Oxacillin Sodium

(BANM, USAN, rINNM)
Synonyms: (5-Methyl-3-phenyl-4-isoxazolyl)penicillin Sodium; Natrii Oxacillinum; Oksacylina sodowa jednowodna; Oksasilliininatriummonohydraatti; Oxacilin sodná sůl monohydrát; Oxacilina sódica; Oxacilline Sodique; Oxacilline sodique monohydratée; Oxacillinnatriummonohydrat; Oxacillinum natricum monohydricum; Oxacillinum Natrium; P12; SQ-16423. Sodium (6R)-6-(5-methyl-3phenylisoxazole-4-carboxamido)penicillanate monohydrate.
Cyrillic synonym: Натрий Оксациллин.

💊 Chemical information

Chemical formula: C19H18N3NaO5S,H2O = 441.4.
CAS — 66-79-5 (oxacillin); 1173-88-2 (anhydrous oxacillin sodium); 7240-38-2 (oxacillin sodium monohydrate).
ATC — J01CF04.
ATC Vet — QJ01CF04.

Pharmacopoeias.

In Chin., Eur., and US.

Ph. Eur. 6.2

(Oxacillin Sodium Monohydrate). A white or almost white powder. Freely soluble in water; practically insoluble in dichloromethane; soluble in methyl alcohol. A 3.0% solution in water has a pH of 4.5 to 7.5.

USP 31

(Oxacillin Sodium). A fine white crystalline powder, odourless or having a slight odour. Freely soluble in water, in dimethyl sulfoxide, and in methyl alcohol; slightly soluble in dehydrated alcohol, in chloroform, in methyl acetate, and in pyridine; insoluble in ether, in ethyl acetate, in ethylene chloride, and in benzene. pH of a 3% solution in water is between 4.5 and 7.5. Store in airtight containers at a mean temperature not exceeding 25°.

Incompatibility.

Oxacillin sodium has been reported to be incompatible with aminoglycosides and tetracyclines.

💊 Adverse Effects and Precautions

Effects on the liver.

References.
1. Onorato IM, Axelrod JL. Hepatitis from intravenous high-dose oxacillin therapy: findings in an adult inpatient population. Ann Intern Med 1978; 89: 497–500
2. Saliba B, Herbert PN. Oxacillin hepatotoxicity in HIV-infected patients. Ann Intern Med 1994; 120: 1048
3. Maraqa NF, et al. Higher occurrence of hepatotoxicity and rash in patients treated with oxacillin, compared with those treated with nafcillin and other commonly used antimicrobials. Clin Infect Dis 2002; 34: 50–4.

Sodium content.

Each g of oxacillin sodium contains about 2.3 mmol of sodium.

💊 Interactions

💊 Antimicrobial Action

Resistance.

The isolation of pneumococci resistant to oxacillin but sensitive to benzylpenicillin has been reported.1,2 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.
1. Johnson AP, et al. Oxacillin-resistant pneumococci sensitive to penicillin. Lancet 1993; 341: 1222
2. Dowson CG, et al. Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible. Antimicrob Agents Chemother 1994; 38: 49–53.

💊 Pharmacokinetics

Oxacillin is incompletely absorbed from the gastrointestinal tract. Absorption is reduced by the presence of food in the stomach and is less than with cloxacillin. Peak plasma concentrations of 3 to 6 micrograms/mL have been achieved 1 hour after an oral dose of 500 mg given to fasting subjects. 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 halflife is prolonged in neonates. The distribution of oxacillin into body tissues and fluids is similar to that of cloxacillin. Oxacillin undergoes some metabolism, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. About 20 to 30% of an oral dose, and 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.

💊 Uses and Administration

Oxacillin is an isoxazolyl penicillin used similarly to flucloxacillin in the treatment of infections due to staphylococci resistant to benzylpenicillin. Oxacillin is given orally or by injection as the sodium salt. Doses are expressed in terms of the equivalent amount of oxacillin; 1.1 g of oxacillin sodium is equivalent to about 1 g of oxacillin. Oral doses should preferably be given at least 1 hour before, or 2 hours after, meals. The usual adult oral dose is 1 g of oxacillin twice daily. 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. The usual oral dose for children is 500 mg twice daily. The parenteral dose for children weighing less than 40 kg is 50 mg/kg daily in 4 to 6 divided doses; the dose may be increased to 100 mg/kg daily for severe infections.

💊 Preparations

USP 31: Oxacillin for Injection; Oxacillin Injection; Oxacillin Sodium Capsules; Oxacillin Sodium for Oral Solution.

Proprietary Preparations

Belg.: Penstapho; Braz.: Oxacil†; Oxanon; Oxapen; Prodoxacilina; Roxacilin†; Staficilin N; Teutocilin†; Cz.: Prostaphlin; Fr.: Bristopen; Ger.: InfectoStaph; Ital.: Penstapho; Philipp.: Prostaphlin; Stafcil; Wydox; Venez.: Biocilina; Oxiclin†; Oxipen; Pebenal†; Prostafilina. Multi-ingredient: Ger.: Optocillin†; Rus.: Oxamp (Оксамп)†.
Published May 08, 2019.