Iopasen

Package leaflet: Information for the user

IOPASEN 408 mg/ml injection solution, 612 mg/ml injection solution, 755 mg/ml injection solution

Iopamidol
Please read all of this leaflet carefully before you are given 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 nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What IOPASEN is and what it is used for

IOPASEN contains the active substance iopamidol, which belongs to a group of medicines called radiological contrast agents. When injected into the body, these agents allow internal body structures to be visualized on X-ray images (because iodine blocks X-rays).
This medicine is for diagnostic use only and must be administered exclusively in hospitals, clinics, and medical facilities by qualified personnel.
The most common uses of IOPASEN are:

• radiological examinations of the brain and nervous system (neuroradiology);
• radiological examination of blood vessels (angiography);
• radiological examination of arteries;
• radiological examination of the urinary tract and bladder (urography);
• contrast enhancement in CT (computed axial tomography, CT);
• radiological examination of joints;
• fistulography (radiological examination used to visualize the course of fistulas);
• hysterosalpingography (radiological examination of the uterus and fallopian tubes).

2. What you should know before IOPASEN is administered

IOPASEN must not be administered

• if you are allergic to iopamidol or to any of the other ingredients of this medicine (listed in section 6);
• if you are being treated with medicines such as corticosteroids administered intrathecally (i.e. into the space around the spinal cord);
• if you have a bone marrow disease (multiple myeloma or Waldenström's paraproteinemia);
• if you have kidney or liver problems;
• if you are pregnant or breastfeeding;
• if you have acute gynecological infections; in this case, do not undergo examinations of the genital system;
• if you have a history of epileptic seizures, presence of blood in the cerebrospinal fluid, or are undergoing treatment with drugs that lower the seizure threshold (neuroleptics,
  analgesics, antihistamines, phenothiazine sedatives);
• if you need to undergo a second radiological examination within the intrathecal space shortly after the first (in case the first examination failed for technical reasons), as repeated administration of IOPASEN may cause adverse effects due to overdose.

Warnings and precautions
Talk to your doctor or nurse before using IOPASEN.
The use of contrast agents may only take place in hospitals, clinics, and healthcare facilities where resuscitation equipment and trained personnel are immediately available.
Certain conditions require special medical caution; therefore, inform healthcare personnel before undergoing the diagnostic examination if:

• you have previously experienced allergic reactions such as nausea, vomiting, shortness of breath, skin redness, hives, or low blood pressure (hypotension) following a similar examination;
• you suffer from reduced heart function (congestive heart failure);
• you have kidney and/or liver problems;
• you suffer from advanced arteriosclerosis and hypertension;
• you may have hyperthyroidism or autonomously functioning thyroid nodules;
• you suffer from severe heart and circulatory problems (recent myocardial infarction/stroke or transient ischemic attacks (TIA), altered permeability of the blood-brain barrier, increased intracranial pressure, arterial hypertension, advanced atherosclerosis, cardiac decompensation, severe systemic disease, cerebral embolism or thrombosis, right heart failure or pulmonary hypertension);
• you have a bone marrow disease (multiple myeloma or other paraproteinemias);
• you have an inherited blood disorder (sickle cell anemia);
• you have a muscle disease (myasthenia gravis);
• you have high levels of calcium in the blood (hypercalcemia);
• you have recently had problems with blood flow to the brain (cerebrovascular disease);
• your doctor suspects you may have a brain tumor or other conditions such as abscesses, hematomas, or hemorrhages;
• you have a history of alcoholism;
• you suffer from an inherited disease affecting the heart, nervous system, and muscles (homocystinuria);
• you have ever developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking IOPASEN or another iodinated contrast agent. Exercise particular caution with IOPASEN: Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (Lyell syndrome or TEN), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with the use of IOPASEN.

