An iodine-containing low osmolality contrast agent called Hexabrix is utilized for medical diagnosis. Both ioxaglate sodium and ioxaglate meglumine are present.

Uses for Hexabrix (ioxaglate sodium and ioxaglate meglumine)

• Imaging:

  • Aortography and selective visceral arteriography
  • Peripheral venography (phlebography)
  • Pediatric angiocardiographyContrast enhancement of computed tomographic head and body imaging
  • Peripheral arteriography
  • Hysterosalpingography
  • Intra-arterial digital subtraction angiography
  • Selective coronary arteriography (with or without left ventriculography)
  • Excretory urography
  • Arthrography
  • Intravenous digital subtraction angiography

Hexabrix dose in adults:

Hexabrix selective coronary arteriography (either with or without the left-sided ventriculography): Intra-arterial:

• Left coronary arteriography:

  • May repeat as needed to a total dose of 150 mL
  • Usual dose: 8 mL (range 2 to 14 mL)

• Left ventriculography:

  • Repeat as required up to a maximum dose of 250 mL (for left ventriculography and selective coronary arteriography)
  • Usual dose (single injection): 45 mL (range: 35 to 45 mL)

• Right coronary arteriography:

  • Can repeat as required to a total dose of 150 mL
  • Standard dose: 5 mL (range: 1 to 10 mL)

Hexabrix (Ioxaglate) Dose in the Peripheral arteriography:

• Intra-arterial: Total therapeutic dose should not exceed 250 mL

  • Common iliac, external iliac, femoral arteries (single dose):

    • 30 mL (10–50 mL range); repeat as necessary

  • Upper limb (single dose):

    • 20 mL (15–30 mL range); repeat as necessary

  • Aorto-iliac runoff studies (single dose):

    • 45 mL (range: 20 to 80 mL); may repeat as necessary

Hexabrix Dose in the Aortography and selective visceral arteriography: Intra-arterial:

The entire dose should not cross 250 mL

• Aorta:

  • 25 to 50 mL; may repeat as necessary

• Celiac artery:

  • 40 mL; may repeat as necessary

• Inferior mesenteric artery:

  • 8 to 15 mL; may repeat as necessary

• Superior mesenteric artery:

  • 20 to 40 mL; may repeat as necessary

Hexabrix Dose in the Cerebral angiography:  Intra-arterial:

The entire dose per therapy should not cross 150 mL

• Common carotid artery:

  • 9 mL (range: 6 to 12 mL)

• Vertebral arteries:

  • 8 mL (range: 5 to 12 mL)

Injections of Hexabrix dose in the aortic arch (4 vessel investigations) along with cerebral angiography:

• Standard dose: 40 mL (range: 30 to 50 mL)

Hexabrix dose in Intra-arterial digital subtraction angiography

• The volume and concentration are typically 50% or less of what is used for standard procedures
• Use sterilized water and a 1:1 dilution for injections.
• Depending on the area being studied and the site's selectivity for injection, different doses and flow rates are used

  Intra-arterial:

  • Carotid arteries:

    • 6 to 10 mL; may repeat as necessary

  • Vertebral arteries:

    • 4 to 8 mL; may repeat as necessary

  • Aorta:

    • 25 to 50 mL; may repeat as necessary

  • Brachial or subclavian arteries:

    • 2 to 10 mL; repeat if need

  • Major branches of the abdominal aorta:

    • 2 to 20 mL; may repeat as necessary

  Hexabrix Dose in the Intravenous digital subtraction angiography:

  • IV: Usual dose 30 to 50 mL (depending on the area being imaged)
  • The total procedural dose should not exceed 250 mL
  • May repeat as necessary

  Hexabrix Dose in the Peripheral venography (phlebography):

  • IV: Usual dose: 50 to 100 mL (undiluted) as a single rapid injection;
  • The dose varies based on patient size and condition, and the technique used.
  • May also use reduced concentrations (reduced to a 20% concentration);
  • The usual dose of diluted contrast media ranges from 75 to 150 mL per extremity.

  Hexabrix (Ioxaglate) Dose in the Excretory urography:

  • IV: Usual dose: (from 0.7 up to 1 mL per kg) 50 to 75 mL
  • higher doses of (from 1.5 up to 2 mL per kg) 100 to 150 mL may be indicated if poor visualization is anticipated.

