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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
OMNIPAQUE 300 (NDA-020608)
(IOHEXOL)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/08/2024 (SUPPL-47)
Boxed Warning
Additions and/or revisions underlined:
WARNING: RISKS ASSOCIATED WITH INTRATHECAL ADMINISTRATION OF OMNIPAQUE INJECTION 140 mg IODINE/mL and 350 mg IODINE/mL
Use only the OMNIPAQUE iodine concentrations and presentations recommended for intrathecal procedure [see Dosage and Administration (2.2, 2.8)]. Intrathecal administration of OMNIPAQUE of a wrong iodine concentration, even if inadvertent, may cause death, convulsions, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema [see Warnings and Precautions (5.1)].
5 Warnings and Precautions
5.1 Risks Associated with Intrathecal Administration of OMNIPAQUE Injection 140 mg Iodine/mL and 350 mg Iodine/mL
Additions and/or revisions underlined:
Use only the iodine concentrations and presentations recommended for intrathecal procedures [see Dosage and Administration (2.2, 2.8)]. Intrathecal administration of OMNIPAQUE of a wrong iodine concentration, even if inadvertent, can cause death, convulsions, seizures, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, rhabdomyolysis, hyperthermia, and brain edema.
5.2 Risks Associated with Parenteral Administration of OMNIPAQUE Oral Solution
Additions and/or revisions underlined:
Adverse reactions such as hemolysis may occur if OMNIPAQUE oral solution is administered intravenously or intraarterially due to low osmolality [see Description (11)]. OMNIPAQUE oral solution is for oral use only.
5.3 Hypersensitivity Reactions
Additions and/or revisions underlined:
OMNIPAQUE can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock. Most severe reactions develop shortly after the start of the injection (within 1 to 3 minutes), but delayed reactions can also occur. There is an increased risk in patients with a history of a previous reaction to contrast agent and known allergic disorders (i.e., bronchial asthma, drug, or food allergies) or other hypersensitivities. Premedication with antihistamines or corticosteroids does not prevent serious life- threatening reactions but may reduce both their incidence and severity.
…
5.13 Interference with Laboratory Test
New subsection added:
OMNIPAQUE can interfere with protein-bound iodine test [see Drug Interactions (7.2)].
5.14 Increased Risk of Seizures with Intrathecal Procedures
New subsection added:
Focal and generalized motor seizures have been reported after intrathecal use of iodinated contrast agents. In several of the cases, higher than recommended doses were administered.
Use of medications that may lower the seizure threshold (phenothiazine derivatives, including those used for their antihistaminic properties; tricyclic antidepressants; MAO inhibitors; CNS stimulants; analeptics; antipsychotic agents) should be carefully evaluated. Consider discontinuing these agents at least 48 hours before and for at least 24 hours following intrathecal administration of OMNIPAQUE.
6 Adverse Reactions
Additions and/or revisions underlined:
The following clinically significant adverse reactions are described elsewhere in the labeling:
Risks Associated with Intrathecal Administration of OMNIPAQUE Injection 140 mg Iodine/mL and 350 mg Iodine/mL [see Warnings and Precautions (5.1)]
Risks Associated with Parenteral Administration of OMNIPAQUE Oral Solution [see Warnings and Precautions (5.2)]
…
6.1 Clinical Trials Experience
Extensive additions and/or revisions, please refer to label for complete information.
7 Drug Interactions
7.1 Drug-Drug Interactions
…
Radioactive Iodine
OMNIPAQUE may interfere with thyroid uptake of radioactive iodine (I-131 and I-123) and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post OMNIPAQUE.
