Easy-Ceft Dailymed

Adverse Reactions

ADVERSE REACTIONS

Ceftriaxone for Injection is generally well tolerated. In clinical trials. the following adverse reactions, which were considered to be related to Ceftriaxone for Injection therapy or of uncertain etiology, were observed: LOCAL REACTIONS- pain, induration, and tenderness was 1% overall. Phlebitis was reported in < 1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/ml and 5% (1/20) after IM administration of 250 mg/ml. GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS-- injection site pain (0.6%). HYPERSENSITIVITY- rash (1.7%) Less frequently reported(< 1%) were pruritus, fever or chills. INFECTIONS AND INFESTATIONS-genital fungal infection (0.1 %) HEMATOLOGIC-eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently reported(< 1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time BLOOD ANO LYMPHATIC OISORDERS---granulocytopenia (0.9%), coagulopathy (0.4%). GASTROINTESTINAL - diarrhea/loose stools (2.7%). Less frequently reported (< 1%) were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS). HEPATIC-elevations of aspartate aminotransferase (AST) (3.1 %) or alanine aminotransferase (ALT) (3.3%). Less frequently reported ( < '1 %) were elevations of alkaline phosphatase and bilirubin. RENAL - elevations of the BUN (1.2%). Less frequently reported(< 1%) were elevations of creatinine and the presence of casts in the urine. CENTRAL NERVOUS SYSTEM - headache or dizziness were reported occasionally(< 1%). GENITOURINARY - moniliasis or vaginitis were reported occasionally (< 1%). MISCELLANEOUS - diaphoresis and flushing were reported occasionally (<1%). INVESTIGATIONS-blood creatinine increased (0.6%). Other rarely observed adverse reactions(< 0.1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness.

Call to report suspected adverse reactions at 1-800-FDA-1088.

Postmarketing Experience

Postmarketing Experience

In addition to the adverse reactions reported during clinical trials, the following adverse experiences have been reported during clinical practice in patients treated with Ceftriaxone for Injection. Data are generally insufficient to allow an estimate of incidence or to establish causation. A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Ceftriaxone for Injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for Injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom Ceftriaxone for Injection and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates. GASTROINTESTINAL - pancreatitis, stomatitis and glossitis. GENITOURINARY - oliguria, ureteric obstruction, post-renal acute renal failure. DERMATOLOGIC - exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) have been reported. HEMATOLOGICAL CHANGES: Isolated cases of agranulocytosis (< 500/mm') have been reported, most of them after 10 days of treatment and following total doses of 20 g or more. NERVOUS SYSTEM DISORDERS: convulsion OTHER, Adverse Reactions: symptomatic precipitation of ceftriaxone calcium salt in the gallbladder, kernicterus, oliguria, and anaphylactic or anaphylactoid reactions.

Cephalosporin Class Adverse Reactions

Cephalosporin Class Adverse Reactions

In addition to the adverse reactions uled above which have been observed in patients treated with ceftriaxone, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics:

Adverse Reactions: Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and superinfection. Altered Laboratory Tests: Positive direct Coombs' test, false-positive test for urinary glucose, and elevated LOH (see PRECAUTIONS). Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

to report suspected adverse reactions, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Overdosage

OVERDOSAGE

In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.

Dosage And Administration:

DOSAGE AND ADMINISTRATION:

Ceftriaxone for Injection may be administered intravenously or intramuscularly. Do not use diluents containing calcium, such as Ringer's solution or Hartman n's solution, to reconstitute Ceftriaxone for Injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for Injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for Injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone for Injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS). There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

NEONATES:

NEONATES:

Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone for Injection. Ceftriaxone for Injection is contraindicated in premature neonates (see CONTRAINDICATIONS). Ceftriaxone: one for Injection is contraindicated in neonates (s 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see CONTRAINDICATIONS). Intravenous doses should be given over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy

PEDIATRIC PATIENTS:

PEDIATRIC PATIENTS:

For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams. For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended (see INDICATIONS AND USAGE). For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams. In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

ADULTS:

ADULTS:

The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. The total daily dose should not exceed 4 grams. If Chlamydia trachomatisis a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism. For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended. For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended. Generally, Ceftriaxone for Injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.

When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days. No dosage adjustment is necessary for patients with impairment of renal or hepatic function (see PRECAUTIONS). The dosages recommended for adults require no modification in elderly patients, up to 2g per day, provided there is no severe renal and hepatic impairment (see PRECAUTIONS).

DIRECTIONS FOR USE:

DIRECTIONS FOR USE:

Intramuscular Administration: Reconstitute Ceftriaxone for Injection powder with the appropriate diluent (see COMPATIBILITY AND STABILITY). Inject diluent into vial, shake vial thoroughly to form solution. Withdraw entire contents of vial into syringe to equal total labeled dose. After reconstitution, each 1ml of solution contains approximately 250 mg or 350 mg equivalent of ceftriaxone according to the amount of diluent indicated below. If required, more dilute solutions could be utilized. As with all intramuscular preparations, Ceftriaxone for Injection should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel.

