OXCIVA

Package leaflet: Information for the patient

OXCIVA 1 000 mg powder for injectable/infusion solution

oxacillin
equivalent medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What OXCIVA is and what it is used for
2. What you need to know before using OXCIVA
3. How to use OXCIVA
4. Possible side effects
5. How to store OXCIVA
6. Contents of the pack and other information

1. What OXCIVA is and what it is used for

OXCIVA contains the active substance oxacillin, which belongs to a class of medicines called beta-lactams, beta-lactamase-resistant penicillins.
Oxacillin acts against susceptible bacteria causing skin, bone, and respiratory tract infections.
OXCIVA is also indicated for severe infections such as endocarditis (inflammation of the inner lining of the heart), meningitis (inflammation of the meninges), and septicemia (blood infection). It may also be used to prevent postoperative infections.
Oxacillin may also be used for other types of infections, as directed by the treating physician.
This medicine is used in adults and children from birth onwards to treat the following infections:

• endocarditis,
• meningitis,
• pneumonia,
• joint infections,
• osteomyelitis,
• skin and soft tissue infections,
• prophylaxis of postoperative infections (including neurosurgery, plastic surgery, etc.),
• bacteraemia associated with or suspected to be associated with the infections listed above,
• prophylaxis of postoperative infections in:
  • neurosurgery: craniotomy and placement of an internal cerebrospinal fluid shunt
  • plastic and reconstructive surgery of varying complexity

Current guidelines for antibiotic use should be taken into consideration.

2. What you need to know before using OXCIVA

Do not use OXCIVA:

• If you are allergic to oxacillin, to other beta-lactam antibiotics (penicillins and cephalosporins), or to any of the other ingredients of this medicine (listed in section 6). If allergic reactions occur, stop treatment immediately and inform your doctor.

Warnings and precautions
Talk to your doctor or pharmacist before using OXCIVA.
Any allergic reaction occurring during treatment must be reported to your doctor immediately.
Before starting this treatment, inform your doctor if you have previously experienced an allergic reaction during antibiotic therapy (even with another class of antibiotics), including: urticaria or other skin rashes, itching, sudden allergic-type swelling of the face and throat (angioedema) (see section 4).
Diarrhoea may occur during treatment with antibiotics, including OXCIVA, and may even appear several weeks after treatment has ended. If severe or persistent diarrhoea occurs, or if you notice blood or mucus in your stools, stop taking OXCIVA immediately. Do not take medicines that block or slow intestinal transit and contact your doctor (see section 4).

Other medicines and OXCIVA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including methotrexate (a medicine used to treat cancer or rheumatoid arthritis), probenecid (a medicine used to treat gout), or another antibiotic, including over-the-counter medicines.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
OXCIVA should not be taken during pregnancy unless specifically recommended by your doctor.

Breastfeeding
Small amounts of penicillins pass into breast milk, and the quantities ingested by the infant are much lower than neonatal therapeutic doses. Nevertheless, caution should be exercised when oxacillin is administered to breastfeeding mothers. If the infant develops adverse effects such as diarrhoea, skin rash, or candidiasis (an infection caused by certain microscopic fungi), inform your doctor immediately, as these effects in the infant may be related to the use of this medicine.
Consult your doctor or pharmacist before taking any medicine.

Driving and using machines
OXCIVA does not affect the ability to drive or operate machinery.

OXCIVA contains sodium
This medicine contains approximately 64 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 3.2% of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use OXCIVA

