Iohexol (Local)


VA CLASSIFICATION
Primary: DX101

Commonly used brand name(s): Omnipaque 140; Omnipaque 180; Omnipaque 210; Omnipaque 240; Omnipaque 300; Omnipaque 350.

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



Category:


Diagnostic aid, radiopaque (urinary tract disorders; uterus and fallopian tube disorders)—
Note: Iohexol is a non-ionic radiopaque contrast agent.



Indications

Accepted

Cystourethrography, retrograde1—Iohexol is indicated in retrograde cystourethrography to evaluate abnormalities of the urethra, bladder, and ureters; and to demonstrate the presence and extent of cystoureteric reflux. {01} {35}

Hysterosalpingography1—Iohexol is indicated for intrauterine instillation to determine the patency of the fallopian tubes and to visualize the uterine and tubal cavities for 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} {26} {27} {28} {29} {30} {31} {32} {35}
—Hysterosalpingography is not recommended during the menstrual period or when menstrual flow is imminent, during pregnancy, for at least 6 months after termination of pregnancy, or for 30 days after conization or curettage. {01} {35}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    821.14


Osmolality
    Low. The osmolality of iohexol injection with iodine concentrations of 140, 180, 210, 240, 300, and 350 mg per mL is 322, 408, 460, 520, 672, and 844 mOsmol per kg of water, respectively {35}

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 {33}. The degree of opacity of these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. The instillation of iohexol into the urinary bladder, kidneys, ureters, uterus, and fallopian tubes allows visualization of these areas. {17} {18} {24}

Absorption:

Intravesical instillation—Small amounts absorbed through the bladder. {17} {20}

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 or peritoneal cavity is absorbed systemically within 60 minutes. May not be absorbed for up to 24 hours if tubes are obstructed and dilated. {21} {22} {35}

Protein binding:

Very low. {01} {23}

Elimination:
    Absorbed iohexol—Eliminated unchanged through the kidneys by glomerular filtration. {01} {35}
    Unabsorbed iohexol—Expelled by spontaneous voiding or vaginally, depending on procedure. {01} {35}


Precautions to Consider

Cross-sensitivity and/or related problems

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

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of iohexol have not been performed. {01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. However, other organically bound iodine–containing preparations administered near term, by intra-amniotic injection, have caused hypothyroidism in some newborns. {01} {04} Also, elective contrast radiography of the abdomen is usually not recommended during pregnancy because of the risks to the fetus from radiation exposure. {01}

Reproduction studies in rats and rabbits have not shown that iohexol, administered in doses up to 100 times the human dose, impairs fertility or causes harm to the fetus.

For intrauterine instillation: Intrauterine instillation is not recommended during pregnancy 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} {35}

FDA Pregnancy Category B. {35}

Breast-feeding

Although it is not known to what extent iohexol is distributed into milk, small amounts of this medium may be absorbed. Therefore, breast feeding is not recommended for at least 24 hours following administration of iohexol. {01}

Pediatrics

For intravesical instillation—Appropriate studies on the relationship of age to the effects of iohexol have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.

For intrauterine instillation—No information is available on the relationship of age to the effects of iohexol for intrauterine instillation in pediatric patients.


Geriatrics


Appropriate studies on the relationship of age to the effects of iohexol for intrauterine or intravesical 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    (iohexol may cause an increase of serum protein–bound iodine [PBI] and a decrease in radioactive iodine or pertechnetate ion uptake for up to 2 weeks; 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} {35})


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:

For hysterosalpingography:
» Genital tract infection    (procedure may increase risk of complications {01} {35})


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 {34})


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


» Sensitivity to iodinated contrast media    (increased risk of anaphylactoid reaction in patients with a history of anaphylactoid reaction to iodinated contrast media {34})


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


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


Side/Adverse Effects

Note: Adverse effects associated with the mechanics of retrograde genitourinary procedures include injury to the urethra, bladder, and ureter, and introduction of infection. {01}
Systemic adverse effects, similar to those that occur with direct intravascular injection of iohexol may also occur with intravesical instillation as a result of inadvertent intravascular entry of the contrast solution due to either bladder absorption or pyelorenal backflow. {01}
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 less frequent
    
Pyelorenal distention (severe abdominal or stomach pain and discomfort, backache)—resulting from the instillation of an excess volume of contrast solution; renal colic and shock may follow{01}

Incidence rare
    
Pseudo-allergic reaction (continuing chills, continuing fever, increased sweating, skin rash or hives, sneezing, swelling of face or skin, swelling of larynx, thickening of the tongue, wheezing, tightness in chest, or troubled breathing)—may be due to entry of medium into venous or lymphatic system{05}{06}{08}{16}{24}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal or stomach pain and discomfort{01}
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. {01}



Incidence less frequent
    
Drowsiness
    
fever
    
nausea and vomiting{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 bladder; visualization of radiopacity possible with x-rays

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—Breast-feeding not recommended for 24 hours after test
Other medical problems, especially genital tract infection and acute pelvic inflammatory disease (for hysterosalpingography)

Preparation for this test
Voiding before procedure {05}

For retrograde cystourethrography
Special diet, use of laxative, and/or other preparatory instructions may apply; patient should inquire in advance

For hysterosalpingography
Enema, vaginal douche, and/or other preparatory instructions may apply; patient should inquire in advance

Precautions after having this test
Possible interference with future thyroid tests


Side/adverse effects
Signs of possible side effects, especially pyelorenal distention or 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. {07}

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: {06} {16} {24} 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 the procedure) and an antihistamine (intramuscular, intravenous, or oral diphenhydramine, 50 mg administered 1 hour before the 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.


