Cefobid

Leaflet attached to the packaging: patient information

Cefobid, 1 g, powder for solution for injection and infusion

Cefoperazone

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• 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 side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Cefobid and what is it used for

The active substance of Cefobid is cefoperazone - a semi-synthetic antibiotic from the cephalosporin group, with a broad spectrum of antibacterial activity, intended exclusively for injection and infusion.
Cefobid 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, cholangitis, and other intra-abdominal infections,
• septicaemia,
• skin and soft tissue infections,
• inflammatory conditions in the pelvic area, endometritis, gonorrhoea, and other genital tract infections,
• for the prevention of postoperative infections in patients undergoing abdominal and pelvic surgery, cardiac surgery, and orthopaedic surgery.

Combination therapy
Due to the broad spectrum of antibacterial activity of Cefobid, in most infections, this antibiotic can be used as monotherapy. However, Cefobid may be used in combination with other antibiotics if necessary. During concomitant use of aminoglycosides, the doctor will recommend monitoring renal function.

2. Important information before using Cefobid

When not to use Cefobid

• If the patient is hypersensitive to cefoperazone (the active substance of this medicine) or any other medicine from the same group, or has a severe hypersensitivity to beta-lactam antibiotics (see section Warnings and precautions).

Warnings and precautions

Before starting treatment with Cefobid, consult your doctor or pharmacist.

• If the patient has a history of hypersensitivity reactions to beta-lactam antibiotics, cephalosporins, or other antibiotics. The risk of such reactions is higher in people with a history of hypersensitivity to multiple allergens.
• Severe skin reactions, in some cases leading to death, have been reported in patients using Cefobid (see section 4). In case of skin reactions, contact your doctor immediately, as it may be necessary to discontinue treatment and initiate appropriate treatment.
• In patients with liver function disorders and/or bile duct obstruction. It may be necessary to monitor the concentration of the medicine in the blood and adjust the dose, especially if there are concomitant renal function disorders.
• If the patient is on a low-calorie diet, is long-term parenterally nourished, or has impaired nutrient absorption. Cefoperazone - the active substance of Cefobid - may inhibit blood coagulation. Severe bleeding, sometimes leading to death, has been reported during treatment with Cefobid. If the patient experiences bleeding symptoms, contact your doctor immediately.
• If the patient is taking anticoagulant medications (medicines that inhibit blood coagulation).
• If the patient experiences diarrhoea, they should consult their doctor to determine the further course of treatment. Diarrhoea may be a symptom of pseudomembranous colitis, a rare complication that can occur in association with antibiotic treatment. In mild cases of pseudomembranous colitis, it is sufficient to discontinue the antibiotic, while in more severe cases, appropriate medication is necessary. It is contraindicated to take anti-diarrheal medications that inhibit peristalsis. Pseudomembranous colitis can occur even after more than two months after administration of antibacterial agents.
• If the medicine is used for a long time, there may be an increase in non-susceptible microorganisms. Therefore, during treatment with Cefobid, the patient should be closely monitored. The doctor may recommend periodic tests to monitor renal, liver, and haematopoietic system function.
• Particular caution should be exercised when using the medicine in newborns, especially premature infants, and in infants and young children.

Children and adolescents

Before starting treatment with Cefobid in premature infants and newborns, the doctor will weigh the potential benefits of administering the medicine against the risks associated with its use.

Cefobid and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Effect on laboratory test results -false-positive results may occur in the glucose test in urine using the Benedict or Fehling method.

Cefobid and alcohol

Do not consume alcohol during treatment with Cefobid. In patients who consumed alcohol during treatment or within 5 days of the last dose of the medicine, a disulfiram-like reaction was observed: facial flushing, sweating, and headaches and accelerated heart rate. A similar reaction has been observed with some other cephalosporins.
In patients fed through a nasogastric tube or parenterally, it is recommended to avoid administering solutions containing ethanol.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Cefobid crosses the placental barrier.
There are no data on the safety of use in pregnant women, so this medicine can only be used during pregnancy if absolutely necessary.
Although Cefobid is excreted into human milk only to a small extent, caution should be exercised when administering the medicine to breastfeeding women.
In preclinical studies in rats, no impairment of fertility was found. Clinical study results on fertility in men and women are not available. As the effect on animals may not be relevant to human reactions, caution should be exercised when a man or woman plans to have a child.

