For Medicinal Usage of Preparation

INSTRUCTION for Medicinal Usage of Preparation OXAMP®- sodium

Registration number Trade name: OXAMP®- sodium International non-proprietary name or group name: Ampicillin + Oxacillin& Dosage form: Powder for preparation of solution for intravenous and intramuscular injection.

Composition for 1 vial Active substances: Ampicillin sodium 133.4 mg 333.5 mg (ampicillin equivalent) Oxacillin sodium 66.6 mg 166.5 mg (oxacillin equivalent)

Appearance Powder of off-white colour.

Pharmacotherapeutic group: Combination antibiotic (semisynthetic antibiotic).

ATX Code: [J01СR50].

Pharmacologic properties Pharmacodynamics. Combination antibiotic integrating the action spectra of ampicillin and oxacillin. Ampicillin is a semisynthetic penicillin, it has bactericidal action; it is acid-resistant. Active in relation to gram-positive microorganisms not forming penicillinase (Staphylococcus spp., Streptococcus spp., Streptococcus pneumoniae) and gram-negative microorganisms (Neisseria gonorrhoeae, Neisseria menin- gitidis, Escherichia coli, Salmonella spp., Shigella spp., Proteus mirabilis, Haemophilus influenzae). Oxacillin is a penicillinase-resistant semisynthetic antibiotic of penicillin group, acid-resistant; it has bactericidal action in relation to gram-positive microorganisms (Staphylococcus spp., Streptococcus spp., including Streptococcus pneumoniae, Actinomyces spp., Bacillus anthracis, Corynebacterium diphtheri- ae, anaerobic spore-forming bacilli, including Clostridium spp.), gram-negative cocci; Escherichia coli, Proteus mirabilis, Haemophilus influenzae, Klebsiella pneumoniae, Actinomyces spp., Treponema spp. Resistant to the action of the preparation are Pseudomonas aeruginosa and other nonfermentative gram- negative bacteria, most strains of Proteus vulgaris, Providencia rettgeri, Morganella morganii. Pharmacokinetics. Time to maximal concentration in blood (ТСmax) of both antibiotics is 0.5 to 1 h after intramuscular injection. Half-period is 1 to 2 hours. The preparation penetrates well various organs and tissues. At intravenous injection, the preparation concentrations exceeding the same at intramuscular injection are quickly formed in blood (in 5 to 10 minutes). Both antibiotics are excreted by kidneys, partially with bile. At repetitive injections they do not cumulate.

Indications for usage Infectious inflammatory diseases caused by agents sensitive to the preparation: sinusitis, tonsillitis, otitis media; bronchitis, pneumonia; cholangitis, cholecystitis; pyelonephritis, pyelitis, cystitis, urethritis, gonorrhoea, cervicitis; infections of skin and soft tissues: erysipelas, impetigo, reinfected dermatoses, etc. Prophylaxis of postoperative complications at surgery (also against the background of immunodeficiency), infections in newborns (infection of amniotic fluid; respiratory impairment in newborns, requiring resus- citation measures; risk of aspiration pneumonia). Sepsis, endocarditis, meningitis, postnatal infection.

1 Contraindications Hypersensitivity, infectious mononucleosis, lymphatic leukemia.

With caution For children born from mothers having hypersensitivity to penicillins. Allergic reactions in anamnesis and/or bronchial asthma, renal insufficiency, bleeding in anamnesis, enterocolitis against the background of antibiotics administration (in anamnesis).

Pregnancy and period of lactation Usage of the preparation during pregnancy is possible only in case the assumed benefit for the mother ex- ceeds the potential risk for the fetus. If it is necessary to administer the preparation during lactation, breast feeding should be abandoned (excreted with mother’s milk).

Method of application and doses Intramuscularly and intravenously (stream or drop-by-drop infusion). The preparation doses specified below are the sums of the ampicillin and oxacillin dosages (sodium salts) in their fixed ratio 2:1 (i.e. in the doses specified below, 0.5 g of the preparation equates to the sum of 333.5 mg ampicillin + 166.5 mg oxacillin). Daily dose for adults and children older than 14 years of age: 3 to 6 g; for newborns, premature infants and children younger than 1 year: 100 to 200 mg/kg/day; from 1 to 6 years old: 100 mg/kg/day; from 7 to 14 years old: 50 mg/kg/day. The daily dose is introduced in 3 to 4 infusions at an interval of 6 to 8 h. If required, the doses specified may be increased 1.5 to 2 times. Duration of the treatment depends on the severity of the disease (from 5 to 10 days up to 2 to 3 weeks; at chronic processes – for several months). For intramuscular introduction, dissolve the content of the vial (133.4 mg + 66.6 mg or 333.5 mg + 166.5 mg) in 2 ml or 5 ml water for injections, respectively. For intravenous stream infusion (for 2 to 3 minutes), dissolve the daily dose in 10 to 15 ml water for injections or 0.9% solution of sodium chloride. For intravenous drop infusion for adults, dissolve the daily dose in 100 to 200 ml of 0.9% solution of sodium chloride or 5% solution of dextrose (glucose) and introduce at a rate of 60 to 80 drop/minute; for children, 30 to 100 ml of 5 to 10% solution of dextrose (glucose) is used as a solvent. The preparation is introduced intravenously for 5 to 7 days, that followed by a transition to intramuscular introduction. The solutions shall be used directly after preparation.