Vial Dosage Size	Amount of Diluent to be Added
	250 mg/mL	350 mg/mL
500 mg	1.8 mL	1.0 mL
1 g	3.6 mL	2.1 mL
2 g	7.2 mL	4.2 mL

Intravenous Administration: Ceftriaxone for Injection should be administered intravenously by infusion over a period of 30 minutes, except in neonates where administration over 60 minutes is recommended to reduce the risk of bilirubin encephalopathy. Concentrations between 10 mg/ml and 40 mg/ml are recommended; however, lower concentrations may be used if desired. Reconstitute vials with an appropriate IV diluent (see COMPATIBILITY AND STABILITY).

Vial Dosage Size	Amount of Diluent to be Added
500 mg	4.8 mL
1 g	9.6 mL
2 g	19.2 mL

After reconstitution, each 1ml of solution contains approximately 100 mg equivalent of ceftriaxone. Withdraw entire contents and dilute to the desired concentration with the appropriate IV diluent.

COMPATIBILITY AND STABILITY

COMPATIBILITY AND STABILITY

Do not use diluents containing calcium, such as Ringer's solution or Hartman n's solution, to reconstitute Ceftriax: one for Injection vials or to further dilute a reconstituted vial for IV administration. Particulate formation can result. Ceftriaxone:one has been shown to be compatible with Flagyl IV (metronidazole hydrochloride). The concentration should not exceed 5 to 7 .5 mg/ml metronidazole hydrochloride with ceftriaxone 10 mg/ml as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (DSW). No compatibility studies have been conducted with the Flagyl® IV RTU® (metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/ml will precipitate. Do not refrigerate the admixture as precipitation will occur. Vancomycin, amsacrine, aminoglycosides, and fluconazole are incompatible with ceftriaxone in admixtures. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations. Ceftriaxone for Injection solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those uled above, due to possible incompatibility (see WARNINGS). Ceftriaxone for Injection sterile powder should be stored at 20° to 25° C(68° to 77° F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Ceftriaxone for Injection intramuscular solutions remain stable (loss of potency less than 10%) for the following time periods:

		Storage
Diluent	Room Temp. (25°C)	Concentration mg/mL	Refrigerated(4°C)
Sterile Water for Injection	100	2 days	10 days
	250, 350	24 hours	3 days
0.9% Sodium Chloride Solution	100	2 days	10 days
	250, 350	24 hours	3 days
5% Dextrose Solution	100	2 days	10 days
	250, 350	24 hours	3 days
Bacteriostatic Water + 0.9	100	24 hours	10 days
Benzyl Alcohol	250, 350	24 hours	3 days
1% Lidocaine Solution	100	24 hours	10 days
(without epinephrine)	250, 350	24 hours	3 days

Ceftriaxone for Injection intravenous solutions, at concentrations of 10, 20 and 40 mg/ml, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:

	Storage
Room Temp. (25°C)	Concentration mg/mL	Refrigerated(4°C)
Sterile Water for Injection	2 days	10 days
0.9% Sodium Chloride Solution	2 days	10 days
5% Dextrose Solution	2 days	10 days
Bacteriostatic Water + 0.9	2 days	10 days
Benzyl Alcohol	2 days	10 days
1% Lidocaine Solution	2 days	Incompatible
(without epinephrine)	2 days	Incompatible

The following intravenous Ceftriaxone for Injection solutions are stable at room temperature (25 ° C) for 24 hours, at concentrations between 10mg/ml and 40 mg/ml: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine Ill (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), lonosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container). After the indicated stability time periods, unused portions of solutions should be discarded.

NOTE: Parenteral drug products should be inspected visually for particulate matter before administration. Ceftriaxone for Injection reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/ml and 40 mg/ml, and then stored in frozen state (-20° C) in PVC or polyolefin containers, remains stable for 26 weeks. Frozen solutions of Ceftriaxone for Injection should be thawed at room temperature before use. After thawing, unused portions should be discarded.

DO NOT REFREEZE.

Animal Pharmacology

ANIMAL PHARMACOLOGY

Concretions consisting of the precipitated calcium salt of ceftriaxone have been found in the gallbladder bile of dogs and baboons treated with ceftriaxone. These appeared as a gritty sediment in dogs that received 100 mg/kg/day for 4 weeks. A similar phenomenon has been observed in baboons but only after a protracted dosing period (6 months) at higher dose levels (335 mg/kg/day or more). The likelihood of this occurrence in huma11s is considered to be low, since ceftriaxone has a greater plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile and the calcium content of human gallbladder bile is relatively low.

How Supplied

HOW SUPPLIED

Ceftriaxone for Injection, USP is supplied as a sterile crystalline powder in glass vials. The following packages are available:

Vials containing 500 mg equivalent of ceftriaxone. NOC 44567-700-25 (carton of 25). Vials containing 1g equivalent of ceftriaxone. NOC 44567-701-25 (carton of 25). Vials containing 2g equivalent of ceftriaxone. NOC 44567-702-25 (carton of 25).

