Each vial contains: Oxacillin sodium eq. to Oxacillin 500 mg.
Pharmacology: Pharmacodynamics: Antimicrobial Action: Oxacillin is bactericidal with a mode of action similar to that of benzylpenicillin, but is resistant to staphylococcal penicillinase. It is active therefore against penicillinase-producing and non-penicillinase-producing staphylococci. Its activity against streptococci such as Streptococcus pneumoniae and Str. pyogenes is less than that of benzylpenicillin, but sufficient to be useful when these organisms are present with penicillin-resistant staphylococci. Oxacillin is virtually ineffective against Enterococcus faecalis.
Resistance: The isolation of pneumococci resistant to oxacillin but sensitive to benzylpenicillin has been reported. The resistance was due to acquisition of a low-affinity penicillin-binding protein and conferred cross-resistance to meticillin and cloxacillin, and, to a lesser degree, to cefotaxime.
Pharmacokinetics: Oxacillin after intramuscular injection of 500 mg, peak plasma concentrations of up to 15 micrograms/mL have been achieved by 30 minutes. Doubling the dose can double the plasma concentration. About 93% of the oxacillin in the circulation is bound to plasma proteins. Oxacillin has been reported to have a plasma half-life of about 0.5 hours. The half life is prolonged in neonates. Oxacillin crosses the placenta and is distributed into breast milk. There is little diffusion into the CSF except when the meninges are inflamed. Therapeutic concentrations can be achieved in pleural and synovial fluids and in bone. Oxacillin undergoes some metabolism, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. More than 40% of an intramuscular dose, is rapidly excreted in the urine. Oxacillin is also excreted in the bile. Plasma concentrations are enhanced by probenecid. Oxacillin is not removed by haemodialysis.
Used in the treatment of infections due to staphylococci resistant to benzylpenicillin. These include bone and joint infections, endocarditis, pneumonia, skin infections (including soft-tissue infections), and toxic shock syndrome.
Oxacillin may be given by intramuscular injection, by slow intravenous injection over about 10 minutes, or by intravenous infusion. Usual parenteral doses for adults are 250 to 500 mg every 4 to 6 hours; doses may be increased to 1 g every 4 to 6 hours for severe infections.
Hypersensitivity to Penicillin: The overall incidence of allergic reactions to penicillin has been reported to vary from about 1 to 10% although some patients may have been incorrectly labelled 'allergic to penicillin'. Anaphylactic reactions occur in about 0.05% of patients, usually after parenteral use. Hypersensitivity to penicillin gives rise to immediate reactions including anaphylaxis, angioedema, urticaria, and some maculopapular rashes. Late reactions may include serum sickness-like reactions and haemolytic anaemia. Reactions are considered to be due mainly to breakdown products produced in vitro before use or to metabolites of penicillin, and possibly penicillin itself. These act as haptens which, when combined with proteins and other macromolecules, produce potential antigens. As the hypersensitivity is related to the basic penicillin structure, patients who are genuinely allergic to penicillin must be assumed to be allergic to all penicillins; sensitised patients may also react to the cephalosporins and other beta-lactam antibiotics.
Tests for hypersensitivity may be used to determine those patients most likely to develop serious allergic reactions to penicillins. Skin tests are used to evaluate the current risk of immediate or accelerated IgE-mediated reactions, the most serious being anaphylaxis. Both the major and minor determinants of penicillin hypersensitivity should be used; the major determinant is available as penicilloyl-polylysine and a minor-determinant mixture consisting of benzylpenicillin and its derivatives, including penicilloic acid and benzylpenicilloylamine, can be used, although if this is not available a solution of benzylpenicillin may be substituted.
Adrenaline should be available in case an anaphylactic reaction develops. The results of skin tests are unreliable if a significant time has elapsed before beginning therapy. A number of in vitro tests including the radioallergosorbent test (RAST) have been developed.
Desensitisation may be attempted in patients allergic to penicillin when treatment with penicillin is considered essential. It involves very small doses of penicillin given at relatively short intervals of 15 minutes or more, and gradually increased to therapeutic concentrations. However, desensitisation may be hazardous and should only be carried out if the patient can be monitored continuously and adrenaline and resuscitation equipment are immediately available. Desensitisation should be regarded as temporary, and allergic reactions may recur during the next exposure to penicillin.
