VALORAN 2 g POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the User

Valoran 1g powder for solution for injection and infusion EFG

Valoran 2g powder for solution for injection and infusion EFG

Cefotaxime (as cefotaxime sodium)

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Valoran and what is it used for

Valoran, which contains cefotaxime (an antibiotic belonging to the group of medicines known as cephalosporins), is a medicine used to combat bacteria.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as the flu or the common cold.

It is essential that you follow the instructions regarding dosage, administration interval, and treatment duration indicated by your doctor.

Do not store or reuse this medicine. If you have any leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Do not throw away medicines via wastewater or household waste.

It is used in severe acute and chronic bacterial infections caused by pathogens sensitive to cefotaxime:

• respiratory infections,
• otorhinolaryngological infections,
• renal and urinary tract infections,
• skin and soft tissue infections,
• bone and joint infections,
• gynecological infections, including gonorrhea,
• abdominal infections (including peritonitis),
• meningitis,
• blood poisoning (sepsis),
• heart inflammation (endocarditis),
• Lyme disease (especially in stages II and III) (infection mainly caused by tick bites)

In addition, for the prevention of infections after surgical interventions in patients with a higher risk of infections.

2. What you need to know before you use Valoran

Do not use Valoran:

• if you are allergic to cefotaxime, other cephalosporins, or any of the other components of this medicine (including those in section 6).
• if you have previously had an acute or severe hypersensitivity reaction to penicillin or other beta-lactam antibiotics. Penicillin and cephalosporins can cause cross-reactions.
• If you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth sores after taking cefotaxime or other cephalosporins

The use of cefotaxime mixed with lidocaine for intramuscular injection is not indicated in children under 30 months of age. The package leaflet for the product containing lidocaine should be taken into account.

Note:

Valoran 2 g should not be administered intramuscularly.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Valoran:

• If you are allergic to penicillin or other beta-lactam antibiotics in any form (for contraindications due to known hypersensitivity reactions, see above in the section "Do not use Valoran").
• If you have an allergic reaction (e.g., hay fever, bronchial asthma, hives) or if you are known to have one. In this case, you have a higher risk of more severe hypersensitivity reactions (which can be life-threatening in exceptional cases). If you experience a feeling of chest tightness, or feel dizzy, sick, or weak, these may be signs of a hypersensitivity reaction (see section 4).
• If a hypersensitivity reaction occurs, treatment should be discontinued.
• If you notice changes in the skin or mucous membranes during treatment (see section 4). Inform your doctor immediately because cefotaxime can cause severe skin reactions that require treatment.
• If you experience severe or persistent diarrhea during treatment or for several weeks after its completion. Inform your doctor immediately, as diarrhea in its most severe form (called pseudomembranous colitis) can be life-threatening and requires treatment. Do not take any medication that limits intestinal activity.
• If you know you have kidney failure. Inform your doctor in this case; if necessary, they may adjust the dose. It is necessary to monitor kidney function.
• If you are receiving concomitant or subsequent treatment with aminoglycosides (other antibiotics) or medications that can cause kidney damage. A doctor should monitor kidney function, as these substances can increase the harmful effects on the kidneys and caution is needed.
• If you experience movement disorders, have seizures, or confusion, or have altered consciousness. These may be signs of what is called encephalopathy. There is a risk of these adverse effects when high doses are administered, in case of overdose, or if you have kidney failure. If these reactions occur, consult your doctor immediately.
• If your treatment lasts more than 7 to 10 days. In this case, control blood tests should be performed because changes in the blood may appear (see also section 4).
• If you have signs of a new infection (e.g., fungal infection of the mucous membranes with redness and a white surface). The use of antibiotics can increase the amount of pathogens that are not sensitive to the used medication. Be vigilant for signs of a new infection and inform your doctor if necessary.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with cefotaxime treatment. Stop using cefotaxime and consult a doctor immediately if you detect any of the symptoms related to these severe skin reactions described in section 4.

Using Valoran with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Other antibiotics

The concomitant use of some antibiotics may reduce the effect of cefotaxime. Inform your doctor if you are taking or have recently taken other antibiotics.