7.2 Drug-Laboratory Test Interactions
Additions and/or revisions underlined:
Protein-Bound Iodine Test
Iodinated contrast agents, including OMNIPAQUE, will temporarily increase protein-bound iodine in blood. Do not perform protein-bound iodine test for at least 16 days following administration of OMNIPAQUE. However, thyroid function tests that do not depend on iodine estimation, e.g., T3 resin uptake or direct thyroxine assays, are not affected.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
…
Intra-arterial or Intravenous Use
Cardiac Ventriculography, Aortography, and Pulmonary Angiography
The safety and effectiveness of OMNIPAQUE have been established in pediatric patients from birth to 17 years of age for cardiac ventriculography, aortography, and pulmonary angiography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for cardiac ventriculography and aortography, in addition to controlled clinical studies in pediatric patients undergoing cardiac ventriculography, including aortography.
Excretory Urography
OMNIPQUE have been established in pediatric patients from birth to 17 years of age for excretory urography. Use of OMNIPAQUE is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth.
…
Selective Coronary Arteriography, Cerebral and Peripheral Arteriography, Intra-arterial Digital Subtraction Angiography, Peripheral Venography, and Intravenous Digital Subtraction Angiography
The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for selective coronary arteriography, cerebral or peripheral arteriography, intra-arterial digital subtraction angiography, peripheral venography, and intravenous digital subtraction angiography.
…
CT of the Abdomen and Pelvis in Conjunction with Intravenous Use
The safety and effectiveness of OMNIPAQUE for CT of the abdomen and pelvis have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen.
…
Body Cavity Use
Voiding Cystourethrography
OMNIPAQUE is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). Use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU.
ERCP, Herniography, and Hysterosalpingography
The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography.
…
8.5 Geriatric Use
Additions and/or revisions underlined:
In clinical studies of OMNIPAQUE for CT of the head and body, 52 (17%) of patients were 70 and over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in safety and effectiveness between the elderly and younger patients.
Iohexol is substantially excreted by the kidney, and the risk of adverse reactions to iohexol may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
8.6 Renal Impairment
New subsection added:
The clearance of iohexol decreases with increasing degree of renal impairment and results in delayed opacification of the urinary system. In addition, preexisting renal impairment increases the risk for acute kidney injury [see Warnings and Precautions (5.4)]. Iohexol can be removed by dialysis.
04/25/2023 (SUPPL-49)
5 Warnings and Precautions
5.9 Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
Additions and/or revisions underlined:
Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media (ICM) in pediatric patients 0 to 3 years of age.
Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after ICM exposure. Pediatric patients with congenital cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures.
An underactive thyroid during early life may be harmful for cognitive and neurological development and may require thyroid hormone replacement therapy. After exposure to ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
…
After exposure to iodinated contrast media, individualize thyroid function monitoring in pediatric patients 0 to 3 years of age based on underlying risk factors, especially in term and preterm neonates [see Warnings and Precautions (5.9) and Adverse Reactions (6.2)].
02/18/2022 (SUPPL-45)
4 Contraindications
CONTRAINDICATIONS
Newly added information:
OMNIPAQUE 140 and OMNIPAQUE 350 are contraindicated for intrathecal use [see Warnings and Precautions (5.1)]
OMNIPAQUE oral solution 9 and 12 are contraindicated for parenteral administration [see Warnings and Precautions (5.2)]
OMNIPAQUE body cavity 240 and 300 for hysterosalpingography is contraindicated during pregnancy or suspected pregnancy, menstruation or when menstruation is imminent, within 6 months after termination of pregnancy, within 30 days after conization or curettage, when signs of infection are present in any portion of the genital tract including the external genitalia, and when reproductive tract neoplasia is known or suspected because of the risk of peritoneal spread of neoplasm.
5 Warnings and Precautions
Additions and/or revisions underlined:
5.1 Risks Associated with Inadvertent Intrathecal Administration
OMNIPAQUE injection 140 and 350 are contraindicated for intrathecal use [see Contraindications (4) and Dosage and Administration (2.1)]. Inadvertent intrathecal administration can cause death …
Newly added subsection:
5.2 Risks Associated with Inadvertent Parenteral Administration
OMNIPAQUE oral solution 9 and 12 are contraindicated for parenteral administration [see Contraindications (4) and Dosage and Administration (2.1)]. Adverse reactions such as hemolysis may occur if administered intravascularly. Do not administer OMNIPAQUE oral solution 9 and 12 parenterally.
