Sulperazon 1 g

Package leaflet: Information for the user

Sulperazon 1 g,
500 mg + 500 mg, powder for solution for injection and infusion
Sulperazon 2 g,
1000 mg + 1000 mg, powder for solution for injection and infusion
Cefoperazone + Sulbactam
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Sulperazon is and what it is used for

Sulperazon is a combination medicine (containing cefoperazone with sulbactam) in the form of a dry powder
which is dissolved to prepare a solution for injection and infusion. Cefoperazone in combination
with sulbactam acts against microorganisms sensitive to cefoperazone.
Sulperazon is indicated for the treatment of the following infections caused by susceptible microorganisms:

• respiratory tract infections (upper and lower),
• urinary tract infections (upper and lower),
• peritonitis, cholecystitis, biliary tract infections, and other intra-abdominal infections,
• sepsis,
• skin and soft tissue infections,
• bone and joint infections,
• pelvic inflammatory disease, endometritis, gonorrhoea, and other genital tract infections.

Combination therapy
Due to the broad antibacterial spectrum of cefoperazone with sulbactam, many infections may be treated
with this medicine alone. However, your doctor may recommend using Sulperazon together with other antibiotics
if combination therapy is indicated. If you are also receiving aminoglycosides, your doctor may advise monitoring
kidney function during treatment.

2. Important information before using Sulperazon

When not to use Sulperazon:

• if the patient is allergic to the active substances or to other medicines in the same group, or if there has been a severe hypersensitivity reaction to beta-lactam antibiotics.

Warnings and precautions
Before starting treatment with Sulperazon, discuss this with your doctor or pharmacist.

• If the patient has previously experienced hypersensitivity reactions to beta-lactam antibiotics, cephalosporins, penicillins or other antibiotics (see section: When not to use Sulperazon). The risk of such reactions is higher in patients with a history of allergy to various allergens.
• If the patient develops severe skin reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome (a disease characterized by numerous skin blisters), or exfoliative dermatitis (erythroderma, a condition characterized by redness and peeling of the skin), Sulperazon must be discontinued immediately and medical advice sought.
• If the patient is taking anticoagulant medicines (medicines that inhibit blood clotting).
• In patients with impaired liver function and/or biliary obstruction. Monitoring of serum drug concentrations and possible dose adjustment may be necessary, especially if renal function is also impaired.
• If the patient is on an inadequate diet, is receiving long-term parenteral nutrition, or has malabsorption. Cefoperazone – one of the active substances in Sulperazon – may inhibit blood clotting. Serious bleeding, sometimes fatal, has been reported during treatment with Sulperazon. If symptoms of bleeding occur, contact a doctor immediately.
• If the patient develops diarrhoea, consult a doctor to determine further treatment. Diarrhoea may be a sign of pseudomembranous colitis, a rare complication that may occur occasionally during antibiotic treatment. Discontinuation of the antibiotic may be necessary; in more severe cases, oral metronidazole or vancomycin may be required. Medicines that inhibit peristalsis are contraindicated. Cases of pseudomembranous colitis have been reported even more than two months after administration of antibacterial agents.
• If Sulperazon is used for prolonged periods, overgrowth of resistant microorganisms may occur. Therefore, the patient should remain under close observation during treatment. The doctor may recommend periodic monitoring of organ and system functions, particularly the kidneys, liver, and haematopoietic system. Particular caution is advised when administering Sulperazon to newborns, especially preterm infants, as well as infants and young children.

Children
Before initiating treatment with Sulperazon in preterm infants and newborns, the doctor will weigh the potential benefits of treatment against the risks involved.

Elderly patients
There is no need to adjust the dosage in elderly patients.

Patients with renal impairment
The doctor will appropriately adjust the dose in patients with impaired renal function.

Patients with hepatic impairment
The doctor will appropriately adjust the dose in patients with impaired liver function or biliary obstruction.

