Rocephin Information
Rocephin ()
Rocephin () Description
Rocephin () is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is (6,7)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo--triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-()-(-methyloxime), disodium salt, sesquaterhydrate.
The chemical formula of ceftriaxone sodium is CHNNaOS•3.5HO. It has a calculated molecular weight of 661.59 and the following structural formula:
Rocephin () is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of Rocephin () solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.
Rocephin () contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.
Rocephin () Clinical Pharmacology
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 gm dose and intramuscular (IM) administration of a single 0.5 (250 mg/mL or 350 mg/mL concentrations) or 1 gm dose in healthy subjects are presented in .
Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM doses ranging from 0.5 to 2 gm at 12- to 24-hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.
Ceftriaxone concentrations in urine are shown in .
Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 gm IV dose, average concentrations of ceftriaxone, determined from 1 to 3 hours after dosing, were 581 µg/mL in the gallbladder bile, 788 µg/mL in the common duct bile, 898 µg/mL in the cystic duct bile, 78.2 µg/gm in the gallbladder wall and 62.1 µg/mL in the concurrent plasma.
Over a 0.15 to 3 gm dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of
The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in . Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in .
Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (); therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 gm per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis; in six of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced.
The elimination of ceftriaxone is not altered when Rocephin () is co-administered with probenecid.
Rocephin () Indications And Usage
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:
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 ).
Rocephin () Contraindications
Rocephin () is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.
Rocephin () Warnings
BEFORE THERAPY WITH Rocephin () IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF SUBCUTANEOUS EPINEPHRINE AND OTHER EMERGENCY MEASURES.
As with other cephalosporins, anaphylactic reactions with fatal outcome have been reported, even if a patient is not known to be allergic or previously exposed.
Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute Rocephin () vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Rocephin () is mixed with calcium-containing solutions in the same IV administration line. Rocephin () 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, Rocephin () and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium (see , and ).
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Rocephin () Precautions
Prescribing Rocephin () in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Although transient elevations of BUN and serum creatinine have been observed, at the recommended dosages, the nephrotoxic potential of Rocephin () is similar to that of other cephalosporins.
Ceftriaxone is excreted via both biliary and renal excretion (see ). Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of Rocephin () are administered.
Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the Rocephin () dosage should not exceed 2 gm daily.
Alterations in prothrombin times have occurred rarely in patients treated with Rocephin () . Patients with impaired vitamin K synthesis or low vitamin K stores (eg, chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during Rocephin () treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.
Prolonged use of Rocephin () may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Rocephin () should be prescribed with caution in individuals with a history of gastrointestinal disease, especially colitis.
Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with Rocephin () . Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of Rocephin () -related biliary precipitation cannot be ruled out.
Patients should be counseled that antibacterial drugs including Rocephin () should only be used to treat bacterial infections. They do not treat viral infections (eg, common cold). When Rocephin () is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Rocephin () or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Of the total number of subjects in clinical studies of Rocephin () , 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with ceftriaxone dosages up to 2 grams per day (see ).
Rocephin () Adverse Reactions
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:
Other rarely observed adverse reactions (
Rocephin () 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.
Rocephin () Dosage And Administration
Rocephin () may be administered intravenously or intramuscularly.
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).
Rocephin () 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 humans 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.
Rocephin () How Supplied
Rocephin () is supplied as a sterile crystalline powder in glass vials. The following packages are available:
Vials containing 500 mg equivalent of ceftriaxone. Box of 1 (NDC 0004-1963-02) and box of 10 (NDC 0004-1963-01).
Vials containing 1 gm equivalent of ceftriaxone. Box of 1 (NDC 0004-1964-04) and box of 10 (NDC 0004-1964-01).
Rocephin ()
Rocephin ()
Rocephin () Principal Display Panel - Mg Vial Carton
NDC 0004-1963-02
Each vial contains ceftriaxone sodium powderequivalent to 500 mg ceftriaxone.
500 mg/15 mL Vial1 Vial
Rocephin () Principal Display Panel - Gram Vial Carton
NDC 0004-1964-04
Each vial contains ceftriaxone sodium powderequivalent to 1 gram ceftriaxone.
1 gram/15 mL Vial1 Vial
