Oxilan

Oxilan® Injection is not indicated for intrathecal use.

Long-term animal studies have not been performed with iOxilan to evaluate carcinogenic potential or effects on fertility. IOxilan was not genotoxic in a series of studies including the Ames test, an in vitro human lymphocytes analysis of chromosomal aberrations, an in vivo mouse micronucleus assay, and in an in vivo mouse dominant lethal assay.

PREGNANCY

Teratogenic Effects: Pregnancy Category B

Reproduction studies performed with iOxilan injection in rats at doses up to 6.5 gI/kg (3.7 times the recommended dose for a 50 kg human, or approximately 0.7 times the human dose following normalization of the data to body surface area estimates) and rabbits at doses up to 3.5 gI/kg (2 times the recommended dose for a 50 kg human, or approximately the same as the human dose following normalization of the data to body surface area estimates) did not reveal evidence of direct harm to the fetus. Embryolethality was not detected. Adequate and well-controlled studies in pregnant women have not been conducted. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

NURSING MOTHERS

It is not known whether iOxilan is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast media are administered to nursing women because of potential adverse reactions, and consideration should be given to temporarily discontinuing nursing.

PEDIATRIC USE

Safety and effectiveness in children have not been established.

For demographics, see CLINICAL TRIALS section.

The following table of incidence of reactions is based upon controlled clinical studies in which Oxilan® was compared with a nonionic contrast agent (iohexol) in 531 patients. It includes all reported adverse events, regardless of attribution.

Adverse reactions are listed by body system and in decreasing order of occurrence greater than 0.5% in the Oxilan® group.

One or more adverse reactions were reported in 76 of 531 (14.3%) of patients in the clinical trials, coincidental with the administration of Oxilan® or within the study follow-up period of 24 to 72 hours. The incidence and type of adverse reactions were similar to those associated with the nonionic comparator (iohexol) used in the clinical trials. Oxilan®, as do other iodinated contrast agents, often causes warmth and/or pain on injection. The rates are similar to that of the iohexol comparator.

Serious, life threatening and fatal reactions have been associated with the administration of iodine-containing contrast media. In all clinical trials 3/835 (0.3%) patients given Oxilan® and 3/542 (0.6%) given iohexol died 4 days or later after drug administration. In the controlled trials 8/531 (1.5%) patients given Oxilan® and 6/542 (1.1%) given iohexol had serious adverse events.

The following adverse reactions were observed ≤ 0.5% of patients receiving Oxilan® Injection:

BODY: allergic reaction, asthenia, chest and back pain, edema of the neck, facial edema, pain, peripheral edema; CARDIOVASCULAR: atrial fibrillation, syncope, tachycardia, vasodilation, ventricular extrasystole; DIGESTIVE: anorexia, constipation, dyspepsia, dysphagia, GI hemorrhage, ileus, liver failure; NERVOUS: hypotonia, nystagmus, paresthesia, somnolence, vertigo; RESPIRATORY: dyspnea, pharyngitis, rhinitis; SKIN: pruritus, sweating; SPECIAL SENSES: amblyopia, conjunctivitis, taste perversion, vision abnormality; UROGENITAL: anuria, dysuria, hematuria, infection of urinary tract, impairment of urination, kidney failure.

Additional adverse events reported in postmarketing surveillance with the use of Oxilan® Injection include: bronchospasm.

The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. Treatment of overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

Oxilan® Injection binds negligibly to plasma or serum protein and can, therefore, be dialyzed.

ADULT DOSAGE AND ADMINISTRATION - General

The combination of volume and Oxilan® concentration to be used should be carefully individualized accounting for factors such as age, body weight, size of the vessel and the rate of blood flow within the vessel. Specific dose adjustments for age, gender, weight, and renal function have not been studied for Oxilan®. As with all iodinated contrast agents, lower doses of Oxilan® Injection may have less risk. The efficacy of Oxilan® Injection below doses recommended has not been studied. Other factors such as anticipated pathology, degree and extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed should also be considered.

The maximum recommended total dose of iodine is 86 grams.

If during administration a reaction occurs, the injection should be immediately stopped.

Patients should be adequately hydrated prior to and following intravascular administration of Oxilan® Injection. (See WARNINGS and PRECAUTIONS.)

INTRAARTERIAL PROCEDURES

Oxilan® Injection (350 mgI/mL) is indicated for intraarterial injection in the radiographic contrast evaluation of coronary arteries and the left ventricle. Injection rates should be approximately equal to flow rate in the vessel being injected.

The usual individual injection volumes for visualization of the coronary arteries and the left ventricle are as follows:

Left and Right Coronary:
   2 mL to 10 mL (0.7 to 3.5 gI) of Oxilan® Injection - 350 (350 mgI/mL)

Left Ventricle:
   25 mL to 50 mL (8.75 to 17.5 gI) of Oxilan® Injection - 350 (350 mgI/mL)

Total dose for the procedure should not usually exceed 250 mL.

When large individual volumes are administered, as in ventriculography and aortography, it is recommended that sufficient time be permitted to elapse between each injection to allow for subsidence of possible hemodynamic disturbances.

Mandatory prerequisites to the procedure are specialized personnel, ECG monitoring apparatus and adequate facilities for immediate resuscitation and cardioversion. Electrocardiograms and vital signs should be routinely monitored throughout the procedure.

Oxilan® Injection (350 mgI/mL) is indicated for intraarterial injection in the radiographic contrast evaluation of the aorta and major visceral arterial branches. The volume and rate of contrast injection should be proportional to the blood flow through the vessels of interest, and related to the vascular and pathological characteristics of the specific vessels being studied.

Total dose for the procedure should not usually exceed 250 mL.