  In contrast-enhanced computed tomographic head imaging, hexabrix dose: IV:

  • Adults >68.2 kg (150 lbs):

    • Standard dose: 135 mL; shouldn't cross 150 mL

  • Adults ≤68.2 kg (150 lbs):

    • Usual dose: 2 mL/kg (0.9 mL/lb)

  Hexabrix dose in computed tomographic body imaging (dose varies depending on the area being examined):

  •  
  • For prolonged enhancement, may require 25 to 50 mL as a quick bolus observed by an infusion of 100 to 125 mL (total dose not to exceed 150 mL)
  • IV: 30 to 150 mL (0.9 to 2 mL/kg [0.4 to 0.9 mL/lb])

  Hexabrix Dose in the Arthrography (amount of contrast depends on the extent of the joint and method used): Intraarticular:

  Note: Lower volumes are generally used for double-contrast examinations.

  • Shoulder, ankle:

    • 5 to 20 mL

  • Temporomandibular:

    • 0.5 to 0.7 mL

  • Knee, hip:

    • 5 to 15 mL

  Hexabrix Dose in the Hysterosalpingography (amount of contrast depends on anatomic variations and/or disease process):

  • Intrauterine: Usual dose: 5 to 15 mL

  Hexabrix dose in children:

  Hexabrix dose in Pediatric angiocardiography:

  • Infants and Young Children:

    • May use small test volumes of ~2 mL to test catheter placement
    • 5 mL/kg (range: 1 to 2 mL/kg)
  •  

  • Injection through a catheter into the heart or other major vessels: 

    • The typical treatment-specific full dose, Which also includes test and diagnostic doses, is 4 mL/kg (range: 1.5 to 5 mL/kg).

  • Older Children:

    • 30 to 45 mL

  Hexabrix dose in Excretory urography: IV:

  • The total dose should not exceed 5 mL/kg

  • Infants over 6 months and Children:

    • 2 mL/kg

   

• Infants under 6 months:

  • 3 mL/kg

• Hexabrix Pregnancy Risk Category: B

  • Contrast media agents containing iodinated contrast may cross the placenta.
  • The theory that free iodide could adversely affect the fetus is a reason to avoid its use.
  • Hysterosalpingography is contraindicated in pregnant patients.

  Use of ioxaglate meglumine or ioxaglate salt during breastfeeding

  • Breast milk contains Ioxaglate Salts.
  • As a result of the low anticipated excretion and low absorption rates from infants' GI tracts, breastfeeding may continue after the administration of an iodinated contrast agent is no longer necessary.
  • Theoretically speaking, milk's taste could be affected if it contains contrast media.
  • Women who choose to temporarily stop breastfeeding can express breast milk or discard it from one breast for 12-24 hours after administration of contrast media.
  • They can store and pump milk before the procedure, then bottle-feed the milk stored during the time (ACR 2018,
  • To prevent any negative effects, bottle feedings should continue for at least 24 hours after administration.

   

  Hexabrix Dose in Kidney Disease:

  • There are no dosage adjustments provided in the drug manufacturer's labeling.
  • Use caution in advanced impairment and in the setting of combined renal and hepatic disease.

   

  Hexabrix Dose in Liver disease:

  • There are no dosage adjustments provided in the drug manufacturer's labeling.
  • Patients who have both hepatic and renal illnesses should be handled carefully.

•  

  Side effects of Hexabrix:

  • Cardiovascular:

    • Altered Blood Pressure (Transient [Cerebral Angiography])
    • Angina Pectoris (Selective Coronary Arteriography)
    • Cardiac Arrest
    • Cardiac Arrhythmia
    • Cardiac Decompensation
    • Cardiac Fibrillation
    • Cerebrovascular Accident (Cerebral Angiography)
    • Coronary Insufficiency
    • Facial Edema
    • Facial Flushing
    • Flushing
    • Hypotension
    • Hypotensive Shock
    • Ischemic Heart Disease
    • Myocardial Infarction
    • Peripheral Edema
    • Shock (Selective Coronary Arteriography)
    • Syncope
    • Thrombophlebitis
    • Thrombosis
    • Vasodilation
    • Venospasm

  • Central Nervous System:

    • Amnesia (Cerebral Angiography)
    • Aphasia
    • Brachial Plexus Injury (Peripheral Arteriography)
    • Burning Sensation (Cerebral Angiography)
    • Chills
    • Coma
    • Confusion (Cerebral Angiography)
    • Convulsions
    • Disorientation (With Hallucination [Cerebral Angiography])
    • Dizziness
    • Flushing Sensation
    • Headache
    • Hyperthermia
    • Neurologic Abnormality (Reversible [Cerebral Angiography])
    • Paralysis (Resulting From Spinal Cord Injury)
    • Paresis
    • Transverse Myelitis
    • Visual Hallucination (Transient [Cerebral Angiography])

