Fortaz

FORTAZ in the dry state should be stored between 15°C and 30°C (59°F and 86°F) and protected from light. FORTAZ is a dry, white to off-white powder supplied in vials as follows:

• NDC 52565-105-10 500-mg* Single-Dose Vial (Tray of 10)
• NDC 52565-106-10 1-g* Single-Dose Vial (Tray of 10)
• NDC 52565-107-10 2-g* Single-Dose Vial (Tray of 10)
• NDC 52565-110-25 1-g TwistVial™ Single-Dose Vial (Tray of 25)
• NDC 52565-111-10 2-g TwistVial™ Single-Dose Vial (Tray of 10)

(The above TwistVial™ vials are to be used only with compatible diluent containers.)

FORTAZ frozen as a premixed solution of ceftazidime sodium should not be stored above -20°C. FORTAZ is supplied frozen in 50-mL, single-dose, plastic containers as follows:

• NDC 52565-112-12 1-g* Plastic Container (Carton of 24)
• NDC 52565-113-12 2-g* Plastic Container (Carton of 24)

*Equivalent to anhydrous ceftazidime.

REFERENCES

5. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.

Distributed by Teligent Pharma, Inc. Buena, NJ 08310. Manufactured by GlaxoSmithKline Verona, Italy 37135. Revised: Jul 2017

Serious side effects have been reported with Fortaz. See the “Drug Precautions” section.

Common side effects of Fortaz include:

• itching
• rash
• fever
• irritation at the site of injection
• diarrhea
• nausea
• vomiting
• headache

This is not a complete list of Fortaz side effects. Ask your doctor or pharmacist for more information.

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

Before taking Fortaz, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Fortaz or to any ingredient of Fortaz
• are allergic to similar antibiotics (penicillins, cephalosporins)

• have kidney problems
• have gastrointestinal (stomach or bowel) problems
• have a history of seizure activity
• are pregnant or are breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Fortaz falls into category B. There are no well-done studies that have been done in humans with Fortaz. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Fortaz has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Fortaz, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

If you are receiving this medication at a clinic, call your doctor if you miss an appointment for your injection.

Contraindications

• Known hypersensitivity to ceftazidime or other cephalosporins.1

Warnings/Precautions

Warnings

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy.1 Careful observation of the patient is essential.1 217 Institute appropriate therapy if superinfection occurs.1 217

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including ceftazidime, and may range in severity from mild diarrhea to fatal colitis.1 217 340 341 342 C. difficile produces toxins A and B which contribute to development of CDAD;1 217 340 hypertoxin-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.1 217

Consider CDAD if diarrhea develops and manage accordingly.1 217 340 341 342 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1 217 340

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 217 340 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 217 340 341 342

Possibility of seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia if inappropriately high dosage used in patients with renal impairment.1 (See Renal Impairment under Cautions.)

Sensitivity Reactions

Possible hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.1 217 a

Hypersensitivity reactions, including anaphylaxis, reported with dextrose-containing solutions;251 usually reported in patients receiving high dextrose concentrations (i.e., 50% dextrose), but also reported when corn-derived dextrose solutions administered to patients with or without history of hypersensitivity to corn products.251

If an allergic reaction occurs, discontinue and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen).1 217

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1 217 a

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1 217 Cautious use recommended in individuals hypersensitive to penicillins:1 217 a avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.a

General Precautions

Use with caution in patients with a history of GI disease, particularly colitis.1 217 (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Possibility of prolonged PT.1 217

Monitor PT in patients at risk, including those with renal or hepatic impairment, poor nutritional state, receiving prolonged therapy, or stabilized on anticoagulant therapy.1 217 Administer vitamin K when indicated.1 217

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftazidime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1 217

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 217 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 217

Resistance caused by inducible type I β-lactamases can develop in some gram-negative bacilli (e.g., Enterobacter, Pseudomonas, Serratia) during treatment, leading to clinical failure in some cases.1

When treating infections caused by these bacteria, perform periodic in vitro susceptibility testing when clinically appropriate.1 If patient fails to respond to monotherapy, an aminoglycoside or similar agent should be considered.1

Possibility of distal necrosis after inadvertent intra-arterial administration.1

Vials, pharmacy bulk packages, and ADD-Vantage vials contain ceftazidime admixed with sodium carbonate to facilitate dissolution.1 217 233 These preparations contain approximately 54 mg (2.3 mEq) of sodium per g of ceftazidime.1 217 233

Like other dextrose-containing solutions, use Duplex drug delivery system containing ceftazidime and dextrose injection with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.251

Specific Populations

Category B.1

Distributed into milk in low concentrations; use with caution.1

To avoid unintentional overdosage, do not use ceftazidime available in Duplex containers in pediatric patients who require less than entire 1- or 2-g dose in the container.251

No overall differences in safety and efficacy in those ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.1

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.1 Select dosage with caution and assess renal function periodically because of age-related decreases in renal function.1 (See Renal Impairment under Dosage and Administration.)