Seek immediate medical advice if you notice any of the symptoms related to these severe skin reactions described in section 4.
Angiography should, as far as possible, be avoided in these cases due to the risk of circulatory problems (thrombotic and embolic events):

• if you have high levels of uric acid in the blood (hyperuricemia);
• if you are undergoing treatment with medicines used for epilepsy (anticonvulsants); in this case, you must continue your treatment prior to the radiological examination. If epileptic seizures occur during the examination, intravenous administration of diazepam or sodium phenobarbital is recommended;
• if you suffer from heart and circulatory disorders (advanced arteriosclerosis, high blood pressure, heart malfunction, severe systemic disease);
• if you have recently had circulation problems affecting the brain (cerebral embolism or thrombosis).

Children
Particular caution is required when administering IOPASEN to neonates, who may be more susceptible to adverse effects.

Other medicines and IOPASEN
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicine.
If you need to undergo a thyroid function test in the weeks following the examination with this medicine, inform your doctor before performing the test.
In particular, inform your doctor if you are taking medicines for:

• diabetes, such as biguanides (metformin). Stop taking it immediately before the examination with IOPASEN and do not resume for up to 48 hours after the examination. Consult your doctor about how to proceed with your treatment;
• heart conditions and/or high blood pressure (diuretics, ACE inhibitors and/or beta-blockers);
• treatment of involuntary contractions of internal organs (papaverine);
• increasing blood pressure (vasopressors);
• if you have recently undergone a procedure called cholecystography to evaluate your gallbladder;
• corticosteroids administered intrathecally for inflammation (see section 2. IOPASEN will not be administered to you);
• medicines that modify the immune system response, such as interleukin-2 and interferon, as adverse reactions such as erythema, fever, or flu-like symptoms may occur;
• ceftriaxone (an antibiotic), due to the risk of particle formation in the blood (precipitation of ceftriaxone-calcium salt).

If you need to undergo thyroid tests or laboratory tests for bilirubin, proteins, and inorganic substances (e.g., iron, copper, calcium, and phosphates) within two weeks after administration of the contrast agent, discuss this with your doctor, as results may be altered.
If you are taking the following medicines, stop taking them 48 hours before the radiological examination. You may resume treatment 12 hours after the radiological examination:

• medicines used for mental disorders (neuroleptics);
• pain-relieving medicines (analgesics);
• medicines used for allergies (antihistamines);
• sedative medicines also used against vomiting (phenothiazines).

Pregnancy and breastfeeding
IOPASEN should be used during pregnancy only if clearly necessary.
Examinations of the female genital system are contraindicated in confirmed or suspected pregnancy.
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or nurse before using this medicine.
Iopamidol passes into human milk only to a small extent.

Driving and using machines
Before driving or operating machinery, assess how IOPASEN affects you and whether any adverse effects occur. If IOPASEN has been administered intrathecally, avoid driving and operating machinery for 6 hours after administration.

3. How to administer IOPASEN

This medicine will be administered to you by a doctor or another healthcare professional trained in the administration of contrast agents. If you have any doubts, consult your doctor or nurse.
You may be injected with up to 2 ml/kg of body weight of the medicine, depending on the type of examination you are undergoing.
If you receive more IOPASEN than you should
If you are concerned that you may have been given too much medicine, inform your doctor or nurse immediately.
Treatment will include maintaining all vital functions and removing the medicine from the body via the urine or through mechanical filtration of the blood (dialysis).
If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

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

The use of iodine-containing solutions may cause side effects, generally mild or moderate and transient in nature. Rarely, more serious allergic-type reactions may occur, which can be fatal.

Most side effects occur within the first few minutes after administration, but sometimes they may appear even after 2-3 or, more rarely, 7 days.

Following intrathecal administration, most side effects occur with a delay of several hours, usually after 24 hours from injection.

Inform your doctor immediately if you suddenly experience wheezing, breathing difficulties, swelling of the eyelids, face or lips, skin rash or itching sensation (especially if widespread over the body). These are signs of an allergic reaction, which may be severe and may require medical intervention.

