearing loss or increased hearing loss; 1%)

Uncommon (0.1% to 1%):
-TOBI(R): Deafness including unilateral deafness (reported as mild to moderate hearing loss or increased hearing loss; 0.5%)

Rare (less than 0.1%):
-Neuromuscular blockade

Frequency not reported:
-Parenteral: Neurotoxicity, eighth-nerve impairment (auditory and vestibular ototoxicity), cochlear hair cell damage, dizziness, vertigo, roaring in ears, hearing loss, numbness, skin tingling, muscle twitching, convulsions, headache
-Inhalation: Transient tinnitus, tinnitus, hearing loss, headache, ototoxicity

Postmarketing reports:
-Inhalation: Hearing loss, tinnitus, aphonia, dysgeusia[Ref]

Parenteral: Ototoxicity may have included loss of auditory or vestibular function secondary to cochlear hair cell damage. Partial or total auditory changes were irreversible and usually bilateral; deafness may have continued to develop after drug was stopped. Eighth-nerve impairment primarily occurred in patients with preexisting renal damage, with normal renal function treated for longer periods and/or at higher doses than recommended, who previously received an ototoxic agent, and who were dehydrated. Risk of drug-induced hearing loss increased with extent of exposure to high peak or high trough serum levels. Ototoxicity may be less likely when tobramycin serum trough levels are less than 2 mg/L after parenteral administration.

Inhalation: Tinnitus may be a sentinel symptom of ototoxicity. Some patients who concurrently received, or previously had prolonged therapy with, parenteral aminoglycosides reported hearing loss.

Rare neurologic side effects have included neuromuscular blockade, particularly in patients who were predisposed, including patients with myasthenia gravis, hypocalcemia, and those receiving a neuromuscular blocking agent.

Headache has been reported in patients using inhaled tobramycin with ciprofloxacin for non-cystic fibrosis bronchiectasis.[Ref]

Renal

Rare (less than 0.1%):
-Inhalation: Acute renal failure

Frequency not reported:
-Parenteral: Nephrotoxicity (usually reversible), renal function changes, rising BUN, rising non-protein nitrogen, rising serum creatinine, oliguria, cylindruria, increased proteinuria[Ref]

Nephrotoxicity primarily occurred in patients with preexisting renal damage and in patients with normal renal function treated for longer periods and/or at higher doses than recommended. Predisposing factors also included advanced age, dehydration, and concomitant use of other potentially nephrotoxic drugs.

The overall incidence of aminoglycoside nephrotoxicity was 2% to 10%, and increased if tobramycin trough levels exceeded 2 mg/L. One study showed that hyperbilirubinemia in patients with biliary obstruction predisposed to aminoglycoside nephrotoxicity.

A 62-year-old female with multiple comorbidities, including chronic renal insufficiency, was started on inhaled tobramycin for healthcare-associated pneumonia. The patient continued inhaled tobramycin for 27 days, during which her serum creatinine gradually rose. After reaching a serum creatinine level of 4.5 mg/dL, the inhaled tobramycin was discontinued on day 28 and the patient was started on hemodialysis due to acute renal failure.[Ref]

Respiratory

Very common (10% or more):
-Bethkis(R): Decreased forced expiratory volume (31%), rales (19%)
-TOBI(R): Cough (31.1%), lung disorder (including pulmonary or cystic fibrosis exacerbations; 30.1%), productive cough (19.6%), dyspnea (12.4%), hemoptysis (12.4%), oropharyngeal pain (10.5%)
-TOBI(R) Podhaler(TM): Cough (up to 48.8%), lung disorder (including pulmonary or cystic fibrosis exacerbations; 33.8%), productive cough (18.2%), dyspnea (15.6%), oropharyngeal pain (14%), dysphonia (up to 13.6%), hemoptysis (13%), pharyngolaryngeal pain (10.9%)

Common (1% to 10%):
-Bethkis(R): Dysphonia (6%), wheezing (5%), epistaxis (3%), pharyngolaryngeal pain (3%), bronchitis (3%), tonsillitis (2%)
-TOBI(R): Upper respiratory tract infection (8.6%), decreased pulmonary function test (8.1%), nasal congestion (7.2%), rales (6.2%), wheezing (6.2%), laryngitis (4.3%), voice alteration/dysphonia (3.8%), chest discomfort (2.9%), throat irritation (1.9%), epistaxis (1.9%), decreased forced expiratory volume (1%), sputum discoloration
-TOBI(R) Podhaler(TM): Nasal congestion (8.1%), rales (7.1%), wheezing (6.8%), upper respiratory tract infection (6.8%), decreased pulmonary function test (6.8%), chest discomfort (6.5%), throat irritation (4.5%), decreased forced expiratory volume (3.9%), epistaxis (2.6%), bronchospasm (1.6%)

Uncommon (0.1% to 1%):
-TOBI(R): Bronchospasm (0.5%), rhinitis, decreased lung function

Frequency not reported:
-Inhalation: Wheeze, cough, dyspnea

Postmarketing reports:
-Inhalation: Bronchospasm, oropharyngeal pain[Ref]

Decreased lung function included reported decreases in pulmonary function tests or decreased lung volume on chest radiograph associated with intercurrent illness or study drug administration.