Pharmacokinetics not affected.1

Possible decreased clearance and increased serum half-life.1

Neurotoxicity reported in some patients with renal impairment who received dosage inappropriately high for their renal status.1 (See Neurotoxicity under Cautions.)

Dosage adjustments necessary in patients with Clcr ≤50 mL/minute.1 See Renal Impairment under Dosage and Administration.

Common Adverse Effects

GI effects, hypersensitivity reactions, local reactions at IV injection sites.1

Specific Drugs and Laboratory Tests

Absorption

Bioavailability

Not absorbed from GI tract; must be given parenterally.3 50

Following IM administration, peak serum concentrations attained in approximately 1 hour.1 6 12 217 May be absorbed more slowly in women than in men following IM injection into the gluteus maximus or vastus lateralis.6 In women, peak serum concentrations may be lower following IM injection into the gluteus maximus than into the vastus lateralis.6

In patients with end-stage chronic renal failure who receive a single dose of the drug via an intraperitoneal catheter, peak serum concentrations attained 2.75 hours after the dose.27

Distribution

Extent

Widely distributed into body tissues and fluids including the gallbladder,24 234 255 bone,1 3 23 147 203 217 220 bile,1 3 10 11 18 24 49 50 147 203 217 255 skeletal muscle,1 3 23 50 203 217 234 prostatic tissue,21 217 234 endometrium,25 myometrium,1 3 25 217 234 heart,1 3 23 50 203 217 skin,1 3 23 50 217 234 adipose tissue,23 50 234 aqueous humor,1 3 16 22 147 203 217 and sputum,1 3 28 30 49 147 154 203 217 and pleural,22 203 peritoneal,1 3 15 50 166 167 217 synovial,1 3 217 ascitic,160 166 lymphatic,1 3 22 217 and blister1 3 22 165 217 fluids.

Generally diffuses into CSF following IV administration;1 11 13 19 20 22 50 147 158 217 223 224 226 CSF concentrations higher in patients with inflamed meninges than in those with uninflamed meninges.10 13 19 20 22 50 147 158

Distributed into bile, but biliary concentrations following IM or IV administration may be lower than concurrent serum concentrations.10 11 18 255

Crosses the placenta3 32 and is distributed into milk.1 3 17 203

Plasma Protein Binding

5–24%.1 4 6 8 10 11 50 147 203

Elimination

Metabolism

Not metabolized.1 3 4 9 10 11 12 24 50 217

Elimination Route

Eliminated unchanged principally in urine by glomerular filtration.1 3 7 10 11 24 47 50 203 217

80–90% of a dose eliminated in urine within 24 hours.1 12 24 161 165 203 217

Half-life

Adults with normal renal and hepatic function: distribution half-life 0.1–0.6 hours and elimination half-life 1.4–2 hours.1 4 5 6 7 24 36 161 166 203 217

Neonates: 2.2–4.7 hours.34 35 147 226

Children 1–12 months of age: 2 hours.155

Special Populations

Patients with impaired hepatic function: serum half-life only slightly prolonged.1 26 166 217

Patients with impaired renal function: serum concentrations higher and serum half-life prolonged.1 9 24 37 153 159 161 162 217 Serum half-life ranges from 9.4–10.3 hours in those with Clcr 13–27 mL/minute and 11–35 hours in those with Clcr<10 mL/minute.

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:

• Abdominal or stomach cramps or tenderness
• bloating
• bluish color
• changes in skin color
• diarrhea, watery and severe, which may also be bloody
• fever
• increased thirst
• itching of the vagina or genital area
• nausea or vomiting
• pain
• pain during sexual intercourse
• swelling at the site of injection
• swelling of the foot or leg
• tenderness
• thick, white vaginal discharge with no odor or with a mild odor
• unusual tiredness or weakness
• unusual weight loss
• white patches in the mouth or throat or on the tongue
• white patches with diaper rash

• Back, leg, or stomach pains
• bleeding gums
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chills
• cough
• dark urine
• difficulty with breathing
• difficulty with swallowing
• dizziness
• fast heartbeat
• general body swelling
• headache
• hives
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nosebleeds
• pale skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shortness of breath
• skin rash
• sore throat
• tightness in the chest
• wheezing
• yellowing of the eyes or skin

