Isovue-M

ISOVUE-200 (lopamidol Injection 41%)

Ten 50 mL single dose vials (NDC 0270-1314-30)
Ten 200 mL single dose bottles (NDC 0270-1314-15)

ISOVUE-250 (lopamidol Injection 51%)

Ten 50 mL single dose vials (NDC 0270-1317-05)
Ten 100 mL single dose bottles (NDC 0270-1317-02)
Ten 150 mL single dose bottles (NDC 0270-1317-09)

ISOVUE-300 (lopamidol Injection 61%)

Ten 30 mL single dose vials (NDC 0270-1315-25)
Ten 50 mL single dose vials (NDC 0270-1315-30)
Ten 75 mL single dose bottles (NDC 0270-1315-47)
Ten 100 mL single dose bottles (NDC 0270-1315-35)
Ten 150 mL single dose bottles (NDC 0270-1315-50)

ISOVUE-370 (lopamidol Injection 76%)

Ten 50 mL single dose vials (NDC 0270-1316-30)
Ten 50 mL single dose bottles (NDC 0270-1316-01)
Ten 75 mL single dose bottles (NDC 0270-1316-52)
Ten 100 mL single dose bottles (NDC 0270-1316-35)
Ten 125 mL single dose bottles (NDC 0270-1316-04)
Ten 150 mL single dose bottles (NDC 0270-1316-37)

Storage

Store at 20-25° C (68-77° F). [See USP]. Protect from light.

lopamidol Injection is also available as ISOVUE-M® for intrathecal administration.

Manufactured for Bracco Diagnostic Inc. – Monroe Township, NJ 08831 by BIPSO GmbH 78224 Singen (Germany). Revised March 2015

Isovue-M (lopamidol Injection) formulations are stable, aqueous, sterile, and nonpyrogenic solutions for intrathecal administration.

Each mL of Isovue-M 200 (lopamidol Injection 41%) provides 408 mg iopamidol with 1 mg tromethamine and 0.26 mg edetate calcium disodium. The solution contains approximately 0.029 mg (0.001 mEq) sodium and 200 mg organically bound iodine per mL.

Each mL of Isovue-M 300 (lopamidol Injection 61%) provides 612 mg iopamidol with 1 mg tromethamine and 0.39 mg edetate calcium disodium. The solution contains approximately 0.043 mg (0.002 mEq) sodium and 300 mg organically bound iodine per mL.

The pH of Isovue-M contrast media has bean adjusted to 6.5-7.5 with hydrochloric acid and/or sodium hydroxide. Pertinent physicochemical data are noted below. Isovue-M (lopamidol Injection) is hypertonic as compared to plasma and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water, respectively).

lopamidol is designated chemically as (S)-N,N’-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]- 2,4,6-triiodo-5-lactamidoisophthalamide. Structural formula:

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.

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 (see CONTRAINDICATIONS).
Reports indicate that such pretreatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity.

The possibility of inducing bacterial meningitis in patients during intrathecal procedures should always be considered. To avoid bacterial contamination during spinal puncture, a sterile field should be maintained at all times.

If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.

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.
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. Advise patients to inform their physician if they develop a rash after receiving Isovue-M.

Drug Interactions

Other drugs should not be admixed with iopamidol (see CONTRAINDICATIONS, and DOSAGE AND ADMINISTRATION, Drug Incompatibilities).

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.

Transitory changes may occur in red cell and leucocyte counts, serum calcium, serum creatinine, serum glutamic oxalacetic 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 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

See DOSAGE AND ADMINISTRATION section.

A dose of 3000 mgl in adults and 2400 mgl in children is sufficient for most myelographic procedures. Doses above these levels may result in an increased frequency and severity of adverse reactions including seizures. However, in myelography, even use of a recommended dose can produce mental aberrations tantamount to overdosage, if incorrect management of the patient during or immediately following the procedure permits inadvertent early intracranial entry of a large portion of the medium.

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.

In adults a solution that is approximately isotonic (Isovue-M 200) is recommended for examination of the lumbar region. For movement of the contrast medium to distant target areas the more concentrated Isovue-M 300 preparation should be used to compensate for dilution of Isovue-M (lopamidol Injection) with cerebrospinal fluid.

The usual recommended adult dose range for iopamidol is 2000-3000 mg iodine. Iopamidol formulated to contain more than 300 mgl/mL should not be used intrathecally in adults. The minimum dose needed to perform a procedure should always be used.

In pediatric patients, a solution that is approximately isotonic (Isovue-M 200) is recommended for all intrathecal procedures. In children, loss of contrast due to mixing on movement of the medium is less apt to occur because of their shorter spinal cord.

