Zosyn

Contraindications

• Hypersensitivity to any penicillin, cephalosporin, or β-lactamase inhibitor.1 33 35

Warnings/Precautions

Warnings

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 33 35 36 37 38 39 40 C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including piperacillin and tazobactam, and may range in severity from mild diarrhea to fatal colitis.1 33 35 36 37 38 39 40 Hyper toxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1 33 35

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 33 35 36 37 38 39 40 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1 33 35 36 37 38 39 40

If CDAD is suspected or confirmed, piperacillin and tazobactam may need to be discontinued.1 33 35 36 37 38 39 40 Some mild cases may respond to discontinuance alone.36 37 38 39 40 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.1 33 35 36 37 38 39 40

Sensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.1 33 35

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.1 33 35 Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1 33 35

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1 33 35

General Precautions

To reduce development of drug-resistant bacteria and maintain effectiveness of piperacillin and tazobactam and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1 33 35

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 33 35 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 33 35

Bleeding manifestation reported with some β-lactam antibiotics, including piperacillin.1 33 35 These reactions have sometimes been associated with abnormal coagulation tests (e.g., clotting time, platelet aggregation, PT) and are most likely to occur in patients with renal failure.1 33 35

Periodically evaluate hematologic function, especially with prolonged treatment (i.e., ≥21 days).1 33 35

If bleeding manifestations occur, discontinue piperacillin and tazobactam and institute appropriate measures.1 33 35

Neuromuscular excitability or seizures reported with some penicillins when higher than recommended dosage used (especially in patients with renal failure).1 33 35

Fixed-combination of piperacillin and tazobactam contains 2.79 mEq (64 mg) of sodium per g of piperacillin.1 33 (See Geriatric Use under Cautions.)

Consider sodium content when used in patients requiring restricted salt intake.1 33 35

Determine electrolyte concentrations periodically in patients with low potassium reserves; consider possibility of hypokalemia in those with potentially low potassium reserves who are receiving cytotoxic therapy or diuretics.1 33 35

Possibility of increased incidence of fever and rash.1 33 35

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.2 Monitoring hematopoietic function is especially important when duration is ≥21 days (see Hematologic Effects under Cautions).1 33 35

Specific Populations

Category B.1 33 35

Piperacillin distributed into milk; not known whether tazobactam is distributed into milk.1 33 35 Use with caution.1 33 35

Use for treatment of appendicitis and/or peritonitis in pediatric patients ≥2 months of age is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and pediatric patients.1 33 35

Safety and efficacy not established in pediatric patients <2 months of age.1 33 35

Piperacillin and tazobactam contains sodium (see Sodium Content and Electrolyte Imbalance under Cautions).1 33 35 Patients receiving the usual IV dosage will receive 768 or 1024 mg (33.5 or 44.6 mEq) of sodium daily.1 33 Geriatric patients may respond to salt loading with blunted natriuresis;1 33 35 this may be clinically important with regard to such diseases as congestive heart failure.1 33 35

Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1 33 35

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.1 33 35 Assess renal function periodically since geriatric patients are more likely to have renal impairment.1 33 35

No dosage adjustments except those related to renal function.1 33 35 (See Renal Impairment under Dosage and Administration.)

Serum half-lives of piperacillin and tazobactam are prolonged in patients with hepatic cirrhosis;1 3 33 35 not considered clinically important.1 3 12 33 35

No dosage adjustment required in patients with hepatic impairment.1 3 12 33 35

Dosage adjustments recommended in adults with Clcr ≤40 mL/minute and in those undergoing hemodialysis or CAPD.1 33 35 No dosage recommendations in pediatric patients with impaired renal function.1 33 35 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adults: GI effects (diarrhea, constipation, nausea); headache; insomnia; fever; dermatologic reactions (rash, pruritus).1 33 35

Pediatric patients with severe intra-abdominal infections (including appendicitis and/or peritonitis): Diarrhea, fever, vomiting, local reaction, abscess, sepsis, abdominal pain, infection, bloody diarrhea, pharyngitis, constipation, increased AST.1 33 35

• Advise patients that antibacterials (including piperacillin and tazobactam) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1 33 35

• Importance of completing full course of therapy, even if feeling better after a few days.1 33 35

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with piperacillin and tazobactam or other antibacterials in the future.1 33 35

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 33 35 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1 33 35

• Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.a

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

Your doctor will check your or your child's progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it. Blood tests may be needed to check for unwanted effects. If your or your child's symptoms do not improve or if they become worse, call your doctor right away.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child has itching, hives, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after you receive this medicine.

Serious skin reactions can occur with this medicine. Check with your doctor right away if you or your child has blistering, peeling, or loosening of the skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills while you are receiving this medicine.

Piperacillin and tazobactam combination may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop receiving this medicine. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.

