CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Intrathecal administration ofcorticosteroids with iopamidol is contraindicated. Because of overdosageconsiderations, immediate repeat myelography in the event of technicalfailure is contraindicated (see interval recommendation under DOSAGE AND ADMINISTRATION). Myelographyshould not be performed in the presence of significant local or systemicinfection where bacteremia is likely.

PREGNANCY SECTION.

Pregnancy: Teratogenic Effects Reproduction studies have been performed in rats andrabbits at doses up to 2.7 and 1.4 times the maximum recommended humandose (1.48 gl/kg in 50 kg individual), respectively, and have revealedno evidence of impaired fertility or harm to the fetus due to iopamidol.There are, however, no adequate and well-controlled studies in pregnantwomen. Because animal reproduction studies are not always predictiveof human response, this drug should be used during pregnancy onlyif clearly needed.

SPL UNCLASSIFIED SECTION.

DIAGNOSTICNONIONIC RADIOPAQUECONTRAST MEDIAFor Intrathecal Administration in NeuroradiologyIncluding Myelography (Lumbar, Thoracic, Cervical,TotalColumnar) Pediatric Myelography (Lumbar, Thoracic),andfor Contrast Enhancement of Computed Tomographic (CECT)Cisternography and Ventriculography.

TERATOGENIC EFFECTS SECTION.

Pregnancy: Teratogenic Effects Reproduction studies have been performed in rats andrabbits at doses up to 2.7 and 1.4 times the maximum recommended humandose (1.48 gl/kg in 50 kg individual), respectively, and have revealedno evidence of impaired fertility or harm to the fetus due to iopamidol.There are, however, no adequate and well-controlled studies in pregnantwomen. Because animal reproduction studies are not always predictiveof human response, this drug should be used during pregnancy onlyif clearly needed.

OVERDOSAGE SECTION.