Side Effects Allergic reactions: itching and peeling of skin, hives, dermahemia, rhinitis, conjunctivitis, angioneurotic edema, rarely: fever, arthralgia, eosinophilia, erythematous and maculopapular rash, exfoliative der- matitis, erythema multiforme (including Stevens-Johnson syndrome), serum sickness-like reactions; in isolated cases, anaphylactic shock, non-allergic ampicillin rash that may vanish without cancelling the preparation. Gastrointestinal tract reactions: disbacteriosis, taste alteration, vomiting, nausea, diarrhea, moderate increase of the “hepatic” transaminases activity, rarely - pseudomembranous colitis. Laboratory findings: leucopenia, neutropenia, anaemia, hematuria, proteinuria. Local reactions: pain in the place of injection, phlebitis and periphlebitis (at intravenous infusion); at intramuscular introduction, an infiltrate in the place of injection. Other: interstitial nephritis, nephropathy, superinfection (especially, in patients with chronic diseases or low- ered organism resistance), vaginal candidosis.

Overdosage Symptoms: Manifestations of toxic action on the central nervous system (especially, in patients with renal insufficiency); nausea, vomiting, diarrhea, water and electrolyte imbalance. 2 Treatment: symptomatic. Excretion with hemodialysis.

Interaction with other medicinal preparations Ampicillin. Pharmaceutically incompatible with aminoglycosides. Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserin, vancomycin, rifampicin) exert a synergistic action; bacteriostatic preparations (macrolides, chloramphenicol, lincosamides, tetracy- clines, sulfanilamides), an antagonist action. Increases the effectiveness of indirect anticoagulants (inhibiting the intestinal microflora, declines the vitamin К synthesis and the prothrombin index); degrades the effectiveness of estrogen-containing peroral contra- ceptives, medicinal agents in the metabolic process of which p-amino-benzoic acid is formed, ethinyl estradiol (in the last case, a risk of “breakthrough” bleedings is increased). Diuretics, allopurinol, oxyphenbutazone, phenylbutazone, nonsteroidal anti-inflammatory preparations and other medicinal agents blocking tubular secretion increase the ampicillin concentration in plasma (due to the reduction of tubular secretion). Allopurinol increases the risk of the skin rash development. Reduces clearance and increases the methotrexate toxicity. Oxacillin. Increases the methotrexate toxicity (competition for tubular secretion); increased doses of cal- cium folinate may be required (antidote of folic acid antagonists) and its more long-term administration. Joint administration with other medicinal agents exerting hepatotoxic action must be avoided. Simultaneous administration with bacteriostatic antibiotics is not recommended (effectiveness degradation). Medicinal agents blocking tubular secretion increase the oxacillin concentration in blood.

Specific Instructions At course treatment, control of the state of the blood-forming organs, liver and kidneys function is necessary. In case signs of anaphylactic shock occur, immediate measures must be taken to bring the patient out of this state: injection of epinephrine (adrenaline), glucocorticosteroids (hydrocortisone or prednisolone) and antihis- taminic agents; if necessary, artificial pulmonary ventilation shall be carried out. The possibility of a superinfection development (due to the growth of microflora insensitive to the preparation) requires a corresponding change of antibacterial therapy. In patients having increased sensitivity to penicillins, allergic cross-reactions with cephalosporin antibiotics are possible. When the preparation is used in high doses in patients with renal impairment, toxical action on central nervous system may occur.

Form of Issue Powder for preparation of solution for intravenous and intramuscular introduction in 133.4 mg + 66.6 mg, 333.5 mg + 166.5 mg. In 133.4 mg + 66.6 mg, 333.5 mg + 166.5 mg to vials of 10 ml or 20 ml capacity, hermetically sealed with rubber plugs, clamped by aluminum caps or combination aluminum caps with plastic covers. 5 vials are placed in a strip cellular pack made of polyvinylchloride film. 1, 5 or 10 vials or 1, 2 strip cellular packs with an instruction for usage are placed in a cardboard box. 50 vials with 5 instructions for usage are placed in cardboard box to be delivered to hospitals.

Storage Conditions List B. Store in a dry place protected from light, at a temperature of not more than 20°С. Keep out of reach of children.

Effective Life 2 years. Do not use after the expiration date.

Dispensing Conditions By prescription. 3 Manufacturer/organization that accepts claims: Open Joint Stock “Kurgan Joint Stock Company of Medical Preparations and Articles “Sintez” (Sintez Joint Stock Company); #7, Prospect Konstitutsii, city of Kurgan, Russian Federation, 640008; Tel. /fax: (3522)481689 Internet-site: http://www.kurgansintez.ru