PAMIDOL

Iopamidol is a contrast agent developed by Bracco with nonionic, low-osmolar properties.

Not Available

The pharmacokinetics of intravenously administered iopamidol in normal subjects conform to an open two-compartment model with first order elimination (a rapid alpha phase for drug distribution and a slow beta phase for drug elimination).

The elimination serum or plasma half-life is approximately two hours; the half-life is not dose dependent.

No significant metabolism, deiodination, or biotransformation occurs.

Iopamidol is rapidly absorbed into the bloodstream from cerebrospinal fluid (CSF); following intrathecal administration, iopamidol appears in plasma within one hour and virtually all of the drug reaches the systemic circulation within 24 hours.

Iopamidol is excreted mainly through the kidneys following intrathecal administration, and the drug is essentially undetectable in the plasma 48 hours later.

In patients with impaired renal function, the elimination half-life is prolonged dependent upon the degree of impairment.

In the absence of renal dysfunction, the cumulative urinary excretion for iopamidol, expressed as a percentage of administered intravenous dose is approximately to 40 percent at 60 minutes, 80 to 90 percent at 8 hours, and 90 percent or more in the 72.

• to 96-hour period after administration.

In normal subjects, approximately 1 percent or less of the administered dose appears in cumulative 72.

• to 96-hour fecal specimens.

Iopamidol displays little tendency to bind to serum or plasma proteins.

No evidence of in vivo complement activation has been found in normal subjects.

Animal studies indicate that iopamidol does not cross the blood-brain barrier to any significant extent following intravascular administration.

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dose of 3000 mgI in adults and 2400 mgI 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.

The need for myelographic examination should be carefully evaluated.

Iopamidol should be administered with caution in patients with increased intracranial pressure or suspicion of intracranial tumor, abscess or hematoma, those with a history of convulsive disorder, severe cardiovascular disease, chronic alcoholism, or multiple sclerosis, and elderly patients.

Particular attention must be given to state of hydration, concentration of medium, dose, and technique used in these patients.

Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when injected intravenously or intra-arterially.

Injection is not injected intravascularly, measurable plasma levels are attained after intrathecal administration of iopamidol.

If frankly bloody cerebrospinal fluid is observed, the possible benefits of a myelographic examination should be considered in terms of risk to the patient.

Patients on anticonvulsant medication should be maintained on this therapy.

Direct intracisternal or ventricular administration for standard radiography (without computerized tomographic enhancement) is not recommended.

Inadvertent intracranial entry of a large or concentrated bolus of the contrast medium, which increases the risk of neurotoxicity, can be prevented by careful patient management.

Also, effort should be directed to avoid rapid dispersion of the medium causing inadvertent rise to intracranial levels (e.g., by active patient movement).

If such intracranial entry of the medium occurs, prophylactic anticonvulsant treatment with diazepam or barbiturates orally for to 48 hours should be considered.

Use of medications that may lower the seizure threshold (phenothiazine derivatives, including those used for their antihistaminic properties; tricyclic antidepressants; MAO inhibitors; CNS stimulants; analeptics; antipsychotic agents) should be carefully evaluated.

While the contributory role of such medications has not been established, some physicians have discontinued these agents at least 48 hours before and for at least 24 hours following intrathecal use.

Focal and generalized motor seizures have been reported after intrathecal use of water-soluble contrast agents including iopamidol.

In several of those cases reported with iopamidol, higher than recommended doses were employed.

Therefore avoid

Deviations from recommended neuroradiologic procedure or patient management.

Use in patients with a history of epilepsy unless medically justified.

Intracranial entry of a bolus or premature diffusion of a high concentration of the medium.

Failure to maintain elevation of the head during the procedure, on the stretcher, and in bed.

Excessive and particularly active patient movement or straining.

Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration.

These reactions include

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).

Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions.

Avoid administering Iopamidol

Injection to patients with a history of a severe cutaneous adverse reaction to Iopamidol Injection.

Intrathecal administration of corticosteroids with iopamidol is contraindicated.

Because of overdosage considerations, immediate repeat myelography in the event of technical failure is contraindicated.

Myelography should not be performed in the presence of significant local or systemic infection where bacteremia is likely.

In adults a solution that is approximately isotonic (Iopamidol Injection, 41%) is recommended for examination of the lumbar region.

For movement of the contrast medium to distant target areas the more concentrated Iopamidol Injection, 61% preparation should be used to compensate for dilution of Iopamidol Injection with cerebrospinal fluid.

The usual recommended adult dose range for iopamidol is 2000-3000 mg iodine.

Iopamidol formulated to contain more than 300 mgI/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 (Iopamidol Injection, 41%) 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 mgI/mL should not be used intrathecally in children.

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.

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 Iopamidol Injection 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 Iopamidol Injection; the combination of dose and Iopamidol Injection 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 Iopamidol Injection.

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).

Injection, 41% (200 mgI/mL) Procedure Age Years Usual Recommended Dose (mL) Lumbar, thoracic myelogram 2-7 7-9 8-12 8-11 13-18 10-12 Adult Dosage Table Concentration of Solution (mgI/mL) Usual Recommended Dose (mL) Lumbar myelogram 200 10 to 15 Thoracic myelogram 200 10 to 15 Cervical myelogram 200 10 to 15 (via lumbar injection) 300 10 Cervical myelogram (via lateral cervical injection) 200 10 Total columnar myelography 300 10 CT cisternography (via lumbar injection) 200 4 to 6 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.

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 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.

Use minimum dose and concentration required for satisfactory contrast.

Inject slowly over 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.

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 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 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.

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.

Injection, USP formulations are clear, colorless to pale yellow, stable, aqueous, sterile, and nonpyrogenic solutions for intrathecal administration.

It is supplied in the following strengths: Iopamidol Injection, USP, 41% Iopamidol Injection, USP, 41% contains 408 mg iopamidol per mL and is supplied in vials as follows: Vial NDC Volume per Vial Package Size (NDC) 70436-124-33 10 mL in single-dose vial 10 vials per carton 70436-124-35 20 mL in single-dose vial 10 vials per carton Iopamidol Injection, USP, 61% Iopamidol Injection, USP, 61% contains 612 mg iopamidol per mL and is supplied in vials as follows: Vial NDC Volume per Vial Package Size (NDC) 70436-126-34 15 mL in single-dose vial 10 vials per carton Discard unused portion.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Protect from light.

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 gI/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.

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.

ADMINISTRATION section.