Ceftriaxone for Injection, USP is also available as follows: Pharmacy Bulk Packages containing 10 g equivalent of ceftriaxone NDC 44567-703-01 (carton of 1). NOT FOR DIRECT ADMINISTRATION.

NOTE: Ceftriaxone for Injection, USP sterile powder should be stored at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature] and protected from light. Sterile, Non Pyrogenic, Preservative-Free. The container closure is not made with natural rubber latex.

Clinical Studies

Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media

In two adequate and well-controlled U.S. clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years. The clinical cure rates and statistical outcome appear in the table below:

Table 5 Clinical Efficacy in Pediatric Patients with Acute Bacterial Otitis Media

Clinical Efficacy in Evaluable Population
Study Day	Ceftriaxone Single Dose	Comparator – 10 Days of Oral Therapy	95% Confidence Interval	Statistical Outcome
Study 1 – U.S.		amoxicillin/clavulanate
14	74% (220/296)	82% (247/302)	(-14.4%, -0.5%)	Ceftriaxone is lower than control at study day 14 and 28.
28	58% (167/288)	67% (200/297)	(-17.5%, -1.2%)
Study 2 – U.S 1		TMP-SMZ
14	54% (113/210)	60% (124/206)	(-16.4%, 3.6%)	Ceftriaxone is Equivalent to control at study day 14 and 28.
28	35% (73/206)	45% (93/205)	(-19.9%, 0.0%)

An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens. The results of this study are tabulated as follows:

Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen:

Table 6 Bacteriologic Eradication Rates by Pathogen

	Study Day 13-15		Study Day 30+2
Organism	No. Analyzed	No. Erad. (%)	No. Analyzed	No. Erad. (%)
Streptococcus pneumoniae	38	32	35	25
		(84)		(71)
Haemophilus influenzae	33	28	31	22
		(85)		(71)
Moraxella catarrhalis	15	12	15	9
		(80)		(60)

References

REFERENCES

1. Barnett ED, Teele OW, Klein JO, et al. Comparison of Ceftriaxone and Trimethoprim-Sulfamethoxazo/e for Acute Otitis Media. Pediatrics. Vol. 99, No.1, January 1997.

References Section

Instructions For Use

Instructions for Use

1. Remove vial flip-top cover



2. Wipe top rubber stopper with alcohol pad



3. Open vial adapter and hold it with packaging



4. Do not touch adapter directly

5. While holding the packaging with the adapter inside, securely snap adapter on medication vial



6. Attach prefilled 2.5ml dilution syringe into vial adapter, inject diluent into vial and remove 2.5ml syringe

7. Swirl vial around to dissolve medication powder

8. Ensure solution is particulate-free and matches description in insert

9. Insert 5ml administration/Injection syringe into adapter, turn upside down and evacuate entire solution



10. For intramuscular injection insert hypodermic needle and inject per prescriber instructions

11. For Intravenous administration administer per prescriber instructions

Recent Major Changes Section

Package Label.principal Display Panel

NDC 79144-101-01

RX ONLY

For use by licensed healthcare professionals authorized to administer prescription medications

Keep out of reach of children

For intramuscular or intravenous use

See dosing and administration on package insert

Single use only

Protect from light prior to dilution

Ceftriaxone 1g

Easy-Ceftâ„¢ 1g

Convenience Injection Kit

Kit Contains:

1g Ceftriaxone Injection Vial USP

and Supplies for dilution and Administration

Kit Contains:

1. Ceftriaxone lg Vial

2. 3ml Sodium Chloride Syringe (Diluent)

3. 5ml Administration Syringe

4. Needle-Free Vial Adapter

5. 3 Alcohol Pads

6. Hypodermic Needle

See medication insert for usage, administration, indications, contraindications, precautions, warnings, dosing and adverse reactions.

Visit americanhealthrx.com

You are encouraged to report

adverse reactions and side

effects of this and any other prescription medication to

the FDA via FDA.gov/medwatch

or by calling 1-800-FDA-1088

• Each vial contains Ceftriaxone Sodium equivalent to lg Ceftriaxone

• Dosage and Administration: See package insert

• Administer in accordance to prescriber's instructions

• Before reconstitution store powder at 20° C to 25° C (68°F to 77°F) [See USP Controlled Room Temperature]

• Storage after reconstitution: See package insert

• Route of Administration: Intravenous/Intramuscular

• Inspect for particulate after dilution and prior to administration

• Solution color ranges from light yellow to amber

• Do not administer if color is not within range or with particulate

• Sterile, preservative-free single-dose vial

Principal Display Panel

PRINCIPAL DISPLAY PANEL - 1 g Vial Label

NDC 44567-701-25 CEFTRIAXONE

for Injection, USP

1 gram*

For IV or IM Use

Single-Use Vial

Rx Only

Principal Display Panel Packet Label

PRINCIPAL DISPLAY PANEL – PACKET LABEL

NDC 68599-5804-1

MCKESSON

Alcohol Prep Pad

STERILE | SATURATED WITH 70% v/v ISOPROPYL ALCOHOL

1.2" x 2.6" (3 cm x 6.5 cm)

DO NOT REUSE

MFR# 58-204