Dosage
OXCIVA is an injectable medicine; it must be administered by a healthcare professional via deep intramuscular injection or intravenous route. The physician will determine the appropriate dose for the patient.
Recommended dose:
Adults
Endocarditis (inflammation of the inner lining of the heart)
Infective endocarditis of native valve: 2 g IV every 4 hours or 3 g IV every 6 hours. Prosthetic valve endocarditis: 2 g IV every 4 hours.
Total daily dose: 12 g/day
Duration of therapy: For complicated right-sided native valve endocarditis and left-sided native valve endocarditis: 6 weeks. For uncomplicated right-sided native valve endocarditis: 2 weeks. For prosthetic valve endocarditis: at least 6 weeks.
Meningitis (inflammation of the meninges)
2 g IV every 4 hours.
Total daily dose: 12 g/day
Duration of therapy: at least 2 weeks
Pneumonia
2 g IV every 4–6 hours
Total daily dose: 12 g/day
Duration of therapy: at least 5 days for community-acquired pneumonia and 7 days for hospital-acquired or ventilator-associated pneumonia; patients must be clinically stable with normal vital signs before discontinuing therapy. Longer treatment courses may be required for severe pneumonia with necrosis; pneumonia complicated by meningitis, endocarditis, or other deep infections; pneumonia caused by non-fermenting Gram-negative bacteria; or pneumonia complicated by infection with less common pathogens (e.g., Burkholderia pseudomallei, Mycobacterium tuberculosis, or endemic fungi).
Joint infections
2 g IV every 4–6 hours
Total daily dose: 12 g/day
Duration of therapy: 4–6 weeks
Osteomyelitis (inflammation of the bone marrow)
1.5–2 g IV every 4–6 hours
Total daily dose: 12 g/day
Duration of therapy: 4–6 weeks
Skin or soft tissue infection
Surgical site infections (incision): 2 g IV every 6 hours.
Skin and soft tissue infections, necrotizing infections: 1–2 g IV every 4 hours.
Total daily dose: 12 g/day
Duration of therapy: The duration of treatment for most bacterial skin or soft tissue infections is 7–14 days. For pyomyositis, 2–3 weeks of therapy are recommended. For erysipelas and cellulitis, the recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within this time. For necrotizing infections, antimicrobial treatment should continue until further surgical interventions are no longer needed, the patient has clinically improved, and the patient has been afebrile for 48–72 hours.
Bacteraemia
2 g IV every 4–6 hours
Total daily dose: 12 g/day
Duration of therapy: 2–6 weeks
Prophylaxis of postoperative infections
2 g IV within 60 minutes before the first incision, followed, if necessary, by 2 g IV every 4 hours or 1 g IV every 2 hours
Total daily dose: 12 g/day
Duration of therapy: should not exceed 48 hours

Use in children and adolescents
Endocarditis
Children aged 1 year and older: 200 mg/kg/day IV, divided into doses every 4–6 hours.
Maximum dose: 12 g/day.
The maximum dose, calculated based on body weight, must not exceed 12 g/day.
Duration of therapy: at least 4–6 weeks.
Menigitis
Neonates from 0 to 7 days: 25 mg/kg IV every 8–12 hours.
Neonates from 8 to 28 days: 50 mg/kg IV every 6–8 hours.
Infants, children, and adolescents: 50 mg/kg IV every 6 hours.
The maximum dose, calculated based on body weight, must not exceed 12 g/day.
Duration of therapy: at least 2 weeks.
Lower doses and longer dosing intervals are recommended for neonates with very low birth weight (<2000 g).
Pneumonia
Infants and children over 3 months of age: 150–200 mg/kg/day IV or IM, given in divided doses every 6–8 hours.
The maximum dose, calculated based on body weight, must not exceed 12 g/day.
Duration of therapy: 5–14 days.
Osteomyelitis
Infants and children over 3 months of age: 150–200 mg/kg/day IV, given in divided doses every 4–6 hours.
Duration of therapy: 3–4 weeks. A longer treatment course may be necessary for diseases caused by MRSA or Salmonella, pelvic or vertebral spine infections, severe/complicated infections, or slow response to therapy.
Joint infections
Infants and children over 3 months of age: 150–200 mg/kg/day IV, given in divided doses every 4–6 hours.
The maximum dose, calculated based on body weight, must not exceed 12 g/day.
Duration of therapy: The total duration of therapy, IV plus oral, should average 2–3 weeks. Longer therapy (up to 4–6 weeks) may be required in cases of methicillin-resistant Staphylococcus aureus infection, Panton-Valentine leukocidin-positive infection, neonates and infants, slow/poor response or complications, or involvement of the pelvis or spine.
Skin or soft tissue infection
Infants and children over 1 month of age: 100–150 mg/kg/day IV, given in divided doses every 6 hours; for necrotizing infection: 200 mg/kg/day IV, given in divided doses every 6 hours.
Duration of therapy: The duration of treatment for most bacterial skin and soft tissue infections (SSTIs) is 7–14 days. For pyomyositis, 2–3 weeks of therapy are recommended. For erysipelas and cellulitis, the recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within this period. For necrotizing infections, antimicrobial treatment should continue until further surgical interventions are no longer needed, the patient has clinically improved, and the patient has been afebrile for 48–72 hours.
Bacteraemia

