Isovue 200

ISOVUE (lopamidol Injection) is indicated for angiography throughout the cardiovascular system, including cerebral and peripheral arteriography, coronary arteriography and ventriculography, pediatric angiocardiography, selective visceral arteriography and aortography, peripheral venography (phlebography), and adult and pediatric intravenous excretory urography and intravenous adult and pediatric contrast enhancement of computed tomographic (CECT) head and body imaging (see below).

CECT Head Imaging

ISOVUE may be used to refine diagnostic precision in areas of the brain which may not otherwise have been satisfactorily visualized.

Tumors

ISOVUE may be useful to investigate the presence and extent of certain malignancies such as: gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas and gangliomas, ependymomas, medulloblastomas, meningiomas, neuromas, pinealomas, pituitary adenomas, craniopharyngiomas, germinomas, and metastatic lesions. The usefulness of contrast enhancement for the investigation of the retrobulbar space and in cases of low grade or infiltrative glioma has not been demonstrated.

In calcified lesions, there is less likelihood of enhancement. Following therapy, tumors may show decreased or no enhancement.

The opacification of the inferior vermis following contrast media administration has resulted in false-positive diagnosis in a number of otherwise normal studies.

Nonneoplastic Conditions

ISOVUE may be beneficial in the image enhancement of nonneoplastic lesions. Cerebral infarctions of recent onset may be better visualized with contrast enhancement, while some infarctions are obscured if contrast media are used. The use of iodinated contrast media results in contrast enhancement in about 60 percent of cerebral infarctions studied from one to four weeks from the onset of symptoms.

Sites of active infection may also be enhanced following contrast media administration.

Arteriovenous malformations and aneurysms will show contrast enhancement. For these vascular lesions, the enhancement is probably dependent on the iodine content of the circulating blood pool.

Hematomas and intraparenchymal bleeders seldom demonstrate any contrast enhancement. However, in cases of intraparenchymal clot, for which there is no obvious clinical explanation, contrast media administration may be helpful in ruling out the possibility of associated arteriovenous malformation.

CECT Body Imaging

ISOVUE (lopamidol Injection) may be used for enhancement of computed tomographic images for detection and evaluation of lesions in the liver, pancreas, kidneys, aorta, mediastinum, abdominal cavity, pelvis and retroperitoneal space.

Enhancement of computed tomography with ISOVUE may be of benefit in establishing diagnoses of certain lesions in these sites with greater assurance than is possible with CT alone, and in supplying additional features of the lesions (e.g., hepatic abscess delineation prior to percutaneous drainage). In other cases, the contrast agent may allow visualization of lesions not seen with CT alone (e.g., tumor extension), or may help to define suspicious lesions seen with unenhanced CT (e.g., pancreatic cyst).

Contrast enhancement appears to be greatest within 60 to 90 seconds after bolus administration of contrast agent. Therefore, utilization of a continuous scanning technique (“dynamic CT scanning”) may improve enhancement and diagnostic assessment of tumor and other lesions such as an abscess, occasionally revealing unsuspected or more extensive disease. For example, a cyst may be distinguished from a vascularized solid lesion when precontrast and enhanced scans are compared; the nonperfused mass shows unchanged x-ray absorption (CT number). A vascularized lesion is characterized by an increase in CT number in the few minutes after a bolus of intravascular contrast agent; it may be malignant, benign, or normal tissue, but would probably not be a cyst, hematoma, or other nonvascular lesion.

Because unenhanced scanning may provide adequate diagnostic information in the individual patient, the decision to employ contrast enhancement, which may be associated with risk and increased radiation exposure, should be based upon a careful evaluation of clinical, other radiological, and unenhanced CT findings.

General

Diagnostic procedures which involve the use of any radiopaque agent should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reaction to the contrast agent itself. After parenteral administration of a radiopaque agent, competent personnel and emergency facilities should be available for at least 30 to 60 minutes since severe delayed reactions may occur. Caution should be exercised in hydrating patients with underlying conditions that may be worsened by fluid overload, such as congestive heart failure.

Diabetic nephropathy may predispose to acute renal impairment following intravascular contrast media administration. Acute renal impairment following contrast media administration may precipitate lactic acidosis in patients who are taking biguanides.

The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis.

Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with advanced vascular disease, diabetic patients, and in susceptible nondiabetic patients (often elderly with preexisting renal disease). Patients should be well hydrated prior to and following iopamidol administration. The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid or cardiovascular reactions, should always be considered (see ADVERSE REACTIONS). Patients at increased risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to iodine per se, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies). The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be hazardous for the patient. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to the injection of any contrast medium, may be more accurate than pretesting in predicting potential adverse reactions. A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of a contrast agent where a diagnostic procedure is thought essential, but caution should be exercised. Premedication with antihistamines or corticosteroids to avoid or minimize possible allergic reactions in such patients should be considered. Recent reports indicate that such pretreatment does not prevent serious life-threatening reactions but may reduce both their incidence and severity.

Pre-existing conditions, such as pacemakers or cardiac medications, specifically beta-blockers, may mask or alter the signs or symptoms of an anaphylactoid reaction, as well as masking or altering the response to particular medications used for treatment. For example, beta-blockers inhibit a tachycardiac response, and can lead to the incorrect diagnosis of a vasovagal rather than an anaphylactoid reaction. Special attention to this possibility is particularly critical in patients suffering from serious, life-threatening reactions.

General anesthesia may be indicated in the performance of some procedures in selected patients; however, a higher incidence of adverse reactions has been reported with radiopaque media in anesthetized patients, which may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia which can reduce cardiac output and increase the duration of exposure to the contrast agent.

Even though the osmolality of iopamidol is low compared to diatrizoate or iothalamate based ionic agents of comparable iodine concentration, the potential transitory increase in the circulatory osmotic load in patients with congestive heart failure requires caution during injection. These patients should be observed for several hours following the procedure to detect delayed hemodynamic disturbances. Injection site pain and swelling may occur. In the majority of cases it is due to extravasation of contrast medium. Reactions are usually transient and recover without sequelae. However, inflammation and even skin necrosis have been seen on very rare occasions.

In angiographic procedures, the possibility of dislodging plaques or damaging or perforating the vessel wall, or inducing vasospasm, and or subsequent ischemic events, should be borne in mind during catheter manipulations and contrast medium injection. Test injections to ensure proper catheter placement are suggested.

Selective coronary arteriography should be performed only in selected patients and those in whom the expected benefits outweigh the procedural risk. The inherent risks of angiocardiography in patients with pulmonary hypertension must be weighed against the necessity for performing this procedure. Angiography should be avoided whenever possible in patients with homocystinuria, because of the risk of inducing thrombosis and embolism. See also Pediatric Use.

In addition to the general precautions previously described, special care is required when venography is performed in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection or a totally obstructed venous system. Extreme caution during injection of contrast media is necessary to avoid extravasation and fluoroscopy is recommended. This is especially important in patients with severe arterial or venous disease.

Information for Patients

Patients receiving injectable radiopaque diagnostic agents should be instructed to:

1. Inform your physician if you are pregnant.
2. Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease, or known thyroid disorder (see WARNINGS).
3. Inform your physician if you are allergic to any drugs, food, or if you had any reactions to previous injections of substances used for x-ray procedures (see PRECAUTIONS-General).
4. Inform your physician about any other medications you are currently taking, including nonprescription drugs, before you have this procedure.
5. Inform your physician if you develop a rash after receiving Isovue.

Drug Interactions

Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by intravascular contrast agents. Administration of intravascular agents should therefore be postponed in any patient with a known or suspected hepatic or biliary disorder who has recently received a cholecystographic contrast agent.

Other drugs should not be admixed with iopamidol.

Drug/Laboratory Test Interactions

The results of PBI and radioactive iodine uptake studies, which depend on iodine estimations, will not accurately reflect thyroid function for up to 16 days following administration of iodinated contrast media. However, thyroid function tests not depending on iodine estimations, e.g., T3 resin uptake and total or free thyroxine (T4) assays are not affected.

Any test which might be affected by contrast media should be performed prior to administration of the contrast medium.

Laboratory Test Findings

In vitro studies with animal blood showed that many radiopaque contrast agents, including iopamidol, produced a slight depression of plasma coagulation factors including prothrombin time, partial thromboplastin time, and fibrinogen, as well as a slight tendency to cause platelet and/or red blood cell aggregation (see PRECAUTIONS-General).

Transitory changes may occur in red cell and leucocyte counts, serum calcium, serum creatinine, serum glutamic oxaloacetic transaminase (SGOT), and uric acid in urine; transient albuminuria may occur.