OVERDOSAGE. dose of 3000 mgl in adults and2400 mgl in children is sufficient for most myelographic procedures.Doses above these levels may result in an increased frequency andseverity of adverse reactions including seizures. However, in myelography,even use of recommended dose can produce mental aberrations tantamountto overdosage, if incorrect management of the patient during or immediatelyfollowing the procedure permits inadvertent early intracranial entryof large portion of the medium.Treatment of an overdose of an injectableradiopaque contrast medium is directed toward the support of all vitalfunctions, and prompt institution of symptomatic therapy.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. The most frequently reported adversereactions following intrathecal administration of iopamidol are headache,nausea, vomiting, and musculoskeletal pain. These reactions usuallyoccur to 10 hours after injection, almost all occurring within 24hours. They are usually mild to moderate in degree, lasting for afew hours and usually disappearing within 24 hours. Rarely, headachesmay be severe or persist for days. Headache is often accompanied bynausea and vomiting, and tends to be more frequent and persistentin patients not optimally hydrated. Backache, neck stiffness, numbnessand paresthesias, leg or sciatic-type pain occurred less frequently,often in the form of transient exacerbation of preexisting symptomatology.Transient alterations in vital signs may occur and their significancemust be assessed on an individual basis.The following table of incidence of reactionsis based on clinical studies with ISOVUE-M (lopamidol Injection) inabout 686 patients.Adverse ReactionsEstimated Overall IncidenceSystem> 1%<= 1%Body as Wholeheadache (16.4%)pyrexiamuscle weaknesshot flashesmalaisefatigueweaknessDigestivenausea (7.3%)vomiting (3.6%)diarrheaheartburnMusculoskeletalback pain (2.2%)leg pain (1.4%)neck pain(1.1%)leg crampssciaticacervicobrachial irritationmeningeal irritationradicular irritation lumbosacralother musculoskeletal paininvoluntarymovementburning sensationCardiovascularhypotension (1.1%)tachycardiahypertensionchest painNervousnoneemotional stressdizzinessparesthesiaconfusionhallucinationslightheadednesssyncopenumbnesscold extremitiesataxiairritabilityUrogenitalnoneurinary retentionRespiratorynonedyspneaSkin and AppendagesnonerashMiscellaneousnoneinjection site painOther adverse effects reportedin clinical literature for iopamidol include facial neuralgia, tinnitus,and sweating.Majormotor seizures have been reported in the clinical literature and sincemarket introduction in the United States. Early onset of seizures(less than two hours) is indicative of early substantial intracranialentry. Transitory EEG changes occur and usually take the form of slowwave activity.Whilenot observed in controlled clinical studies with ISOVUE-M (lopamidolInjection), the following adverse reactions may occur because theyhave been reported with ISOVUE-M and other nonionic water solublecontrast agents: cardiovascular (arrhythmias); pulmonary (apnea);bacterial meningitis, and aseptic meningitis syndrome; allergy oridiosyncrasy (chills, pruritus, nasal congestion, Guillain-Barre syndrome);CNS irritation (psycho-organic syndrome: mild and transitory perceptualaberrations such as depersonalization, anxiety, depression, hyperesthesia,disturbances in speech, sight, or hearing, and disorientation; inaddition, hyperreflexia or areflexia, hypertonia or flaccidity, restlessness,tremor, echoacousia, echolalia, asterixis or dysphasia have occurred).Profound mental disturbances have rarely been reported (various formsand degrees of aphasia, mental confusion or disorientation); the onsetis usually at to 10 hours and lasts for about 24 hours without aftereffects.However, occasionally they have been manifest as apprehension, agitationor progressive withdrawal to the point of stupor or coma. In fewcases, these have been accompanied by transitory hearing loss or otherauditory symptoms and visual disturbances (believed subjective ordelusional). Persistent cortical loss of vision in association withconvulsions, and ventricular block have been reported. Rarely, persistentthough transitory weakness in the leg or ocular muscles has been reported. Peripheral neuropathies have been rare and transitory. Theyinclude sensory and/or motor or nerve root disturbances, myelitis,persistent leg muscle pain or weakness, or sixth nerve palsy, or caudaequina syndrome. Muscle cramps, fasciculation or myoclonia, spinalconvulsion, paralysis, or spasticity are unusual.. General Adverse ReactionsTo Contrast Media. Reactions known to occur with parenteral administration of iodinatedionic contrast agents (see the listing below) are possible with anynonionic agent. Approximately 95 percent of adverse reactions accompanyingthe use of other water-soluble intravascularly administered contrastagents are mild to moderate in degree. However, life-threatening reactionsand fatalities, mostly of cardiovascular origin, have occurred. Reportedincidences of death from the administration of other iodinated contrastmedia range from 6.6 per million (0.00066 percent) to in 10,000patients (0.01 percent). Most deaths occur during injection or to10 minutes later, the main feature being cardiac arrest with cardiovasculardisease as the main