Additions and/or revisions underlined:
5.4 Contrast-Induced Acute Kidney Injury
Acute kidney injury, including renal failure, may occur after parenteral administration of OMNIPAQUE. Risk factors include …
… Use the lowest necessary dose of OMNIPAQUE in patients with renal impairment. Adequately hydrate patients prior to and following parenteral administration of OMNIPAQUE. Do not use laxatives, diuretics, or preparatory dehydration prior to OMNIPAQUE administration.
5.5 Cardiovascular Adverse Reactions
Life-threatening or fatal cardiovascular reactions including hypotension, shock, cardiac arrest have occurred with the parenteral administration of OMNIPAQUE. Most deaths occur during injection or five to ten minutes later, with cardiovascular disease as the main aggravating factor. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography.
Based upon clinical literature reported deaths from the administration of iodinated contrast agents range from 6.6 per million (0.00066%) to 1 in 10,000 (0.01%). Use the lowest necessary dose of OMNIPAQUE in patients with congestive heart failure and always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.
Newly added subsection:
5.6 Thromboembolic Events
Angiocardiography
Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiocardiography procedures with both ionic and nonionic contrast media. During these procedures, increased thrombosis and activation of the complement system occurs. Risk factors for thromboembolic events include: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications.
To minimize thromboembolic events, use meticulous angiographic techniques, and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases the risk of clotting. Avoid angiocardiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.
Additions and/or revisions underlined:
5.7 Extravasation and Injection Site Reactions
Extravasation of OMNIPAQUE during intravascular injection may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease. Ensure intravascular placement of catheters prior to injection …
Newly added subsection:
5.9 Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media. Among patients 0 to 3 years of age exposed to iodinated contrast media, thyroid dysfunction has been reported in 1% to 15% depending on the age of the patient and the dose of the iodinated contrast agent.
Younger age, very low birth weight, prematurity, and the presence of other conditions, such as, admission to neonatal or pediatric intensive care units, and cardiac conditions are associated with an increased risk. Pediatric patients with cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures, such as catheterization and computed tomography (CT).
Pediatric patients 0 to 3 years of age warrant closer monitoring because an underactive thyroid during early life may be harmful for motor, hearing, and cognitive development and may require transient T4 replacement therapy. Evaluate thyroid function in all pediatric patients 0 to 3 years of age within 3 weeks following exposure to iodinated contrast media, especially in term and preterm neonates. If thyroid dysfunction is detected, treat and monitor thyroid function as clinically needed.
Additions and/or revisions underlined:
5.10 Hypertensive Crisis in Patients with Pheochromocytoma
Hypertensive crisis has occurred after the use of iodinated contrast agents in patient with pheochromocytoma. Monitor patients when administering OMNIPAQUE intravascularly if pheochromocytoma or catecholamine-secreting paragangliomas are suspected …
6 Adverse Reactions
Additions and/or revisions underlined:
Risks Associated with Inadvertent Parenteral Administration [see Warnings and Precautions (5.2)]
Hypersensitivity Reactions [see Warnings and Precautions (5.3)]
Contrast-Induced Kidney Injury [see Warnings and Precautions (5.4)]
Cardiovascular Adverse Reactions [see Warnings and Precautions (5.5)]
Thromboembolic Events [see Warnings and Precautions (5.6)]
Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings and Precautions (5.9)]
Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.12)]
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information.
6.2 Post-marketing Experience
Additions and/or revisions underlined:
Endocrine Disorders: Hyperthyroidism, hypothyroidism
7 Drug Interactions
7.1 Drug-Drug InteractionsNewly added information:
Drugs that Lower Seizure Threshold
Drugs that lower seizure threshold, especially phenothiazine derivatives including those used for their antihistaminic or antinauseant properties, are not recommended for use with intrathecal administration of OMNIPAQUE.
