Sorbitol

3.3% Sorbitol Irrigation

Nonelectrolyte Irrigating Fluid for Urologic Irrigation Only.

Not for Injection.

Sorbitol Description

Each 100 mL contains:

Sorbitol (from Sorbitol Solution USP) 3.3 g

Water for Injection USP qs

pH: 5.3 (5.0–7.0)

Calculated Osmolarity: 185 mOsmol/liter, hypotonic

The formula of the active ingredient is:

Ingredient	Molecular Formula	Molecular Weight
Sorbitol		182.17

Sorbitol is chemically designated D-glucitol (C6H14O6).

Sorbitol, an isomer of mannitol, is a hexitol naturally occurring in many fruits, and is produced commercially by the reduction of glucose.

3.3% Sorbitol Irrigation is a prediluted, sterile, nonpyrogenic aqueous solution suitable for urologic irrigation. The solution is slightly hypotonic.

The solution contains no antimicrobial or bacteriostatic agents or added buffers.

The plastic container is a copolymer of ethylene and propylene formulated and developed for parenteral drugs. The copolymer contains no plasticizers and exhibits virtually no leachability. The plastic container is also virtually impermeable to vapor transmission and therefore, requires no overwrap to maintain the proper drug concentration. The safety of the plastic container has been confirmed by biological evaluation procedures. The material passes Class Vl testing as specified in the U.S. Pharmacopeia for Biological Tests — Plastic Containers. These tests have shown that the container is nontoxic and biologically inert.

The PIC Container is PVC-free and DEHP-free.

Sorbitol - Clinical Pharmacology

In humans, Sorbitol is nontoxic and rapidly metabolized. Sorbitol will either be excreted in the urine by the kidneys, or metabolized to carbon dioxide and dextrose.

When Sorbitol is absorbed intravascularly in amounts which depend primarily on the extent of the surgery, it produces osmotic diuresis.

As a 3.3% solution, Sorbitol is recommended for irrigation of the urinary bladder and prostatic bed during transurethral prostatectomy. Unlike dextrose solutions, Sorbitol solutions are not sticky, and if administered in the above dilution, are not hemolytic.

Sorbitol is nonelectrolytic and is therefore nonconductive making it suitable for urologic irrigation during electrosurgical procedures.

Indications and Usage for Sorbitol

3.3% Sorbitol Irrigation is indicated for use as a urologic irrigation fluid.

Contraindications

3.3% Sorbitol Irrigation is not for injection. It is contraindicated in patients with anuria.

Warnings

FOR UROLOGIC IRRIGATION ONLY. NOT FOR INJECTION.

Solutions for urologic irrigation must be used with caution in patients with severe cardiopulmonary or renal dysfunction.

Since irrigating fluids used during transurethral prostatectomy have been demonstrated to enter the systemic circulation in relatively large volumes, any irrigation solution must be regarded as a systemic drug.

Absorption of large amounts of fluids containing Sorbitol and the resultant osmotic diuresis may significantly affect cardiopulmonary and renal dynamics.

Hyperglycemia from metabolism of Sorbitol may occur in patients with diabetes mellitus.

Hyperlactatemia from metabolism of Sorbitol may potentially produce a significant lactic acidemia in metabolically compromised patients.

3.3% Sorbitol Irrigation must be used with caution in patients unable to metabolize Sorbitol rapidly enough to avoid the development of hyperosmolar states.

Do not warm above 150°F (66°C).

After opening container, its contents should be used promptly to minimize the possibility of bacterial growth or pyrogen formation. Discard unused portion of irrigating solution since it contains no preservatives.

Precautions

General

Use aseptic technique when preparing and administering sterile irrigation solutions.

Use only if solution is clear and container and seal are intact.

Cardiovascular status, especially in patients with cardiac disease, should be carefully determined before and during transurethral resection of the prostate when using Sorbitol irrigation as an irrigant. The fluid absorbed into the systemic circulation via severed prostatic veins may produce significant extracellular fluid expansion and lead to fulminating congestive heart failure.

Shift of sodium-free intracellular fluid into the extracellular compartment following systemic absorption of 3.3% Sorbitol Irrigation may lower serum sodium concentration and aggravate pre-existing hyponatremia.

Excessive loss of water and electrolytes may lead to serious imbalances. Continuous administration of 3.3% Sorbitol Irrigation may cause loss of water in excess of electrolytes and produce hypernatremia.

Sustained diuresis from transurethral irrigation with 3.3% Sorbitol Irrigation may obscure and intensify inadequate hydration or hypovolemia.

When used for irrigation via appropriate irrigation equipment, the administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start up of each cycle or repeat procedure. For repeated irrigations of urethral catheters, a separate container should be used for each patient.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with 3.3% Sorbitol Irrigation have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with 3.3% Sorbitol Irrigation. It is also not known whether 3.3% Sorbitol Irrigation can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

3.3% Sorbitol Irrigation should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Caution should be exercised when 3.3% Sorbitol Irrigation is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of 3.3% Sorbitol Irrigation did not include a sufficient number of patients age 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. See WARNINGS.

Adverse Reactions

Occasional adverse reactions may occur which include slight increases in postoperative serum glucose, inhibition of intestinal absorption of vitamin B12, fluid and electrolyte disturbances, such as acidosis, electrolyte loss, edema, dryness of the mouth, thirst and dehydration, cardiovascular/pulmonary disorders such as pulmonary congestion, hypotension, tachycardia and angina-like pains. In addition, patients unable to metabolize Sorbitol rapidly enough may develop hyperosmolar states.

If an adverse reaction does occur, discontinue administration of the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination, if deemed necessary.

Overdosage

In the event of dehydration or fluid or solute overload, discontinue the irrigant, evaluate the patient and institute appropriate corrective treatment. See WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.

Sorbitol Dosage and Administration

As required for urologic irrigation.

3.3% Sorbitol Irrigation should be administered only by the appropriate transurethraI urologic instrumentation.

Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.

Solutions should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permits.

