Ioxaglate (Local)


VA CLASSIFICATION
Primary: DX102

Commonly used brand name(s): Hexabrix; Hexabrix-320.

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



Category:


Diagnostic aid, radiopaque (uterus and fallopian tube disorders)—
Note: Ioxaglate is an ionic radiopaque contrast agent.



Indications

Accepted

Hysterosalpingography—Ioxaglate meglumine and ioxaglate sodium injection is indicated for hysterosalpingography, by which the patency of the fallopian tubes may be determined and uterine and tubal cavities may be visualized for the evaluation of abnormal conditions, such as tumors, of the uterus and fallopian tubes. Hysterosalpingography is used as a diagnostic tool in cases of infertility and other abnormal gynecological conditions; it serves as an adjunct to laparoscopy and ultrasound imaging in discovering subtle abnormalities, such as endometrial polyps and salpingitis isthmica nodosa. {01} {04} {20} {21} {22} {23} {24} {25} {26} {27} {31} {32}
—Hysterosalpingography is not recommended during the menstrual period or when menstrual flow is imminent, when infection is present in any portion of the genital tract, during pregnancy or for 6 months after termination of pregnancy, or for 30 days after conization or curettage. {01} {31}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
{30}    Ioxaglate meglumine: 1464.10
    Ioxaglate sodium: 1290.87


Osmolality
    Low (approximately 600 mOsmol per kg of water for a solution containing 320 mg of iodine per mL) {01}

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 {28}. 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. Instillation of ioxaglate meglumine and ioxaglate sodium solution into the uterus and fallopian tubes allows visualization of these areas. {13}

Absorption:

Intrauterine instillation—Most of the medium within the uterine cavity is discharged into the vagina immediately upon termination of procedure. However, any medium retained in the uterine cavity is absorbed systemically. {14} {15} {16}

Protein binding:

Very low. {01}

Elimination:
    Absorbed medium—Primarily renal. {01}
    Unabsorbed medium—Expelled vaginally, following the procedure. {16}


Precautions to Consider

Cross-sensitivity and/or related problems

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

Pregnancy/Reproduction

Pregnancy—
Ioxaglate meglumine and ioxaglate sodium injection for intrauterine instillation is not recommended during pregnancy since ioxaglate may cross the placenta, or for at least 6 months after the termination of pregnancy since the procedure may increase the risk of complications such as intrauterine infection. {01} {16}

Also, other organically bound iodine–containing preparations administered near term by intra-amniotic injection have caused hypothyroidism in some newborns. In addition, elective contrast radiography of the abdomen is usually not recommended during pregnancy because of the risks to the fetus from radiation exposure. {01} {02}

Breast-feeding

Problems in humans have not been documented. However, since small amounts of this medium may be absorbed and ioxaglate is known to be distributed unchanged into breast milk when administered intravascularly, breast-feeding is not recommended for at least 24 hours following its administration. {01} {16}

Pediatrics

No information is available on the use of ioxaglate for hysterosalpingography in pediatric patients. {32}


Geriatrics


Appropriate studies on the relationship of age to the effects of ioxaglate for intrauterine instillation have not been performed in geriatric patients. However, no geriatrics-specific problems have been documented to date.

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
Thyroid function determinations and
Thyroid imaging    (absorbed ioxaglate may cause an increase of serum protein–bound iodine [PBI] and a decrease in radioactive iodine or pertechnetate ion uptake for a period varying from 1 week to several months; thyroid test should be performed prior to administration of contrast medium. Other thyroid function tests not based on measurement of iodine, such as resin triiodothyronine uptake, are not affected {01} {32})


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).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Genital tract infection    (procedure may increase risk of complications {01} {32})


Risk-benefit should be considered when the following medical problems exist
Allergic reaction (anaphylaxis) to penicillins or to skin allergens, previous    (increased risk of anaphylactoid reaction {29})


Allergies or asthma, history of    (increased risk of idiosyncratic response or anaphylactoid reaction {01} {06})


» Pelvic inflammatory disease, acute    (condition may be aggravated {01})


» Sensitivity to iodinated contrast media    (increased risk of anaphylactoid reaction in patients with a history of anaphylactoid reaction to iodinated contrast media {01} {06} {29})


Caution is also recommended just after cervical or uterine surgery to avoid the risk of complications.{01}


Side/Adverse Effects

Note: Systemic adverse effects, although rare, are possible with intrauterine instillation if medium is absorbed systemically after being retained in the uterine cavity or spilled into the peritoneal cavity. {01}

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 rare
    
Pseudo-allergic reaction (increased sweating; skin rash or hives; sneezing; stuffy nose; swelling of face or skin; swelling of the larynx; thickening of the tongue; wheezing, tightness in chest, or troubled breathing)—may be due to entry of medium into venous or lymphatic system{01}{17}{18}{19}
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. {29}





Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal or stomach pain and discomfort{01}{16}
Note: Abdominal pain and discomfort may be associated with the insertion and positioning of the instillation device. If occurring later during the procedure, may indicate spillage of contrast medium into the peritoneal cavity.