The usual recommended pediatric dose range for iopamidol is 1400-2400 mg iodine. Iopamidol formulated to contain more than 200 mgl/mL should not be used intrathecally in children. The minimum dose needed to perform a procedure should always be used. See pediatric dosage table for recommended dosage.

Anesthesia is not necessary. However, young children may require general anesthesia for technical reasons. Premedication with sedatives or tranquillizers is usually not needed. In patients with a history of seizure activity who are not on anticonvulsant therapy, premedication with barbiturates or phenytoin should be considered.

Lumbar puncture is usually made between L3 and L4; if pathology is suspected at this level, the interspace immediately above or below may be selected. A lateral cervical puncture may also be used.

Rate of Injection: To avoid excessive mixing with cerebrospinal fluid and consequent loss of contrast as well as premature cephalad dispersion, injection must be made slowly over one to two minutes; the needle may then be removed.

An interval of at least 48 hours should be allowed before repeat examination; however, whenever possible five to seven days is recommended.

As with all radiopaque contrast agents, only the lowest dose of Isovue-M 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-M; the combination of dose and Isovue-M concentration to be used should be carefully individualized, and factors such as age, body size, 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. Following are the usual recommended pediatric and adult doses of Isovue-M.

The pediatric doses listed below, intended as a guideline, are based on age rather than weight because the brain and CSF capacity is independent of weight. Variations will depend on such factors as height, suspected pathology, the patient’s condition, technique used, etc. (e.g. CT or standard radiology or movement of the contrast media directed distal to the site of injection).

Following subarachnoid injection, conventional radiography will continue to provide good diagnostic contrast for at least 30 minutes. At about one hour, diagnostic degree of contrast will not usually be available. However, sufficient contrast for CT myelography will be available for several hours. CT myelography following conventional myelography should be deferred for at least four hours to reduce the degree of contrast.

Aspiration of iopamidol is unnecessary following intrathecal administration (see CLINICAL PHARMACOLOGY).

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 intrathecal use be at body temperature when injected. Withdrawal of contrast agents from their containers should be accomplished under aseptic conditions with sterile syringes. Spinal puncture must always be performed under sterile conditions.

Patients should be well hydrated prior to and following Isovue-M (Iopamidol Injection) administration.

Suggestions for Usual Patient Management

Preprocedure

• See WARNINGS regarding discontinuation of neuroleptic agents.
• Maintain normal diet up to 2 hours before procedure.
• Ensure hydration-fluids up to time of procedure.

During Procedure

• Use minimum dose and concentration required for satisfactory contrast.
• Inject slowly over 1 to 2 minutes to avoid excessive mixing.
• Abrupt or active patient movement causes excessive mixing with CSF.
• Instruct patient to remain passive. Move patient slowly and only as necessary.
• To maintain as a bolus, move medium to distal area very slowly under fluoroscopic control.
• In all positioning techniques keep the patient’s head elevated above highest level of spine.
• Do not lower head of table more than 15° during thoraco-cervical procedures.
• In patients with excessive lordosis, consider lateral position for injection and movement of the medium cephalad.
• Avoid intracranial entry of a bolus.
• Avoid early and high cephalad dispersion of the medium.
• At completion of direct cervical or lumbo-cervical procedures, raise head of table steeply (45°) for about 2 minutes to restore medium to lower levels.

Postprocedure

• Raise head of stretcher to at least 30° before moving patient onto it.
• Movement onto stretcher, and off the stretcher to bed, should be done slowly with patient completely passive, maintaining head up position.
• Before moving patient onto bed, raise head of bed 30° to 45° and maintain the patient in this position under close observation for 12 to 24 hours.
• Advise patient to remain still in bed, in head up position for the first 24 hours.
• Obtain visitors cooperation in keeping the patient quiet and in head up position, especially in first few hours.
• Encourage oral fluids and diet as tolerated.
• Antinauseants of the phenothiazine class should not be administered to the treat postprocedural nausea or vomiting (see WARNINGS). Since persistent nausea and vomiting may result in dehydration, prompt consideration of volume replacement by intravenous fluids is recommended.

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.

Isovue-M 200 (lopamidol Injection 41%)

Ten 10 mL single dose vials (NDC 0270-1411-11)
Ten 20 mL single dose vials (NDC 0270-1411-25)

Isovue-M 300 (lopamidol Injection 61%)

Ten 15 mL single dose vials (NDC 0270-1412-15)

Storage

Store at 20-25° C (68-77° F). [See USP]. Protect from light.

Manufactured for
Bracco Diagnostics Inc.
Monroe Township, NJ 08831
by BIPSO GmbH
78224 Singen (Germany)

Revised March 2017

CL63A04

Isovue-M is a registered trademark of Bracco Diagnostics Inc.

Isovue-M 200:10x 10mL Box label
NDC 0270-1411-11

Isovue-M 300:10x 15mL Box label
NDC 0270-1412-15