Label: Information for the User

1 g powder for injectable solution and for infusion EFG

2 g powder for injectable solution and for infusion EFG

Cefotaxime (as cefotaxime sodium)

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

Valoran, which contains cefotaxime (an antibiotic that belongs to a group of medications known as cephalosporins), is a medication used to combat bacteria.

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

• respiratory infections,
• otolaryngological 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 stagesII and III) (infection primarily caused by tick bites)

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

Do not use Valoran:

• if you are allergic to cefotaxime, other cephalosporins, or any of the other components of this medication (including those in section6).
• if you have had a previous acute or severe hypersensitivity reaction to penicillin or other beta-lactam antibiotics. Penicillin with cephalosporins can cause cross-reactions.
• if you have ever developed a severe skin rash or peeling of the skin, 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 30months of age. Please refer to the prospectus for the product containing lidocaine.

Nota:

Valoran 2g should not be administered intramuscularly.

Advertencias 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 known hypersensitivity reactions, see earlier in the section «No use Valoran»).
• if you have an allergic reaction (e.g., hay fever, asthma, hives) or if you have a history of it. In this case, you have a higher risk of more severe hypersensitivity reactions (fatal 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 section4).
• if you experience a hypersensitivity reaction, treatment should be discontinued.
• if you notice changes in the skin or mucous membranes during treatment (see section4). Inform your doctor immediately, as cefotaxime can cause severe skin reactions that require treatment.
• if you experience severe or persistent diarrhea during treatment or several weeks after its completion. Inform your doctor immediately, as diarrhea in its most severe form (called pseudomembranous colitis) could be fatal and should be treated. Do not take any medication that limits intestinal activity.
• if you know you have kidney insufficiency. Inform your doctor in this case; if necessary, your dose may be adjusted. Your kidney function should be monitored.
• if you are receiving concomitant or subsequent treatment with aminoglycosides (other antibiotics), probenecid (for gout), or other medications that can cause kidney damage. A doctor should monitor your kidney function, as these substances can increase the harmful effects on the kidneys and caution is needed.
• if you experience a movement disorder, seizures, confusion, or altered consciousness. These may be signs of what is called encephalopathy. There is a risk of these adverse effects occurring when high doses are administered, in cases of overdose, or if you have kidney insufficiency. If these reactions occur, consult your doctor immediately.
• if your treatment lasts more than 7 to 10days. In this case, blood tests should be performed for control, as variations in the blood may occur (see also section4).
• if you experience 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 medication used. Be vigilant to detect 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 your doctor immediately if you detect any of the symptoms related to these severe skin reactions described in section 4.

Use of Valoran with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Other antibiotics

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

Diuretics and potentially nephrotoxic medications

When cefotaxime is used concomitantly with medications that can have a nephrotoxic effect, such as aminoglycosides (other antibiotics) or medications with a high capacity to cause dehydration (diuretics, such as furosemide), the nephrotoxic effect of these medications may be increased. If they are administered concomitantly, kidney function should be monitored (see section2 «Advertencias 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, as probenecid limits the elimination of cefotaxime by the kidneys. Inform your doctor if you are taking probenecid, especially if you have kidney insufficiency, so that, if necessary, your dose may be adjusted.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

There are insufficient data on the use of cefotaxime in women in animals. 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.

Lactation

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

Driving and operating machines

According to previous experience, cefotaxime at low and medium doses has no effect on concentration or reaction capacity.

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

Valoran contains sodium

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

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

Follow exactly the administration instructions of this medication as indicated by your doctor. The dose, form of administration, and intervals between injections depend on the dose, pathogen sensitivity, severity of the infection, and patient condition.

Unless your doctor indicates otherwise, the recommended dose is:

Adults and children over 12 years old generally receive 1 to 2 grams of cefotaxime every 12 hours. In severe cases, the daily dose can be increased up to 12 grams of cefotaxime. Daily doses up to 6 grams can be divided into at least two fractional doses administered at an interval of 12 hours. 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 dosing schedule:

For the treatment of gonorrhea in adults, a single dose of 0.5 grams of cefotaxime should be administered intramuscularly. In less sensitive pathogens, a higher dose may be required. Before starting treatment, check for syphilis.

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

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

Combined treatment

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

In cases of Pseudomonas aeruginosa infection, combined treatment with other effective antibiotics against Pseudomonas may also be indicated.

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

Children under 12 years old receive 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 should be divided into 2 or more identical fractional doses, administered at intervals of 12 (6) hours. 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, renal function is not yet fully developed, and the dose should not exceed 50 mg of cefotaxime per kilogram of body weight per day.

In patients with severe renal insufficiency (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 the normal dose, maintaining the administration interval.

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

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

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

2 grams is administered intravenously (in a vein).

Older patients

In older patients, renal function should be closely monitored, and if necessary, the dose should be adjusted.

Intravenous injection

To administer i.v., dissolve 1 gram of cefotaxime in at least 4 ml of water for injection and, subsequently, inject directly into the vein over a period of 3 to 5 minutes.

Perfusion intravenously

To administer a rapid i.v. perfusion, dissolve 1 or 2 grams of cefotaxime in 40 and 50 ml of water for injection or in a dissolved solution, and then perfuse i.v. over a period of 20 minutes.

