Pneumosolv

Each vial of reconstituted sterile powder for injection contains: Ceftriaxone sodium, USP 1 g.

Pharmacology: Bactericidal action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes. Cephalosporins inhibit bacterial septum and cell wall synthesis, probably by acylation of membrane bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and elongation of susceptible bacteria and lysis frequently occur. Rapidly dividing bacteria are those most susceptible to the action of cephalosporins.
Pharmacokinetics: Ceftriaxone demonstrates non-linear dose-dependent pharmacokinetics because of its protein-binding; about 85 to 95% is bound to plasma protein depending on the plasma concentration of ceftriaxone.
Mean peak plasma concentrations of about 40 and 80 g per mL have been reported 2 hours after intramuscular injection of 0.5 and 1 g of ceftriaxone respectively. The plasma half-life of ceftriaxone is not dependent on the dose and varies between 6 and 9 hours; it may be prolonged in neonates. The half-life does not change appreciably in patients with moderate renal impairment, but it may be prolonged in severe renal impairment especially when there is also hepatic impairment.
Ceftriaxone is widely distributed in body tissues and fluids. It crosses both inflamed and non-inflamed meninges, generally achieving therapeutic concentrations in the CSF. It crosses the placenta and low concentrations have been detected in breast milk. High concentrations are achieved in bile.
About 40 to 65% of a dose of ceftriaxone is excreted unchanged in the urine, principally by glomerular filtration; the remainder is excreted in the bile and is ultimately found in the feces as unchanged drug and microbiologically inactive compounds.

Ceftriaxone is a third-generation cephalosporin antibiotic used similarly to cefotaxime for the treatment of susceptible infections. They include chancroid, endocarditis, gastro-enteritis (invasive salmonellosis; shigellosis), gonorrhea, Lyme disease, meningitis (including meningococcal meningitis prophylaxis), septicemia, surgical infection (prophylaxis), syphilis, typhoid fever and Whipple's disease.

Intramuscular (IM)/Intravenous (IV): Ceftriaxone is administered as the sodium salt by slow intravenous injection over 2 to 4 minutes, by intermittent intravenous infusion over at least 30 minutes, or by deep intramuscular injection. If more than 1 gram is to be injected intramuscularly then the dose should be divided between more than one site. Doses are expressed in terms of the equivalent amount of ceftriaxone.
Adults: 1 to 2 grams daily as a single dose or in two divided doses; in severe infections up to 4 grams daily may be given.
Uncomplicated gonorrhea: IM, single dose of 250 mg.
Surgical infection: Single dose of 1 gram may be administered 0.5 to 2 hours prior to surgery; a 2 gram dose is suggested before colorectal surgery.
Prevention of secondary cases of meningococcal meningitis: IM, 250 mg.
Children and Infants: 20 to 50 mg per kg body weight once daily; in severe infections up to 80 mg per kg daily may be given.
Prevention of secondary cases of meningococcal meningitis: IM, 125 mg.
Neonates: Maximum dose should not exceed 50 mg per kg; intravenous dose in neonates should be given over 60 minutes. Doses above 50 mg per kg should be administered by intravenous infusion only.
A reduction of dosage may be necessary in patients with severe renal impairment and in those with both impaired renal and hepatic function; plasma concentrations should be monitored in such patients.
Or as prescribed by the physician.
Preparation of Dosage Form: To prepare initial dilution for intramuscular use, 0.9 mL of sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, bacteriostatic water for injection (with 0.9% benzyl alcohol), or 1% lidocaine hydrochloride injection (without epinephrine) should be added to each 250 mg vial, 1.8 mL of diluent should be added to each 500 mg vial, 3.6 mL of diluent should be added to each 1 gram vial or 7.2 mL of diluent should be added to each 2 gram vial to provide a concentration approximately 250 mg per mL. Alternatively, to reduce the volume of intramuscular injection, a solution of 350 mg per mL may be prepared by adding 1 mL of diluent to each 500 mg vial, 2.1 mL of diluent to each 1 gram vial or 4.2 mL of diluent to each 2 gram vial. The 350 mg per mL solution is bioequivalent to a 250 mg per mL solution.
To prepare initial dilution for intravenous use, 2.4 mL of appropriate diluent should be added to each 250 mg vial, 4.8 mL of diluent should be added to each 500 mg vial, 9.6 mL diluent should be added to each 1 gram vial, or 19.2 mL of diluent should be added to each 2 gram vial to provide concentration of approximately 100 mg per mL. The reconstituted solution may be further diluted to 50 or 100 mL with an appropriate diluent for intravenous infusion.

Should not be used when the following medical problem exists: History of previous allergic reactions (anaphylaxis) to penicillins, penicillin derivatives, penicillamine, or cephalosporins.
Risk-benefit should be considered when the following medical problems exist: History of gastrointestinal disease especially, ulcerative colitis, regional enteritis, or antibiotic-associated colitis.
Renal function impairment.

