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Metrizamide (Systemic)


VA CLASSIFICATION
Primary: DX101

Commonly used brand name(s): Amipaque.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:

Note: Metrizamide is a nonionic radiopaque contrast agent.



Diagnostic aid, radiopaque (central nervous system disorders)—

Diagnostic aid, radiopaque (cerebrospinal fluid disorders)—

Diagnostic aid, radiopaque (brain disorders)—

Diagnostic aid, radiopaque (cardiac disease)—

Diagnostic aid, radiopaque (vascular disease)—

Diagnostic aid, radiopaque (urinary tract disorders)—

Indications

Accepted

Intrathecal
Myelography (lumbar, thoracic, cervical, total columnar)—Metrizamide is indicated in adults and pediatric patients for lumbar, thoracic, cervical, and total columnar myelography to determine the presence of abnormalities in the spinal column, spinal canal, and central nervous system (CNS). {01} {02} {43} {61}

Cisternography—Metrizamide is indicated in pediatric patients for cisternography by direct injection using standard radiologic techniques to visualize the basal cistern of the brain. {01} {02} {61}

Cisternography, computed tomographic—Metrizamide is indicated in adults and pediatric patients for computerized tomography (CT) of the intracranial subarachnoid spaces. {01} {02} {61}

Ventriculography—Metrizamide is indicated in pediatric patients for ventriculography by direct injection using standard radiologic techniques to visualize the cerebral ventricles. {01} {02} {61}

Intravascular
Angiocardiography—Metrizamide is indicated in pediatric angiocardiography to visualize lesions or malformations of the heart and obstructions or anomalies of the major thoracic vessels. {01} {02} {61}

Arteriography—Metrizamide is indicated in adult peripheral arteriography to visualize specific regions of the vascular system and blood flow in such areas to help in the diagnosis and evaluation of neoplasms (known or suspected) or vascular diseases (congenital or acquired) that may cause changes in normal vascular anatomy or physiology. Metrizamide is also indicated in adults for intravenous digital arteriography of head and neck. {01} {02} {61} {62}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    789.10 {01} {61}


Osmolality
    Low. The osmolalities of the injections with iodine concentrations of 170 and 300 mg per mL are 300 and 484 mOsmol per kg of water, respectively {01} {22} {61}

Note: Metrizamide is isotonic with the cerebrospinal fluid (CSF) at an approximate concentration of 170 mg of iodine per mL of solution.


Mechanism of action/Effect:

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. {47} The degree of opacity produced by these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. After intrathecal administration into the subarachnoid space, diffusion of metrizamide in the CSF allows the visualization of the subarachnoid spaces of the head and spinal canal. After intravascular administration, metrizamide makes opaque those vessels in its path of flow, allowing visualization of the internal structures until significant hemodilution occurs. {01}


Other actions/effects:

Competitive inhibitor of the glucose site of brain hexokinase. {04}

Absorption:

Oral/Rectal—Absorption from gastrointestinal tract is negligible. {02} {22} {26}

Distribution:

Intrathecal—Diffuses upward through the CSF; rapidly penetrates into nerve root sleeves, nerve rootlets, and narrow areas of the subarachnoid space. Also, enters extracellular fluid of the brain tissue and pial surface of cerebral and cerebellar tissue adjacent to subarachnoid areas. In patients with normal CSF dynamics, it is eliminated from CSF into the blood within several hours.

Intravascular—Rapidly distributed throughout extracellular fluid following intravenous administration.


Time to peak opacification


Standard myelography:

Immediate and for up to 30 minutes. {01} {61}



CT myelography {01} {61}:

Lumbar region: Immediate.

Thoracic region: 1 hour.

Cervical region: 2 hours.

Basal cisterns: 3 to 4 hours.


Peak serum concentration

Intrathecal—1 to 3 hours after lumbar subarachnoid injection.