Bronchospasm has been reported with nebulized tobramycin in cystic fibrosis patients. To help prevent bronchospasm, a bronchodilator should be used in conjunction with nebulized tobramycin. The preserved parenteral formulation has been associated with more bronchospasm than the preservative-free solution for inhalation.

Wheeze, cough, and dyspnea have been reported in patients using inhaled tobramycin with ciprofloxacin for non-cystic fibrosis bronchiectasis.[Ref]

Hypersensitivity

Rare (less than 0.1%):
-Parenteral: Serious allergic reactions (including anaphylaxis and dermatologic reactions), allergic-type reactions (including anaphylactic symptoms and life-threatening or less severe asthmatic episodes)
-Hypersensitivity reactions (including eosinophilia, pruritus, fever, rash, exfoliative dermatitis)

Frequency not reported:
-Cross-sensitivity among aminoglycosides

Postmarketing reports:
-Inhalation: Hypersensitivity[Ref]

Severe and sometimes fatal allergic reactions (including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome) have been reported rarely.

The sodium metabisulfite preservative in some formulations may cause allergic-type reactions (including anaphylactic symptoms and life-threatening or less severe asthmatic episodes) in some susceptible patients.[Ref]

Dermatologic

Contact dermatitis in a patient using tobramycin-containing ear drops has been reported.

A case of exfoliative dermatitis was associated with IV and intraperitoneal tobramycin (the active ingredient contained in Kitabis Pak) [Ref]

Common (1% to 10%):
-TOBI(R): Rash (2.4%)
-TOBI(R) Podhaler(TM): Rash (2.3%)

Rare (less than 0.1%):
-Parenteral: Exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome
-Contact dermatitis (at least 1 case)

Frequency not reported:
-Parenteral: Rash, itching, urticaria

Postmarketing reports:
-Inhalation: Pruritus, urticaria, rash[Ref]

Other

Toxic trough levels have been reported with nebulized tobramycin (the active ingredient contained in Kitabis Pak) administered by positive pressure ventilation to a patient with renal dysfunction. No symptoms of toxicity were noted.

Fatigue has been reported in patients using inhaled tobramycin with ciprofloxacin for non-cystic fibrosis bronchiectasis.[Ref]

Very common (10% or more):
-TOBI(R): Pyrexia (12.4%)
-TOBI(R) Podhaler(TM): Pyrexia (15.6%)

Uncommon (0.1% to 1%):
-TOBI(R): Malaise

Frequency not reported:
-Parenteral: Fever
-Inhalation: Toxic trough levels, fatigue[Ref]

Gastrointestinal

Nausea has been reported in patients using inhaled tobramycin (the active ingredient contained in Kitabis Pak) with ciprofloxacin for non-cystic fibrosis bronchiectasis.[Ref]

Common (1% to 10%):
-Bethkis(R): Diarrhea (2%)
-TOBI(R): Nausea (9.6%), vomiting (5.7%), diarrhea (1.9%)
-TOBI(R) Podhaler(TM): Nausea (7.5%), vomiting (6.2%), diarrhea (4.2%), dysgeusia (up to 6.5%)

Uncommon (0.1% to 1%):
-TOBI(R): Dysgeusia (0.5%)

Frequency not reported:
-Parenteral: Nausea, vomiting, diarrhea, Clostridium difficile associated diarrhea
-Inhalation: Nausea[Ref]

Hematologic

Common (1% to 10%):
-Bethkis(R): Increased red blood cell sedimentation rate (8%), eosinophilia (2%)

Frequency not reported:
-Parenteral: Anemia, granulocytopenia, thrombocytopenia, leukopenia, leukocytosis, eosinophilia[Ref]

Metabolic

Renal tubular toxicity may have resulted in renal magnesium wasting, which may have resulted in hypocalcemia (due to magnesium-dependent parathormone secretion) and clinical tetany in rare cases.[Ref]

Common (1% to 10%):
-TOBI(R) Podhaler(TM): Increased blood glucose (2.9%)

Uncommon (0.1% to 1%):
-TOBI(R): Increased blood glucose (0.5%)

Rare (less than 0.1%):
-Clinical tetany

Frequency not reported:
-Parenteral: Increased serum lactate dehydrogenase, decreased serum calcium, decreased serum magnesium, decreased serum sodium, decreased serum potassium
-Hypophosphatemia[Ref]

Musculoskeletal

Common (1% to 10%):
-TOBI(R): Musculoskeletal chest pain (4.8%), myalgia (4.7%)
-TOBI(R) Podhaler(TM): Musculoskeletal chest pain (4.5%)[Ref]

Hepatic

Rare (less than 0.1%):
-Parenteral: Elevated liver function tests, hepatotoxicity

Frequency not reported:
-Parenteral: Increased serum transaminases (AST, ALT), increased serum bilirubin[Ref]

Immunologic

Common (1% to 10%):
-Bethkis(R): Increased immunoglobulins (2%)

Psychiatric

Rare (less than 0.1%):
-Delirium

Frequency not reported:
-Parenteral: Lethargy, mental confusion, disorientation[Ref]

A rare case of delirium has been reported in a patient who was receiving tobramycin, but there was concomitant opiate administration and underlying infection, which makes implication of tobramycin difficult.[Ref]

Local

Frequency not reported:
-Parenteral: Pain at injection site[Ref]

Some side effects of Kitabis Pak may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.