Incidence less frequent
    
Fever{01}





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

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

Description of use
Instillation into uterus and fallopian tubes; visualization of radiopacity possible with x-rays

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

Pregnancy—Risk to the fetus from radiation exposure; intrauterine instillation contraindicated during pregnancy and for at least 6 months after delivery





Breast-feeding—May be distributed into breast milk; breast-feeding not recommended for 24 hours after use
Other medical problems, especially acute pelvic inflammatory disease or genital tract infection

Preparation for this test
Enema, vaginal douche, and/or other special preparatory instructions may be given; patient should inquire in advance

Voiding before procedure

Precautions after having this test
Possible interference with future thyroid tests


Side/adverse effects
Signs of possible side effects, especially pseudo-allergic reaction


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. {05} {17} {18}

Pretreatment with corticosteroids and/or antihistamines is recommended 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 penicillin). 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 considering the use of a contrast agent, the following protocols are recommended: {05} {06} {07} {08} {09} {10} {11} {12} 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 antihistamine (intramuscular, intravenous, or oral diphenhydramine, 50 mg administered 1 hour before 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.


An enema and vaginal douche before the examination are optional. Patient should empty her bladder before the procedure. {01}

Ioxaglate meglumine and ioxaglate sodium injection for intrauterine instillation is to be instilled directly into the uterus via a sterile syringe attached to a uterine cannula, or via a tubal insufflator with a salpingogram attachment. It is recommended that instillation into the uterine cavity be performed under controlled pressure with fluoroscopic monitoring. Excessive pressure and overfilling should be avoided. {16}

During and for at least 30 to 60 minutes after administration of contrast media, the patient should be observed for possible severe reactions; competent personnel and emergency facilities should be available during this period. {01}

Any unabsorbed contrast medium is expelled spontaneously upon removal of the cannula.


Local Dosage Forms

IOXAGLATE MEGLUMINE AND IOXAGLATE SODIUM INJECTION

Usual adult and adolescent dose
Hysterosalpingography
Intrauterine instillation, 5 to 15 mL of a solution containing the equivalent of 320 mg of iodine per mL administered slowly in fractional doses of 1 to 2 mL and without undue pressure. {01} {31} {32}


Usual pediatric dose
Dosage has not been established.

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


39.3% (393 mg per mL) of ioxaglate meglumine and 19.6% (196 mg per mL) of ioxaglate sodium with 32% (320 mg per mL) of iodine (Rx) [Hexabrix (0.10 mg of edetate calcium disodium) (3.48 mg or 0.15 mEq of sodium, per mL)]

Canada—


39.3% (393 mg per mL) of ioxaglate meglumine and 19.6% (196 mg per mL) of ioxaglate sodium with 32% (320 mg per mL) of iodine (Rx) [Hexabrix-320 (0.10 mg of edetate calcium disodium) (3.48 mg or 0.15 mEq of sodium, per mL)]

Packaging and storage:
Store below 30 °C (86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing. {32}

Stability:
Ioxaglate meglumine and ioxaglate sodium injection is a clear, colorless to pale yellow solution. Do not use if turbid or discolored. {32}

Crystals may form in the solution at very cold temperatures but are readily redissolved by bringing the container of solution to room temperature and gently shaking it. {32}

Any unused portion remaining in the container should be discarded.



Revised: 06/01/1995



References
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  1. Omnipaque package insert (Winthrop—US), Rev 04/90.
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  1. USP Advisory Nonradioactive Diagnostic Agents Panel meeting, 4/9/91.
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  1. Reviewers' comments per 8/90 revision of Diatrizoates (Mucosal).
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  1. Reviewers' comments per 8/88 revision of Diatrizoate and Iodipamide (Mucosal).
  1. Reviewers' comments per 7/88 revision of Ioxaglate (Mucosal).
  1. Elias JA. Systemic reaction to radiocontrast media during hysterosalpingography. J Allergy Clin Immunol 1980; 66: 242.
  1. Schuitmaker NW, Helmerhorst FM, Tham RT, et al. Late anaphylactic shock after hysterosalpingography. Fertil Steril 1990; 54(3): 535-6.
  1. Greenberger PA. Contrast media reactions. J Allergy Clin Immunol 1984; 74: 600-5.
  1. Sanfilippo JS, Yussman MA, Smith O. Hysterosalpingography in the evaluation of infertility: a six-year review. Fertil Steril 1978; 30: 636.
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  1. Bonilla-Musoles F, Simon C, Serra V, et al. An assessment of hysterosalpingosonography (HSSG) as a diagnostic tool for uterine cavity defects and tubal patency. J Clin Ultrasound 1992 Mar-Apr; 20(3): 175-81.
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  1. Sauer MV. Investigation of the female pelvis. J Reprod Med 1993 Apr; 38(4): 269-76.
  1. Allahbadia GN. Fallopian tubes and ultrasonography: the Sion experience. Fertil Steril 1992 Nov; 58(5): 901-7.
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  1. Hexabrix package insert (Mallinckrodt—US), Rev 6/94, Rec 2/95.
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