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}

For retrograde cystourethrography
A low-residue diet the day before and a laxative the night before the procedure are generally recommended. {20}

Iohexol labeled for retrograde cystourethrography is not for intravascular injection. It is to be instilled, after the bladder is emptied, directly into the bladder or ureter and renal pelvis by gravity flow, using an appropriate venoclysis set or syringe. Excessive pressure should be avoided with either method of administration. {20}

Dosage and concentration of iohexol for intravesical instillation should be individualized and are usually in proportion to the age of the patient and the technique and equipment used. {01}

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

Iohexol solution when used for hysterosalpingography 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. {01}

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


Local Dosage Forms

IOHEXOL INJECTION USP

Usual adult and adolescent dose
Cystourethrography, retrograde 1
Intravesical instillation, 50 to 300 mL of a solution containing the equivalent of 100 mg of iodine per mL or 50 to 600 mL of a solution containing the equivalent of 50 mg of iodine per mL, depending on age and bladder capacity. {01}

Hysterosalpingography 1
Intrauterine instillation, 15 to 20 mL of a solution containing the equivalent of 240 mg or 300 mg of iodine per mL. {01}


Usual pediatric dose
Cystourethrography, retrograde 1
See Usual adult and adolescent dose .

Hysterosalpingography 1
Dosage has not been established.


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


302 mg of iohexol with 140 mg of iodine per mL (Rx) [Omnipaque 140]


388.3 mg of iohexol with 180 mg of iodine per mL (Rx) [Omnipaque 180]


453 mg of iohexol with 210 mg of iodine per mL (Rx) [Omnipaque 210]


517.7 mg of iohexol with 240 mg of iodine per mL (Rx) [Omnipaque 240]


647.1 mg of iohexol with 300 mg of iodine per mL (Rx) [Omnipaque 300]


755 mg of iohexol with 350 mg of iodine per mL (Rx) [Omnipaque 350]

Canada—


302 mg of iohexol with 140 mg of iodine per mL (Rx) [Omnipaque 140]


388.3 mg of iohexol with 180 mg of iodine per mL (Rx) [Omnipaque 180]


453 mg of iohexol with 210 mg of iodine per mL (Rx) [Omnipaque 210]


517.7 mg of iohexol with 240 mg of iodine per mL (Rx) [Omnipaque 240]


647.1 mg of iohexol with 300 mg of iodine per mL (Rx) [Omnipaque 300]


755 mg of iohexol with 350 mg of iodine per mL (Rx) [Omnipaque 350]

Note: All formulations above contain 1.21 mg of tromethamine and 0.1 mg of edetate calcium disodium.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a light-resistant container. Protect from freezing. {35}

Preparation of dosage form:
{35}

Iohexol solution
desired
(mg I/mL)
Amount (mL) of sterile
water for injection
to add per 100 mL of a:
 
  24%*
solution
30%*
solution
35%*
solution
100
140
200
250
90
167
233
289
80
200
275
338
70
243
330
400
60
300
400
483
50
380
500
600
* Iohexol solution 24% (240 mg of iodine per mL), 30% (300 mg of iodine per mL), and 35% (350 mg of iodine per mL).

Stability:
Iohexol is a clear, colorless to pale yellow solution. Do not use if turbid or discolored.

Any unused portion remaining in the container should be discarded.



Revised: 05/18/1995



References
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  1. Radiology 1987; 162: 1-8.
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  1. USP Advisory Nonradioactive Diagnostic Agents Panel meeting on 4/9/91.
  1. Yocum MW, Heller AM, Abels RI. Efficacy of intravenous pretesting and antihistamine prophylaxis in radiocontrast media sensitive patients. J Allergy Clin Immunol 1978; 62: 309-15.
  1. Fisher HW, Doust VL. An evaluation of pretesting in the problem of serious and fatal reactions to excretory urography. Radiology 1972; 103: 497-501.
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  1. Reviewers' comments per Diatrizoates (Mucosal) monograph revision of 08/90.
  1. Reviewers' comments per Iohexol (Mucosal) monograph revision of 8/90.
  1. Diatrizoates (Hypaque sodium 50%, Winthrop—US). In: PDR Physicians' desk reference. 39th ed. 1985. Oradell, NJ: Medical Economics Company, 1985: 3034.
  1. Diatrizoate and iodipamide package insert (Sinografin, Squibb—US), Rev 3/86.
  1. Reviewers' comments per Diatrizoate and Iodipamide (Mucosal) monograph revision of 08/88 .
  1. Omnipaque package insert (Winthrop—US), Rev 4/90.
  1. Reviewers' comments per revision of other radiopaque (mucosal) agents on 4/92.
  1. Omnipaque package insert (Winthrop—US), Rev 4/89.
  1. Swanson DP, Chilton HM, Thrall JH, editors. Pharmaceuticals in medical imaging. New York: Macmillan Publishing Company, 1990: 231-5.
  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.
  1. Rajah R, McHugo JM, Obhrai M. The role of hysterosalpingography in modern gynaecological practice. Br J Radiol 1992 Oct; 65(778): 849-51.
  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.
  1. Gutmann JN. Imaging in the evaluation of female infertility. J Reprod Med 1992 Jan; 37(1): 54-61.
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  1. Omnipaque package insert (Sanofi Winthrop—US), Rev 10/93.
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