Diuretics and potentially kidney-damaging medications

When cefotaxime is used in conjunction with medications that may have a harmful effect on the kidneys, such as aminoglycosides (other antibiotics) or medications with a high capacity to cause dehydration (diuretics, such as furosemide), it can increase the harmful effect on the kidneys of these medications. If administered concomitantly, kidney function should be monitored (see section 2 "Warnings and precautions").

Probenecid

The simultaneous administration of probenecid results in an increase in the concentration of cefotaxime in the serum and, therefore, an extension of its effect because probenecid limits the elimination of cefotaxime by the kidneys. Inform your doctor if you are taking probenecid, especially if you have kidney failure, so that, if necessary, they can adjust the dose.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy

There are no sufficient data on the use of cefotaxime in pregnant women. Animal experiments did not show signs of teratogenic properties of cefotaxime.

However, cefotaxime should only be used during pregnancy, especially in the first trimester, after a strict evaluation of the risks and benefits of treatment by a specialist.

Breastfeeding

Cefotaxime is excreted in breast milk only in small amounts. If you receive cefotaxime during breastfeeding, it may cause alterations in the intestinal flora with diarrhea, fungal growth, and also may cause sensitization. The doctor will decide whether it is necessary to interrupt breastfeeding or discontinue treatment with cefotaxime, considering the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Driving and using machines

According to previous experience, cefotaxime in low and medium doses does not have any effect on concentration or reaction capacity.

If you experience adverse effects such as dizziness or encephalopathy, which can be associated with seizures, confusion, altered consciousness, and movement disorders, you should not drive or use machines.

Valoran contains sodium

Valoran 1 g contains 48 mg (2.09 mmol) of sodium per dose, which is equivalent to 2.4% of the maximum daily recommended sodium intake in the diet for an adult.

Valoran 2 g contains 96 mg (4.18 mmol) of sodium per dose, which is equivalent to 4.8% of the maximum daily recommended sodium intake in the diet for an adult.

3. How to use Valoran

Follow the instructions for administration of this medicine exactly as indicated by your doctor. The dose, method of administration, and time intervals between injections depend on the dose, sensitivity of the pathogen, severity of the infection, and the patient's condition.

Unless the doctor indicates otherwise, the recommended dose is:

Adults and children over 12yearsusually receive 1 to 2 g of cefotaxime every 12 hours. In severe cases, the daily dose may be increased up to 12 g of cefotaxime. Daily doses up to 6 g can be divided into at least two fractional doses administered at 12-hour intervals. Higher daily doses should be divided into at least 3-4 fractional doses with administration intervals of 6 or 8 hours.

The following table can be considered a guideline for administration:

For the treatment of gonorrheain adults, a single dose of 0.5 g of cefotaxime should be administered intramuscularly. In less sensitive pathogens, a dose increase may be necessary. Before starting treatment, check for the presence of syphilis.

For perioperative prophylaxis of infections, the administration of 1-2 g of cefotaxime 30-60 minutes before surgery is recommended. Less sensitive pathogens may require a higher dose. Before starting treatment, check for the presence of syphilis.

For Lyme disease, the daily dose is 6 g of cefotaxime (for 14 to 21 days). In most cases, the daily dose is divided into 3 fractional doses (2 g of cefotaxime 3 times a day), but in some cases, it has been administered in 2 fractional doses (3 g of cefotaxime 2 times a day). The recommendations of the dosage guideline are not based on comparative clinical trials but on observations of individual patients.

Combination treatment

In severe infections that pose a vital risk, combination treatment with cefotaxime and aminoglycosides without an antibiogram is indicated. When combined with aminoglycosides, kidney function should be monitored.

In cases of Pseudomonas aeruginosainfection, combination treatment with other antibiotics effective against Pseudomonasmay also be indicated.

For the prophylaxis of infections in patients with a weakened immune system, combination treatment with other appropriate antibiotics may also be indicated.

Infants and children up to 12yearsreceive 50 to 100 mg of cefotaxime (up to 150 mg) per kilogram of body weight daily, depending on the severity of the infection. The daily dose will be divided into 2 or more identical fractional doses, which will be administered at 12 (to 6) hour intervals. In individual cases, especially in life-threatening situations, the daily dose can be increased to 200 mg of cefotaxime per kilogram of body weight.

In premature babies, it should be taken into account that kidney function is not yet fully developed and the dose of 50 mg of cefotaxime per kilogram of body weight per day should not be exceeded.