How is Sorbitol Supplied

3.3% Sorbitol Irrigation is supplied sterile and nonpyrogenic in PIC™ (Plastic Irrigation Containers). The 2000 mL containers are packaged 8 per case and the 4000 mL containers are packaged 4 per case.

NDC	Cat. No.	Size
3.3% Sorbitol Irrigation
0264-2301-50	R6015-01	2000 mL
0264-2301-70	R6017	4000 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Do not warm above 150°F (66°C).

Rx only

Revised: March 2009

PIC is a trademark of B. Braun Medical Inc.

Directions For Use of PIC™ (Plastic Irrigation Containers)

Not for injection.

Aseptic technique is required.

1. Caution – Before use, perform the following checks:
   

   (a)

   
   

   Read the label. Ensure solution is the one ordered and is within the expiration date.

   
   

   (b)

   
   

   Invert container and inspect the solution in good light for cloudiness, haze or particulate matter; check the container for leakage or damage. Any container which is suspect should not be used.

   
   

Use only if solution is clear and container and seal are intact.

Single dose container. Discard unused portion.

2.

Outer Closure Removal – Grasp the container with one hand and turn the breakaway ring counterclockwise with the other hand until slight resistance is felt. Then, twisting the container in the opposite direction, turn the breakaway ring sharply until the entire outer cap is loose and can be lifted off.

3.

Connect the administration set through the sterile set port according to set instructions or remove screw cap and pour.

4.

Do not warm above 150°F to assure minimal bottle distortion. Keep bottles upright.

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

Y36-002-700

PRINCIPAL DISPLAY PANEL - 2000 mL Label

3.3% Sorbitol Irrigation

For Urologic Irrigation Only

REF R6015-01

NDC 0264-2301-50

2000 mL

Lot

Exp.

Each 100 mL contains: Sorbitol

(from Sorbitol Solution USP) 3.3 g

Water for Injection USP qs

pH: 5.3 (5.0–7.0)

Calc. Osmolarity: 185 mOsmol/liter,

hypotonic

Not for Injection. Use only if solution is

clear and container and seal are intact.

Sterile, nonpyrogenic.

Single dose container.

Warning: Do not warm above

150°F (66°C).

Recommended Storage:

Room temperature (25°C).

Avoid excessive heat.

Protect from freezing.

See Package Insert.

Rx only

PVC-free and DEHP-free

B|BRAUN

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

Y37-002-323

PRINCIPAL DISPLAY PANEL - 4000 mL Label

3.3% Sorbitol Irrigation

For Urologic Irrigation Only

REF R6017

NDC 0264-2301-70

4000 mL

Lot

Exp.

Each 100 mL contains: Sorbitol

(from Sorbitol Solution USP) 3.3 g

Water for Injection USP qs

pH: 5.3 (5.0–7.0)

Calc. Osmolarity: 185 mOsmol/liter,

hypotonic

Not for Injection. Use only if solution is

clear and container and seal are intact.

Sterile, nonpyrogenic.

Single dose container.

Warning: Do not warm above

150°F (66°C).

Recommended Storage:

Room temperature (25°C).

Avoid excessive heat.

Protect from freezing.

See Package Insert.

Rx only

PVC-free and DEHP-free

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

Y37-002-324

Sorbitol  Sorbitol  irrigant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0264-2301 Route of Administration IRRIGATION DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Sorbitol (Sorbitol) Sorbitol 3.3 g  in 100 mL

Inactive Ingredients Ingredient Name Strength Water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0264-2301-50 8 CONTAINER In 1 CASE contains a CONTAINER 1 2000 mL In 1 CONTAINER This package is contained within the CASE (0264-2301-50) 2 0264-2301-70 4 CONTAINER In 1 CASE contains a CONTAINER 2 4000 mL In 1 CONTAINER This package is contained within the CASE (0264-2301-70)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA016741	02/16/1978

Labeler - B. Braun Medical Inc. (002397347)

Establishment
Name	Address	ID/FEI	Operations
B Braun Medical Inc		037425308	MANUFACTURE

Revised: 03/2010B. Braun Medical Inc.

More Sorbitol resources

• Sorbitol Support Group
• 0 Reviews · Be the first to review/rate this drug

• Sorbitol Irrigation Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• sorbitol Concise Consumer Information (Cerner Multum)

Sucralfate

soo-KRAL-fate

Commonly used brand name(s)

In the U.S.

• Carafate

In Canada

• Sulcrate Suspension Plus

Available Dosage Forms:

• Suspension


• Tablet

Therapeutic Class: Antiulcer, Protectant

Uses For sucralfate

Sucralfate is used to treat and prevent duodenal ulcers. sucralfate may also be used for other conditions as determined by your doctor.

Sucralfate works by forming a ``barrier'' or ``coating'' over the ulcer. This protects the ulcer from the acid of the stomach, allowing it to heal. Sucralfate contains an aluminum salt.

sucralfate is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, sucralfate is used in certain patients with the following medical conditions:

• Gastric ulcers


• Gastroesophageal reflux disease (a condition in which stomach acid washes back into the esophagus)


• Stomach or intestinal ulcers resulting from stress or trauma damage or from damage caused by medication used to treat rheumatoid arthritis

Before Using sucralfate

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For sucralfate, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to sucralfate or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

sucralfate has been tested in a limited number of children. In effective doses, the medicine has not been shown to cause different side effects or problems than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing the use of sucralfate in the elderly with use in other age groups, sucralfate is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking sucralfate, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using sucralfate with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ciprofloxacin


• Digoxin


• Fleroxacin


• Gemifloxacin


• Grepafloxacin


• Moxifloxacin


• Norfloxacin


• Ofloxacin


• Sparfloxacin


• Trovafloxacin Mesylate


• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of sucralfate. Make sure you tell your doctor if you have any other medical problems, especially:

• Gastrointestinal tract obstruction disease—Sucralfate may bind with other foods and drugs and cause obstruction of the gastrointestinal tract

• Kidney failure—Use may lead to a toxic increase of aluminum blood levels

Proper Use of sucralfate

Sucralfate is best taken with water on an empty stomach 1 hour before meals and at bedtime, unless otherwise directed by your doctor.