Sulperazon and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, or those planned for use.

Laboratory test interference – false positive results may occur in urine glucose tests using Benedict's or Fehling's method.

Sulperazon and alcohol
A disulfiram-like reaction (flushing of the face, sweating, headache, and tachycardia – heart rate exceeding 120 beats per minute) has been observed in patients who consumed alcohol during treatment with Sulperazon or within 5 days after the last dose. Alcohol should not be consumed during therapy with Sulperazon.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor.

Sulperazon may be used during pregnancy only if, in the opinion of the doctor, the expected benefit to the mother outweighs the risk to the foetus.

Sulperazon should not be used during breastfeeding unless otherwise directed by a doctor.

Preclinical studies in rats have shown no impairment of fertility. Sulperazon crosses the placental barrier. Clinical data on fertility in men and women are not available.

Driving and operating machinery
It is unlikely that Sulperazon affects the patient's ability to drive or operate machinery.

Sulperazon contains sodium

Sulperazon 1 g, 500 mg + 500 mg, powder for solution for injection and infusion contains 67.1 mg of sodium (the main component of table salt) in each vial. This corresponds to 3.4% of the maximum recommended daily intake of sodium in the adult diet.

The maximum recommended daily dose of this medicine contains 536.8 mg of sodium (present in table salt). This corresponds to 26.8% of the maximum recommended daily intake of sodium in the adult diet.

Patients taking 6 or more vials per day over a long period, especially those monitoring sodium intake in their diet, should consult their doctor or pharmacist.

Sulperazon 2 g, 1000 mg + 1000 mg, powder for solution for injection and infusion contains 134.2 mg of sodium (the main component of table salt) in each vial. This corresponds to 6.7% of the maximum recommended daily intake of sodium in the adult diet.

The maximum recommended daily dose of this medicine contains 536.8 mg of sodium (present in table salt). This corresponds to 26.8% of the maximum recommended daily intake of sodium in the adult diet.

Patients taking 3 or more vials per day over a long period, especially those monitoring sodium intake in their diet, should consult their doctor or pharmacist.

This medicine may be prepared for administration using solutions containing sodium (see section "Information intended exclusively for healthcare professionals"). This should be taken into account when calculating total sodium content, particularly in patients on a low-sodium diet.

3. How to use Sulperazon

The medicine is administered under strict medical supervision by healthcare professionals. If in doubt, consult your doctor or nurse.

Sulperazon contains cefoperazone and sulbactam in a 1:1 ratio.

Use in adults
The recommended dose of Sulperazon for adults is 2 g to 4 g (1 g to 2 g of cefoperazone per day), given intravenously or intramuscularly in evenly divided doses every 12 hours.

In severe or treatment-resistant infections, the doctor may decide to increase the dose of Sulperazon up to 8 g per day, administered intravenously in evenly divided doses every 12 hours. The recommended maximum daily dose of sulbactam is 4 g (8 g of Sulperazon).

Use in children
Children should be given Sulperazon at doses of 40 to 80 mg/kg body weight/day, i.e. 20 to 40 mg/kg body weight/day of cefoperazone and 20 to 40 mg/kg body weight/day of sulbactam. The medicine should be administered every 6 to 12 hours, in 2 or 4 evenly divided doses.

In severe or treatment-resistant infections, the doctor may decide to increase the dose up to 160 mg/kg body weight/day (i.e. 80 mg/kg body weight/day of cefoperazone). The medicine should be administered in 2 to 4 evenly divided doses.

Use in newborns
In newborns under one week of age, Sulperazon should be administered every 12 hours. The maximum daily dose of sulbactam that may be used in newborns should not exceed 80 mg/kg body weight/day (160 mg/kg body weight/day of Sulperazon).

If a dose of cefoperazone higher than 80 mg/kg body weight/day is required, additional cefoperazone alone should be administered.

