Drug Study: Prostaphlin

Generic name: cloxacillin sodium
Brand name: Prostaphlin-A 250 mg and 500 mg capsules
Category: antibacterial

Description: Prostaphlin-A (cloxacillin sodium) is a penicillinase-resistanct, acid-resistant semisynthetic penicillin

Formulation: each capsule contains Cloxacillin (as Sodium) 250 mg and 500 mg. Inactive ingredients in Prostaphlin-A capsules: magnesium stearate.

Clinical Pharmacology:
Cloxacillin is resistant to destruction by acid. Absorption of cloxacillin after oral administration is rapid but incomplete (approximately 50%). Studies with an oral dose of 1-g demonstrated average serum levels at 60 minutes of 1.4. mcg/mL. at 4 hours, average levels were 2 mcg/mL. in one study, single oral 500-mg doses of cloxacillin produced peak serum concentrations of 7.5 to 14.4 mcg/mL at 1 to 1.5 hours. Oral absorption of cloxacillin is delayed when the drug is administered after meals.

Approximately 94% of cloxacillin binds to serum protein, mainly albumin. It is distributed in therapeutic concentrations into pleural, bile, and amniotic fluids and reaches insignificant concentrations in cerebrospinal and ascetic fluids.

The plasma half-life of cloxacillin is between 0.5 and 1.5 hours. Cloxacillin is partially metabolized to microbiologically active and inactive metabolites. Cloxacillin and its metabolites are rapidly excreted in the urine by glomerular filtration and active tubular secretion. Cloxacillin is also partly excreted in feces via biliary elimination.

Reduced plasma concentrations of cloxacillin seen in patients with cystic fibrosis have been attributed to enhanced nonrenal clearance of the drug.


Cloxacillin exerts a bactericidal action against penicillin-susceptible microorganisms during active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.

Cloxacillin is highly resistant to inactivation by staphylococcal penicillinase and is active against penicillinase-producing and non-penicillinase-producing strains of Staphylococcus aureus. Cloxacillin is active in vitro against a variety of other bacteria.

Cloxacillin has been demonstrated to be efficacious in the treatment of susceptible penicillinase-producing staphylococcal infections. Cloxacillin is also effective in the treatment of other commonly encountered gram-positive coccal infections, including beta-hemolytic streptococci, pneumonocci, and non-penicillinase-producing staphylococci.

Indications and Usage:

Prostaphlin-A is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Cultures and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug.

Prostaphlin-A may be used to initiate therapy in suspected cases of infections due to penicillinase-producing staphylococci prior to the availability of laboratory test results.

Prostaphlin-A should be used only in infections caused by penicillinase-producing staphylococci. It should not be used in infections due to organisms susceptible to penicillin G.

Prostaphlin-A is contraindicated in persons who have shown hypersensitivity to any of the penicillins or any component of the formulation.

Serious and occasionally fatal anaphylactic reactions have occurred in patients receiving penicillins. Serious anaphylactic reactions require immediate emergency treatment with epinephrine, intravenous fluids and steroids, oxygen and airway management, including intubation, as indicated. Although anaphylaxis is more frequent following parenteral administration, it has occurred in patients receiving oral penicillins.

Before therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. There is clinical and laboratory evidence of cross-allergenicity among the penicillins and partial cross-allergenicity among bicyclic beta-lactam antibiotics including penicillins, cephalosporins, cephamycins, 1-oxa-beta-lactams, and carbapenems. If an allergic reaction occurs, the drug should be discontinued and appropriate measure taken.

The use of antibiotics may result has been reported with nearly all antibacterial agents, and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antimicrobial agents. After the diagnosis of colitis has been established, therapeutic measures should be initiated.

Bacteriologic studies to determine the causative organisms and their susceptibility to the penicillinase-resistant penicillins should be performed. In the treatment of suspected staphylococci infections, therapy should be changed to another active agent if culture tests fail to demonstrate the presence of staphylocci.

Periodic assessment of organ system function including renal, hepatic, and hematopoietic should be made during prolonged therapy with the penicillinase-resistant penicillins.

Blood cultures, white blood cell counts and differential cell counts should be obtained prior to initiation of therapy and at least weekly during therapy with penicillinase-resistant penicillins.

Periodic urinalysis should be performed, and blood urea nitrogen, creatinine, AST (SGOT), and ALT (SGPT) concentrations should be determined during therapy with the penicillinase-resistant penicillins. Dosage alterations should be considered if these values become elevated.