Take sucralfate for the full time of treatment, even if you begin to feel better. Also, it is important that you keep your doctor's appointments for check-ups so that your doctor will be better able to tell you when to stop taking sucralfate.

Dosing

The dose of sucralfate will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of sucralfate. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (suspension):
  
  • To treat duodenal ulcers:
    
    • Adults and teenagers—One gram four times a day, one hour before each meal and at bedtime. Some people may take two grams two times a day, when they wake up and at bedtime on an empty stomach.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  


• For oral dosage form (tablets):
  
  • To treat duodenal ulcers:
    
    • Adults and teenagers—One gram four times a day, one hour before each meal and at bedtime.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  
  • To prevent duodenal ulcers:
    
    • Adults and teenagers—One gram two times a day on an empty stomach.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of sucralfate, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using sucralfate

Antacids may be taken with sucralfate to help relieve any stomach pain, unless your doctor has told you not to use them. However, antacids should not be taken within 30 minutes before or after sucralfate. Taking these medicines too close together may keep sucralfate from working properly.

sucralfate Side Effects

Along with its needed effects, a medicine 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:

Signs of aluminum toxicity

• Drowsiness


• convulsions (seizures)

Some side effects 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:

More common

• Constipation

Less common or rare

• Backache


• diarrhea


• dizziness or lightheadedness


• dryness of mouth


• indigestion


• nausea


• skin rash, hives, or itching


• stomach cramps or pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: sucralfate side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More sucralfate resources

• Sucralfate Side Effects (in more detail)
• Sucralfate Use in Pregnancy & Breastfeeding
• Drug Images
• Sucralfate Drug Interactions
• Sucralfate Support Group
• 16 Reviews for Sucralfate - Add your own review/rating

• Sucralfate Prescribing Information (FDA)


• Sucralfate Professional Patient Advice (Wolters Kluwer)


• Sucralfate Monograph (AHFS DI)


• Sucralfate MedFacts Consumer Leaflet (Wolters Kluwer)


• Carafate Prescribing Information (FDA)


• Carafate Consumer Overview

Compare sucralfate with other medications

• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• GERD
• Hyperphosphatemia of Renal Failure
• Stomach Ulcer
• Stomatitis
• Stress Ulcer Prophylaxis

Treximet

Pronunciation: SOO-ma-TRIP-tan/na-PROX-en
Generic Name: Sumatriptan/Naproxen
Brand Name: Treximet

Treximet contains a nonsteroidal anti-inflammatory drug (NSAID). It may cause an increased risk of serious and sometimes fatal heart and blood vessel problems (eg, a heart attack, stroke). The risk may be greater if you already have heart problems or if you take Treximet for a long time. Do not take Treximet right before or after bypass heart surgery.

Treximet may cause an increased risk of serious and sometimes fatal stomach or bowel ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs.

Treximet is used for:

Treating migraine attacks in adults.

Treximet is a serotonin 5-HT₁ receptor agonist ("triptan") and NSAID combination. The "triptan" works by narrowing blood vessels in the brain, which helps to relieve migraines. The NSAID may work to relieve pain by blocking certain substances in the body.

Do NOT use Treximet if:

• you are allergic to any ingredient in Treximet


• you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or another NSAID (eg, ibuprofen, celecoxib)


• you have liver problems, severe kidney problems, uncontrolled high blood pressure, or certain types of migraines (eg, hemiplegic, basilar)


• you are in the last 3 months of pregnancy


• you have recently had or will be having bypass heart surgery


• you have a history of ischemic heart disease (eg, angina, a heart attack), coronary artery disease (CAD), other moderate to severe heart problems, brain blood vessel disease (eg, a stroke, transient ischemic attack), or other blood vessel disease (eg, Raynaud syndrome, ischemic bowel disease)


• you are taking sibutramine or another medicine that contains naproxen


• you are taking a monoamine oxidase inhibitor (MAOI) (eg, phenelzine), or have taken an MAOI within the past 14 days


• you have used certain other migraine medicines (eg, an ergot derivative [eg, dihydroergotamine, methysergide], another serotonin 5-HT₁ receptor agonist [eg, eletriptan, rizatriptan]) within the past 24 hours

Contact your doctor or health care provider right away if any of these apply to you.

Before using Treximet:

Some medical conditions may interact with Treximet. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of lung or breathing problems (eg, asthma), runny nose, growths in the nose (nasal polyps), or severe dizziness due to previous NSAID use


• if you have a history of liver or kidney problems, diabetes, other types of headaches (eg, cluster headaches), stomach or bowel problems (eg, bleeding, perforation, ulcers), mouth inflammation, or seizures (eg epilepsy)


• if you have a history of high blood pressure, blood disorders, bleeding or clotting problems, diabetes, heart problems (eg, heart failure, irregular heartbeat), heart bypass surgery, a stroke, blood vessel disease, or high cholesterol, or if you are at risk of any of these diseases


• if you have shortness of breath, chest pain, poor health, fluid retention, dehydration or low fluid volume, or low blood sodium levels


• if you are on a low-salt (sodium) diet, are very overweight, smoke, drink alcohol, or have a history of alcohol abuse


• if you have a family member who has had heart disease or a stroke


• if you are a woman who is past menopause or who has had your ovaries removed (oophorectomy)


• if you are a man who is older than 40 years old


• if your headache feels different than usual or you have not previously been diagnosed with a migraine headache

Some MEDICINES MAY INTERACT with Treximet. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin), antiplatelet medicines (eg, clopidogrel), aspirin, corticosteroids (eg, prednisone), heparin, rivaroxaban, or other NSAIDs (eg, ibuprofen) because the risk of stomach or bowel bleeding may be increased


• Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine), or sibutramine because the risk of a serious side effect called serotonin syndrome may be increased. Symptoms of serotonin syndrome may include mental or mood changes, hallucinations, fast heartbeat, fever, loss of coordination, muscle spasms, increased sweating, nausea, vomiting, or diarrhea


• MAOIs (eg, phenelzine) or probenecid because they may increase the risk of Treximet's side effects


• Bisphosphonates (eg, alendronate), cyclosporine, ergot derivatives (eg, dihydroergotamine, methysergide), lithium, methotrexate, quinolones (eg, ciprofloxacin), or other serotonin 5-HT₁ receptor agonists (eg, eletriptan, rizatriptan) because the risk of their side effects may be increased by Treximet


• Beta-blockers (eg, propranolol) because their effectiveness may be decreased by Treximet


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Treximet and the risk of kidney problems may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Treximet may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Treximet:

Use Treximet as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Treximet comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Treximet refilled.