Use in patients with hepatic impairment
In patients with severe biliary obstruction, severe liver disease, or other liver function disorders, or in patients with concomitant renal impairment, the doctor may decide to adjust the dosage regimen. In such cases, the daily dose of the medicine will not exceed 2 g of cefoperazone per day.

Use in patients with renal impairment
In patients with significantly impaired renal function, the doctor may decide to adjust the dosage regimen. In cases of severe infections, additional administration of cefoperazone may be necessary.

Method of administration
Intravenous and intramuscular administration. Detailed instructions are provided at the end of this leaflet in the section intended for healthcare professionals.

Use of a higher than recommended dose of Sulperazon
Neurological symptoms, including seizures, may occur following overdose. Since the medicine will be administered under strict medical supervision, administration of a dose higher than recommended is unlikely. However, if a higher than recommended dose is administered, always inform the doctor.

Cefoperazone and sulbactam are removed from the body during hemodialysis; therefore, this procedure may accelerate elimination of the drug components in cases of overdose in patients with renal impairment.

Missed dose of Sulperazon
Since the medicine will be administered under strict medical supervision, a missed dose is unlikely. However, if a missed dose is suspected, always inform the doctor or nurse. Do not administer a double dose to make up for a missed dose.

Stopping Sulperazon treatment
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Very common (may occur in more than 1 in 10 people):

• neutropenia (reduced number of neutrophils), leukopenia (reduced number of white blood cells), positive direct Coombs test, decreased hemoglobin concentration, decreased hematocrit, thrombocytopenia (reduced number of blood platelets)
• increased enzyme activity: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase

Common (may occur in no more than 1 in 10 people):

• coagulopathy (bleeding disorders)
• eosinophilia (increased number of eosinophils)
• diarrhoea, nausea, vomiting
• increased blood bilirubin concentration

Uncommon (may occur in no more than 1 in 100 people):

• headache
• itching, urticaria
• phlebitis at injection site, pain at injection site, fever, chills

Frequency not known (cannot be estimated from available data):

• hypoprothrombinaemia (deficiency of prothrombin – a protein involved in the blood clotting process)
• anaphylactic shock, anaphylactic reactions, anaphylactoid reactions, including shock (a severe condition characterised, among others, by a sudden drop in blood pressure, which is life-threatening), hypersensitivity reactions
• bleeding, vasculitis, hypotension
• pseudomembranous colitis (see section 2. Warnings and precautions)
• jaundice
• toxic epidermal necrolysis, Stevens-Johnson syndrome (a severe skin reaction characterised by blistering, mainly in the mouth and genital areas, possibly accompanied by fever and joint pain), exfoliative dermatitis (a condition characterised by redness and peeling of the skin), maculopapular rash
• haematuria

Reporting of adverse effects
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder or the representative of the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Sulperazon

Keep this medicine out of sight and reach of children.
Store below 25°C.
The prepared solution may be stored for 24 hours after reconstitution.
Do not use this medicine after the expiry date stated on the carton after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Sulperazon contains
Sulperazon 1 g
The active substances are cefoperazone and sulbactam.
Each vial contains 500 mg of cefoperazone in the form of cefoperazone sodium (517 mg) and 500 mg of sulbactam in the form of sulbactam sodium (547 mg).
Sulperazon 2 g

• The active substances are cefoperazone and sulbactam. Each vial contains 1000 mg of cefoperazone in the form of cefoperazone sodium (1034 mg) and 1000 mg of sulbactam in the form of sulbactam sodium (1094 mg).