aggravating factor. Isolated reports of hypotensivecollapse and shock are found in the literature. The incidence of shockis estimated to be out of 20,000 (0.005 percent) patients.Adverse reactions to injectablecontrast media fall into two categories: chemotoxic reactions andidiosyncratic reactions. Chemotoxic reactions result from the physicochemicalproperties of the contrast medium, the dose, and the speed of injection.All hemodynamic disturbances and injuries to organs or vessels perfusedby the contrast medium are included in this category. During intrathecaluse, there is lower incidence of electroencephalographic changesas well as neurotoxicity by virtue of the intrinsic properties ofthe iopamidol molecule.Idiosyncratic reactions include all other reactions. They occur morefrequently in patients 20 to 40 years old. Idiosyncratic reactionsmay or may not be dependent on the amount of drug injected, the speedof injection, the mode of injection, and the radiographic procedure.Idiosyncratic reactions are subdivided into minor, intermediate, andsevere. The minor reactions are self-limited and of short duration;the severe reactions are life-threatening and treatment is urgentand mandatory.The reportedincidence of adverse reactions to contrast media in patients witha history of allergy is twice that for the general population. Patientswith history of previous reactions to contrast medium are threetimes more susceptible than other patients. However, sensitivity tocontrast media does not appear to increase with repeated examinations.Most adverse reactions to intravascular contrast agents appear withinone to three minutes after the start of injection, but delayed reactionsmay occur (see PRECAUTIONS-General).Because measurableplasma levels are attained following the intrathecal administrationof iopamidol, adverse reactions reported with the use of intravascularcontrast agents are theoretically possible. These include:Cardiovascular: vasodilation (feeling of warmth), cerebral hematomas, hemodynamic disturbances, sinus bradycardia, transient electrocardiographic abnormalities,ventricular fibrillation, petechiae.Digestive: nausea, vomiting,severe unilateral or bilateral swelling of the parotid and submaxillaryglands. Nervous: paresthesia, dizziness, convulsions, paralysis, coma.Respiratory: increasedcough, asthma, dyspnea, laryngeal edema, pulmonary edema, bronchospasm,rhinitis.Urogenital: osmotic nephrosis of proximal tubular cells, renal failure, pain.Special Senses: perversion of taste; bilateral ocular irritation; lacrimation; itching;conjunctival chemosis, infection, and conjunctivitis.Endocrine: Thyroid functiontests indicative of hypothyroidism or transient thyroid suppressionhave been uncommonly reported following iodinated contrast media administrationto adult and pediatric patients, including infants. Some patientswere treated for hypothyroidism.Skin and Subcutaneous Tissue Disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticariaand skin discoloration) to severe: [e.g. Stevens-Johnson syndromeand toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematouspustulosis (AGEP) and drug reaction with eosinophilia and systemicsymptoms (DRESS)]. Injection site pain usually due to extravasationand/or erythematous swelling, skin necrosis, urticaria.The following reactions may alsooccur: neutropenia, thrombophlebitis, flushing, pallor, weakness,severe retching and choking, wheezing, cramps, tremors, and sneezing.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term studies in animals have not beenperformed to evaluate carcinogenic potential. No evidence of genetictoxicity was obtained in vitro tests.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. The pharmacokinetics of intravenously administerediopamidol in normal subjects conform to an open two-compartment modelwith first order elimination (a rapid alpha phase for drug distributionand slow beta phase for drug elimination). The elimination serumor plasma half-life is approximately two hours; the half-life is notdose dependent. No significant metabolism, deiodination, or biotransformationoccurs.Iopamidol israpidly absorbed into the bloodstream from cerebrospinal fluid (CSF);following intrathecal administration, iopamidol appears in plasmawithin one hour and virtually all of the drug reaches the systemiccirculation within 24 hours. Iopamidol is excreted mainly throughthe kidneys following intrathecal administration, and the drug isessentially undetectable in the plasma 48 hours later. In patientswith impaired renal function, the elimination half-life is prolongeddependent upon the degree of impairment. In the absence of renal dysfunction,the cumulative urinary excretion for iopamidol, expressed as percentageof administered intravenous dose is approximately 35 to 40 percentat 60 minutes, 80 to 90 percent at hours, and 90 percent or morein the 72- to 96-hour period after administration. In normal subjects,approximately percent or less of the administered dose appears incumulative 72- to 96-hour fecal specimens.Iopamidol displays little tendency to bindto serum or plasma proteins.No evidence of in vivo complementactivation has been found in normal subjects.Animal studies indicate that iopamidol doesnot cross the blood-brain barrier to any significant extent followingintravascular administration.