• It is best to take a dose of Treximet as soon as you notice symptoms of a migraine attack.


• Take Treximet by mouth with or without food. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach of bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset.


• Swallow Treximet whole. Do not break, crush, or chew before swallowing.


• If your symptoms do not improve after the first dose, do not take a second dose for the same attack. Contact your doctor.


• If your doctor has instructed you to take a second dose, do not take the second dose for at least 2 hours after the previous dose. Do not take more than 2 tablets in 24 hours.


• Do not treat more than 5 headaches within 30 days without checking with your doctor.


• If you miss a dose of Treximet and you still have a headache, follow your doctor's dosing instructions. Contact your doctor right away if you are unsure of what to do if you miss a dose. Do not take Treximet more often than prescribed. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Treximet.

Important safety information:

• Treximet may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Treximet with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Overuse of Treximet can cause your headache to become worse. Do NOT take more than the recommended dose or take more often than prescribed without checking with your doctor. Tell your doctor if your headaches become worse or if they occur more often.


• Treximet should not be used to prevent or reduce the number of migraine headaches you have. If you have a headache that is different than your usual migraine headaches, check with your doctor before taking Treximet.


• Serious stomach or bowel ulcers or bleeding can occur with the use of Treximet. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Treximet with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling.


• Rarely, serious heart problems (eg, a heart attack, irregular heartbeat) have been reported within a few hours of taking Treximet. Contact your doctor at once if fast or irregular heartbeat; chest, jaw, or neck pain or numbness; numbness of an arm or leg; severe stomach pain, dizziness, or vomiting; fainting; or vision changes occur. Discuss any questions or concerns with your doctor.


• Serotonin syndrome is a possibly fatal syndrome that can be caused by Treximet. Your risk may be greater if you take Treximet with certain other medicines (eg, SSRIs, SNRIs). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.


• Treximet has naproxen in it. Before you start any new medicine, check the label to see if it has naproxen or any other NSAID (eg, ibuprofen) in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Check with your doctor before you take aspirin while you are taking Treximet.


• Treximet may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Treximet.


• Lab tests, including blood pressure, complete blood cell counts, heart function, kidney function, or liver function, may be performed while you use Treximet. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Treximet with caution in the ELDERLY; they may be more sensitive to its effects, especially stomach or bowel bleeding and kidney problems.


• Treximet should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Treximet may harm the fetus. Do not take it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Treximet while you are pregnant. Treximet is found in breast milk. Do not breast-feed while taking Treximet.

Possible side effects of Treximet:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; gas; heartburn; mild feeling of heaviness or pressure; mild numbness or tingling of the skin; nausea; stomach upset; tiredness; warm/hot sensation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); bloody diarrhea; bloody or black, tarry stools; change in the amount of urine produced; chest, neck, or jaw pain, tightness, or pressure; confusion; dark urine; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; loss of appetite; loss of vision or other vision changes; mental or mood changes (eg, depression); numbness of an arm or leg; one-sided weakness; pale stools; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe or prolonged flushing; severe vomiting; shortness of breath; slurred speech or other speech changes; sudden or unexplained weight gain; swelling of hands, legs, or feet; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; very cold or blue fingers or toes; vomit that looks like coffee grounds; wheezing; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Treximet side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased urination; heartburn; loss of consciousness; seizures; severe dizziness or drowsiness; severe nausea or stomach pain; slow or shallow breathing; sluggishness; unusual bleeding or bruising; vomit that looks like coffee grounds.

Proper storage of Treximet:

Store Treximet at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store in original packaging until just before use. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Treximet out of the reach of children and away from pets.

General information:

• If you have any questions about Treximet, please talk with your doctor, pharmacist, or other health care provider.


• Treximet is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is summary only. It does not contain all information about Treximet. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Treximet resources

• Treximet Side Effects (in more detail)
• Treximet Use in Pregnancy & Breastfeeding
• Treximet Drug Interactions
• Treximet Support Group
• 57 Reviews for Treximet - Add your own review/rating

• Treximet Prescribing Information (FDA)


• Treximet Advanced Consumer (Micromedex) - Includes Dosage Information


• Treximet Consumer Overview

Compare Treximet with other medications

• Migraine

Tobi

Generic Name: Tobramycin Sulfate
Class: Aminoglycosides
VA Class: AM300
CAS Number: 49842-07-1

• Neurotoxicity and Ototoxicity


• 
  

  Neurotoxicity (manifested as both auditory and vestibular ototoxicity) can occur.^{b c} Other neurotoxicity manifestations include numbness, skin tingling, muscle twitching, and seizures.^{b c}

  
  


• 
  

  Eighth-cranial nerve impairment develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.^{b c}

  
  


• 
  

  Aminoglycoside-induced ototoxicity is irreversible, usually bilateral, and may be partial or total.^{b c}

  
  


• 
  

  Risk of hearing loss increases with degree of exposure to either high peak or high trough serum concentrations.^{b c}

  
  


• 
  

  Patients developing cochlear damage may not have symptoms during aminoglycoside treatment to warn them of eighth-cranial nerve toxicity and total or partial, irreversible, bilateral deafness may occur after drug discontinued.^{b c}

  
  