  • Dermatologic:

    • Pruritus
    • Skin Discoloration
    • Skin Rash
    • Toxic Epidermal Necrolysis
    • Urticaria
    • Acute Generalized Exanthematous Pustulosis
    • Erythema
    • Maculopapular Rash
    • Stevens-Johnson Syndrome

  • Endocrine & Metabolic:

    • Altered Thyroid Hormone Levels (Transient Suppression; Premature Infants And Infants With Underlying Medical Conditions May Be More Vulnerable)
    • Hypothyroidism

  • Gastrointestinal:

    • Nausea
    • Vomiting
    • Abdominal Cramps (Hysterosalpingography)
    • Abdominal Pain (Hysterosalpingography)
    • Abdominal Tenderness (Hysterosalpingography)

  • Hypersensitivity:

    • Anaphylactoid Reaction
    • Angioedema
    • Hypersensitivity Reaction
    • Choking Sensation
    • Diaphoresis
    • Xerostomia

  • Hematologic & Oncologic:

    • Disseminated Intravascular Coagulation

  • Immunologic:

    • DRESS Syndrome

  • Local:

    • Warm Sensation At Injection Site
    • Arterial Thrombosis At Injection Site (Peripheral Arteriography)
    • Pain At Injection Site
    • Bleeding At Injection Site (Peripheral Arteriography)

  • Neuromuscular & Skeletal:

    • Laryngospasm
    • Muscle Spasm
    • Arthralgia (Arthrography)
    • Tremor

  • Ophthalmic:

    • Conjunctival Abnormalities
    • Vision Loss (Sometimes Lasting 1 Week [Cerebral Angiography])
    • Visual Field Defect (Cerebral Angiography)
    • Visual Field Loss

  • Renal:

    • Renal Disease
    • Renal Failure (Temporary)

  • Respiratory:

    • Apnea
    • Asthma
    • Bronchospasm
    • Cough
    • Cyanosis
    • Dyspnea
    • Nasal Congestion
    • Pulmonary Edema
    • Sneezing
    • Wheezing

  • Miscellaneous:

    • Fever (Hysterosalpingography)

   

  Contraindications to Hexabrix (Ioxaglate meglumine and ioxaglate sodium):

  • Hypersensitivity/Allergy to ioxaglate or any component of the formulation
  • Pregnant women
  • Where cervical conization or curettage was performed in less than 30 days
  • Hysterosalpingography should not be performed during the menstrual period
  • Patients with a genital tract infection are at greater risk.
  • An infection near or in the joint should be avoided during arthrography.
  • Use in myelography

  Warnings and precautions

  • Contrast media reactions

    • There have been significant adverse reactions, including delayed reactions, that have the potential to be fatal.
    • Even while the majority of cases are minor, serious and sometimes fatal reactions can happen at any time. These reactions frequently resemble allergic reactions.
    • Before administering, obtain allergy and hypersensitivity information.
    • An allergic reaction is more likely to occur in patients with bronchial asthma, allergies (including food allergies), or a family history of allergies.
    • It is possible to not accurately predict the possibility of allergic reactions by pretesting.
    • Inpatients at high risk of allergic reactions should consider taking antihistamines and corticosteroids to lower the severity and incidence.
    • Prior to employing contrast media, begin taking corticosteroids as soon as you can. 24 hours after administration, keep going.
    • Within 30 minutes of administering the contrast agent, antihistamines should be given.
    • If you experience a severe reaction, monitor closely for between 30 and 60 minutes.
    • Patients who received general anesthesia had a higher rate of adverse reactions.

  • Dermatological effects

    • From 1 hour after administration, severe cutaneous adverse reactions have been reported (including Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], acute exanthematous pustulosis [AGEP], drug response with eosinophilia or systemic symptoms [DRESS]).
    • Repeat administration may result in greater severity of the reaction and a shorter time for onset.
    • Iothalamate-related severe cutaneous reactions in the past should not be administered to patients.

  • Endotoxemia:

    • Endotoxemia patients should exercise caution when comparing media.

  • Extravasation:

    • It is a vesicant. Before and during administration, ensure that the needle/catheter/line is properly placed.
    • Monitor infusion site.
    • Avoid infiltration
    • Hypertonic is ioxaglate meglumine, ioxaglate salt.
    • Extravasation has been associated with burning pain, hematomas, bruising as well as tissue necrosis.

  • Hyperthermia

    • Patients with high body temperatures should exercise caution when comparing media.