DESCRIPTION SECTION.

DESCRIPTION. ISOVUE-M (lopamidol Injection) formulationsare stable, aqueous, sterile, and nonpyrogenic solutions for intrathecaladministration.EachmL of ISOVUE-M 200 (lopamidol Injection 41%) provides 408 mg iopamidolwith mg tromethamine and 0.26 mg edetate calcium disodium. The solutioncontains approximately 0.029 mg (0.001 mEq) sodium and 200 mg organicallybound iodine per mL.Each mL of ISOVUE-M 300 (lopamidol Injection 61%) provides 612 mgiopamidol with mg tromethamine and 0.39 mg edetate calcium disodium.The solution contains approximately 0.043 mg (0.002 mEq) sodium and300 mg organically bound iodine per mL.The pH of ISOVUE-M contrast media has beanadjusted to 6.5-7.5 with hydrochloric acid and/or sodium hydroxide.Pertinent physicochemical data are noted below. ISOVUE-M (lopamidolInjection) is hypertonic as compared to plasma and cerebrospinal fluid(approximately 285 and 301 mOsm/kg water, respectively).IopamidolParameter41%61%Concentration (mgl/mL)200300Osmolality 37 (mOsm/kg water)413616Viscosity (cP) 37 C2.04.7 20 C3.38.8Specific Gravity 37 C1.2161.328lopamidol is designatedchemically as (S)-N,N-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]- 2,4,6-triiodo-5-lactamidoisophthalamide.Structural formula:. Isovue-M structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. In adults solution that isapproximately isotonic (ISOVUE-M 200) is recommended for examinationof the lumbar region. For movement of the contrast medium to distanttarget areas the more concentrated ISOVUE-M 300 preparation shouldbe used to compensate for dilution of ISOVUE-M (lopamidol Injection)with cerebrospinal fluid.The usual recommended adult dose range for iopamidol is 2000-3000mg iodine. Iopamidol formulated to contain more than 300 mgl/mL shouldnot be used intrathecally in adults. The minimum dose needed to performa procedure should always be used.In pediatric patients, solutionthat is approximately isotonic (ISOVUE-M 200) is recommended for allintrathecal procedures. In children, loss of contrast due to mixingon movement of the medium is less apt to occur because of their shorterspinal cord.The usualrecommended pediatric dose range for iopamidol is 1400-2400 mg iodine.Iopamidol formulated to contain more than 200 mgl/mL should not beused intrathecally in children. The minimum dose needed to performa procedure should always be used. See pediatricdosage table for recommended dosage.Anesthesia is not necessary. However, youngchildren may require general anesthesia for technical reasons. Premedicationwith sedatives or tranquillizers is usually not needed. In patientswith history of seizure activity who are not on anticonvulsant therapy,premedication with barbiturates or phenytoin should be considered.Lumbar puncture is usually madebetween L3 and L4; if pathology is suspected at this level, the interspaceimmediately above or below may be selected. lateral cervical puncturemay also be used.Rate of Injection: To avoid excessive mixing with cerebrospinalfluid and consequent loss of contrast as well as premature cephaladdispersion, injection must be made slowly over one to two minutes;the needle may then be removed.An interval of at least 48 hours should beallowed before repeat examination; however, whenever possible fiveto seven days is recommended.As with all radiopaque contrast agents,only the lowest dose of ISOVUE-M necessary to obtain adequate visualizationshould be used. lower dose reduces the possibility of an adversereaction. Most procedures do not require use of either maximum doseor the highest available concentration of ISOVUE-M; the combinationof dose and ISOVUE-M concentration to be used should be carefullyindividualized, and factors such as age, body size, anticipated pathologyand degree and extent of opacification required, structure(s) or areato be examined, disease processes affecting the patient, and equipmentand technique to be employed should be considered. Following are the usual recommended pediatric and adult doses ofISOVUE-M.Thepediatric doses listed below, intended as guideline, are based onage rather than weight because the brain and CSF capacity is independentof weight. Variations will depend on such factors as height, suspectedpathology, the patients condition, technique used, etc. (e.g. CTor standard radiology or movement of the contrast media directed distalto the site of injection).Pediatric Dosage TableISOVUE-M 200 (200 mgl/mL)ProcedureAgeYearsUsualRecommendedDose (mL)Lumbar, thoracic myelogram2-77-98-128-1113-1810-12Adult Dosage TableConcentrationof Solution(mgI/mL)UsualRecommendedDose(mL)Lumbar myelogram20010 to 15Thoracic myelogram20010 to 15Cervical myelogram20010 to 15 (via lumbar injection)30010Cervical myelogram20010 (via lateral cervical injection)Total columnar myelography30010CT cisternography2004 to (via lumbar injection)Following subarachnoidinjection, conventional radiography will continue to provide