Seek immediate medical advice if you notice any of the following symptoms:

• Red, flat, circular or "target-shaped" skin spots, often with central blisters, skin peeling, or ulcers affecting the mouth, throat, nose, genitals and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• Widespread scaly red rash, with subcutaneous swellings and blisters, associated with fever. Symptoms usually appear at the beginning of treatment (generalized pustular exanthema). The frequency of these side effects is unknown.

Following intravascular administration, the following side effects have been reported:

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

• Headache;
• Nausea;
• Feeling of warmth.

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

• Dizziness, taste disturbances;
• Heart problems (cardiac arrhythmias such as extrasystoles, atrial fibrillation, ventricular tachycardia and ventricular fibrillation);
• Severe drop in blood pressure (hypotension) or rise in blood pressure (hypertension);
• Dilation of blood vessels (vasodilation with flushing);
• Vomiting, diarrhoea, abdominal pain, dry mouth;
• Skin irritation (rash, urticaria, pruritus, erythema), increased sweating;
• Back pain;
• Kidney problems (acute renal failure, increased creatinine);
• Chest pain or tightness, injection site pain, fever, sensation of warmth or cold.

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

• Confusion;
• Tingling in the extremities (paraesthesia);
• Slowing of heart rate (bradycardia);
• Fluid accumulation in the lungs (pulmonary oedema);
• Breathing problems (asthma, bronchospasm);
• Involuntary muscle contractions (muscle spasms), neck stiffness, sciatica-type leg pain.

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

• Reduction in the number of platelets in the blood (thrombocytopenia);
• Allergic reactions (anaphylaxis, anaphylactoid reactions);
• Coma, transient ischaemic attack, dizziness and loss of consciousness (syncope), decreased level of consciousness or loss of consciousness, seizures, memory loss (amnesia), muscle disorders (paralysis, paresis), somnolence, tremors, agitation, involuntary muscle contractions;
• Inability to move one side of the body;
• Visual disturbances (transient loss of vision, conjunctivitis, photophobia);
• Changes in heart rhythm and rate (tachycardia);
• Bluish discoloration of the skin and mucous membranes due to lack of oxygen in the blood (cyanosis);
• Chest pain (angina pectoris);
• Heart attack caused by an allergic reaction;
• Heart problems (cardiorespiratory arrest, myocardial ischaemia or infarction, heart failure);
• Rapid and sometimes severe drop in blood pressure (circulatory collapse or shock);
• Pallor;
• Circulatory problems;
• Swelling of the larynx (laryngeal oedema), difficulty breathing (dyspnoea, rhinitis), respiratory problems (respiratory arrest, apnoea, respiratory failure, acute respiratory distress syndrome, respiratory distress);
• Enlargement of the salivary glands, increased salivary secretion;
• Swelling of the face (facial oedema);
• Muscle problems (musculoskeletal pain, muscle weakness);
• Stiffness, pain, malaise;
• Changes in certain diagnostic tests (alterations in electrocardiographic trace including ST segment depression);
• Kidney problems caused by calcium-ceftriaxone deposits. Pain during urination or reduced urine output may occur;
• Transiently inactive thyroid gland in newborns.

Following intrathecal administration, the following side effects have been reported:

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

• Headache.

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

• Heart problems (cardiac arrhythmias such as extrasystoles, atrial fibrillation, ventricular tachycardia and ventricular fibrillation);
• Dilation of blood vessels (vasodilation);
• Nausea, vomiting;
• Back pain, neck pain, limb pain, feeling of heaviness, muscle cramps.

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

• Slowing of heart rate (bradycardia);
• Skin rash, increased sweating.