Intravascular—Immediate, but concentration falls rapidly as metrizamide becomes distributed throughout the extravascular compartment. {01}

Elimination:


Intrathecal—
        Normal renal function: Primarily renal (60% of dose excreted unchanged within 48 hours). {01} {61}
        Severe renal function impairment or renal failure: Fecal elimination via biliary tract becomes primary route of elimination. {01}



Intravascular—
        Renal: 94% of dose is excreted unchanged in 24 hours.
        Fecal: 5% of dose. {03}



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to iodine or other iodinated contrast media may be sensitive to metrizamide also. {01} {02}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. {01} However, other organically bound iodine–containing preparations administered near term by intra-amniotic injection have caused hypothyroidism in some newborns. {10}

Also, elective contrast radiography of the abdomen is usually not recommended during pregnancy because of the risks to the fetus from radiation exposure. {01} {02}

Reproduction studies in rats and rabbits have not shown that metrizamide, administered in doses up to 70 times the human dose, impairs fertility or causes harm to the fetus.

FDA Pregnancy Category B.

Breast-feeding

Up to 1 mg of the injected myelographic dose of metrizamide is distributed into the breast milk over 2 days. {01}

Pediatrics


For intravascular use:

Dehydration and/or the risk of renal failure may be exacerbated in infants and young children, especially those with polyuria, oliguria, diabetes, or pre-existing dehydration, by the the contrast media; adequate hydration is recommended before and following administration of metrizamide. {01}



Geriatrics



For all procedures:

Elderly patients may be more sensitive to the effects of metrizamide on thyroid function. Iodine-induced thyrotoxicosis may occur 4 to 12 weeks following contrast radiography. Thyroid function monitoring may be needed in geriatric patients. {60}



For intravascular use:

Diagnostic studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of metrizamide in the elderly. However, elderly patients are more likely to have age-related renal function impairment, which may require lower dosage in patients receiving metrizamide. {28} {40}

Dehydration and/or the risk of renal failure may be exacerbated in geriatric patients, especially those with polyuria, oliguria, diabetes, or pre-existing dehydration, by the contrast media; adequate hydration is recommended before and following administration of metrizamide. {01}



For intrathecal use:

Geriatric patients may be prone to develop mental confusion with the intrathecal administration of metrizamide. {08}


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antidepressants, tricyclic or
CNS stimulation–producing medications (See Appendix II ) or
Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline or
» Phenothiazines or
» Trimeprazine    (concurrent use with intrathecal administration of metrizamide may increase risk of seizures because of lowered seizure threshold effect of these medications; it is recommended that these medications be discontinued for at least 48 hours before and 24 hours after myelography {03} {43})


Beta-adrenergic blocking agents    (concurrent intravascular administration of metrizamide with beta-adrenergic blocking agents may increase the risk of moderate to severe anaphylactoid reaction and may exacerbate hypotensive effects; discontinuation of the beta-adrenergic blocking agent before administration of contrast media may be advisable in patients with other risk factors {41} {43} {48} {49} {50} {58})


Cholecystographic agents, oral    (the risk of renal toxicity may be increased if an oral cholecystographic agent is given before the intravascular administration of metrizamide, especially in patients with hepatic function impairment {01})


Glucocorticoids, intrathecal    (concurrent intrathecal administration of metrizamide with intrathecal administration of glucocorticoids may increase risk of arachnoiditis {01} {03})


Hypotension-producing medications, other (See Appendix II )    (the risk of severe hypotension may be increased if metrizamide is given concurrently with other medications that produce hypotension {43})


Interleukin-2    (incidence of delayed reactions to intravenous contrast media [e.g., hypersensitivity, fever, skin rash, flu-like symptoms, joint pain, flushing, pruritus, emesis, hypotension, dizziness occurring more than 1 hour after administration] may be increased in patients who have received interleukin-2; some symptoms may resemble a ``recall'' reaction to interleukin-2; supportive medical treatment may be necessary if symptoms are significant; delaying contrast media administration until 6 weeks after administration of interleukin-2 may reduce incidence of these reactions {51} {52} {53} {54} {55})


Nephrotoxic medications, other (See Appendix II )    (concurrent intrathecal or intravascular administration of metrizamide with other nephrotoxic medications may increase the potential for nephrotoxicity {43})


Diagnostic interference
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With other diagnostic test results
Electroencephalogram (EEG) readings    (intrathecal administration of metrizamide may cause transient increases in slow wave activity; pre-existing EEG changes may also be exacerbated in some patients {01})


Leukocyte counts and
Red cell counts    (may be temporarily decreased {42})


Prothrombin time (PT) and
Thromboplastin time    (may be increased with metrizamide since in vitro studies with animal blood have shown other nonionic contrast media to slightly inhibit all stages of coagulation {27} {43})