gooddiagnostic contrast for at least 30 minutes. At about one hour, diagnosticdegree of contrast will not usually be available. However, sufficientcontrast for CT myelography will be available for several hours. CTmyelography following conventional myelography should be deferredfor at least four hours to reduce the degree of contrast.Aspiration of iopamidol is unnecessaryfollowing intrathecal administration (see CLINICALPHARMACOLOGY).Parenteral drug products should be inspectedvisually for particulate matter and discoloration prior to administration,whenever solution and container permit. Iopamidol solutions shouldbe used only if clear and within the normal colorless to pale yellowrange. Discard any productwhich shows signs of crystallization or damage to the container-closuresystem, which includes the glass container, stopper and/or crimp.It is desirable that solutionsof radiopaque diagnostic agents for intrathecal use be at body temperaturewhen injected. Withdrawal of contrast agents from their containersshould be accomplished under aseptic conditions with sterile syringes.Spinal puncture must always be performed under sterile conditions.Patients should be wellhydrated prior to and following ISOVUE-M (Iopamidol Injection) administration.. Suggestions for UsualPatient Management. PreprocedureSee WARNINGS regardingdiscontinuation of neuroleptic agents.Maintain normal diet up to hours before procedure.Ensure hydration-fluids up to time of procedure.. See WARNINGS regardingdiscontinuation of neuroleptic agents.. Maintain normal diet up to hours before procedure.. Ensure hydration-fluids up to time of procedure.. During ProcedureUse minimum dose and concentration required for satisfactorycontrast.Inject slowly over to minutes to avoid excessive mixing.Abrupt or active patient movement causes excessive mixingwith CSF.Instruct patient to remain passive. Movepatient slowly and only as necessary.To maintain as bolus, move medium to distal area very slowly under fluoroscopic control.In all positioning techniques keep the patients head elevatedabove highest level of spine.Do not lower head of table more than 15 during thoraco-cervicalprocedures.In patients with excessive lordosis, consider lateral positionfor injection and movement of the medium cephalad.Avoid intracranial entry of 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 minutes to restore mediumto lower levels.. Use minimum dose and concentration required for satisfactorycontrast.. Inject slowly over to minutes to avoid excessive mixing.. Abrupt or active patient movement causes excessive mixingwith CSF.. Instruct patient to remain passive. Movepatient slowly and only as necessary.. To maintain as bolus, move medium to distal area very slowly under fluoroscopic control.. In all positioning techniques keep the patients head elevatedabove highest level of spine.. Do not lower head of table more than 15 during thoraco-cervicalprocedures.. In patients with excessive lordosis, consider lateral positionfor injection and movement of the medium cephalad.. Avoid intracranial entry of 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 minutes to restore mediumto lower levels.. PostprocedureRaise head of stretcher to at least 30 before moving patientonto it.Movement onto stretcher, and off the stretcher to bed, shouldbe done slowly with patient completely passive, maintaining head up position.Before moving patient onto bed, raise head of bed 30 to45 and maintain the patient in this position under close observationfor 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 quietand in head up position, especially in first fewhours.Encourage oral fluids and diet as tolerated.Antinauseants of the phenothiazine class should not be administeredto the treat postprocedural nausea or vomiting (see WARNINGS). Since persistent nausea and vomitingmay result in dehydration, prompt consideration of volume replacementby intravenous fluids is recommended.. Raise head of stretcher to at least 30 before moving patientonto it.. Movement onto stretcher, and off the stretcher to bed, shouldbe done slowly with patient completely passive, maintaining head up position.. Before moving patient onto bed, raise head of bed 30 to45 and maintain the patient in this position under close observationfor 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 quietand in head up position, especially in first fewhours.. Encourage oral fluids and diet as tolerated.. Antinauseants of the phenothiazine class should not be administeredto the treat postprocedural nausea or vomiting (see WARNINGS). Since persistent nausea and vomitingmay result in dehydration, prompt consideration of volume replacementby intravenous fluids is recommended.. Drug Incompatibilities. Many radiopaque contrast agentsare incompatible in vitro with some antihistaminesand many other drugs; therefore, no other pharmaceuticals should beadmixed with contrast agents.