CNS Active Drugs
Drugs such as monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, CNS stimulants, psychoactive drugs described as analeptics, major tranquilizers, or antipsychotic drugs. Such medications should be discontinued at least 48 hours before myelography, should not be used for the control of nausea or vomiting during or after myelography, and should not be resumed for at least 24 hours post procedure. In non-elective procedures in patients on these drugs, consider prophylactic use of anticonvulsants.
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined:
Risk Summary
Hysterosalpingography is contraindicated in pregnant women due to the potential risk to the fetus from an intrauterine procedure [see Contraindications (4)]. There are no data with iohexol use in pregnant women to inform any drug-associated risks. Iohexol crosses the placenta and reaches fetal tissues in small amounts (see Data). In animal reproduction studies, no developmental toxicity occurred with intravenous iohexol administration to rats and rabbits at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose (see Data).
Data
Human Data
Literature reports show that intravenously administered iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth.
Animal Data
Iohexol was neither embryotoxic nor teratogenic in either rats or rabbits at the following dose levels tested: 1.0, 2.0, 4.0 g iodine/kg in rats, administered intravenously to 3 groups of 25 dams once daily during days 6 through 15 of pregnancy; 0.3, 1.0, 2.5 g iodine/kg in rabbits, administered intravenously to 3 groups of 18 rabbits dosed once a day during days 6 through 18 of pregnancy. Iohexol was not embryotoxic or teratogenic in either species at the dose levels tested.
Additions and/or revisions underlined:
Risk Summary
Published literature reports that breast feeding after intravenous iohexol administration to the mother would result in the infant receiving an oral dose of approximately 0.7% of the maternal intravenous dose; however, lactation studies have not been conducted with oral, intrathecal, or intracavity administration of iohexol. There is no information on the effects of the drug on the breastfed infant or on milk production. Iodinated contrast agents are excreted unchanged …
Additions and/or revisions underlined:
Intrathecal Use
The safety and effectiveness of OMNIPAQUE 180 have been established in pediatric patients 2 weeks to 17 years of age for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography). Use of OMNIPAQUE 180 is supported by controlled clinical studies in adults for myelography, in addition to clinical studies in pediatric patients undergoing myelography. The safety and effectiveness of OMNIPAQUE 180 have not been established for intrathecal use in patient pediatric patients less than 2 weeks of age. The safety and effectiveness of OMNIPAQUE 240 and 300 have not been established in pediatric patients for myelography (lumbar, thoracic, cervical, total columnar) and for CT (myelography, cisternography, or ventriculography).
Intravascular Use
Angiocardiography (Ventriculography, Pulmonary Arteriography, Venography, and Studies of the Collateral Arteries) and Aortography
The safety and effectiveness of OMNIPAQUE 300 have been established in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography) and of OMNIPAQUE 350 in pediatric patients from birth to 17 years of age for angiocardiography (ventriculography, pulmonary arteriography, venography, and studies of the collateral arteries) and aortography. Use of OMNIPAQUE 300 and 350 is supported by controlled clinical studies in adults for angiocardiography and aortography, in addition to controlled clinical studies in pediatric patients undergoing angiocardiography, including aortography. The safety and effectiveness of OMNIPAQUE 300 have not been established in pediatric patients for aortography.
Intra-arterial Digital Subtraction Angiography, Intravenous Digital Subtraction Angiography, Cerebral Arteriography, or Peripheral Arteriography and Venography
The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, cerebral arteriography, or peripheral arteriography and venography.
CT of the Head and Body
The safety and effectiveness of OMNIPAQUE 240 and 300 have been established in pediatric patients from birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE 240 and 300 is supported by controlled clinical studies in adults for head and body CT, in addition to clinical studies in pediatric patients undergoing head CT and in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE. The safety and effectiveness of OMNIPAQUE 350 have not been established in pediatric patients for CT imaging of the head and body.