The medicine does not contain any other ingredients.
What Sulperazon looks like and contents of the pack
A vial made of colourless glass, sealed with a silicone-coated, grey bromobutyl rubber stopper, covered with a Teflon or EFTE layer, and closed with an aluminium flip-off cap with a plastic flip-off cap.
The carton box contains 1 vial with 500 mg cefoperazone and 500 mg sulbactam (Sulperazon 1 g) or 1000 mg cefoperazone and 1000 mg sulbactam (Sulperazon 2 g).
Marketing Authorisation Holder:
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium
Manufacturer:
Haupt Pharma Latina S.r.l., Latina (LT), Strada Statale 156 Km 47,600, 04100 Borgo San Michele, Italy
For further information about this medicine, please contact the Marketing Authorisation Holder:
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00

Information intended exclusively for medical professionals

Pharmaceutical incompatibilities
Aminoglycosides
Due to physical incompatibility, the Sulperazon solution should not be mixed with aminoglycosides. If combination therapy is considered, it may be administered via consecutive short intravenous infusions using two separate intravenous lines, with flushing of the lines using an appropriate diluent between administration of Sulperazon and aminoglycosides. It is also recommended that doses of Sulperazon be scheduled throughout the day so that the time interval between administration of Sulperazon and aminoglycosides is as long as possible.
Ringer's lactate solution
Due to the possibility of incompatibility, Ringer's lactate solution should not be used for initial reconstitution of the drug. However, during a two-step reconstitution process, if water for injections is used for initial reconstitution and Ringer's lactate solution is used for subsequent dilution, incompatibility does not occur.
Lidocaine
Due to the possibility of incompatibility, 2% lidocaine hydrochloride solution should not be used for initial reconstitution of the drug. However, if water for injections is used for initial reconstitution and 2% lidocaine hydrochloride solution is used for subsequent dilution, such incompatibility does not occur.
Preparation of the medicinal product for administration
The medicinal product containing cefoperazone and sulbactam is available in vials containing 1.0 g or 2.0 g of the drug.

It has been demonstrated that Sulperazon, a medicinal product containing cefoperazone and sulbactam, is compatible with the following solvents: water for injections, 5% dextrose solution, 0.9% sodium chloride solution, 5% dextrose in 0.225% sodium chloride solution, and 5% dextrose in 0.9% sodium chloride solution.
Cefoperazone is compatible at concentrations ranging from 10 to 250 mg/ml of solvent. Sulbactam is compatible at concentrations ranging from 5 to 125 mg/ml of solvent.

Ringer's lactate solution
For initial reconstitution of the medicinal product, water for injections should be used. In a two-step reconstitution process, after dissolving the medicinal product in water for injections (as shown in the table above), the solution is further diluted with Ringer's lactate solution to achieve a sulbactam concentration of 5 mg/ml (2 ml of solution after initial reconstitution in water for injections added to 50 ml, or 4 ml of solution after initial reconstitution in water for injections added to 100 ml of Ringer's lactate solution).

Lidocaine
For initial reconstitution of the medicinal product, water for injections should be used. In a two-step reconstitution process, to obtain a cefoperazone concentration of 250 mg/ml or higher, after dissolving the medicinal product in water for injections (as shown in the table above), the solution is further diluted with 2% lidocaine solution to yield solutions containing up to 250 mg of cefoperazone and 125 mg of sulbactam per 1 ml in lidocaine hydrochloride solution at a concentration of approximately 0.5%.

Administration method

Intravenous administration
For short-term intravenous infusions, the contents of each Sulperazon vial should be dissolved in an appropriate volume of 5% glucose solution, 0.9% sodium chloride solution, or sterile water for injections, and then diluted with the same solution to a final volume of 20 ml. The infusion should last between 15 and 60 minutes.

Ringer's lactate solution may be used for intravenous administration; however, it should not be used for the initial reconstitution of the medicinal product. It may, however, be used for intravenous infusion as a diluent for Sulperazon powder previously reconstituted.

For intravenous injection, the contents of each vial should be dissolved as described above. The medicinal product should be administered over at least 3 minutes.

Intramuscular administration
For dilution of the solution intended for intramuscular administration, a 2% lidocaine hydrochloride solution may be used; however, it should not be used for the initial reconstitution of the medicinal product.