DRUG & OR LABORATORY TEST INTERACTIONS SECTION.

Drug/Laboratory Test Interactions. The results of PBI and radioactive iodineuptake studies, which depend on iodine estimations, will not accuratelyreflect thyroid function for up to 16 days following administrationof iodinated contrast media. However, thyroid function tests not dependingon iodine estimations, e.g., T3 resin uptake and total or free thyroxine(T4) assays are not affected.Any test which might be affected by contrastmedia should be performed prior to administration of the contrastmedium.

DRUG INTERACTIONS SECTION.

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

GENERAL PRECAUTIONS SECTION.

General. Diagnosticprocedures which involve the use of any radiopaque agent should becarried out under the direction of personnel with the prerequisitetraining and with thorough knowledge of the particular procedureto be performed. Appropriate facilities should be available for copingwith any complication of the procedure, as well as for emergency treatmentof severe reaction to the contrast agent itself. After parenteraladministration of radiopaque agent, competent personnel and emergencyfacilities should be available for at least 30 to 60 minutes sincesevere delayed reactions may occur.Preparatory dehydration is dangerous and maycontribute to acute renal failure in patients with advanced vasculardisease, diabetic patients, and in susceptible nondiabetic patients(often elderly with preexisting renal disease). Patients shouldbe well hydrated prior to and following iopamidol administration. The possibility ofa reaction, including serious, life-threatening, fatal, anaphylactoidor cardiovascular reactions, should always be considered (see ADVERSE REACTIONS). Patients at increasedrisk include those with history of previous reaction to contrastmedium, patients with known sensitivity to iodine per se, and patientswith known clinical hypersensitivity (bronchial asthma, hay fever,and food allergies). The occurrence of severe idiosyncratic reactionshas prompted the use of several pretesting methods. However, pretestingcannot be relied upon to predict severe reactions and may itself behazardous for the patient. It is suggested that thorough medicalhistory with emphasis on allergy and hypersensitivity, prior to theinjection of any contrast medium, may be more accurate than pretestingin predicting potential adverse reactions. positive history of allergiesor hypersensitivity does not arbitrarily contraindicate the use ofa contrast agent where diagnostic procedure is thought essential,but caution should be exercised. Premedication with antihistaminesor corticosteroids to avoid or minimize possible allergic reactionsin such patients should be considered (see CONTRAINDICATIONS). Reports indicate that such pretreatmentdoes not prevent serious life-threatening reactions, but may reduceboth their incidence and severity.The possibility of inducing bacterial meningitisin patients during intrathecal procedures should always be considered.To avoid bacterial contamination during spinal puncture, sterilefield should be maintained at all times.If nondisposable equipment is used, scrupulouscare should be taken to prevent residual contamination with tracesof cleansing agents.

HOW SUPPLIED SECTION.

HOW SUPPLIED. ISOVUE-M 200 (lopamidol Injection41%)Ten 10 mL singledose vials (NDC 0270-1411-11)Ten 20 mL single dose vials(NDC 0270-1411-25)ISOVUE-M300 (lopamidol Injection 61%)Ten 15 mL single dose vials (NDC 0270-1412-15). Storage. Store at 20-25 (68-77 F).[See USP]. Protect from light.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. ISOVUE-M (lopamidol Injection)is indicated for intrathecal administration in adult neuroradiologyincluding myelography (lumbar, thoracic, cervical, total columnar),and for contrast enhancement of computed tomographic (CECT) cisternographyand ventriculography. ISOVUE-M 200 (lopamidol Injection) is indicatedfor thoraco-lumbar myelography in children over the age of two years.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. Patients receiving injectable radiopaque diagnosticagents should be instructed to:Inform your physician if you are pregnant.Inform your physician if you are diabetic or if you havemultiple myeloma, pheochromocytoma, homozygous sickle cell disease,or known thyroid disorder.Inform your physician if you are allergic to any drugs,food, or if you had any reactions to previous injections of substancesused for x-ray procedures (see PRECAUTIONS-General).Inform your physician about any other medications you arecurrently taking, including nonprescription drugs, before you havethis procedure.Advise patients to inform their physician if they developa rash after receiving Isovue-M.. Inform your physician if you are pregnant.. Inform your physician if you are diabetic or if you havemultiple myeloma, pheochromocytoma, homozygous sickle cell disease,or known thyroid disorder.. Inform your physician if you are allergic to any drugs,food, or if you had any reactions to previous injections of substancesused for x-ray procedures (see PRECAUTIONS-General).. Inform your physician about any other medications you arecurrently taking, including nonprescription drugs, before you havethis procedure.. Advise patients to inform their physician if they developa rash after receiving Isovue-M.

LABORATORY TESTS SECTION.

Laboratory Test Findings. In vitro studieswith animal blood showed that many radiopaque contrast agents, includingiopamidol, produced slight depression of plasma coagulation factorsincluding prothrombin time, partial thromboplastin time, and fibrinogen,as well as slight tendency to cause platelet and/or red blood cellaggregation.Transitorychanges may occur in red cell and leucocyte counts, serum calcium,serum creatinine, serum glutamic oxalacetic transaminase (SGOT), anduric acid in urine; transient albuminuria may occur.These findings have not been associated withclinical manifestations.

NURSING MOTHERS SECTION.