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

• Inflammation of the meninges (aseptic meningitis, bacterial meningitis as a consequence of procedural risk);
• Metabolic and nutritional disorders (acidosis);
• Allergic reactions (anaphylaxis, anaphylactoid reactions);
• Confusion, agitation, disorientation, depression, hallucinations, depersonalization, psychosis, anxiety, irritability, fatigue, restlessness;
• Speech disorder (echolalia);
• Coma, dizziness and feeling of fainting (syncope), seizures, decreased level of consciousness or loss of consciousness, amnesia, muscle disorders (paralysis), altered sensation in hands and feet (paraesthesiae), reduced sensation (hypoesthesia);
• Irritation of the meninges without inflammation, with symptoms such as neck stiffness, headache, photophobia, dull sensorium and memory loss (meningism);
• Nervous system disorders affecting movement (Guillain-Barré syndrome, ataxia, sensorimotor disorders, radiculopathies or cauda equina syndrome);
• Increased muscle tone (hypertonia);
• Dizziness, cervical pain, somnolence;
• Loss of appetite (dysphagia);
• Burning sensation, tremors;
• Involuntary muscle contractions and muscle spasms;
• Temporary loss of vision and other eye disorders such as conjunctivitis, increased lacrimation, eye itching, light disturbance;
• Heart problems (cardiorespiratory arrest, myocardial ischaemia or infarction, heart failure, angina pectoris);
• Heart attack caused by an allergic reaction;
• Hearing loss and ringing in the ears (tinnitus);
• Changes in heart rhythm (arrhythmias), changes in heart rate and rhythm (tachycardia);
• Bluish discoloration of the skin and mucous membranes due to lack of oxygen in the blood (cyanosis);
• Increased blood pressure (hypertension), hot flushes, coldness in hands and feet;
• Difficulty breathing (dyspnoea, apnoea), respiratory arrest;
• Diarrhoea;
• Kidney problems (acute renal failure) with urinary problems (oliguria, incontinence), presence of blood in urine (haematuria) or poor urinary excretion (urinary retention, renal blockage);
• Malaise, fever, muscle stiffness (rigor), chest pain, fatigue, irritability;
• Changes in kidney function test results and disturbances in blood electrolyte levels;
• Transiently inactive thyroid gland in newborns.

As with other contrast media, very rare severe skin reactions such as mucocutaneous syndrome, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and erythema multiforme, may occur after administration of iopamidol.

Administration into a body cavity (intracavitary)

After injection of iodinated contrast medium, most reactions occur several hours later due to slow absorption from the site of administration and slow distribution throughout the body.

Reporting of side effects

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

5. How to store IOPASEN

Keep this medicine out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the packaging after the wording
"Expiry".
The expiry date refers to the last day of that month.
IOPASEN should be stored in the original packaging at a temperature not exceeding 25°C and protected from light.
Do not dispose of medicines 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 IOPASEN contains
IOPASEN 408 mg/ml

• The active substance is iopamidol. Each ml of solution contains 408 mg of iopamidol.
• The other components are: trometamol, sodium calcium edetate, concentrated hydrochloric acid, water for injections.

IOPASEN 612 mg/ml

• The active substance is iopamidol. Each ml of solution contains 612 mg of iopamidol.
• The other components are: trometamol, sodium calcium edetate, concentrated hydrochloric acid, water for injections.

IOPASEN 755 mg/ml

• The active substance is iopamidol. Each ml of solution contains 755 mg of iopamidol.
• The other components are: trometamol, sodium calcium edetate, concentrated hydrochloric acid, water for injections.

Description of the appearance of IOPASEN and contents of the pack
IOPASEN 408 mg/ml Solution for injection
Packages containing 1 vial and 10 vials of 10 ml glass vials
IOPASEN 612 mg/ml Solution for injection
Packages containing 1 vial and 10 vials of 10 ml glass vials
Packages containing 1 type I glass bottle of 30 ml, 50 ml, 100 ml, 200 ml
IOPASEN 755 mg/ml Solution for injection
Packages containing 1 vial and 10 vials of 10 ml glass vials
Packages containing 1 type I glass bottle of 30 ml, 50 ml, 100 ml, 200 ml

Marketing Authorization Holder and Manufacturer
INDUSTRIA FARMACEUTICA GALENICA SENESE S.r.l.
Via Cassia Nord, 351 - 53014
Monteroni d’Arbia (SI)

The following information is intended exclusively for physicians or healthcare professionals

CLINICAL INFORMATION
Therapeutic Indications
Non-ionic, water-soluble contrast medium for radiological investigations: neuroradiology, angiography, digital subtraction angiography (D.S.A.), urography, contrast enhancement in computed tomography (C.T.), arthrography, fistulography, and hysterosalpingography.