Oxilan® Injection (350 mgI/mL) is indicated for intraarterial injection in the radiographic contrast evaluation of peripheral arteries. Injection rates should be approximately equal to flow rate in the vessel being injected. The usual individual injection volumes for visualization of various peripheral arteries are as follows:

Aortic bifurcation for distal runoff:
   45 mL to 100 mL (26 to 70 gI) of Oxilan® Injection - 350 (350 mgI/mL)

Subclavian or femoral artery:
   10 mL to 40 mL (4 to 14 gI) of Oxilan® Injection - 350 (350 mgI/mL)

Total dose for the procedure should not usually exceed 250 mL. Pulsation should be present in the artery to be injected.

Oxilan® Injection (300 mgI/mL) is indicated for intraarterial injection in the radiographic contrast evaluation of arterial lesions of the brain. The usual individual volumes per injection are 8 mL to 12 mL (2.4 to 3.6 gI) of Oxilan® Injection - 300 (300 mgI/mL).

Total dose for the procedure should not usually exceed 150 mL.

INTRAVENOUS PROCEDURES

Oxilan® Injection (300 mgI/mL or 350 mgI/mL) is indicated for intravenous injection for routine excretory urography. A volume of contrast which gives a dose of approximately 250 to 390 mgI/kg of body weight is recommended as suitable for adults with normal renal function.

Total dose for the procedure should not usually exceed 100 mL.

Oxilan® Injection (300 mgI/mL or 350 mgI/mL) is indicated for intravenous injection for contrast-enhancement in the evaluation of neoplastic and non- neoplastic lesions of the head and body (intrathoracic, intraabdominal, and retroperitoneal regions).

CECT of the Head:

The usual dose is 100 mL to 200 mL (30 to 60 gI) of Oxilan® Injection (300 mgI/mL) or 86 mL to 172 mL of Oxilan® Injection (350 mgI/mL). Scanning may be performed immediately after completion of the intravenous administration.

Total dose for the procedure should not usually exceed 200 mL.

CECT of the Body:

Oxilan® Injection (300 mgI/mL or 350 mgI/mL) may be administered intravenously by bolus, by rapid infusion, or by a combination of both. The usual dose is 50 mL to 200 mL (15 to 60 gI) of Oxilan® (300 mgI/mL) or 43 mL to 172 mL of Oxilan® (350 mgI/mL).

Total dose for the procedure should not usually exceed 200 mL.

DRUG HANDLING:

As with all contrast media, because of the potential for chemical incompatibility, Oxilan® Injection should not be mixed with, or injected in, intravenous administration lines containing other drugs, solutions, or total nutritional admixtures.

Sterile technique must be used in all vascular injections involving contrast media.

It is desirable that intravascularly administered iodinated contrast agents be at or close to body temperature when injected.

If non-disposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleaning agents.

Withdrawal of contrast agents from their containers should be accomplished under aseptic conditions using only sterile syringes and transfer devices. Contrast agents which have been transferred into other delivery systems should be used immediately.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. IOxilan solutions should be used only if clear and within the normal colorless to pale yellow range.

Oxilan® formulations are supplied in single dose containers. Discard unused portion.

Direction for proper use of Oxilan®, Pharmacy Bulk Package

1. The transfer of Oxilan® (iOxilan Injection) from the Pharmacy Bulk Package is restricted to a suitable work area, such as a laminar flow hood.
2. The container closure may be penetrated only one time, utilizing a suitable transfer device and aseptic technique.
3. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of [4] hours from initial closure entry is permitted to complete fluid transfer operations. The container should not be removed from the aseptic area during the entire 4 hour period.
4. The temperature of the container should not exceed 30°C, after the closure has been entered.

Oxilan® (IOxilan Injection) 300 mgI/mL -

   Ten 50 mL single dose bottles, NDC 67684-1000-1

   Ten 100 mL single dose bottles, NDC 67684-1000-2

   Ten 150 mL single dose bottles, NDC 67684-1000-3

Oxilan® (IOxilan Injection) 350 mgI/mL -

   Ten 50 mL single dose bottles, NDC 67684-1001-1

   Ten 100 mL single dose bottles, NDC 67684-1001-2

   Ten 150 mL single dose bottles, NDC 67684-1001-3

   Ten 200 mL single dose bottles, NDC 67684-1001-4

Oxilan® (IOxilan Injection) 300 mgI/mL Pharmacy Bulk Package - Six 500 mL bottles, NDC 67684-1000-5

Oxilan® (IOxilan Injection) 350 mgI/mL Pharmacy Bulk Package - Six 500 mL bottles, NDC 67684-1001-5

This drug should be used during pregnancy only if clearly needed. US FDA pregnancy category: B

Animal reproduction studies have failed to demonstrate a risk to the fetus. Embryolethality was not detected. There are no controlled data in human pregnancy. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Summary of Use during Lactation

Intravenous iodinated contrast media are poorly excreted into breastmilk and poorly absorbed orally so they are not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. Guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives a iodine-containing contrast medium.[1][2][3][4] However, because there is no published experience with ioxilan during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Diatrizoate, Iohexol

References

1. American College of Radiology Committee on Drugs and Contrast Media. Administration of contrast media to breast-feeding mothers. In, ACR manual on contrast media. 2015;Version 10.1:99-100. http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/Contrast%20Manual/2015_Contrast_Media.pdf

2. Webb JA, Thomsen HS, Morcos SK et al. The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol. 2005;15:1234-40. PMID: 15609057

3. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008;112:333-40. PMID: 18669732

4. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. Committee Opinion No. 656: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol. 2016;127:e75-e80. DOI: doi:10.1097/AOG.0000000000001316

Substance Name

Ioxilan

CAS Registry Number

107793-72-6

Drug Class

Contrast Agents

Diagnostic Agents