Nursing Mothers. It is not known whether this drugis excreted in human milk. Because many drugs are excreted in humanmilk, caution should be exercised when iopamidol is administered toa nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Isovue-M 200:10x 10mL Box label NDC0270-1411-11. ISOVUE-M 200 10x10mL.

PEDIATRIC USE SECTION.

Pediatric Use. See DOSAGEAND ADMINISTRATION section.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Diagnosticprocedures which involve the use of any radiopaque agent should becarried out under the direction of personnel with the prerequisitetraining and with thorough knowledge of the particular procedureto be performed. Appropriate facilities should be available for copingwith any complication of the procedure, as well as for emergency treatmentof severe reaction to the contrast agent itself. After parenteraladministration of radiopaque agent, competent personnel and emergencyfacilities should be available for at least 30 to 60 minutes sincesevere delayed reactions may occur.Preparatory dehydration is dangerous and maycontribute to acute renal failure in patients with advanced vasculardisease, diabetic patients, and in susceptible nondiabetic patients(often elderly with preexisting renal disease). Patients shouldbe well hydrated prior to and following iopamidol administration. The possibility ofa reaction, including serious, life-threatening, fatal, anaphylactoidor cardiovascular reactions, should always be considered (see ADVERSE REACTIONS). Patients at increasedrisk include those with history of previous reaction to contrastmedium, patients with known sensitivity to iodine per se, and patientswith known clinical hypersensitivity (bronchial asthma, hay fever,and food allergies). The occurrence of severe idiosyncratic reactionshas prompted the use of several pretesting methods. However, pretestingcannot be relied upon to predict severe reactions and may itself behazardous for the patient. It is suggested that thorough medicalhistory with emphasis on allergy and hypersensitivity, prior to theinjection of any contrast medium, may be more accurate than pretestingin predicting potential adverse reactions. positive history of allergiesor hypersensitivity does not arbitrarily contraindicate the use ofa contrast agent where diagnostic procedure is thought essential,but caution should be exercised. Premedication with antihistaminesor corticosteroids to avoid or minimize possible allergic reactionsin such patients should be considered (see CONTRAINDICATIONS). Reports indicate that such pretreatmentdoes not prevent serious life-threatening reactions, but may reduceboth their incidence and severity.The possibility of inducing bacterial meningitisin patients during intrathecal procedures should always be considered.To avoid bacterial contamination during spinal puncture, sterilefield should be maintained at all times.If nondisposable equipment is used, scrupulouscare should be taken to prevent residual contamination with tracesof cleansing agents.. Information for Patients. Patients receiving injectable radiopaque diagnosticagents should be instructed to:Inform your physician if you are pregnant.Inform your physician if you are diabetic or if you havemultiple myeloma, pheochromocytoma, homozygous sickle cell disease,or known thyroid disorder.Inform your physician if you are allergic to any drugs,food, or if you had any reactions to previous injections of substancesused for x-ray procedures (see PRECAUTIONS-General).Inform your physician about any other medications you arecurrently taking, including nonprescription drugs, before you havethis procedure.Advise patients to inform their physician if they developa rash after receiving Isovue-M.. Inform your physician if you are pregnant.. Inform your physician if you are diabetic or if you havemultiple myeloma, pheochromocytoma, homozygous sickle cell disease,or known thyroid disorder.. Inform your physician if you are allergic to any drugs,food, or if you had any reactions to previous injections of substancesused for x-ray procedures (see PRECAUTIONS-General).. Inform your physician about any other medications you arecurrently taking, including nonprescription drugs, before you havethis procedure.. Advise patients to inform their physician if they developa rash after receiving Isovue-M.. Drug Interactions. Other drugs should not be admixedwith iopamidol (see CONTRAINDICATIONS, and DOSAGE AND ADMINISTRATION, Drug Incompatibilities).. Drug/Laboratory Test Interactions. The results of PBI and radioactive iodineuptake studies, which depend on iodine estimations, will not accuratelyreflect thyroid function for up to 16 days following administrationof iodinated contrast media. However, thyroid function tests not dependingon iodine estimations, e.g., T3 resin uptake and total or free thyroxine(T4) assays are not affected.Any test which might be affected by contrastmedia should be performed prior to administration of the contrastmedium.. Laboratory Test Findings. In vitro studieswith animal blood showed that many radiopaque contrast agents, includingiopamidol, produced slight depression of plasma coagulation factorsincluding prothrombin time, partial thromboplastin time, and fibrinogen,as well as slight tendency to cause platelet and/or red blood cellaggregation.Transitorychanges may occur in red cell and leucocyte counts, serum calcium,serum creatinine, serum glutamic oxalacetic transaminase (SGOT), anduric acid in urine; transient albuminuria may occur.These findings have not been associated withclinical manifestations.. Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term studies in animals have not beenperformed to evaluate carcinogenic potential. No evidence of genetictoxicity was obtained in vitro tests.. . Pregnancy: Teratogenic Effects Reproduction studies have been performed in rats andrabbits at doses up to 2.7 and 1.4 times the maximum recommended humandose (1.48 gl/kg in 50 kg individual), respectively, and have revealedno evidence of impaired fertility or harm to the fetus due to iopamidol.There are, however, no adequate and well-controlled studies in pregnantwomen. Because animal reproduction studies are not always predictiveof human response, this drug should be used during pregnancy onlyif clearly needed.. Nursing Mothers. It is not known whether this drugis excreted in human milk. Because many drugs are excreted in humanmilk, caution should be exercised when iopamidol is administered toa nursing woman.. Pediatric Use. See DOSAGEAND ADMINISTRATION section.