Use of diluents containing benzyl alcohol is not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, repsiratory problems, renal failure, hypotension and possibly seizures and intracranial hemorrhages has been associated with this use.

Cross-sensitivity and/or related problems: Patients allergic to one cephalosporin may be allergic to other cephalosporins.
Patients allergic to penicillins, penicillin derivative, or penicillamine may be allergic to cephalosporins.
Carcinogenicity: Long-term studies in animals to evaluate the carcinogenic potential of these cephalosporins have not been done.
Mutagenicity: Studies have not shown that these cephalosporins are mutagenic.
Dental: Long-term therapy with cephalosporins may allow for the overgrowth of Candida albicans, resulting in oral candidiasis.
Fertility: Adequate and well-controlled studies in humans have not been done.
Use in Pregnancy: Cross the placenta. Adequate and well-controlled studies in humans have not been done. However, studies in animals have not shown that these cephalosporins cause adverse effects in the fetus.
Use in Lactation: Distributed into breast milk, usually in low concentrations. However, problems in humans have not been documented to date.
Use in Children: Lower metabolic and/or renal clearance of cephalosporins, with resulting prolonged half-life, has been reported in newborn infants. However, Ceftriaxone has been found to have shorter half-life in infants than it does in adults.
Because Ceftriaxone is very highly bound to plasma proteins, it may be more likely than some other cephalosporins to displace bilirubin from serum albumin. Ceftriaxone should be used with caution in hyperbilirubinemic neonates, especially premature neonates.
Use in Elderly: Cephalosporins have been used in the geriatric population, and no-geriatrics-specific problems has been documented to date. However, elderly patients are more likely to have an age-related decrease in renal function, which may require adjustment in dosage and/or dosing interval in patients receiving cephalosporins.

Fertility: Adequate and well-controlled studies in humans have not been done.
Use in Pregnancy: Cross the placenta. Adequate and well-controlled studies in humans have not been done. However, studies in animals have not shown that these cephalosporins cause adverse effects in the fetus.
Use in Lactation: Distributed into breast milk, usually in low concentrations. However, problems in humans have not been documented to date.

Incidence less frequent or rare: Hypoprothrombinemia (unusual bleeding or bruising); Pseudomembranous colitis (abdominal or stomach cramps and pain, severe abdominal tenderness, watery and severe diarrhea, which may also be bloody, fever).
Incidence rare: Allergic reactions, specifically anaphylaxis; Erythema multiforme or Steven-Johnson syndrome; Hearing loss; Hemolytic anemia, immune, drug-induced; Hypersensitivity reaction; Renal dysfunction; Serum-sickness like reactions; Thrombophlebitis; Biliary "sludge" or pseudolithiasis.
Need for medical attention only if they continue or are bothersome: Gastrointestinal reactions; Headache; Oral candidiasis; Vaginal candidiasis.
Possible pseudomembranous colitis and the need for medical attention if they occur after medication is discontinued: Abdominal or stomach cramps and pain, severe; Abdominal tenderness; Diarrhea, watery and severe, which may also be bloody; Fever.

Platelet aggregation inhibitors: hypothrombonemia induced by large dose of salicylates and/or cephalosporins, and the gastrointestinal ulcerative or hemorrhagic potential of non-steroidal anti-inflammatory drug (NSAIDs), salicylates, or sulfinpyrazone may increase the risk of hemorrhage.
Unlike many cephalosporins, probenecid does not affect the renal excretion of ceftriaxone.

Stability: After reconstitution for intramuscular use, solutions retain at least 90% of their potency for 1 to 3 days at room temperature or for 3 to 10 days if refrigerated at 4°C, depending on concentration and diluent. After reconstitution for intravenous use, solutions retain at least 90% of their potency for 3 days at room temperature or for 10 days if refrigerated at 4°C, when stored in glass or polyvinyl chloride (PVC) containers in suitable diluents.
After reconstitution for intravenous use with 5% dextrose injection or 0.9% sodium chloride injection, solutions at concentrations of 10-40 mg per mL retain their potency for 26 weeks at 20°C when stored in PVC or polyolefin containers. Frozen solutions should be thawed at room temperature. Once thawed, solutions should not be refrozen.
Solutions may vary in color from light yellow to amber, depending on length of time in storage, concentration and diluent.
Incompatibilities: The admixture of Ceftriaxone with other medications, including pentamidine isethionate, or with labetatol hydrochloride is not recommended.
The admixture of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If they are administered concurrently, they should be administered in separate sites. Do not mix them in the same intravenous bag or bottle.

Store at temperatures not exceeding 25°C and protect from light.

Cephalosporins

J01DD04 - ceftriaxone ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

Rx