These findings have not been associated with clinical manifestations.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. No evidence of genetic toxicity was obtained in in vitro tests.

Pregnancy: Teratogenic Effects

Pregnancy Category B Reproduction studies have been performed in rats and rabbits at doses up to 2.7 and 1.4 times the maximum recommended human dose (1.48 gl/kg in a 50 kg individual), respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to iopamidol. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when iopamidol is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children has been established in pediatric angiocardiography, computed tomography (head and body) and excretory urography. Pediatric patients at higher risk of experiencing adverse events during contrast medium administration may include those having asthma, a sensitivity to medication and/or allergens, cyanotic heart disease, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.

Treatment of an overdose of an injectable radiopaque contrast medium is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

General

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Iopamidol solutions should be used only if clear and within the normal colorless to pale yellow range. Discard any product which shows signs of crystallization or damage to the container-closure system, which includes the glass container, stopper and/or crimp.

It is desirable that solutions of radiopaque diagnostic agents for intravascular use be at body temperature when injected. Withdrawal of contrast agents from their containers should be accomplished under aseptic conditions with sterile syringes. Sterile techniques must be used with any intravascular injection, and with catheters and guidewires.

Patients should be well hydrated prior to and following ISOVUE (lopamidol Injection) administration.

As with all radiopaque contrast agents, only the lowest dose of ISOVUE necessary to obtain adequate visualization should be used. A lower dose reduces the possibility of an adverse reaction. Most procedures do not require use of either a maximum dose or the highest available concentration of ISOVUE; the combination of dose and ISOVUE concentration to be used should be carefully individualized, and factors such as age, body size, size of the vessel and its blood flow rate, anticipated pathology and degree and extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed should be considered.

Cerebral Arteriography

ISOVUE-300 (lopamidol Injection, 300 mgl/mL) should be used. The usual individual injection by carotid puncture or transfemoral catheterization is 8 to 12 mL, with total multiple doses ranging to 90 mL.

Peripheral Arteriography

ISOVUE-300 usually provides adequate visualization. For injection into the femoral artery or subclavian artery, 5 to 40 mL may be used; for injection into the aorta for a distal runoff, 25 to 50 mL may be used. Doses up to a total of 250 mL of ISOVUE-300 have been administered during peripheral arteriography.

Peripheral Venography (Phlebography)

ISOVUE-200 (lopamidol Injection, 200 mgl/mL) should be used. The usual dose is 25 to 150 mL per lower extremity. The combined total dose for multiple injections has not exceeded 350 mL.

Selective Visceral Arteriography and Aortography

ISOVUE-370 (lopamidol Injection, 370 mgl/mL) should be used. Doses up to 50 mL may be required for injection into the larger vessels such as the aorta or celiac artery; doses up to 10 mL may be required for injection into the renal arteries. Often, lower doses will be sufficient. The combined total dose for multiple injections has not exceeded 225 mL.

Pediatric Angiocardiography

ISOVUE-370 should be used. Pediatric angiocardiography may be performed by injection into a large peripheral vein or by direct catheterization of the heart.

The usual dose range for single injections is provided in the following table:

The usual recommended dose for cumulative injections is provided in the following table:

Coronary Arteriography and Ventriculography

ISOVUE-370 should be used. The usual dose for selective coronary artery injections is 2 to 10 mL. The usual dose for ventriculography, or for nonselective opacification of multiple coronary arteries following injection at the aortic root is 25 to 50 mL. The total dose for combined procedures has not exceeded 200 mL. EKG monitoring is essential.

Excretory Urography

ISOVUE-250 ISOVUE-300 or ISOVUE-370 may be used. The usual adult dose for ISOVUE-250 is 50 to 100 mL, for ISOVUE-300 is 50 mL and for ISOVUE-370 is 40 mL administered by rapid intravenous injection.

Pediatric Excretory Urography

ISOVUE-250 or ISOVUE-300 may be used. The dosage recommended for use in children for excretory urography is 1.2 mL/kg to 3.6 mL/kg for ISOVUE-250 and 1.0 mL/kg to 3.0 mL/kg for ISOVUE-300. It should not be necessary to exceed a total dose of 30 grams of iodine.

Computed Tomography

ISOVUE-250 or ISOVUE-300 may be used.

CECT OF THE HEAD: The suggested dose for ISOVUE-250 is 130 to 240 mL and for ISOVUE-300 is 100 to 200 mL by intravenous administration. Imaging may be performed immediately after completion of administration.