WARNINGS SECTION.

WARNINGS. The need for myelographic examinationshould be carefully evaluated. Iopamidol should be administered withcaution in patients with increased intracranial pressure or suspicionof intracranial tumor, abscess or hematoma, those with history ofconvulsive disorder, severe cardiovascular disease, chronic alcoholism,or multiple sclerosis, and elderly patients.Particular attention must be given to stateof hydration, concentration of medium, dose, and technique used inthese patients.Contrastmedia may promote sickling in individuals who are homozygous for sicklecell disease when injected intravenously or intra-arterially. AlthoughISOVUE-M is not injected intravascularly, measurable plasma levelsare attained after intrathecal administration of iopamidol.If frankly bloody cerebrospinalfluid is observed, the possible benefits of myelographic examinationshould be considered in terms of risk to the patient.Patients on anticonvulsant medication shouldbe maintained on this therapy.Direct intracisternal or ventricular administrationfor standard radiography (without computerized tomographic enhancement)is not recommended. Inadvertent intracranial entry of large or concentratedbolus of the contrast medium, which increases the risk of neurotoxicity,can be prevented by careful patient management. Also, effort shouldbe directed to avoid rapid dispersion of the medium causing inadvertentrise to intracranial levels (e.g., by active patient movement). Ifsuch intracranial entry of the medium occurs, prophylactic anticonvulsanttreatment with diazepam or barbiturates orally for 24 to 48 hoursshould be considered.Use of medications that may lower the seizure threshold (phenothiazinederivatives, including those used for their antihistaminic properties;tricyclic antidepressants; MAO inhibitors; CNS stimulants; analeptics;antipsychotic agents) should be carefully evaluated. While the contributoryrole of such medications has not been established, some physicianshave discontinued these agents at least 48 hours before and for atleast 24 hours following intrathecal use.Focal and generalized motor seizures havebeen reported after intrathecal use of water-soluble contrast agentsincluding iopamidol. In several of those cases reported with iopamidol,higher than recommended doses were employed. Therefore avoid: Deviations from recommended neuroradiologic procedure orpatient management.Use in patients with history of epilepsy unless medicallyjustified.Overdosage.Intracranial entry of bolus or premature diffusion ofa 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 CutaneousAdverse Reactions Severe cutaneous adverse reactions (SCAR)may develop from hour to several weeks after intravascular contrastagent administration. These reactions include Stevens-Johnson syndromeand toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematouspustulosis (AGEP) and drug reaction with eosinophilia and systemicsymptoms (DRESS). Reaction severity may increase and time to onsetmay decrease with repeat administration of contrast agent; prophylacticmedications may not prevent or mitigate severe cutaneous adverse reactions.Avoid administering Isovue-M to patients with history of severecutaneous adverse reaction to Isovue-M.. Deviations from recommended neuroradiologic procedure orpatient management.. Use in patients with history of epilepsy unless medicallyjustified.. Overdosage.. Intracranial entry of bolus or premature diffusion ofa 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.