  • Hyperthyroidism:

    • Patients with hyperthyroidism, or with a functioning thyroid nodule, have experienced a thyroid storm after intravascular administrations of iodinated contrast medium.
    • Iodine-containing contrast agents have the potential to change the outcomes of thyroid function tests that rely on iodine estimation. They may also affect radioiodine absorption studies. These studies should be performed prior to any diagnostic tests using iodinated contrast media.

  • Hypothyroidism:

    • Thyroid function tests that indicate hypothyroidism, or transient thyroid suppression (uncommon) have been reported in both pediatric and adult patients (including infants); some were treated for hypothyroidism.

  • Neurotoxicity:

    • Serious neurologic consequences, including permanent paralysis, may follow cerebral arteriography, selective spinal arteriography, and arteriography vessels supplying the spinal cord.
    • Contrast media should not be injected after vasopressors have been administered.
    • Neurologic effects may be potentiated

  • Failure of the renal system:

    • Patients with liver damage who underwent intravascular radiocontrast imaging after receiving an oral cholecystographic drug and diabetics with problems from diabetes (eg, patients with preexisting kidney disease, patients with diabetes, and those with occult kidney disease, particularly patients with hypertension and diabetes) have experienced acute renal failure (ARF).
    • These patients should avoid fluid restrictions and keep their hydration normal.
    • In newborns, children, and elderly patients, as well as those who already have renal impairment, multiple myeloma, severe vascular disease, and diabetes, preparatory dehydration can result in acute renal failure.

  • Events that are thromboembolic:

    • There are serious but rarely fatal thromboembolic events that can result in stroke and MI, according to angiographic methods utilizing both non-ionic and ionic contrast media.
    • Contrast media containing ionic iodinated contrast media can inhibit blood coagulation more than nonionic media.
    • When performing angiographic procedures, ensure that you use meticulous intravascular administration techniques.
    • Clotting can occur when in vitro blood is in contact with nonionic contrast media syringes. According to some reports, the danger of in vitro bleeding is reduced but not entirely eliminated by using plastic syringes.

  • Cardiovascular disease

    • Patients with advanced vascular disease may be at risk of developing acute renal failure from pre-hydration. Fluid restriction should be avoided to maintain normal hydration.

  • Diabetes:

    • Preparatory dehydration can lead to acute renal failure in diabetics. Avoid fluid restriction and maintain normal water intake in these patients.

  • Hepatic impairment

    • Patients with combined renal impairment and hepatic impairment should be cautious; excretion could be impaired.

  • Homocystinuria

    • Patients with homocystinuria should avoid angiography; they may be at high risk of embolism and thrombosis.

  • Multiple myeloma

    • Patients with multiple myeloma should be cautious when using intravascular contrast agents. They can cause irreversible anuria, renal impairment and even death.
    • The cause of myeloma may be dehydration. Partial dehydration during preparation for procedures can precipitate myeloma proteins in the renal tubules. This is why it is not recommended for myeloma patients.

  • Pheochromocytoma:

    • Patients with pheochromocytoma (known, suspected) should be used with caution.
    • Reduce intravascular administration of contrast agent and monitor blood pressure during the procedure.
    • It is important to have access to therapy for hypertensive crises.

  • Renal impairment

    • Patients with advanced renal disease should be cautious.
    • Excretion can be affected; only use if absolutely necessary.
    • Impaired excretion is more likely to occur in patients with recent kidney transplants, combined renal and liver disease, severe hypertension, or heart failure.
    • Patients with preexisting renal impairment may be at risk of developing acute renal failure by undergoing preparative dehydration.

  • Sickle cell disease:

    • Take care when treating homozygous sickle cell patients.
    • Contrast media administration can cause disease exacerbation.
    • Fluid restriction is not advised.

  • Subarachnoid hemorrhage:

    • Contrast administration can cause a deterioration of clinical status in patients suffering from subarachnoid hemorrhage (including seizures and fatalities).
    • Use extreme caution.

  Ioxaglate meglumine and ioxaglate sodium: Drug Interaction

  Risk Factor C (Monitor therapy)
  Aldesleukin	Iodinated contrast agents may be more likely to cause allergic or hypersensitive reactions.
  Risk Factor D (Consider therapy modification)
  MetFORMIN	Iodinated contrast agents may intensify MetFORMIN's unfavorable/toxic effects. Lactic acidosis associated with metformin may result from a renal impairment that may be brought on by iodinated contrast agents. Management: The guidance on management differs. For more information, consult the medication interaction monograph in its entirety.