In patients with severe kidney failure(creatinine clearance less than 10 ml/minute), after the initial normal dose (the first dose at the start of treatment), the maintenance dose can be reduced to half of the normal dose, maintaining the administration interval.

Patients on hemodialysis receive 1 to 2 g of cefotaxime daily, depending on the severity of the infection. On the day of hemodialysis, cefotaxime should be administered after dialysis.

Patients on peritoneal dialysis receive 1 to 2 g of cefotaxime daily, depending on the severity of the infection. Cefotaxime is not eliminated by peritoneal dialysis.

Valoran 1 g is administered intravenously (in a vein), but it can also be administered intramuscularly.

Valoran 2 g is administered intravenously (in a vein).

Elderly patients

In elderly patients, kidney function should be carefully monitored and, if necessary, the dose should be adjusted.

Intravenous injection

For i.v. injection, dissolve 1 g of cefotaxime in at least 4 ml of water for injectable preparations and then inject directly into the vein over a period of 3 to 5 minutes.

Intravenous infusion

For rapid intravenous infusion, dissolve 1 or 2 g of cefotaxime in 40 and 50 ml of water for injectable preparations or in a dissolved solution, and then infuse i.v. over 20 minutes.

For slow intravenous infusion, dissolve 2 g of cefotaxime in 100 ml of isotonic sodium chloride solution or a dissolved glucose solution, and then infuse i.v. over a period of 50 to 60 minutes. Another compatible solution for infusion can be used for the solution.

Intramuscular injection

For intramuscular injection, dissolve 1 g of cefotaxime in 4 ml of water for injectable preparations. The injection should then be administered by deep intragluteal injection. The pain during i.m. injection can be avoided by dissolving 1 g of cefotaxime in 4 ml of 1% lidocaine solution. Intravascular injection (injection into a blood vessel) should be avoided because lidocaine administered intravascularly can cause restlessness, tachycardia, conduction disorders, as well as vomiting and seizures. The cefotaxime and lidocaine compound should not be administered to children under 30 months of age. The package leaflet for the product containing lidocaine should be taken into account.

It is recommended not to inject more than 4 ml on the same side. If the daily dose exceeds 2 g of cefotaxime or if cefotaxime is injected more than twice a day, i.v. injection is recommended.

Valoran 2 g should not be administered intramuscularly.

Compatibility

Unless physical and chemical compatibility with other infusion solutions has been demonstrated, the cefotaxime solution should be administered, in principle, separately from them.

Cefotaxime is not compatible with:

• sodium bicarbonate solution,
• infusion solutions with a pH above 7,
• aminoglycosides.

In general, cefotaxime should not be mixed or administered with other antibiotics or medications in the same syringe. Cefotaxime should not be mixed with aminoglycoside antibiotics in the infusion equipment or syringe.

Compatibility with infusion solutions

Cefotaxime can also be dissolved in sodium lactate solution or Ringer's solution.

The duration of treatment depends on the course of the disease.

If you use more Valoran than you should

Beta-lactam antibiotics, including cefotaxime, can cause encephalopathies, which are accompanied by central nervous system excitement, myoclonus, seizures, confusion, altered consciousness, and movement disorders. There is a risk of these adverse effects when higher doses are used, in case of overdose, and in patients with impaired kidney function or who suffer from epilepsy or meningitis.

If cefotaxime is injected through a central venous catheter (CVC) too quickly (in less than 1 minute), it can cause a severe cardiac arrhythmia.

If you think you have received too much cefotaxime, talk to your doctor or medical staff immediately.

If you forget to use Valoran

Your doctor or nurse will have instructions on when to administer the medicine, so it is unlikely that you will not receive the medicine according to the instructions. If you think you have forgotten a dose, talk to your doctor or nurse.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking cefotaxime and inform your doctor immediately if you detect any of the following symptoms:

• Seizures (uncommon, may affect up to 1 in 100 people)
• Frequency not known (cannot be estimated from available data)
• • Severe acute hypersensitivity reactions and life-threatening allergic reactions, as well as swelling (Quincke's edema) and narrowing of the airways (bronchospasm). If you experience chest tightness, or feel dizzy, sick, or weak, these may be signs of a hypersensitivity reaction.
  • Non-blistering reddish patches, target-like or circular, on the trunk, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genital organs, and eyes. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • Widespread skin rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
  • Widespread, reddish, and scaly skin rash, with small bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
  • Severe persistent diarrhea or blood in the stool due to possible life-threatening intestinal inflammation.
  • Decrease in red blood cells (hemolytic anemia), change in urine color (to a reddish-brown color).
  • Acute kidney failure.