• Agitation
• bloody or cloudy urine
• blurred vision
• change in consciousness
• chest pain
• clay-colored stools
• confusion
• coughing up blood
• decreased frequency or amount of urine
• diarrhea
• difficult or painful urination
• drowsiness
• hallucinations
• increased blood pressure
• increased menstrual flow or vaginal bleeding
• increased thirst
• irritability
• loss of consciousness
• lower back or side pain
• muscle twitching or jerking
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• rhythmic movement of the muscles
• seizures
• sores, ulcers, or white spots on the lips or in the mouth
• stiff neck
• sudden decrease in the amount of urine
• swelling of the face, fingers, or lower legs
• swollen or painful glands
• troubled breathing
• unpleasant breath odor
• unusual bleeding or bruising
• vomiting of blood
• watery or bloody diarrhea
• weight gain

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:

• Red streaks on the skin
• swelling, tenderness, or pain at the injection site

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.

• If you need to store Fortaz at home, talk with your doctor, nurse, or pharmacist about how to store it.

For Intravenous or Intramuscular Use

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Fortaz and other antibacterial drugs, Fortaz should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria

2 gram Single-Dose Container Label

Fortaz® (ceftazidime injection)

12 - 50 mL Single-Dose Containers ISO-osmotic

Do Not Store Above -20oC. Do Not Refreeze.

2 g

Covis Pharmaceuticals, Inc.
Cary, NC 27511

COVIS

NDC 24987-413-00
Code 2G3536

(01) 20324987413009

GALAXY Container

Each 50 mL contains: ceftazidime sodium equivalent to 2 g of ceftazidime with approx. 1.6 g of Dextrose Hydrous, USP added to adjust osmolality. pH adjusted with sodium hydroxide and may have been adjusted with hydrochloric acid. pH 5.0 to 7.5.

Dosage: Intravenously as directed by a physician. See prescribing information.

Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks by squeezing thawed bag firmly. If leaks are found, discard bag as sterility may be impaired. Do not use unless solution is clear.

Rx only

Sterile, Nonpyrogenic

Do not store above -20oC. Thaw at room temperature (25oC) or under refrigeration (5oC). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution is stable for 3 days under refrigeration or 8 hours at room temperature. Do not refreeze.

Fortaz is a registered trademark of GlaxoSmithKline

GALAXY is a trademark of Baxter International Inc.

Distributed by Covis Pharmaceuticals, Inc., Cary, NC 27511

Manufactured by Baxter Healthcare Corporation, Deerfield, IL 60015 USA

PL 2040 Plastic

Made in England

100014

07-04-68-559

Rev. 5/12

Applies to ceftazidime: injection powder for solution

Along with its needed effects, ceftazidime (the active ingredient contained in Fortaz) 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 while taking ceftazidime:

• Abdominal or stomach cramps or tenderness
• bloating
• bluish color
• changes in skin color
• diarrhea, watery and severe, which may also be bloody
• fever
• increased thirst
• itching of the vagina or genital area
• nausea or vomiting
• pain
• pain during sexual intercourse
• swelling at the site of injection
• swelling of the foot or leg
• tenderness
• thick, white vaginal discharge with no odor or with a mild odor
• unusual tiredness or weakness
• unusual weight loss
• white patches in the mouth or throat or on the tongue
• white patches with diaper rash

• Back, leg, or stomach pains
• bleeding gums
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chills
• cough
• dark urine
• difficulty with breathing
• difficulty with swallowing
• dizziness
• fast heartbeat
• general body swelling
• headache
• hives
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nosebleeds
• pale skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shortness of breath
• skin rash
• sore throat
• tightness in the chest
• wheezing
• yellowing of the eyes or skin

• Agitation
• bloody or cloudy urine
• blurred vision
• change in consciousness
• chest pain
• clay-colored stools
• confusion
• coughing up blood
• decreased frequency or amount of urine
• diarrhea
• difficult or painful urination
• drowsiness
• hallucinations
• increased blood pressure
• increased menstrual flow or vaginal bleeding
• increased thirst
• irritability
• loss of consciousness
• lower back or side pain
• muscle twitching or jerking
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• rhythmic movement of the muscles
• seizures
• sores, ulcers, or white spots on the lips or in the mouth
• stiff neck
• sudden decrease in the amount of urine
• swelling of the face, fingers, or lower legs
• swollen or painful glands
• troubled breathing
• unpleasant breath odor
• unusual bleeding or bruising
• vomiting of blood
• watery or bloody diarrhea
• weight gain

Some side effects of ceftazidime 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:

• Red streaks on the skin
• swelling, tenderness, or pain at the injection site