Rocephin

Before instituting treatment with Rocephin, appropriate specimens should be obtained for isolation of the causative organism and for determination of its susceptibility to the drug. Therapy may be instituted prior to obtaining results of susceptibility testing.

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

Rocephin is indicated for the treatment of the following infections when caused by susceptible organisms:

LOWER RESPIRATORY TRACT INFECTIONS caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or Serratia marcescens.

ACUTE BACTERIAL OTITIS MEDIA caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase producing strains) or Moraxella catarrhalis (including beta-lactamase producing strains).

NOTE: In one study lower clinical cure rates were observed with a single dose of Rocephin compared to 10 days of oral therapy. In a second study comparable cure rates were observed between single dose Rocephin and the comparator. The potentially lower clinical cure rate of Rocephin should be balanced against the potential advantages of parenteral therapy (see Clinical Studies).

SKIN AND SKIN STRUCTURE INFECTIONS caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Viridans group streptococci, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii,* Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis* or Peptostreptococcus species.

URINARY TRACT INFECTIONS (complicated and uncomplicated) caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae.

UNCOMPLICATED GONORRHEA (cervical/urethral and rectal) caused by Neisseria gonorrhoeae, including both penicillinase- and nonpenicillinase-producing strains, and pharyngeal gonorrhea caused by nonpenicillinase-producing strains of Neisseria gonorrhoeae.

PELVIC INFLAMMATORY DISEASE caused by Neisseria gonorrhoeae. Rocephin, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and Chlamydia trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

BACTERIAL SEPTICEMIA caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae or Klebsiella pneumoniae.

BONE AND JOINT INFECTIONS caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae or Enterobacter species.

INTRA-ABDOMINAL INFECTIONS caused by Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridium species (Note: most strains of Clostridium difficile are resistant) or Peptostreptococcus species.

MENINGITIS caused by Haemophilus influenzae, Neisseria meningitidis or Streptococcus pneumoniae. Rocephin has also been used successfully in a limited number of cases of meningitis and shunt infection caused by Staphylococcus epidermidis* and Escherichia coli.*

*Efficacy for this organism in this organ system was studied in fewer than ten infections.

SURGICAL PROPHYLAXIS: The preoperative administration of a single 1 gm dose of Rocephin may reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated (eg, vaginal or abdominal hysterectomy or cholecystectomy for chronic calculous cholecystitis in high-risk patients, such as those over 70 years of age, with acute cholecystitis not requiring therapeutic antimicrobials, obstructive jaundice or common duct bile stones) and in surgical patients for whom infection at the operative site would present serious risk (eg, during coronary artery bypass surgery). Although Rocephin has been shown to have been as effective as cefazolin in the prevention of infection following coronary artery bypass surgery, no placebo-controlled trials have been conducted to evaluate any cephalosporin antibiotic in the prevention of infection following coronary artery bypass surgery.

When administered prior to surgical procedures for which it is indicated, a single 1 gm dose of Rocephin provides protection from most infections due to susceptible organisms throughout the course of the procedure.

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

• are allergic to Rocephin or to any ingredient of Rocephin 
• are allergic to similar antibiotics (penicillins, cephalosporins)
• have kidney problems
• have liver problems
• have gastrointestinal (stomach or bowel) problems
• have a history of seizure activity
• are receiving an infusion that contains calcium
• are pregnant or are breastfeeding

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

Absorption

Bioavailability

Not appreciably absorbed from GI tract; must be given parenterally.170

Appears to be completely absorbed following IM administration in healthy adults;1 52 57 84 peak serum concentrations attained 1.5–4 hours after the dose.1 48 52 57

Multiple-dose studies in healthy adults indicate serum concentrations at steady state on day 4 of therapy are 15–36% higher than serum concentrations attained with a single dose.1 56 84 170

Distribution

Extent

Following IM or IV administration, widely distributed into body tissues and fluids including the gallbladder,1 84 104 lungs,104 159 355 bone,68 104 489 heart,378 bile,1 69 72 84 104 prostate adenoma tissue,157 uterine tissue,71 104 atrial appendage,68 sputum,104 tears,104 middle ear fluid,1 488 and pleural,104 peritoneal,104 synovial,104 ascitic,104 105 and blister104 170 fluids.

Generally diffuses into CSF following IM or IV administration;1 60 61 62 64 65 84 104 105 107 141 170 CSF concentrations are higher in patients with inflamed meninges.65 84 104

Crosses the placenta and is distributed into amniotic fluid.66 84 104 Distributed into milk.66 84 104

Plasma Protein Binding

Degree of protein binding is concentration dependent; decreases nonlinearly with increasing concentrations of the drug.1 49 50 54 55 56 59 84 104 105 162 170 205 Principally binds to albumin.84 104 170

93–96% bound to plasma proteins at <70 mcg/mL,1 84 105 170 205 84–87% at 300 mcg/mL,1 84 105 170 and ≤58% at 600 mcg/mL.170

Protein binding is lower in neonates and children than in adults because of decreased plasma albumin concentrations in this age group.59 104 178 Also less protein bound in patients with renal or hepatic impairment as the result of decreased plasma albumin concentrations or displacement from protein binding sites by bilirubin and other endogenous compounds that may accumulate.74 76