To administer a slow i.v. perfusion, dissolve 2 grams of cefotaxime in 100 ml of isotonic sodium chloride solution or a glucose solution, and then perfuse i.v. over a period of 50 to 60 minutes. Another solution for perfusion compatible with the solution can be used.

Intramuscular injection

To administer an i.m. injection, dissolve 1 gram of cefotaxime in 4 ml of water for injection. Subsequently, the injection should be administered intragluteally deep. Pain during i.m. injection can be avoided by dissolving 1 gram of cefotaxime in 4 ml of lidocaine solution 1%. The lidocaine administered intravascularly can cause restlessness, tachycardia, conduction disorders, as well as vomiting and convulsions. The cefotaxime-lidocaine compound should not be administered to children under 30 months of age. The prospectus for the product containing lidocaine should be taken into account.

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

2 grams should not be administered intramuscularly.

Compatibility

Unless the physical-chemical compatibility with other perfusion solutions is demonstrated, the cefotaxime solution should be administered separately from them.

Cefotaxime is not compatible with:

• sodium bicarbonate solution,
• perfusion solutions with a pH greater than 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 aminoglycosides in the perfusion equipment or in the syringe.

Compatibility with perfusion solutions

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

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

If you use more Valoran than you should

Betalactam antibiotics, including cefotaxime, can cause encephalopathies, which are accompanied by central nervous system excitation, myoclonus, convulsions, confusion, altered consciousness, and movement disorders. This risk exists when higher doses are used, in cases of overdose, and in patients with renal dysfunction 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 believe you have received too much cefotaxime, speak immediately with your doctor or medical staff.

If you forgot to use Valoran

Your doctor or nurse will have instructions on when to administer the medication, so it is unlikely that they will not administer the medication according to the instructions. If you believe you have forgotten a dose, speak with your doctor or nurse.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• Seizures (rare, may affect up to 1 in 100 people)
• Unknown frequency (cannot be estimated from available data)
• • Severe acute hypersensitivity reactions and life-threatening allergic reactions, as well as Quincke's edema and bronchospasm. If you experience chest tightness, dizziness, nausea, or weakness, they may be signs of a hypersensitivity reaction.
  • Non-pitting, target-shaped or circular red patches on the trunk, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genital organs, and eyes. These severe skin eruptions may be preceded by fever and symptoms similar to the flu (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • Generalized skin eruption, elevated body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
  • Generalized, red, scaly skin eruption, with small swellings under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized pustular exanthema).
  • Persistent severe diarrhea with blood in the stool due to possible life-threatening intestinal inflammation.
  • Decrease in red blood cells (hemolytic anemia), change in urine color to a brownish-red.
  • Acute renal failure.

Inform your doctor or nurse if you experience any of the following side 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 may be detected by the appearance of acute signs of infection, as well as inflammation of the oral, nasal, pharyngeal, genital, and anal areas.
• Significant decrease in the number of all blood cells and bone marrow insufficiency. You may also experience acute signs of infection and inflammation (see above), bleeding, bruising (decreased platelets), fatigue, pallor, or difficulty breathing (decreased red blood cells).

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

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

Rare (may affect up to 1 in 100 people)

• Increased eosinophils (eosinophilia).
• Decreased platelets (thrombocytopenia) and certain white blood cells (leukopenia, granulocytopenia).
• Jarisch-Herxheimer reaction (see explanation below).
• Diarrhea.
• Loss 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.
• Renal function limitation, e.g., increased creatinine and urea concentrations in serum.
• Fever.
• Inflammatory reactions in the injection area and venous inflammation (phlebitis/thrombophlebitis).

Unknown frequency (cannot be estimated from available data)

• Overlapping infections caused by bacteria or fungi (e.g., in the mouth or vagina).
• Decreased number of certain white blood cells (neutropenia).
• Tachycardia, arrhythmia (after rapid administration through a central venous access).
• Central nervous system stimulation, alteration of consciousness, confusion, movement disorders, muscle spasms (encephalopathy symptoms, especially with high doses, in cases of overdose, or with renal function deterioration).
• Headache.
• Dizziness.
• Nausea, vomiting, abdominal pain.
• Renal inflammation (interstitial nephritis).
• Intolerance reactions in the form of feeling hot or nausea with rapid 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, decreased white blood cells, increased liver enzymes, difficulty breathing, and joint pain. These symptoms correspond partially to the symptoms of the underlying disease in patients being treated.

Reporting of side effects:

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

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label. The expiration date is the last day of the month indicated.

This medication does not require any special temperature for preservation. Store in the original packaging to protect it from light.

Reconstituted Solution

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

Medicines should not be disposed of through drains or trash. Ask your pharmacist how to dispose of containers and medications that you no longer need. This will help protect the environment.

Composition of Valoran

• The active principle 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 contents of the packaging

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

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

Only some sizes of packaging may be commercially available.

Marketing authorization holder and responsible 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

For further information about this medicine, please contact the local representative of the marketing authorization holder:

Medochemie Iberia S.A., Sucursal en España

Avenida de las Águilas, nº 2 B; planta 5 oficina 6,

28044 Madrid

SPAIN

Last review date of this leaflet: May 2024

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