CECT OF THE BODY: The usual adult dose range for ISOVUE-250 is 130 to 240 mL and for ISOVUE-300 is 100 to 200 mL administered by rapid intravenous infusion or bolus injection. Equivalent doses of ISOVUE-370 based on organically bound iodine content may also be used. The total dose for either CECT procedure should not exceed 60 grams of iodine.

Pediatric Computed Tomography

ISOVUE-250 or ISOVUE-300 may be used. The dosage recommended for use in children for contrast enhanced computed tomography is 1.2 mL/kg to 3.6 mL/kg for ISOVUE-250 and 1.0 mL/kg to 3.0 mL/kg for ISOVUE-300. It should not be necessary to exceed a total dose of 30 grams of iodine.

Drug Incompatibilities

Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many other drugs; therefore, no other pharmaceuticals should be admixed with contrast agents.

Iopamidol is in a group of drugs called radiopaque (RAY dee oh payk) contrast agents. Iopamidol contains iodine, a substance that absorbs x-rays. Radiopaque contrast agents are used to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on a CT scan or other radiologic (x-ray) examination.

Iopamidol is used to help diagnose certain disorders of the heart, brain, blood vessels, and nervous system.

Iopamidol may also be used for purposes not listed in this medication guide.

Since iopamidol is used only during your radiologic test, you will not be on a dosing schedule.

Iopamidol injection is used to help diagnose or find problems in the brain, heart, head, blood vessels, and other parts of the body. It is an iodinated contrast agent. Contrast agents are used to create a clear picture of the different parts of the body during certain medical procedures such as CT scans and angiography.

This medicine is to be given only by or under the supervision of a doctor.

Use Isovue-200 as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Your doctor will give this medicine.
• You will need to be sure that you are not dehydrated before getting Isovue-200 (iopamidol). Check with your doctor to see if you need to drink extra fluids before getting this medicine.
• Drink lots of noncaffeine liquids after using Isovue-200 unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Isovue-200, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Isovue-200. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Isovue-200.

Review Date: October 4, 2017

Applies to iopamidol: injection solution

Along with its needed effects, iopamidol (the active ingredient contained in Isovue-200) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking iopamidol:

• Arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• chest tightness or heaviness
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast or irregular heartbeat
• feeling of warmth
• hives
• lightheadedness, dizziness, or fainting
• nausea
• redness of the face, neck, arms, and occasionally, upper chest
• shortness of breath
• slow or irregular heartbeat
• sudden sweating
• unusual tiredness or weakness

• Blue lips and fingernails
• changes in skin color
• chills
• coughing that sometimes produces a pink frothy sputum
• decrease in the frequency of urination
• decrease in urine volume
• difficult, fast, noisy breathing, sometimes with wheezing
• difficulty in passing urine (dribbling)
• dizziness
• fainting
• fast, pounding, or irregular heartbeat or pulse
• fever
• headache
• hives or welts, itching, or skin rash
• increased sweating
• nervousness
• numbness or tingling in the face, arms, or legs
• pain or discomfort in the arms, jaw, back, or neck
• pain, tenderness, or swelling of the foot or leg
• painful urination
• pale skin
• pounding in the ears
• redness of the skin
• severe, unusual tiredness or weakness
• trouble speaking, thinking, or walking
• vomiting

• Double vision
• inability to move the arms, legs, or facial muscles
• pain in the chest, groin, or legs, especially the calves
• severe, sudden headache
• slow speech
• slurred speech
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• vision changes

• Change in consciousness
• heart stops
• loss of consciousness
• no breathing
• no pulse or blood pressure
• no sensation in the legs
• not able to pass urine
• pain, redness, or pale skin at the injection site
• seizures
• unable to move the legs

Some side effects of iopamidol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bad, unusual, or unpleasant (after) taste
• change in taste
• discouragement
• disturbed color perception
• feeling sad or empty
• halos around lights
• irritability
• loss of appetite
• loss of interest or pleasure
• loss of vision
• night blindness
• overbright appearance of lights
• stuffy nose
• trouble concentrating
• trouble sleeping
• tunnel vision
• weight loss

• Abdominal or stomach cramps
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• discharge or excessive tearing
• general feeling of discomfort or illness
• loss of memory
• problems with memory
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• runny nose
• sneezing
• trembling or shaking of the hands or feet