Before you have any medical tests, tell the doctor in charge that you or your child are using this medicine. The results of some tests may be affected by this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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 or nurse immediately if any of the following side effects occur:

• Diarrhea

• Bladder pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• burning upper abdominal or stomach pain
• changes in urination
• chest pain
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fever or sweating
• headache
• inflammation or swelling at the injection site
• lower back or side pain
• nausea or vomiting
• pain, tenderness, or swelling of the foot or leg
• pain, warmth, or burning in the fingers, toes, and legs
• problems with vision or hearing
• skin rash
• slow or fast heartbeat
• troubled breathing

• Abdominal or stomach cramps, pain, or tenderness
• agitation
• bone pain
• bruising
• chills
• cold sweats
• cough
• deep or fast breathing with dizziness
• depression
• diarrhea, watery and severe, which may also be bloody
• drowsiness
• dry mouth
• hives
• hostility
• itching of the vagina or genital area
• lethargy
• muscle pain or cramps
• muscle stiffness or twitching
• nightmares
• numbness or tingling in the hands, feet, or lips
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• sore throat
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• swollen glands
• temporary blindness
• thick, white vaginal discharge with no odor or with a mild odor
• total body jerking
• unexplained weight loss
• unusual bleeding or bruising

• Back or leg pain
• blistering, peeling, or loosening of the skin
• high fever
• joint or muscle pain
• red skin lesions, often with a purple center
• yellow eyes or skin

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:

• Difficulty having a bowel movement (stool)
• trouble sleeping

• Acid or sour stomach
• cracks in the skin at the corners of the mouth
• hiccup
• irritation and redness of the skin
• runny nose
• sneezing
• stuffy nose
• white patches in the mouth or on the tongue

• Body aches or pain
• burning feeling in the chest or stomach
• change in taste or bad unusual or unpleasant (after) taste
• feeling of constant movement of self or surroundings
• sensation of spinning
• severe sleepiness
• tenderness in stomach area
• vision changes
• voice changes

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.

• It is used to treat bacterial infections.

• Tell all of your health care providers that you take Zosyn. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Do not use longer than you have been told. A second infection may happen.
• If you have high blood sugar (diabetes), do not use Clinitest®. Use some other urine glucose testing like Clinistix® or Tes-Tape®.
• Very bad and sometimes deadly allergic side effects have rarely happened. Talk with your doctor.
• Some patients may get low white blood cell counts. Tell the doctor right away about any fever, sore throat, or other signs of infection.
• If you are on a low-sodium or sodium-free diet, talk with your doctor. Some of these products have sodium.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking Zosyn.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Zosyn while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Any unexplained bruising or bleeding.
• Seizures.
• Extra muscle action.
• It is common to have diarrhea when taking Zosyn. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Zosyn is a combination product consisting of a penicillin-class antibacterial, piperacillin, and a β-lactamase inhibitor, tazobactam, indicated for the treatment of patients with moderate to severe infections caused by susceptible isolates of the designated bacteria in the conditions listed below.

Intra-abdominal Infections

Appendicitis (complicated by rupture or abscess) and peritonitis caused by β-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus. The individual members of this group were studied in fewer than 10 cases.

Skin and Skin Structure Infections

Uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by β-lactamase producing isolates of Staphylococcus aureus.

Female Pelvic Infections

Postpartum endometritis or pelvic inflammatory disease caused by β-lactamase producing isolates of Escherichia coli.

Community-acquired Pneumonia

Community-acquired pneumonia (moderate severity only) caused by β-lactamase producing isolates of Haemophilus influenzae.

Nosocomial Pneumonia

Nosocomial pneumonia (moderate to severe) caused by β-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) [see Dosage and Administration (2)].

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zosyn and other antibacterial drugs, Zosyn should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Zosyn® (piperacillin and tazobactam) for Injection is supplied as a white to off-white powder in vials of the following sizes:

Each Zosyn 2.25 g vial provides piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam.

Each Zosyn 3.375 g vial provides piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam.

Each Zosyn 4.5 g vial provides piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam.

Each Zosyn 40.5 g pharmacy bulk vial contains piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams tazobactam.

NDC 0206-4501-01

4.5 gram Single Use Vial

Zosyn®

(piperacillin and
tazobactam for
injection, USP)

4.5 gram

For IV Use Only
Rx only

PREMIERPro™ Rx

NDC 0206-5501-01
Rx only

Zosyn®
(Piperacillin and Tazobactam
for Injection, USP)

40.5 gram vial

PHARMACY BULK PACKAGE
Not for Direct Infusion

RECONSTITUTED STOCK SOLUTION MUST BE
TRANSFERRED AND FURTHER DILUTED
FOR I.V. INFUSION

PREMIERPro™ Rx

Zosyn is injected into a vein through an IV. You may be shown how to use an IV at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Zosyn is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Prepare your dose only when you are ready to give an injection. Do not use if the medicine has changed colors or has particles in it. Call your pharmacist for new medicine.

Use Zosyn for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. This medicine will not treat a viral infection such as the common cold or flu.

While using Zosyn, you may need frequent blood tests.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Zosyn.

Each single-use vial (bottle) of Zosyn is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Store the unmixed Zosyn powder and the liquid diluent at cool room temperature, away from moisture and heat. Do not freeze the vial.

Medicine mixed in an IV bag must be used within 24 hours if you keep it at room temperature.

Medicine mixed in a syringe can be stored in a refrigerator for up to 48 hours. Mixed medication in an IV bag can also be stored in the refrigerator for up to 7 days. Do not freeze. Throw away any unused mixture that has not been used within these times.

Mixed medicine in an infusion pump must be used within 12 hours if you keep it at room temperature.

If your medicine is frozen when you receive it, store the medicine container in a freezer until you are ready to prepare your dose.

You may thaw frozen medicine either in a refrigerator or at room temperature. Do not heat the medicine under hot water or in a microwave.