• Nephrotoxicity


• 
  

  Potentially nephrotoxic.^{b c}

  
  


• 
  

  Aminoglycoside-induced nephrotoxicity usually is reversible.^{b c}

  
  


• 
  

  Nephrotoxicity develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.^{b c}

  
  


• 
  

  Rarely, nephrotoxicity may become apparent several days after discontinuance.^{b c}

  
  

• Patient Monitoring


• 
  

  Patients should be under close clinical observation because of potential ototoxicity and nephrotoxicity.^{b c}

  
  


• 
  

  Closely monitor renal and eighth-cranial nerve function, especially in patients with known or suspected renal impairment at start of treatment and also in those whose renal function is initially normal but who develop renal dysfunction during treatment.^{b c}

  
  


• 
  

  Monitor serum tobramycin concentrations periodically to ensure adequate concentrations and avoid potentially toxic and prolonged peak concentrations (>12 mcg/mL).^{b c}

  
  


• 
  

  Rising trough concentrations (>2 mcg/mL) may indicate tissue accumulation.^{b c}

  
  


• 
  

  Tissue accumulation, excessive peak concentrations, cumulative dose, advanced age, and dehydration may contribute to ototoxicity and nephrotoxicity.^{b c}

  
  


• 
  

  Evaluate urine for decreased specific gravity and increased excretion of protein, cells, and casts; periodically determine BUN, S_cr, and Cl_cr.^{b c}

  
  


• 
  

  When feasible, perform serial audiograms in patients old enough to be tested, particularly high-risk patients.^{b c}

  
  


• 
  

  Discontinue tobramycin or adjust dosage if there is evidence of impaired renal, vestibular, or auditory function.^{b c}

  
  


• 
  

  Use with caution in neonates and premature infants because of their renal immaturity and prolonged tobramycin serum half-life.^{b c}

  
  

• Interactions


• 
  

  Avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs, particularly other aminoglycosides, cephaloridine (no longer available in US), viomycin, polymyxin B, colistin, cisplatin, and vancomycin.^{b c c}

  
  


• 
  

  Avoid concurrent use of potent diuretics (e.g., ethacrynic acid, furosemide) since diuretics themselves may cause ototoxicity and IV diuretics enhance toxicity by altering serum and tissue aminoglycoside concentrations.^{b c}

  
  

• Pregnancy


• 
  

  Aminoglycosides can cause fetal harm when administered to a pregnant woman.^{b c}

  
  

Introduction

Antibacterial; aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius.^{a b c}

Uses for Tobi

Bone and Joint Infections

Treatment of serious bone and joint infections caused by susceptible Staphylococcus aureus, Enterobacter, Escherichia coli, Klebsiella, Proteus, or Pseudomonas aeruginosa.^{b c} Used as an adjunct to other appropriate anti-infectives.^e

Intra-abdominal Infections

Treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible Enterobacter, E. coli, or Klebsiella.^{b c} Used as an adjunct to other appropriate anti-infectives.^e

Meningitis and Other CNS Infections

Treatment of CNS infections (meningitis) caused by susceptible gram-negative bacteria.^{b c e}

Aminoglycosides should not be used alone for treatment of meningitis;ⁱ usually used as an adjunct to other anti-infectives in initial treatment.^{f i} Used in conjunction with ampicillin for initial empiric treatment of neonatal Streptococcus agalactiae (group B streptococci) meningitis or for Listeria monocytogenes meningitis.^f

Respiratory Tract Infections

Treatment of serious respiratory tract infections caused by susceptible S. aureus, Enterobacter, E. coli, Klebsiella, Serratia, or Ps. aeruginosa.^{b c d e} Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of nosocomial pneumonia.^e

Administered by oral inhalation via nebulization for management of bronchopulmonary Ps. aeruginosa infections in cystic fibrosis patients ≥6 years of age.^{241 243 244 245 248} Safety and efficacy not established in pediatric patients < 6 years of age, in patients with forced expiratory volume in 1 second (FEV₁) <25% or >75% of the predicted value, or in patients colonized with Burkholderia cepacia (formerly Ps. cepacia).²⁴¹

Septicemia

Treatment of septicemia caused by susceptible E. coli, Klebsiella, or Ps. aeruginosa.^{b c d e}

Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of life-threatening septicemia.^e

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible S. aureus, Enterobacter, E. coli, Klebsiella, Proteus, or Ps. aeruginosa.^{b c} Used as an adjunct to other appropriate anti-infectives.^e

Urinary Tract Infections (UTIs)

Treatment of serious complicated and recurrent UTIs caused by susceptible S. aureus, Citrobacter, Enterobacter, E. coli, Klebsiella, Proteus, Providencia, Serratia, or Ps. aeruginosa.^{b c d e} Used as an adjunct to other appropriate anti-infectives.^e

Not indicated for uncomplicated UTIs unless causative organism is resistant to other less-toxic alternatives.^{b c}

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.^{d e i j} Used in conjunction with an appropriate antipseudomonal cephalosporin (e.g., ceftazidime, ceftriaxone), extended-spectrum penicillin (e.g., ticarcillin, piperacillin and tazobactam, ticarcillin and clavulanate), or carbapenem (e.g., imipenem, meropenem).^{e j}

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.^j Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.^j

Tobi Dosage and Administration

Administration

Administer by IV infusion or IM injection.^{b c}

Tobramycin solution for oral inhalation is administered via nebulization; the oral inhalation solution should not be administered IV, IM, sub-Q, or intrathecally.²⁴¹

IV Infusion

Reconstitution and Dilution

Prepare IV solutions from the pharmacy bulk package according to the manufacturer's directions.^h

ADD-Vantage vials should be diluted according to the manufacturer’s directions prior to IV infusion.^h

IV infusions are prepared by diluting the calculated dose of tobramycin with 50–100 mL of a compatible IV infusion solution.^h In pediatric patients, the volume of infusion solution depends on the patient’s needs, but should be sufficient to allow an infusion period of 20–60 minutes.^h