   

  Monitoring parameters:

  • Renal function,
  • blood pressure,
  • hydration;
  • monitor for extravasation during IV administration;
  • monitor for hypersensitivity reactions for ≥30 to 60 minutes.

  Pediatric angiocardiography:

  • Monitor ECG and vital signs throughout the procedure

  Peripheral arteriography/intra-arterial (brachial) injections:

  • Monitor blood pressure for ~10 minutes after injection
  • During the administration of large doses, continuously monitor vital signs

   

  How to administer Hexabrix (Ioxaglate meglumine and ioxaglate sodium)?

  • When injected, contrast material ought to be at or nearly at body temperature.
    The meal eaten before the exam should not be consumed by the patients.
    Before the examination, proper premedication (that may include a barbiturate, sedative, or analgesic) may be given.

  Peripheral arteriography:

  • Peripheral arteriography is usually performed with local anesthesia;
  • It rarely requires general anesthesia.
  • Fluoroscopy is recommended to avoid extravasation.

  Cerebral angiography:

  • A local or general anesthetic is typically used during cerebral angiography.

  Intra-arterial digital subtraction angiography:

  • Before the surgery, patients need to drink plenty of water.
  • Inject at a flow rate that is almost equivalent to the vessel's flow rate.

  Intravenous digital subtraction angiography:

  • Before the surgery, patients need to drink plenty of water.
  • Inject either centrally into the right atrium, the superior or inferior vena cava, or a peripheral arm vein.
  • To lessen the chance of extravasation, utilize a catheter length of no more than 20 cm for peripheral injections.
  • Based on where the catheter site is placed, the injection rate will change.
  • Peripheral injections often occur at a rate of 12 to 20 mL/second, while central catheter injections typically occur at a rate of 10 to 30 mL/second.
  • If using an arm vein, flush the area immediately after administering the contrast agent with 20 to 25 mL D W or NS.

  Head imaging using computed tomography with contrast enhancement

  • Patients should be well hydrated prior to the procedure.

  Body imaging using computed tomography with contrast enhancement:

  • The patient should be well hydrated.

  Peripheral venography (phlebography):

  • Upper- or lower-extremity vein injection or infusion
  • Following the procedure, flush with D W or NS
  • may also massage and elevate the extremity.
  • Fluoroscopy is recommended to avoid extravasation.

  Excretory urography:

  • A low residue diet the day before the exam and a laxative the night before the exam are both acceptable unless they are contraindicated.
  • Do not fluid restrict for infants and small children.
  • Injection of the entire dose takes between 30 and 90 seconds.

  Arthrography:

  • Concomitant epinephrine is not needed due to the low osmolality (rate of contrast media absorption is reduced).
  • Typically, a local anesthetic is required. The medium is spread throughout the joint using passive or active manipulation.

  Hysterosalpingography:

  • Perform exam 8 to 10 days after onset of menses.
  • Before the examination, the patient should empty their bladder. Under fluoroscopic control, administer slowly; do not apply excessive pressure.
  • To prevent extravasation, it is important to establish correct needle or catheter insertion both before and during the infusion.

  Extravasation management:

  • In case extravasation occurs, immediately stop infusion and disconnect; remove needle/cannula; elevate extremity.
  • The aspiration of extravasated contrast media is not suggested. Information conflicts regarding the use of hyaluronidase;
  • The American College of Radiology (ACR) Manual on Contrast Media does not recommend hyaluronidase in the management of contrast media extravasation (ACR 2018);
  • other sources suggest its use in extravasation management.

  If using hyaluronidase: Intradermal or SubQ:

  • Administer a total of 1 to 1.7 mL (15 units/mL) as 5 separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into the extravasation area at the leading edge in a clockwise manner or administration of a total of 5 mL (150 units/mL) as 5 separate 1 mL injections around the extravasation site has been also used successfully.

   

  Mechanism of action of Hexabrix (Ioxaglate meglumine and ioxaglate sodium):

  • Radiolucent contrast material. It obscures the vessels in the contrast medium's flow route. This makes it possible to see internal body structures on radiographs.

  Distribution:

  • Rapid (following intravascular administration)

  Half-life elimination: u92 minutes Time to peak:

  • IV: 2 minutes

  Excretion:

  • Urine (primarily and as an unchanged drug);
  • feces (minor)

   

  Ioxaglate meglumine and ioxaglate sodium brands sold internationally:

  • Hexabrix

   

  Ioxaglate meglumine and ioxaglate sodium Brand Names in Pakistan:

  No Brands Available in Pakistan.