Thyroid function determinations and
Thyroid imaging    (intravascular or intrathecal administration of metrizamide may cause an alteration of serum protein–bound iodine [PBI] concentrations and radioactive iodine and pertechnetate ion uptake for up to 16 days {01}; thyroid test should be performed prior to administration of metrizamide. Other thyroid function tests not based on measurement of iodine, such as resin triiodothyronine uptake, may not be affected)


Urinalysis    (metrizamide may interfere with some chemical determinations made on urine, such as protein and specific gravity; urine should be collected prior to or at least 2 days after intravenous administration of metrizamide)

With physiology/laboratory test values
Cerebrospinal fluid (CSF) leukocyte count and
CSF protein count    (may be increased transiently following intrathecal administration of metrizamide)


Creatinine, serum    (concentration may be increased with metrizamide since temporary increases of serum creatinine have occurred with other nonionic contrast media {27} {28} {43})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist {02} {04} {05}

For all procedures:
Allergic reaction (anaphylaxis) to penicillins or to skin allergens, previous    (although the risk of anaphylactoid reaction may be less with metrizamide than with high-osmolality contrast agents, caution is recommended when administering metrizamide to patients who have had a previous reaction to penicillins or to skin allergens {44} {48} {49} {56} {58})


Allergies or asthma, history of    (although the risk of idiosyncratic response or anaphylactoid reaction may be less with metrizamide than with high-osmolality contrast agents, caution is recommended when administering metrizamide to patients with a history of allergies or asthma {01} {44} {45} {48} {49} {56} {58})


» Dehydration, especially associated with pre-existing renal disease, advanced vascular disease, or diabetes mellitus; or in infants, young children, and elderly patients    (intravascular administration may increase risk of acute renal failure; incidence and severity of headaches may be increased with intrathecal administration)


» Hepatorenal disease    (elimination of metrizamide may be delayed or impaired {01})


Renal function impairment, severe    (elimination of metrizamide may be delayed; because of the risk of inducing temporary oliguria, an interval of 48 hours should elapse before repeat examination {01})


» Sensitivity to iodinated contrast media{01}    (increased risk of anaphylactoid reaction in patients with history of prior reactions to contrast media)


For intrathecal use:
Alcoholism, chronic{01}    (increased risk of side effects because of possible brain or liver damage {43})


Bleeding, subarachnoid    (increased risk of meningeal irritation or arachnoiditis {01})


Epilepsy, history of    (increased risk of seizures {01} {43})


Infection, local or systemic, significant{01}
Multiple sclerosis{01}{43}
For intravascular use:
Hyperthyroidism    (administration of metrizamide may precipitate thyroid storm)


» Pheochromocytoma    (administration of metrizamide may precipitate severe hypertension; amount of metrizamide injected should be kept to a minimum and blood pressure should be monitored during the procedure; pretreatment with the alpha-adrenergic blocking agent, phentolamine, is recommended {44})


Sickle cell disease    (metrizamide may promote sickling in patients who are homozygous for sickle cell disease; however, sickling potential of metrizamide is less compared to high-osmolality ionic agents {43})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For intravascular use
Blood pressure determinations    (may be required during examination, especially in patients with known or suspected pheochromocytoma or hemodynamic compromise or instability {01} {47})


Thyroid function determinations    (iodine-induced thyrotoxicosis may occur 4 to 12 weeks following contrast radiography in geriatric patients; thyroid function monitoring may be needed {60})