Dosage and Administration
NEURORADIOLOGY
Concentration (mg I/ml)  Recommended Doses (ml)
Myelography/radiculography  200–300  5–15
Cisternography  200–300  3–15
Ventriculography  200–300  3–15

ANGIOGRAPHY
Concentration (mg I/ml)  Recommended Dose (ml)
Cerebral arteriography  300  5–10 as bolus
Coronary arteriography  370  8–15 as bolus
Angiocardiography  370  1.0–1.2/Kg
Thoracic aortography  370  1.0–1.2/Kg
Abdominal aortography  370  1.0–1.2/Kg
Selective visceral arteriography  300–370  According to the procedure
Peripheral arteriography  300–370  40–50
Digital subtraction angiography (D.S.A.)  150–370  According to the procedure
Phlebography  300  30–50

UROGRAPHY
The recommended dose for this type of investigation is 30–50 ml in adults. The low osmotic diuresis makes IOPASEN 755 mg/ml particularly suitable for use in patients with moderate or mild renal insufficiency and in neonates. Even in patients with severe renal failure, a diagnostically valid nephrographic effect can be achieved.

OTHER INVESTIGATIONS
Concentration (mg I/ml)  Recommended Dose (ml)
Contrast enhancement in C.T.  300–370  0.5–2/Kg
Arthrography  300
Fistulography  300
Hysterosalpingography  200–300–370  5–20

Regarding contrast enhancement in computed axial tomography, the contrast medium may be administered either as a bolus, by infusion, or by a combination of both methods.
In hysterosalpingography, the total dose to be injected depends on the anatomical, biological, and pathological condition of the patient.

Special Warnings and Precautions for Use
The container, once opened, must be used immediately; any remaining contrast medium should not be reused. Protect the solution from strong light.

Rarely, a vial of IOPASEN may contain crystals. This phenomenon has been shown to indicate a damaged or otherwise defective container, and therefore the use of such a vial is not recommended.

Like other iodinated contrast media, IOPASEN may interact with metallic surfaces containing copper (e.g., brass); therefore, the use of equipment in which the product comes into direct contact with such surfaces should be avoided.

The use of these agents should be limited to cases where there is a clear clinical indication for contrast imaging, which must be evaluated in relation to the patient's clinical status, particularly in the presence of known cardiovascular, urogenital, or hepatobiliary disorders.

Cardio-angiographic procedures using these products should be performed only in clinics, hospitals, or medical facilities where resuscitation equipment and trained personnel are immediately available. For other, more commonly performed contrast imaging procedures, radiology departments—whether public or private—must have immediately available the supportive devices and medications proven effective by experience (Ambu bag, oxygen, antihistamines, vasoconstrictors, corticosteroids, etc.).

Administration must be stopped at the first sign of alarm. The patient should be placed in a horizontal position, airway patency ensured, and oxygen administered in case of severe dyspnea, or artificial ventilation initiated if necessary.

In infants and children, fluid intake should not be restricted. Prior to administration of hyperosmolar contrast agents, any disturbances in water and electrolyte balance should be corrected.

Radiological examinations during pregnancy and in patients with hyperthyroidism should only be performed if the physician considers them absolutely necessary.

Patients with severe hepatic, renal, or hepatorenal insufficiency should not undergo contrast examinations unless absolutely essential.

Repeat examinations should not be performed earlier than 5–7 days after the previous one.

If a diagnostic thyroid examination using radioactive iodine is planned, it should be noted that iodine uptake by thyroid tissue may be reduced for several days, sometimes up to two weeks, following the administration of iodinated contrast media excreted renally.

In neuroradiology, it should be noted that in cases of obstructed cerebrospinal fluid flow (blockage), the contrast medium should be removed as completely as possible.

If the patient's history reveals epilepsy, this may constitute a relative contraindication to the use of organo-iodinated contrast media.