Driving and using machines

It is unlikely that the use of Cefobid will affect the ability to drive and use machines.

Cefobid contains sodium

The medicine contains 35.6 mg of sodium (the main component of common salt) per vial. This corresponds to 1.8% of the maximum recommended daily intake of sodium in the diet for adults.
The maximum recommended daily dose of this medicine contains 569.6 mg of sodium (present in common salt). This corresponds to 28.5% of the maximum recommended daily intake of sodium in the diet for adults. You should discuss this with your pharmacist or doctor if you take Cefobid every day for a long time, especially if you are on a low-sodium diet.
If you take 11 or more vials per day for a long time, especially if you control your sodium intake, you should contact your doctor or pharmacist.
This medicine can be prepared for administration using a solution containing sodium (see "Information intended exclusively for healthcare professionals"). This should also be taken into account when calculating the total amount of sodium, especially if the patient is on a low-sodium diet.

3. How to use Cefobid

Always use this medicine exactly as your doctor has told you. If you are not sure, ask your doctor.

Dosage for adults

Typically, the daily dose of Cefobid for adults is 2 to 4 grams, administered in divided doses every 12 hours. In severe infections, the doctor may increase the dose to 8 grams per day, administered in divided doses every 12 hours. A dose of 12 grams per day was administered in three divided doses every 8 hours. Cefobid can be administered in 2, 3, or 4 divided doses. Do not administer more than 4 grams at a time. Patients with impaired immune function have been administered doses of up to 16 grams per day in continuous intravenous infusion without complications. The doctor may recommend starting treatment before receiving the results of the antibiogram.

Dosage in patients with renal impairment

Excretion in the urine is not the primary route of elimination of Cefobid, so in patients with renal function disorders, there is no need to modify the dose of Cefobid if the medicine is administered in the usual doses (2-4 grams per day). In patients with a glomerular filtration rate of less than 18 ml/min or a serum creatinine level greater than 3.5 mg/dl, the maximum dose of cefoperazone is 4 grams per day.
Haemodialysis slightly shortens the half-life of Cefobid in the serum. Therefore, the medicine should be administered immediately after dialysis.

Dosage in patients with hepatic impairment

The doctor may recommend changing the dose in patients with severe bile duct obstruction, severe liver disease, or concomitant renal function disorders. In this group of patients, do not administer more than 2 grams of Cefobid per day, unless the serum concentrations of the medicine are monitored.

Method of administration

The medicine can be administered intramuscularly - in deep intramuscular injections (into the gluteus maximus muscle or the anterior thigh) or intravenously - in short-term intravenous infusion or continuous intravenous infusion.
The method of preparing the solution and administering the medicine is described at the end of the leaflet, in the section "The following information is intended exclusively for healthcare professionals or healthcare workers".

Use of a higher than recommended dose of Cefobid

After an overdose, the side effects described in this leaflet may worsen.
Haemodialysis may accelerate the elimination of the medicine from the body in case of overdose in patients with renal impairment.
If you have taken more than the recommended dose of the medicine, contact your doctor or pharmacist immediately.

Missing a dose of Cefobid

Cefobid is administered under close medical supervision. If you suspect that you have missed a dose of the medicine, always inform your doctor or nurse.

Stopping treatment with Cefobid

Do not stop treatment without consulting your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common(may affect more than 1 in 10 people):

• decreased haemoglobin level (red blood cell pigment that carries oxygen),
• decreased haematocrit (ratio of the volume of morphological elements of blood to the total volume of blood).

Common(may affect up to 1 in 10 people):

• neutropenia (decreased number of granulocytes),
• positive direct Coombs test (diagnostic test that allows the detection of incomplete antibodies),
• thrombocytopenia (decreased platelet count)*,
• eosinophilia (increased number of one type of white blood cell),
• phlebitis at the injection site,
• diarrhoea,
• increased liver enzyme activity in the blood (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase),
• jaundice*,
• pruritus*,
• urticaria,
• maculopapular rash.

Uncommon(may affect up to 1 in 100 people):

• vomiting*,
• pain at the injection site,
• fever.

Rare(may affect up to 1 in 1,000 people):

• hypoprothrombinaemia (prothrombin deficiency, involved in the blood coagulation process),
• bleeding*.