Side/Adverse Effects

Note: Adverse effects may vary directly with the concentration of the contrast agent, the amount and technique used, and the underlying pathology. Increases in osmolality, volume, concentration, viscosity, and rate of administration of the solution may increase the incidence and severity of adverse effects. {06}
Most of the adverse effects are usually self-limited and of short duration.
Overall incidence of adverse effects with nonionic contrast agents, such as metrizamide, has been reported to be less than with ionic contrast agents. {17}
Nonionic contrast media, such as metrizamide, have been reported to produce fewer and less severe alterations in cardiac hemodynamics (e.g., bradycardia, hypotension) and electrocardiograms than standard ionic contrast agents during cardiac angiography. {18} {19} {20}
Low-osmolality agents, such as metrizamide, are reported to cause less heat and pain on injection than high-osmolality agents, such as diatrizoates and iothalamate. {01} {29}
Thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with nonionic contrast media; however, these events appear to be technique-related. {21}
Major motor seizures have occurred rarely with intrathecal administration of metrizamide in patients with a history of epilepsy, with overdosage, with inadvertent intracranial entry of a large or concentrated bolus dose, with concurrent administration of neuroleptic medications or phenothiazine antiemetics, and with excessive patient movement or failure to maintain proper head elevation. {01}
Severe mental disturbances have rarely been reported following intrathecal administration of metrizamide. These usually have an onset of 8 to 10 hours and may last 24 hours. They are more prevalent following cervical myelography and may be related to metrizamide's competitive inhibition for the glucose site of brain hexokinase; they may also be dose-related. {01}
Headaches following intrathecal administration of metrizamide may be more frequent, severe, and persistent in those patients not adequately hydrated. {01}
Dehydration may be exacerbated by the osmotic diuretic action of the hypertonic contrast solutions of metrizamide and in some cases cause a shock-like state, following intravascular administration of metrizamide in infants and young children and in geriatric, azotemic, and dehydrated or debilitated patients. {01}
Cardiac arrest and shock have also been reported rarely during or a few minutes after administration of metrizamide. {01}
Transient global amnesia has been reported in 2 patients after cerebral angiography, in which 20 mL of another low-osmolality nonionic contrast agent (containing the equivalent of 240 mg of iodine per mL) was administered into the ascending aorta. The possibility that metrizamide may cause a similar response must be considered. {59}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
With all procedures {02} {04} {05} {14} {15} {16} {43} {44}
    
Cardiotoxic effects, with ventricular tachycardia or fibrillation (fast or irregular heartbeat)
    
hypotension (severe tiredness or weakness)
    
pseudo-allergic reaction (skin rash or hives; stuffy nose; swelling of face or skin; swelling of the tongue, wheezing, tightness in chest, or troubled breathing)
    
pulmonary edema (severe wheezing or troubled breathing)
Note: Pseudo-allergic reactions are usually transient. However, they may be initial manifestations of more severe anaphylactoid reactions. The anaphylactoid reaction may progress to respiratory arrest and vasomotor collapse if appropriate treatment is not administered. {49}




Incidence rare
With intrathecal administration
    
CNS effects (paralysis of one side of body or of legs and arms)
    
hallucinations
    
severe nausea and vomiting
    
seizures, focal or generalized grand mal
Note: In case of severe vomiting, the use of phenothiazine antiemetics may increase the risk of seizures; however, risk-benefit must be considered.
Seizures usually occur 4 to 12 hours following injection of metrizamide. May be dose-related. Seizures that occur within 2 hours of administration may indicate early substantial intracranial entry. {01}






Those indicating need for medical attention only if they continue or are bothersome {01}
Incidence more frequent
With all procedures
    
Nausea and vomiting, mild to moderate
    
restlessness
    
trembling
Note: Nausea and vomiting may occur 3 to 8 hours after intrathecal injection and last for a few hours, usually disappearing within 24 hours; or, after intravascular injection, may occur immediately and last for a few minutes.



With intrathecal administration
    
Mild to moderate headache
Note: Mild to moderate headache may occur 3 to 8 hours after injection and last for a few hours, usually disappearing within 24 hours. Often accompanied by nausea and/or less frequently by vomiting. {01}




Incidence less frequent or rare
With intrathecal administration
    
Backache
    
chills
    
CNS effects (blurred or double vision or other changes in vision; confusion, especially in the elderly{08}; dizziness; severe headache; ringing or buzzing in ears; speech difficulty{01}{09}; unusual tiredness or weakness)
    
fever —more frequent in children
    
increased sweating
    
meningeal irritation (stiffness of neck)

With intravascular administration
    
Increase in amount of urine
    
unusual warmth and flushing of skin






Overdose

Treatment of overdose
Specific treatment—Intravenous diazepam or administration of phenobarbital sodium, for the control of seizures. {01}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopaque Agents (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body:

• Injection into spinal canal; visualization of radiopacity in head and spinal cord possible with x-rays


• Injection into vein or artery; visualization of radiopacity in heart and blood vessels possible with x-rays


• Direct injection into region to be studied; visualization of radiopacity in joint spaces


Before having this test
»   Conditions affecting use, especially:
Sensitivity to iodine or other iodinated contrast media