The maximum dose, calculated according to body weight, must not exceed 12 g/day.
Duration of therapy: 2 – 6 weeks.
Prophylaxis of postoperative infections
50 mg/kg i.v. within 60 minutes before the first incision, followed by 50 mg/kg i.v. every 4 hours if necessary.
The maximum dose, calculated according to body weight, must not exceed 12 g/day.
Duration of therapy: must not exceed 48 hours.
Elderly patients
When administering intravenously, care must be taken regarding the possibility of thrombophlebitis, particularly in elderly patients.
Renal impairment
In patients with severe renal impairment, dose adjustment is required. Creatinine clearance should be taken into account, and monitoring of drug levels is recommended.
Treatment should continue for at least 48 hours after resolution of signs and symptoms of infection.
Method of administration
Oxacillin is administered by deep intramuscular (i.m.) injection, by intravenous (i.v.) injection, or by intravenous (i.v.) infusion after reconstitution with a compatible solvent.
Duration of treatment
To be effective, this antibiotic must be used regularly at the prescribed doses and for the duration indicated by the physician. The disappearance of fever or any other symptom does not mean that complete recovery has occurred. Any feeling of fatigue is not due to the antibiotic treatment but to the infection itself. Reducing or interrupting treatment will not alleviate this sensation in any way, but may delay recovery.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Inform your doctor or healthcare professional immediately if you notice any of the following side effects: you may need urgent medical treatment:

• allergic shock: difficulty breathing, drop in blood pressure, rapid pulse (very rare),
• severe watery diarrhoea, with stomach pain and possibly blood and mucus (very rare) (see section 2. Warnings and precautions),
• allergic reaction (frequency not known) such as skin rash, itching or hives, breathing problems, swelling of the face and neck,
• fever, unusual bleeding, seizures (frequency not known).

Inform your doctor as soon as possible if you notice any of the following side effects:
Rare side effects (may affect up to 1 in 1,000 people)

• increase in certain liver enzymes (transaminases, alkaline phosphatase), hepatitis with jaundice.

Side effects with frequency not known

• insufficient number of red blood cells (anaemia) or of certain white blood cells (leucopenia) or of blood cells involved in clotting (platelets) (thrombocytopenia), which is reversible upon discontinuation of treatment,
• increase in certain white blood cells in the blood (eosinophilia),
• nausea, vomiting, diarrhoea,
• kidney disorder (acute interstitial nephropathy),
• fatigue,
• neurological disorders such as loss of consciousness, confusion, abnormal movements, involuntary muscle contractions, reported after administration of high doses of oxacillin-based antibiotic, particularly in case of renal impairment,
• fungal superinfection (vaginal candidiasis).

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects may help provide more information on the safety of this medicine.

5. How to store OXCIVA

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What OXCIVA contains

• The active substance is oxacillin: each vial contains 1,000 mg (as monohydrate sodium oxacillin).
• The other component is anhydrous disodium phosphate.

Description of the appearance of OXCIVA and contents of the pack
OXCIVA is a white or almost white powder in a clear glass vial sealed with a grey rubber stopper and an aluminium seal with a flip-off cap.
Pack sizes: boxes containing 1, 10, 25 or 50 vial(s).
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder
Avas Pharmaceuticals S.r.l.
Ripa di Porta Ticinese, 39
20143 Milan, Italy

Manufacturer
Mitim S.r.l.
Via Giovanni Battista Cacciamali, 34-38
25125 Brescia, Italy

This medicinal product is authorized in the European Economic Area (EEA) Member States under the following names:
Czech Republic: Oxacilin AVMC
Slovakia: Oxacilin AVMC
Poland: Oxacilin Norameda
Estonia: Oxacillin Auxilia
Italy: Oxciva

The following information is intended for healthcare professionals only:

Reconstitution and Dilution
Intramuscular administration
To prepare the injectable solution for intramuscular administration, add 5.7 mL of water for injections or 0.9% sodium chloride solution to the vial.
Shake the vial until the solution is clear. The solution should be administered by deep intramuscular injection immediately after preparation or within 8 hours, provided it is stored at 2–8°C.

Intravenous administration
For intravenous administration, add 10 mL of water for injections or 10 mL of 0.9% sodium chloride solution. Shake the vial until the solution is clear.
The solution must be administered slowly by intravenous infusion over 10 minutes. The reconstituted solution should be used immediately or within 8 hours, provided it is stored at 2–8°C.

The reconstituted solution should be further diluted with one of the following infusion solutions:

• Isotonic sodium chloride solution
• 5% glucose solution in water for injections
• 5% glucose in isotonic sodium chloride solution
• 10% D-fructose solution in water for injections
• 10% D-fructose in isotonic sodium chloride solution
• Ringer's lactate solution for infusion
• Injectable potassium chloride and sodium chloride with lactate solution
• 10% invert sugar solution in water for injections
• 10% invert sugar solution in isotonic sodium chloride solution
• 10% invert sugar + 0.3% potassium chloride solution in water for injections

The chemical and physical stability of the solution (either as reconstituted or reconstituted and further diluted for infusion as described above) has been demonstrated for 6 hours at room temperature when using the following diluent infusion solutions: isotonic sodium chloride solution, 5% glucose solution in water for injections, and 5% glucose in isotonic sodium chloride solution. Other diluents have demonstrated stability for 8 hours at 2°C–8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user.