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

• coagulopathy (blood coagulation disorders)*,
• anaphylactic shock (a type of sudden, severe allergic or non-allergic reaction that can sometimes be fatal)*,
• anaphylactic reaction*,
• anaphylactoid reaction (severe allergic reaction), including shock*,
• hypersensitivity (allergy)*,
• pseudomembranous colitis (a specific type of colon infection)*,
• toxic epidermal necrolysis (exfoliation of the outer layer of skin all over the body)*,
• Stevens-Johnson syndrome (severe systemic allergic reaction with blisters and skin and mucous membrane redness)*,
• exfoliative dermatitis*,
• haematuria (blood in the urine)*.

*Side effects reported after the medicine was placed on the market.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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
Side effects can also be reported to the marketing authorisation holder or its representative.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Cefobid

Keep the medicine out of the sight and reach of children.
The vials of powder should be stored at a temperature not exceeding 25°C.
The prepared solution can be stored for 24 hours in the refrigerator, i.e., at a temperature between 2°C and 8°C.
Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month stated.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Cefobid contains

• The active substance of Cefobid is cefoperazone in the form of sodium salt. 1 vial contains 1 g of cefoperazone.

Cefobid does not contain any other ingredients.

What Cefobid looks like and contents of the pack

1 glass vial with powder for solution for injection and infusion, in a cardboard box.

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
To obtain more detailed information about this medicine, please contact the representative of the marketing authorisation holder:
Pfizer Polska Sp. z o.o.
phone: 22 335 61 00

Date of last revision of the leaflet: 12/2021

Information intended exclusively for healthcare professionals

Instructions for the administration and preparation of the medicine for use
Shake the vial before use.
Intramuscular administration
The medicine is administered in deep intramuscular injections into the gluteus maximus muscle or the anterior thigh.
To prepare a solution of cefoperazone for intramuscular injection, water for injection can be used. To administer the medicine at a concentration of 250 mg/ml or higher, a lidocaine solution should also be used, which is prepared by mixing water for injection with a 2% lidocaine hydrochloride solution to obtain approximately a 0.5% lidocaine hydrochloride solution.
A two-stage dilution process is recommended:

• 1. Add the required volume of water for injection to the vial with cefoperazone, shake until the medicine is completely dissolved.
• 2. Add the required volume of 2% lidocaine solution and mix.

* The vial contains a sufficient excess of the medicine, so only a specified volume is administered, and a specified volume is discarded.
Intravenous administration

• 1. To prepare a solution for short-term intravenous infusion, the contents of a 1-gram vial of cefoperazone should be dissolved in 20 to 100 ml of a suitable sterile solution for intravenous infusion and administered over a period of 15 minutes to 1 hour. If water for injection is the preferred diluent, it should not be used in a volume greater than 20 ml per vial of cefoperazone.
• 2. For continuous intravenous infusion, each 1 gram of cefoperazone should be dissolved in 5 ml of water for injection, and the resulting solution should be added to a suitable intravenous infusion solution.
• 3. For direct intravenous injection, the maximum dose of cefoperazone for adults is 2 grams. The medicine should be dissolved in a suitable solution to achieve a concentration of 100 mg/ml and administered by injection over a period of not less than 3 to 5 minutes.

First, a concentrate of the cefoperazone solution for intravenous injection is prepared. To do this, cefoperazone in the form of a sterile powder is dissolved in one of the solutions for intravenous administration listed below in Table 1, in a ratio of at least 2.8 ml of solvent per 1 gram of cefoperazone.
It is recommended to use 5 ml of the suitable solution per 1 gram of cefoperazone to facilitate preparation.

Table 1. Solutions for preparing a concentrate of the solution for intravenous injection

• 5% glucose solution
• 5% glucose solution with 0.9% sodium chloride solution
• 5% glucose solution with 0.2% sodium chloride solution
• 10% glucose solution
• 0.9% sodium chloride solution
• water for injection

The entire amount of the resulting concentrate should be further diluted in one of the following intravenous injection solutions (Table 2):

Table 2. Solutions for intravenous administration

• 5% glucose solution
• 5% glucose solution with lactated Ringer's solution
• 5% glucose solution with 0.9% sodium chloride solution
• 5% glucose solution with 0.2% sodium chloride solution
• 10% glucose solution
• lactated Ringer's solution
• 0.9% sodium chloride solution