Pregnancy—Risk to the fetus from radiation exposure; possible risk of hypothyroidism in newborn





Breast-feeding—Distributed into breast milk





Use in children—Possible exacerbation of dehydration (with intravascular use)






Use in the elderly—Possible exacerbation of dehydration; increased risk of thyrotoxicosis
Other medications, especially phenothiazines, tricyclic antidepressants, and trimeprazine (with intrathecal use)
Other medical problems, especially dehydration, hepatorenal disease, and pheochromocytoma

Preparation for this test
Adequate intake of fluids to prevent dehydration

Special preparatory instructions may be given; patient should inquire in advance

With intrathecal use
Normal diet up to 2 hours before procedure; moderate amounts of clear fluids may continue up to time of procedure

Precautions after having this test
Possible interference with future thyroid tests

With intrathecal use
Avoiding movement during and for several hours after administration

Keeping head position as instructed during and after examination

With intravascular use
For digital arteriography of head and neck: Not moving or swallowing during and immediately after administration


Side/adverse effects
Signs of possible side effects, especially pseudo-allergic reaction or cardiac effects; hallucinations, severe nausea and vomiting, paralysis of one side of body or of arm(s) or leg(s), and seizures (with intrathecal use), severe tiredness or weakness, severe wheezing, or troubled breathing


General Dosing Information
Manufacturer's package insert or other appropriate literature should be consulted for specific techniques and procedures for the administration of contrast media.

Sensitivity test doses are not usually recommended since severe or fatal reactions to contrast media are not predictable from a patient's history or a sensitivity test. On some occasions, severe or fatal reactions have occurred with a test dose or with a full dose in patients who did not react to the test dose. {04}

Pretreatment with corticosteroids and/or antihistamines has been used to minimize the incidence and severity of reactions in patients with a history of severe reactions to contrast media or with other high-risk conditions (e.g., asthma or history of allergies, positive allergy history to skin allergens or penicillins, dehydration, history of seizures, pheochromocytoma). In some studies, the additional use of ephedrine has been shown to be beneficial in preventing anaphylactoid reactions (except in patients with a history of hypertension or cardiovascular disease). When the use of a contrast agent is being considered, the following protocols are recommended: {01} {32} {33} {34} {35} {36} {37} {38} {39} {43} {44} {46} {47} {49} {57} {58} For high-risk patients—

   • Use of a high-osmolality contrast agent plus pretreatment with a corticosteroid (oral prednisone 50 mg administered 13 hours, 7 hours, and 1 hour before procedure) and an antihistamine (intramuscular, intravenous, or oral diphenhydramine, 50 mg administered 1 hour prior to procedure) or
   • Use of a low-osmolality contrast agent if pretreatment is not feasible or
   • Use of a low-osmolality contrast agent plus corticosteroid pretreatment.
For low-risk patients—

   • Use of a high-osmolality contrast agent or
   • Use of a high-osmolality contrast agent and corticosteroid pretreatment.


Adequate hydration is recommended for all patients. Intravenous or oral intake of fluids may continue up to time of administration of metrizamide. {01}

During and for at least 30 to 60 minutes after intravascular injection, and for at least 12 hours (up to 24 hours in some cases) after intrathecal administration, of contrast media the patient should be observed for possible severe reactions; competent personnel and emergency facilities should be available during this period. {04}

Dosage of metrizamide is expressed in terms of iodine.

Dosage and concentration of iodine as metrizamide injection are dependent upon the degree and extent of contrast needed in the areas under examination and on the equipment and technique used.

For intrathecal use
Pretreatment with barbiturates or phenytoin may be used in patients who have a history of seizures but who are not on anticonvulsant therapy. Patients who are on anticonvulsant therapy should continue receiving their medication when using metrizamide. {01}

A normal diet may be ingested up to 2 hours prior to the administration of metrizamide. Moderate amounts of clear liquids are permissible and even recommended by some clinicians to prevent dehydration.

To minimize the risk of seizures, treatment with anticonvulsants may be used if inadvertent intracranial entry of a large or concentrated bolus of metrizamide occurs. {01}

Direct intracisternal or ventricular administration of metrizamide for standard radiography is not recommended. {01}

During and for several hours after the procedure the patient must remain inactive to minimize high cephalad dispersion of metrizamide.

Information on patient management and positioning during and after procedure is included in the manufacturer's package insert.