Rate of Administration

IV infusions should be given over 20–60 minutes.^h Infusion periods of <20 minutes should not be used because they may result in peak serum concentrations >12 mcg/mL.^h

IM Injection

For IM injection, the appropriate dose should be withdrawn from a vial or should be injected directly using a commercially available prefilled syringe.^h

Solutions prepared from or commercially available in pharmacy bulk packages, those available in ADD-Vantage vials, or the commercially available injections in 0.9% sodium chloride should not be used for IM administration.^h

Oral Inhalation

Administer tobramycin solution for oral inhalation using a PARI LC PLUS nebulizer (a hand-held, reusable nebulizer) connected to a DeVilbiss Pulmo-Aide compressor.^{241 245}

Review manufacturers’ information to ensure thorough familiarity with the use and maintenance of the nebulizer and compressor.²⁴¹

Administer the solution for oral inhalation while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer;²⁴¹ breathing through the mouth may be aided by using nose clips.²⁴¹

A nebulizer treatment period of about 15 minutes usually required to completely administer the usual tobramycin dose.²⁴¹

Tobramycin solution for oral inhalation should not be diluted prior to administration and should not be admixed with other drugs (e.g., dornase alfa) in the nebulizer.^{241 245}

Tobramycin solution for oral inhalation usually is used in conjunction with various other standard therapies recommended for patients with cystic fibrosis.^{241 245} Patients should receive such therapies prior to doses of tobramycin solution for oral inhalation.^{241 245}

Based on protocols used in clinical studies evaluating tobramycin solution for oral inhalation, patients should receive doses of inhaled bronchodilators first, then dornase alfa administered by oral inhalation, then chest physiotherapy, then tobramycin solution administered by oral inhalation.²⁴⁵

If orally inhaled corticosteroids, cromolyn sodium, or nedocromil sodium also are indicated in the patient, administer these following the tobramycin dose.²⁴⁵

Dosage

Available as tobramycin sulfate or tobramycin; dosage expressed in terms of tobramycin.^{a b c}

Dosage is identical for either IV or IM administration.^{b c}

Parenteral dosage should be based on patient's pretreatment body weight and renal status.^{b c}

Many clinicians recommend that parenteral dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data; susceptibility of the causative organism; severity of infection; and the patient’s immune and clinical status.^{200 201 202 203 204}

Determine peak and trough serum tobramycin concentrations periodically during parenteral therapy.^{221 222 223 224 225 226 227 228 229} Adjust dosage to maintain desired serum concentrations whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely.^{221 222 223 224 225 226 227 228 229}

In general, desirable peak serum tobramycin concentrations during parenteral therapy are 4–12 mcg/mL and trough concentrations should not be >1–2 mcg/mL.^h Some evidence suggests that an increased risk of toxicity may be associated with prolonged peak tobramycin serum concentrations >10–12 mcg/mL and/or trough concentrations >2 mcg/mL.^h

Once-daily administration† of parenteral aminoglycosides is at least as effective as, and may be less toxic than, conventional parenteral dosage regimens employing multiple daily doses.^{204 205 206 207 208 209 210 211 212 213 214 215 216 217 229 230 231 232 233 234 235 236 237 238 239 240}

Usual duration of parenteral treatment is 7–10 days.^{b c} In difficult and complicated infections, reevaluate use of tobramycin if >10 days of treatment is being considered.^{b c}

If the drug is continued, monitor serum tobramycin concentrations and renal, auditory, and vestibular functions closely.^{b c}

Pediatric Patients

General Dosage for Neonates

IV or IM

Manufacturer recommends ≤4 mg/kg daily given in 2 divided doses every 12 hours in premature or full-term neonates ≤1 week of age.^{b c}

Neonates <1 week of age: AAP recommends 2.5 mg/kg every 18–24 hours for those weighing <1.2 kg and 2.5 mg/kg every 12 hours for those weighing ≥1.2 kg.^f

Neonates 1–4 weeks of age: AAP recommends 2.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 2.5 mg/kg every 8 or 12 hours for those weighing 1.2–2 kg, and 2.5 mg/kg every 8 hours for those weighing >2 kg.^f

General Dosage for Infants and Children

IV or IM

Older infants and children: Manufacturer recommends 6–7.5 mg/kg daily given in 3 or 4 equally divided doses (2–2.5 mg/kg every 8 hours or 1.5–1.89 mg/kg every 6 hours).^{b c}

Children ≥1 month of age: AAP recommends 3–7.5 mg/kg daily given in 3 divided doses for treatment of severe infections.^f Inappropriate for mild to moderate infections according to AAP.^f

Ps. aeruginosa Infections in Cystic Fibrosis Patients

Inhalation

Children ≥6 years of age: 300 mg twice daily for 28 days.^{241 245} Doses should be administered using the recommended nebulizer system every 12 hours (or at intervals as close to every 12 hours as possible); doses should not be administered at intervals <6 hours.²⁴¹ Each 28-day regimen should be followed by a 28-day period when the drug is not administered.^{241 245}

Adults

General Adult Dosage

Treatment of Serious Infections

IV or IM

3 mg/kg daily given in 3 equally divided doses every 8 hours.^{b c}

Treatment of Life-threatening Infections

IV or IM

≤5 mg/kg daily given in 3 or 4 equally divided doses.^{b c} Dosage may be reduced to 3 mg/kg daily when clinically indicated.^{b c}

Ps. aeruginosa Infections in Cystic Fibrosis Patients

Inhalation

300 mg twice daily for 28 days.^{241 245} Doses should be administered using the recommended nebulizer system every 12 hours (or at intervals as close to every 12 hours as possible); doses should not be administered at intervals <6 hours.²⁴¹ Each 28-day regimen should be followed by a 28-day period when the drug is not administered.^{241 245}

Prescribing Limits

Pediatric Patients

Treatment of Infections

IV or IM

Maximum of 4 mg/kg daily in neonates ≤1 week of age.^{b c}

Adults

Treatment of Life-threatening Infections

IV or IM

Maximum 5 mg/kg daily unless serum concentrations are monitored.^{b c}

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.^{b c} Whenever possible, monitor serum tobramycin concentrations.^{b c}

Various methods have been used to determine aminoglycoside dosage for patients with renal impairment and there is wide variation in dosage recommendations for these patients.^h

Manufacturer recommends an initial loading dose of 1 mg/kg followed by subsequent dosage that involves 1-mg/kg doses given at intervals (in hours) calculated by multiplying the patient’s steady-state serum creatinine (in mg/dL) by 6.^{b c}

The dosing method of Sarubbi and Hull (based on corrected Cl_cr) also has been recommended.^h Specialized references should be consulted for specific information on dosage for patients with renal impairment.

Dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.^h

In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.^h

Serum tobramycin concentrations should be monitored in dialysis patients and dosage adjusted to maintain desired concentrations.^h

Geriatric Patients

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.^{b c}

No dosage adjustments except those related to renal impairment.^{b c} (See Renal Impairment under Dosage and Administration.)

Cautions for Tobi

Contraindications

• 
  

  History of hypersensitivity or serious toxic reactions to tobramycin or other aminoglycosides.^{a b c}

  
  

Warnings/Precautions

Warnings

Ototoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.^{a b c}

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosage or prolonged treatment.^{b c}

Serial audiograms should be obtained, if feasible, in patients old enough to be tested, particularly in high-risk patients.^{b c}

Discontinue tobramycin or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) or nephrotoxicity.^{b c}

Some aminoglycosides have caused fetal ototoxicity when administered to pregnant women.^{b c} (See Pregnancy under Cautions.)

Nephrotoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity.^{b c} Renal function should be assessed prior to and periodically during therapy.^{b c}

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.^{b c}

Dosage reduction may be desirable if other evidence of renal dysfunction occurs (e.g., decreased Cl_cr, decreased urine specific gravity, increased BUN or serum creatinine, oliguria).^{b c}

If azotemia increases or if a progressive decrease in urinary output occurs, discontinue tobramycin.^{b c}

Neuromuscular Blockade

Neuromuscular blockade and respiratory paralysis reported with high tobramycin dosage (40 mg/kg).^{b c} Possibility of prolonged or secondary apnea should be considered.^{b c}

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.^{b c}

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.^{b c}

Sensitivity Reactions

Cross-sensitivity

Cross-sensitivity occurs among the aminoglycosides.^{b c}

Sulfite Sensitivity

Tobramycin injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^{b c}

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{b c} Discontinue drug and institute appropriate therapy if superinfection occurs.^{b c}

Interactions

Because of possible additive toxicity, avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs (systemic, oral, or topical), particularly bacitracin, cisplatin, amphotericin B, cephaloridine (no longer available in US), paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides.^{b c}

Do not administer concurrently with potent diuretics (e.g., ethacrynic acid, furosemide).^{b c} (See Specific Drugs under Interactions.)

Consider possibility of neuromuscular blockade and respiratory paralysis in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium).^{b c} (See Specific Drugs under Interactions.)

Use with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since drugs used in these patients may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.^{b c}

Topical Instillation

Aminoglycoside may be absorbed in significant quantities from body surfaces after topical instillation† and may cause neurotoxicity and nephrotoxicity.^{b c}

Specific Populations

Pregnancy

Category D.^{b c}

Possibility of fetal harm if administered to a pregnant woman.^{a b c} Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.^{b c}

If used during pregnancy or if patient becomes pregnant while receiving tobramycin, patient should be apprised of the potential hazard to the fetus.^{a b c}

Lactation

Low concentrations of aminoglycosides may be distributed into milk.ⁱ Use with caution.ⁱ

Pediatric Use

Use with caution in neonates and premature infants because renal immaturity in these patients may result in prolonged serum half-life.^{b c}

Safety and efficacy of tobramycin for oral inhalation not established in children <6 years of age.^a

Geriatric Use

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.^{b c d}

Monitoring renal function during aminoglycoside therapy is particularly important in geriatric patients.^{b c d} Cl_cr may be more useful than determining BUN or serum creatinine.^{b c d}

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal damage than in other patients.^{b c}

Renal function should be assessed prior to and during therapy.^{b c}

Eighth-cranial nerve function should be monitored closely, especially in patients who have known or suspected renal impairment at the start of treatment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment.^{b c}

Common Adverse Effects

Ototoxicity or nephrotoxicity.^{b c i}

Interactions for Tobi

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, cephalosporins, colistin, cephaloridine, viomycin, polymyxin B, colistin, cisplatin, vancomycin) may result in additive toxicity and should be avoided, if possible.^{b c i}

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concurrently with potent diuretics (e.g., ethacrynic acid, furosemide).^{b c i}

Specific Drugs

Drug	Interaction	Comments
Carbapenems (imipenem)	In vitro evidence of additive or synergistic antibacterial effects with aminoglycosides against some gram-positive bacteria (E. faecalis, S. aureus, L. monocytogenes)i
Chloramphenicol	Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi
Clindamycin	Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi
Diuretics (ethacrynic acid, furosemide)	Possible increased risk of ototoxicity (diuretics themselves may cause ototoxicity) or increased risk of other aminoglycoside-related adverse effects (diuretics may alter aminoglycoside serum or tissue concentrations)b c
β-Lactam antibiotics (cephalosporins, penicillins)	In vitro evidence of additive or synergistic antibacterial effects between penicillins and aminoglycosides against some enterococci, Enterobacteriaceae, or Ps. aeruginosa;i used to therapeutic advantagei Possible increased incidence of nephrotoxicity reported with some cephalosporins; cephalosporins may spuriously elevate creatinine concentrationsb c Potential in vitro and in vivo inactivation of aminoglycosidesb c HID i	Do not admix; administer IV solutions of the drugs separatelyHID i Monitor serum aminoglycoside concentrations, especially when high penicillin doses are used or patient has renal impairmenti
Neuromuscular blocking agents and general anesthetics (succinylcholine, tubocurarine)	Possible potentiation of neuromuscular blockade and respiratory paralysisb c i	Use concomitantly with caution; observe closely for signs of respiratory depressioni
NSAIAs	Possible increased serum aminoglycoside concentrations reported with indomethacin in premature neonates; may be related to indomethacin-induced decreases in urine outputi	Closely monitor aminoglycoside concentrations and adjust dosage accordinglyi
Probenecid	Does not affect renal tubular transport of tobramycinb c
Tetracyclines	Some in vitro evidence of antagonism with aminoglycosides;i in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityi

Tobi Pharmacokinetics

Absorption

Bioavailability

Not absorbed orally; must be given parenterally.^{d i}

Rapidly absorbed following IM injection;^{b c} peak serum concentrations attained within 30–90 minutes.^{b c d h}

Following oral inhalation via nebulization, tobramycin remains concentrated principally in the airways; the drug does not readily cross epithelial membranes.²⁴¹

Distribution

Extent

Distributed into bone, heart, gallbladder, lung tissue, bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.^{b c d h}

Only low concentrations distributed into CSF following IM or IV administration.^{b c i}

Crosses placenta.^{b c d}

Aminoglycosides may be distributed into milk in low concentrations.ⁱ

Plasma Protein Binding

Only minimally bound to plasma proteins^{b c d}

Elimination

Metabolism

Not metabolized.ⁱ

Elimination Route

Up to 84% of a single IM dose is excreted unchanged by glomerular filtration within 8 hours and up to 93% is excreted unchanged within 24 hours.^h

When administered by oral inhalation using a nebulizer, any drug that is not absorbed systemically probably is eliminated principally in expectorated sputum.²⁴¹

Half-life

2–3 hours in adults with normal renal function.^{b c h}

4.6 hours in full-term infants and 8.7 hours in low birth-weight infants.^h

Special Populations

Half-life is 5–70 hours in adults with impaired renal function.^d

Stability

Storage

Parenteral

Injection for IV Infusion or IM Injection

15–30°C.^{b c}

Oral Inhalation

Solution for Nebulization

2–8°C.²⁴¹ If refrigeration not available, intact or opened foil pouches containing ampuls of the solution for oral inhalation may be stored at room temperature ≤25°C for ≤28 days.²⁴¹

Do not expose ampuls to intense light.²⁴¹

Solution may darken if stored at room temperature; this does not indicate a change in quality.²⁴¹

Discard any solution for oral inhalation that is cloudy or has visible particles.²⁴¹

Discard any solution for oral inhalation that has been stored at 2–8°C beyond the expiration date stamped on the ampul or stored for >28 days at room temperature.²⁴¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Amino acids 4.25%, dextrose 25%
Dextran 40 10% in dextrose 5% in water
Dextrose 5% in sodium chloride 0.9%
Dextrose 5 or 10% in water
Invert sugar 5% in Electrolyte #2
Invert sugar 10% in Electrolyte #3
Mannitol 15%, dextrose 5% in sodium chloride 0.45%
Mannitol 20%
Normosol M or R in dextrose 5% in water
Normosol R
Normosol R, pH 7.4
Ringer’s injection
Ringer’s injection, lactated
Sodium chloride 0.9%
Sodium lactate (1/6) M
Incompatible
Alcohol 5% in dextrose 5%
Dextrose 5% in Polysal or Polysal M
Isolyte E, M, or P in dextrose 5% in water

Drug Compatibility

Admixture CompatibilityHID

Compatible
Aztreonam
Bleomycin sulfate
Calcium gluconate
Cefoxitin sodium
Ciprofloxacin
Clindamycin phosphate
Furosemide
Linezolid
Metronidazole
Metronidazole HCl with sodium bicarbonate
Ofloxacin
Ranitidine HCl
Verapamil HCl
Incompatible
Cefepime HCl

Y-site CompatibilityHID

Compatible
Acyclovir sodium
Aldesleukin
Amifostine
Amiodarone HCl
Amsacrine
Aztreonam
Bivalirudin
Cefepime HCI
Ceftazidime
Ciprofloxacin
Cyclophosphamide
Dexmedetomidine HCl
Diltiazem HCl
Docetaxel
Doxorubicin HCl liposome injection
Enalaprilat
Esmolol HCl
Etoposide phosphate
Filgrastim
Fenoldopam mesylate
Fluconazole
Fludarabine phosphate
Foscarnet sodium
Furosemide
Gemcitabine HCl
Granisetron HCl
Hetastarch in lactated electrolyte injection (Hextend)
Hydromorphone HCl
Labetalol HCl
Linezolid
Magnesium sulfate
Melphalan HCl
Meperidine HCl
Midazolam HCl
Milrinone lactate
Morphine sulfate
Nicardipine HCl
Perphenazine
Remifentanil HCl
Tacrolimus
Teniposide
Theophylline
Thiotepa
Tolazoline HCl
Vinorelbine tartrate
Zidovudine
Incompatible
Allopurinol sodium
Amphotericin B cholesteryl sulfate complex
Azithromycin
Drotrecogin alfa (activated)
Heparin sodium
Hetastarch in sodium chloride 0.9%
Indomethacin sodium trihydrate
Lansoprazole
Pemetrexed disodium
Propofol
Sargramostim

Actions and SpectrumActions

• 
  

  Usually bactericidal.^{b c i}

  
  


• 
  

  Inhibits protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.^{b c i}

  
  


• 
  

  In vitro spectrum of activity includes many gram-negative aerobic bacteria (including most Enterobacteriaceae and Pseudomonas aeruginosa) and some aerobic gram-positive bacteria.^{b c d i h} Inactive against fungi, viruses, and most anaerobic bacteria.^{d i h}

  
  


• 
  

  Gram-positive aerobes: Active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis.^{b c d i} May be active against some strains of oxacillin-resistant (methicillin-resistant) staphylococci.^{b c d} Streptococcus pyogenes (group A β-hemolytic streptococci), S. pneumoniae,