Drug Interactions:
Probenecid increases and prolongs serum penicillin levels. Probenecid administered concomitantly with penicillins slows the rate of excretion by competitively inhibiting renal tubular secretions of penicillin..

Aminoglycosides and penicillins are physically and/or chemically incompatible and can mutually inactive each other in vitro. Penicillins can inactivate aminoglycosides in vitro in serum samples from patients receiving both drugs, which could produce falsely decreased results in serum aminoglycosides assays of the serum samples.

Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been conducted with these drugs.

Safety for use in pregnancy has not been established.
Cloxacillin passes through the placenta into the fetal circulation.
Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins. While human experience with the penicillins during pregnancy has not shown conclusive evidence of adverse effects on the fetus, no adequate or well-controlled studies have been done to exclude this possibility. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing women:
Cloxacillin is distributed into human milk. Therefore, caution should be exercised when cloxacillin is administered to a nursing woman.

Pediatric use:
Because of incompletely developed renal function in newborns, penicilinase-resistant penicillins (especially methicillin) may not be completely excreted, resulting in abnormally high blood levels. Frequent blood level determinations and dosage adjustments when necessary are advisable in these patients. All newborns treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects.

Adverse events:
Hypersensitivity: Two types of allergic reactions to penicillin are noted clinically, immediate and delayed.

Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria, and pruritus to angioedema, laryngospasms, bronchospasm, hypotension, vascular collapse, and death. Such events are very rare. They usually occur after parenteral therapy but have occurred in patients receiving oral therapy. Another type of immediate reaction, an accelerated reaction, may occur 20 minutes to 48 hours after administration and include urticaria, pruritus, wheezing, sneezing, and fever. Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon.

Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy. Manifestations of this type of reaction include serum sickness-like symptoms (i.e. fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes.

Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin thrapy. Pseudomembraneous colitis has been reported rarely with penicillinase-resistant penicillins.

Neurologic: neurotoxicity similar to that observed with penicillin G (e.g. lethargy, confusion, twitching, multifocal myoclonus, localized or generalized epileptiform seizures) may occur with large intravenous doses of the penicillinase-resistant penicillins especially in patients with renal insufficiency.

Renal: renal tubular damage and interstitial nephritis have been associated with the administration of methicillin sodium and infrequently with the administration of nafcillin, oxacillin, and cloxacillinl. Manifestations of this may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency. Nepropathy does not appear to be dose-related and is generally reversible upon prompt discontinuation of therapy.

Hematologic: eosinophilia, hemolytic anemia, agranulocytosis, neutropenia, leukopenia, granulocytopenia, thrombocytopenia and bone marrow depression have been associated with the use of penicillinase-resistant penicillins.

Hepatic: hepatoxicity characterized by fever, nausea, and vomiting associated with abnormal liver function tests mainly elevated AST (SGOT) levels, has been associated with the use of penicilinase-resistant penicillins. Asymptomatic, transient increase in serum concentrations of alkaline phosphatase, AST (SGOT), and ALT (SGPT) have been reported.

No specific treatment can be recommended. Treatment is symptomatic only. Cloxacillin is not dialyzable and is only minimally removed by hemodialysis or peritoneal dialysis (up to 5%)

Dosage and Administration:
Bacteriologic studies to determine the causative organisms and their susceptibility to the penicillinase-resistant penicillins should be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient. Therefore, it should be determined by the clinical and bacteriologic response of the patient. Therapy should be continued for at least 48 to 72 hours after the patient has become asymptomatic and cultures are negative. In severe staphylococcal infections, therapy with penicillinase-resistant penicillins should be continued for at least 14 days. The treatment of endocardities and osteomyelitis requires a longer term of therapy.

Doses should be taken 1 hour before or 2 hours after meals.

Mild to moderate infections: 250 mg every 6 hours
Severe infections: 500 mg or higher every 6 hours. Maximum recommended dosage is 6g/day.

Children (Patients weighing <20kg):
Mild to moderate infections: 50mg/kg/day in equally divided doses every 6 hours.
Severe infections: 100mg/kg/day or higher in equally divided doses every 6 hours. Maximum recommended dosage is 4g/day.

Renal impairment: adjustment of dosage is generally unnecessary in patients with renal impairment.

Store below 25 degrees Celsius.

Availability: Prostaphlin-A capsules, cloxacillin sodium equivalent to 250 mg or 500 mg per capsule, box of 150’s (15 x 10’s blister strip).

Also available Prostaphlin (oxacillin sodium) vials of 250 mg and 500 mg, dry-filled for IM/IV use.

Manufactured by: Bristol-Myers Squibb Co., Latina, Sermoneta, Italy

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