For intravascular use
Nonionic contrast media, such as metrizamide, inhibit blood coagulation, in vitro , less than ionic contrast media. Blood cell aggregation has been reported when blood remains in contact with syringes containing nonionic contrast media. Thus, thromboembolic events causing myocardial infarction and stroke, reported during angiographic procedures, may have resulted from aggregation of blood that had come in contact with the contrast agent outside the body. Risk factors for aggregation should be minimized by performing the procedure in the shortest time possible, using plastic rather than glass syringes, and flushing catheters with heparinized saline solutions. {21}

During and immediately after administration of metrizamide for intravenous digital arteriography of neck and head, the patient must remain inactive. Otherwise, poor arterial visualization may result. Swallowing must also be avoided during and after the injection of metrizamide for carotid-cerebral arteriography. {01}

For treatment of adverse effects
Recommended treatment consists of the following: {01} {35} {41} {42}

   • For major or life-threatening reactions, careful monitoring of vital signs and emergency therapy, including artificial respiration with oxygen, if needed for respiratory depression, and cardiac massage in the event of cardiac arrest.
   • To restore blood pressure, administration of intravenous fluids and/or vasopressors. If hypotension necessitates the use of vasopressors, slow infusion of 0.008 to 0.012 mg per minute of norepinephrine or 0.1 to 0.18 mg per minute of phenylephrine, appropriately diluted. If hypotension is due to increased vagal activity (vasovagal reaction), intravenous administration of 1 mg of atropine, repeated in 1 to 2 hours if needed.
   • Other specific treatment may include— {55}

• Diphenhydramine: For minor allergic-like reactions—An antihistamine such as diphenhydramine hydrochloride (except in epileptic patients) may be administered intravenously.


• Epinephrine: For acute allergic-like or anaphylactoid reactions—Slow intravenous infusion of 0.1 mg of epinephrine (1:10,000).For mild to moderate bronchospasm—0.1 to 0.2 mg of epinephrine (1:1000) may be administered subcutaneously, except in hypotension. In extreme emergency, 0.1 mg of epinephrine (1:10,000) may be given slowly by intravenous route, followed by a continuous intravenous infusion at an initial rate of 0.001 mg per minute, the rate may be increased to 0.004 mg per minute if necessary.(Note: Patients on beta-adrenergic blocking agents should not receive epinephrine since they are at risk of unopposed alpha-adrenergic stimulation, which may result in hypertension, reflex bradycardia, and heart-block. In these patients, isoproterenol and norepinephrine are used instead of epinephrine to overcome bronchospasm and hypotension, respectively.)For cardiac arrest—0.1 to 1 mg of epinephrine may be administered by the intravenous route.


• Diazepam or phenobarbital: To control convulsions—5 to 10 mg of diazepam by slow, intravenous administration or phenobarbital sodium may be given intravenously or intramuscularly at a rate not to exceed 30 to 60 mg per minute.



Parenteral Dosage Forms

METRIZAMIDE FOR INJECTION

Usual adult and adolescent dose
Intrathecal


Myelography:
Lumbar myelography by lumbar injection—10 to 15 mL of a solution containing the equivalent of 170 to 190 mg of iodine per mL.

Thoracic myelography by lumbar injection—12 mL of a solution containing the equivalent of 220 mg of iodine per mL.

Cervical myelography by lumbar injection—10 mL of a solution containing the equivalent of 250 to 300 mg of iodine per mL.

Cervical myelography by lateral cervical injection—10 mL of a solution containing the equivalent of 220 mg of iodine per mL.

Total columnar myelography by lumbar injection—10 mL of a solution containing the equivalent of 250 to 280 mg of iodine per mL.



CT cisternography by lumbar injection:
4 to 6 mL of a solution containing the equivalent of 170 to 190 mg of iodine per mL.

Note: Injection should be given slowly over a period of 1 to 2 minutes.
Immediate repeat intrathecal administration is not recommended because of risk of overdose; 48 hours, or preferably 5 to 7 days, should elapse before repeat examination. {01}



Intravascular—As a solution containing the equivalent of 370 mg of iodine per mL


Arteriography, peripheral:
Via catheter, 25 to 65 mL into the femoral artery, or advanced to the level of the renal artery if necessary. Two or more injections may be needed.



Digital arteriography of the head and neck:
Intravenous, 30 to 60 mL. Three injections may be needed, up to a total volume of 120 mL.