Tell your doctor or nurse if you experience any of the following adverse effects with an unknown frequency (cannot be estimated from available data):

• Jaundice as a sign of possible hepatitis.
• Severe decrease in white blood cells (agranulocytosis), which can be detected by the appearance of acute signs of infection, as well as inflammation of the oral, nasal, pharyngeal, genital, and anal areas.
• Sharp decline in the number of all blood cells and bone marrow failure. Signs of acute infection and inflammation (see above), bleeding, bruising (decrease in platelets), fatigue, pallor, or difficulty breathing (decrease in red blood cells) may also appear.

Tell your doctor or nurse if any of the following adverse effects worsen or last more than a few days:

Very common(may affect more than 1 in 10 people)

• Pain at the injection site, also hardening due to intramuscular administration.

Common(may affect up to 1 in 10 people)

• Joint problems (e.g., swelling).

Uncommon(may affect up to 1 in 100 people)

• Increased eosinophils in the blood (eosinophilia).
• Decrease in platelets (thrombocytopenia) and certain white blood cells (leukopenia, granulocytopenia).
• Jarisch-Herxheimer reaction (see explanation below).
• Diarrhea.
• Lack of appetite.
• Increased bilirubin (bile pigment in the blood) and liver enzymes in serum (SGOT, SGPT, γ-GT, alkaline phosphatase, LDH).
• Allergic reactions in the form of rash, itching, hives.
• Limitation of renal function, e.g., increased creatinine and urea concentrations in serum.
• Fever.
• Inflammatory reactions at the injection site and vein inflammation (phlebitis/thrombophlebitis).

Frequency not known(cannot be estimated from available data)

• Superinfections caused by bacteria or fungi (e.g., in the mouth or vagina).
• Decrease in the number of certain white blood cells (neutropenia).
• Tachycardia, cardiac arrhythmia (after rapid administration through a central venous access).
• Excitement of the central nervous system, altered consciousness, confusion, movement disorders, muscle spasms (symptoms of encephalopathy, especially with high doses, in case of overdose, or with impaired renal function).
• Headache.
• Dizziness.
• Nausea, vomiting, abdominal pain.
• Kidney inflammation (interstitial nephritis).
• Intolerance reactions in the form of a feeling of heat or nausea with faster intravenous administration.

Jarisch-Herxheimer Reaction:

When starting treatment for spirochetal infections (e.g., Lyme disease), you may experience fever, chills, headache, and joint pain. After several weeks of treatment for Lyme disease, one or more of the following symptoms have been described: rash, itching, fever, decrease in white blood cells, increase in liver enzymes, difficulty breathing, and joint pain. These symptoms partially correspond to the underlying symptoms of the treated patients.

Adverse Effect Notification

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Valoran

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the label. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature. Store in the original packaging to protect it from light.

Reconstituted Solution

The chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C. However, from a microbiological point of view, unless the opening/reconstitution method prevents the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition ofValoran

• The active ingredient is cefotaxime (as cefotaxime sodium).

Valoran 1 g contains 1 g of cefotaxime (as cefotaxime sodium).

Valoran 2 g contains 2 g of cefotaxime (as cefotaxime sodium).

• There are no other components.

Appearance of the Product and Package Contents

The powder is white or slightly yellowish in transparent glass vials, sealed with a bromobutyl rubber stopper and an aluminum cap.

The vials are supplied in boxes containing 1, 10, 50, or 100 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Medochemie Ltd.

1-10 Constantinoupoleos Street

3011 Limassol

Cyprus

Manufacturer

Medochemie Limited (Factory C)

2 Michael Erakleous street,

Agios Athanassios, Industrial Area,

4101 Agios Athanassios, Limassol,

Cyprus

You can request more information about this medicine by contacting the local representative of the Marketing Authorization Holder:

Medochemie Iberia S.A., Branch in Spain

Avenida de las Águilas, nº 2 B; 5th floor, office 6,

28044 Madrid

SPAIN

Date of the last revision of this prospectus: May 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es