Neutropenia: Neutropenia has been widely reported in patients given high doses of beta lactams and an incidence of from 5 to more than 15% has been reported in patients treated for 10 days or more. Warning signs include fever, rash, and eosinophilia. Monitoring of the leucocyte count is recommended during long-term treatment with high doses. Some have proposed a direct toxic effect whereas others have postulated an immune mechanism.
Patients known to be hypersensitive to penicillins should be given an antibacterial of another class. However, sensitised patients may also react to the cephalosporins and other beta lactams. Desensitisation may be attempted if treatment with a penicillin is considered essential. Penicillins should be given with caution to patients with a history of allergy, especially to drugs. Care is necessary if very high doses of penicillins are given, especially if renal function is poor, because of the risk of neurotoxicity. The intrathecal route should be avoided. Renal, hepatic, and haematological status should be monitored during prolonged and high-dose therapy. Because of the Jarisch-Herxheimer reaction, care is also necessary when treating patients with spirochaete infections, particularly syphilis. Skin contact with penicillins should be avoided since sensitisation may occur. Penicillin therapy changes the normal bacterial flora and can lead to superinfection with penicillin-resistant organisms including Clostridium difficile or Candida, particularly with prolonged use. Penicillins may interfere with some diagnostic tests such as those for urinary glucose using copper sulfate, direct antiglobulin (Coombs') tests, and some tests for urinary or serum proteins. Penicillins may interfere with tests that use bacteria, for example the Guthrie test for phenylketonuria using Bacillus subtilis organisms.
The most common adverse effects of oxacillin are hypersensitivity reactions, especially skin rashes; anaphylaxis occasionally occurs and has sometimes been fatal.
Other adverse effects have generally been associated with large intravenous doses of oxacillin; patients with renal impairment are also at increased risk. These adverse effects include haemolytic anaemia and neutropenia, both of which might have some immunological basis; prolongation of bleeding time and defective platelet function; convulsions and other signs of CNS toxicity (encephalopathy has followed intrathecal dosage and can be fatal); and electrolyte disturbances because of the large amounts of sodium are used.
Hepatitis and cholestatic jaundice have been reported rarely with some penicillins, notably penicillinase-resistant penicillins.
Some patients with syphilis and other spirochaete infections may experience a Jarisch-Herxheimer reaction shortly after starting treatment with penicillin, which is probably due to the release of endotoxins from the killed treponemes and should not be mistaken for a hypersensitivity reaction. Symptoms include fever, chills, headache, and reactions at the site of the lesions. The reaction can be dangerous in cardiovascular syphilis, or where there is a serious risk of increased local damage, such as with optic atrophy.
Probenecid prolongs the half-life of Oxacillin by competing with it for renal tubular secretion and may be used therapeutically for this purpose. Oxacillin may also interact with bacteriostatic antibacterials such as chloramphenicol and tetracyclines, and may be incompatible in vitro with other drugs, including some other antibacterials. The possibility of a prolonged bleeding time after oral treatment with a broad-spectrum drug like ampicillin should be borne in mind in patients receiving anticoagulants.
Hormonal contraceptives: It is recommended that additional contraceptive precautions should be used while taking penicillin, and for 7 days after stopping, a short course of any broad-spectrum antibacterial. If these 7 days run into the last 7 days of the cycle, then the tablet-free interval (or the 7 inert tablets) should be omitted and the next cycle of tablets started immediately. If the course of antibacterial exceeds 3 weeks the intestinal flora develop resistance and additional precautions become unnecessary.
The effect of penicillins on methotrexate, Various penicillins have been reported to markedly decrease the clearance of methotrexate given intravenously for treatment of neoplasms.
Various penicillins have been reported to markedly decrease the clearance of methotrexate given intravenously for treatment of neoplasms. There have also been a few reports of penicillins possibly exacerbating the toxicity of low-dose methotrexate in patients being treated for psoriasis or rheumatoid arthritis, but a small study found that although flucloxacillin decreased methotrexate clearance slightly, this was not clinically significant.
Direction for Reconstitution: Dissolve the content with sterile water for injection in 3 mL for intravenous and 1.5 mL for intramuscular.
The reconstituted solution is stable for 12 hours.
Store at temperatures not exceeding 30°C.
J01CF04 - oxacillin ; Belongs to the class of beta-lactamase resistant penicillins. Used in the systemic treatment of infections.
Powd for inj (vial) 500 mg x 5's.