The presence of blood in the cerebrospinal fluid may also be considered a contraindication to the use of IOPASEN. In such cases, the operator must weigh the diagnostic necessity against potential risks to the patient. Patients on anticonvulsant therapy should continue their treatment during radiological investigations.

If convulsive seizures occur during the procedure, intravenous diazepam or sodium phenobarbital is recommended. Neuroleptics, analgesics, antihistamines, and phenothiazine sedatives should be avoided, as they lower the epileptogenic threshold. If possible, therapy with these drugs should be suspended at least 48 hours before the radiological examination and resumed no earlier than 12 hours after the procedure.

In cerebral angiography, the use of IOPASEN may cause generally transient or mild secondary effects. A sensation of warmth in the face and neck is frequently reported; headache is rarely observed. Cardiovascular reactions—such as bradycardia and decreased systemic arterial pressure—may occur with some frequency but are transient and usually require no treatment.

Severe neurological reactions such as tonic-clonic seizures, aphasia, syncope, transient visual field defects, hemiparesis, or coma may be directly related to pre-existing patient conditions.

Advanced arteriosclerosis, hypertension, cardiac decompensation, severe systemic disease, or recent cerebral embolism or thrombosis may increase the risk associated with the procedure.

During angiographic procedures, particular attention should be paid to the condition of the right heart and pulmonary circulation. In cases of insufficiency, supplementary volumes of organo-iodinated contrast media may cause circulatory overload, leading to bradycardia and decreased systemic arterial pressure.

In pediatric patients, injection into the right heart requires special caution in cyanotic neonates with pulmonary hypertension and impaired cardiac function.

During aortic arch imaging, careful attention should be paid to catheter tip positioning. Excessive pressure transmitted by the injector into the brachiocephalic vessels may cause hypotension, bradycardia, and central nervous system damage.

In abdominal angiography, excessive pressure from automated pumps may lead to renal infarction, spinal cord injury, retroperitoneal hemorrhage, or intestinal infarction and necrosis.

In peripheral arteriography, the use of IOPASEN 755 mg/ml may cause painful effects not observed with the 612 mg/ml concentration.

In vitro studies have shown that non-ionic contrast media have less inhibitory effect on hemostatic mechanisms than ionic contrast media at equal concentrations. Therefore, proper angiographic techniques should be followed: catheters should be flushed frequently, and prolonged contact between blood and contrast medium in catheters and syringes should be avoided.

Interactions with Other Medicinal Products and Other Forms of Interaction
It is recommended not to mix other drugs with the contrast medium.

Neuroleptics must be strictly avoided, as they lower the epileptogenic threshold. This also applies to analgesics, antiemetics, antihistamines, and phenothiazine sedatives. If possible, treatment with these drugs should be suspended at least 48 hours before the radiological examination and resumed no earlier than 12 hours after the procedure.

Overdose
Do not exceed the dosages indicated in the section “Dosage and Administration,” as they may cause potentially life-threatening adverse reactions.

Most side effects are not dose-dependent and therefore require therapeutic intervention (see section 4, “Possible Undesired Effects”). In cases of accidental or intentional administration of excessive doses, elimination—primarily via the urinary tract—should be facilitated by ensuring adequate patient hydration.

In cases of pre-existing or post-administration renal insufficiency, the contrast medium can be readily removed by dialysis.

Administration must be stopped at the first sign of alarm: the patient should be placed in a horizontal position, airway patency ensured, and oxygen administered in case of severe dyspnea, or artificial ventilation initiated if necessary.

Management of overdose should include vital function support and prompt initiation of symptomatic therapy.

Intravascular Administration
In case of overdose, fluid and electrolyte losses should be corrected by infusion. Renal function should be monitored for at least three days.

Intrathecal Administration
Signs of overdose may include ascending hyperreflexia, tonic-clonic spasms progressing to sudden convulsive seizures, and, in cases of severe central involvement, hyperthermia, stupor, and respiratory depression.

For further information, please consult the Summary of Product Characteristics.