Elimination

Metabolism

Metabolized to a small extent in the intestines after biliary elimination.84

Elimination Route

Eliminated by renal and nonrenal mechanisms.1 72 84 104 170

33–67% eliminated in urine by glomerular filtration as unchanged drug; remainder eliminated in feces via bile as unchanged drug and microbiologically inactive metabolites.72 84 104 170

Half-life

Adults with normal renal and hepatic function: Distribution half-life 0.12–0.7 hours55 57 172 and elimination half-life 5.4–10.9 hours.1 48 51 52 53 54 55 56 57 58 84 104 105 170 172

Neonates: 16.2 hours in those 1–4 days of age and 9.2 hours in those 9–30 days of age.60

Children 2–42 months of age: Distribution half-life 0.25 hours and elimination half-life 4 hours.61

Special Populations

Patients with moderately impaired renal function: Elimination half-life averages 10–16 hours.48 77 85 104 170

Elimination half-life averages 12.2–18.2 hours in patients with creatinine clearances <5 mL/min48 73 74 75 77 and 15–57 hours in uremic patients.73 74 77 104 170

If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

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 have itching; hives; hoarseness; shortness of breath; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive this medicine.

Ceftriaxone may cause diarrhea, and in some cases it can be severe. 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.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Do not take other medicines unless they have been discussed with your doctor. This includes calcium-containing solutions for injection, 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:

• Black, tarry stools
• chest pain
• chills
• cough
• fever
• painful or difficult urination
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness

• Diarrhea

• Abdominal or stomach cramps or tenderness
• back, leg, or stomach pains
• bleeding gums
• bloating
• blood in the urine or stools
• bloody nose
• bluish color
• changes in skin color
• clay-colored stools
• convulsions
• cough or hoarseness
• dark urine
• diarrhea, watery and severe, which may also be bloody
• difficulty with breathing
• difficulty with swallowing
• dizziness
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of discomfort
• feeling of warmth
• fever with or without chills
• general body swelling
• general feeling of tiredness or weakness
• headache
• hives
• increased sweating
• increased thirst
• inflammation of the joints
• itching
• loss of appetite
• lower back or side pain
• muscle aches
• nausea or vomiting
• noisy breathing
• nosebleeds
• pain
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rash
• redness of the face, neck, arms, and occasionally, upper chest
• shortness of breath
• skin rash
• swelling of the foot or leg
• swollen lymph glands
• tenderness
• tightness in the chest
• troubled breathing with exertion
• unpleasant breath odor
• unusual weight loss
• vomiting of blood
• watery or bloody diarrhea
• wheezing
• yellowing of the eyes or skin

• Blistering, peeling, or loosening of the skin
• chest pain
• coughing up blood
• decrease in the amount of urine
• excessive muscle tone
• increased menstrual flow or vaginal bleeding
• muscle stiffness, tension, or tightness
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red irritated eyes
• red or black, tarry stools
• red or dark brown urine
• red skin lesions, often with a purple center
• restlessness
• skin rash with a general disease
• swelling
• trouble sitting still
• unpleasant breath odor

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:

• Acid or sour stomach
• belching
• bloated
• change in taste
• dizziness
• excess air or gas in the stomach or intestines
• full feeling
• headache
• heartburn
• indigestion
• itching of the vagina or genital area
• loss of taste
• pain during sexual intercourse
• passing gas
• stomach discomfort, upset, or pain
• thick, white vaginal discharge with no odor or with a mild odor

• Hives or welts
• redness, swelling, or soreness of the tongue
• swelling or inflammation of the mouth

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 or prevent bacterial infections.

For all patients taking Rocephin (ceftriaxone):

• If you have an allergy to ceftriaxone or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

Children:

• If your child is a premature newborn. This medicine is not for use in certain ages of premature newborns.
• If your child is a newborn. Do not give to a newborn whose skin or eyes are yellow or who has high bilirubin levels in the blood. Do not give to a newborn who is getting a drug with calcium in it through a vein.

This is not a list of all drugs or health problems that interact with Rocephin.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where the shot is given.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Rocephin is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to Rocephin therapy or of uncertain etiology, were observed:

LOCAL REACTIONSpain, 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 CONDITIONSinjection site pain (0.6%).

HYPERSENSITIVITYrash (1.7%). Less frequently reported (<1%) were pruritus, fever or chills.

INFECTIONS AND INFESTATIONSgenital fungal infection (0.1%).

HEMATOLOGICeosinophilia (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 AND LYMPHATIC DISORDERSgranulocytopenia (0.9%), coagulopathy (0.4%).

GASTROINTESTINALdiarrhea/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).

HEPATICelevations of aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) (3.3%). Less frequently reported (<1%) were elevations of alkaline phosphatase and bilirubin.

RENALelevations of the BUN (1.2%). Less frequently reported (<1%) were elevations of creatinine and the presence of casts in the urine.

CENTRAL NERVOUS SYSTEMheadache or dizziness were reported occasionally (<1%).

GENITOURINARYmoniliasis or vaginitis were reported occasionally (<1%).

MISCELLANEOUSdiaphoresis and flushing were reported occasionally (<1%).

INVESTIGATIONSblood 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.

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 Rocephin. 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 Rocephin and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Rocephin 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 Rocephin 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/mm3) 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

In addition to the adverse reactions listed 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 LDH (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.

Other drugs may interact with ceftriaxone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.