Usual adult prescribing limits
Intrathecal—Up to the equivalent of 3 grams of iodine.

Intravascular—Up to the equivalent of 87.5 grams of iodine {01} {03}.

Usual pediatric dose
Intrathecal


Myelography:


Lumbar and—



Thoracic myelography by lumbar injection—
The following amounts of a solution containing the equivalent of 170 to 190 mg of iodine per mL:

Children up to 2 months of age—2 to 3 mL.

Children 2 months to 2 years of age—2 to 4 mL.

Children 3 to 7 years of age—4 to 8 mL.

Children 8 to 12 years of age—7 to 9 mL.

Children 13 to 18 years of age—8 to 10 mL.



Cervical myelography by lumbar injection—
Children up to 2 months of age—2 to 3 mL of a solution containing the equivalent of 170 to 210 mg of iodine per mL.

Children 2 months to 2 years of age—2 to 4 mL of a solution containing the equivalent of 170 to 200 mg of iodine per mL.

Children 3 to 7 years of age—4 to 8 mL of a solution containing the equivalent of 170 to 210 mg of iodine per mL.

Children 8 to 12 years of age—7 to 9 mL of a solution containing the equivalent of 170 to 230 mg of iodine per mL.

Children 13 to 18 years of age—8 to 10 mL of a solution containing the equivalent of 170 to 230 mg of iodine per mL.



Cervical myelography by lateral cervical injection—
Children up to 8 years of age—Dosage must be individualized by the physician.

Children 8 to 18 years of age—3 to 5 mL of a solution containing the equivalent of 200 to 220 mg of iodine per mL.




Cisternography by direct injection1:
Children up to 2 months of age—2 to 3 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.

Children 2 months to 8 years of age—Dosage must be individualized by the physician.

Children 8 to 18 years of age—2 to 5 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.



Cisternography by lumbar injection:
Children 2 months to 2 years of age—2 to 3 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.

Children 3 to 7 years of age—3 to 5 mL of a solution containing the equivalent of 170 to 190 mg of iodine per mL.

Children 8 to 12 years of age—5 to 6 mL of a solution containing the equivalent of 170 to 190 mg of iodine per mL.



CT cisternography by lumbar injection:
Children up to 3 years of age—Dosage must be individualized by physician.

Children 3 to 18 years of age—3 to 5 mL of a solution containing the equivalent of 170 to 190 mg of iodine per mL.



Ventriculography by direct injection:
Children up to 2 years of age—2 to 3 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.

Children 3 to 12 years of age—2 to 4 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.

Children 13 to 18 years of age—2 to 5 mL of a solution containing the equivalent of 190 to 220 mg of iodine per mL.



Ventriculography by lumbar injection:
Children up to 2 years of age—2 to 3 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.



CT ventriculography by direct injection of a solution containing the equivalent of 170 to 220 mg of iodine per mL:
Children up to 2 years of age—2 mL.

Children 3 to 7 years of age—3 mL.



CT ventriculography by lumbar injection:
Children 3 to 7 years of age—3 mL of a solution containing the equivalent of 170 to 220 mg of iodine per mL.


Intravascular
Angiocardiography: 1.5 mL of a solution containing the equivalent of 370 mg of iodine per mL per kg of body weight.


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients with renal function impairment may be more sensitive to the effects of the usual adult dose; lower dosages are recommended.


Strength(s) usually available
U.S.—


3.75 grams of metrizamide with 1.81 grams of iodine, per 20-mL vial (Rx) [Amipaque (1.2 mg edetate calcium disodium)]{61}


6.75 grams of metrizamide with 3.26 grams of iodine, per 50-mL vial (Rx) [Amipaque (2.16 mg edetate calcium disodium)]{61}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a light-resistant container, unless otherwise specified by manufacturer. {61}

Preparation of dosage form:
Metrizamide for injection is reconstituted to the specific iodine concentration by adding the appropriate volume of diluent (0.005% sodium bicarbonate injection) provided by the manufacturer. See maufacturer's package insert for preparation of solutions. {61}

Stability:
After reconstitution, solution must be used immediately. The diluent provided by the manufacturer contains no preservative.

Any unused portion remaining in the container should be discarded.

1 Not included in Canadian product labeling.


Revised: 08/16/1995



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

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