Urography
The safety and effectiveness of OMNIPQUE 300 have been established in pediatric patients from birth to 17 years of age for urography. Use of OMNIPAQUE 300 is supported by controlled clinical studies in adults for urography, in addition to controlled clinical studies in pediatric patients undergoing urography and clinical safety data in pediatric patients down to birth.
Oral or Rectal Use
Undiluted OMNIPAQUE Injection
The safety and effectiveness of OMNIPAQUE 180, 240, and 300 administered orally and rectally have been established in pediatric patients, from birth to 17 years of age for examination of the GI tract. Use of OMNIPAQUE 180, 240, and 300 administered orally and rectally is supported by controlled studies in adults for examination of the GI tract, in addition to clinical studies in pediatric patients undergoing examination of the GI tract.
Oral Use in Conjunction with Intravenous Use
Diluted OMNIPAQUE Injection
The safety and effectiveness of OMNIPAQUE injection diluted to concentrations from 9 to 21 mg iodine/mL administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen have been established in pediatric patients from birth to 17 years of age. Use is supported by clinical trials in adults, in addition to clinical studies in 69 pediatric patients undergoing CT of the abdomen after oral administration of diluted OMNIPAQUE plus intravenous administration of OMNIPAQUE.
OMNIPAQUE Oral Solution
The safety and effectiveness of OMNIPAQUE oral solution 9 and 12 administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients have been established in pediatric patients from birth to 17 years of age. Use is supported by the data establishing safety and effectiveness for OMNIPAQUE injection diluted and administered orally in conjunction with OMNIPAQUE injection administered intravenously for CT of the abdomen in pediatric patients.
Intraarticular Use
The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for arthrography.
Body Cavity Use
OMNIPAQUE 240, 300, 350 diluted to concentrations from 50 mg iodine/mL to 100 mg iodine/mL is indicated for use in pediatric patients from birth to 17 years of age for voiding cystourethrography (VCU). The use for voiding cystourethrography is supported by clinical studies in 51 pediatric patients undergoing VCU. The safety and effectiveness of OMNIPAQUE have not been established in pediatric patients for ERCP, herniography, or hysterosalpingography.
In general, the frequency of adverse reactions in pediatric patients was similar to that seen in adults [see Adverse Reactions (6.1)]. Pediatric patients at higher risk of experiencing adverse events during contrast-medium administration may include those having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.
Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration in pediatric patients, including term and preterm neonates. Some patients were treated for hypothyroidism. Monitor pediatric patients 0 to 3 years of age closely, particularly those with one or more potential risk factors, for thyroid dysfunction [see Warnings and Precautions (5.9) and Adverse Reactions (6.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONNewly added information:
Thyroid Dysfunction
Advise parents/caregivers about the risk of developing thyroid dysfunction after OMNIPAQUE administration. Advise parents/caregivers about when to seek medical care for their child to monitor for thyroid dysfunction [see Warnings and Precautions (5.8)].
11/09/2017 (SUPPL-38)
8 Use in Specific Populations
8.1 Pregnancy(PLLR conversion)
Risk Summary
Postmarketing data with OMNIPAQUE use in pregnant women are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes. Iohexol crosses the placenta and reaches fetal tissues in small amounts (see Data). In animal reproduction studies, no adverse developmental effects were observed following intravenous iohexol administration to pregnant rats and rabbits during organogenesis at doses up to 0.4 (rat) and 0.5 (rabbit) times the maximum recommended human intravenous dose (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively.
Data
Human Data
Literature reports show that iohexol crosses the placenta and is visualized in the digestive tract of exposed infants after birth.
Animal Data
Reproduction studies were performed in rats and rabbits with intravenous administration of iohexol at the following dose levels: 1.0, 2.0, 4.0 g iodine/kg in rats, in 3 groups of 25 dams once daily during days 6 through 15 of pregnancy; 0.3, 1.0, 2.5 g iodine/kg in rabbits, in 3 groups of 18 doses once a day during days 6 through 18 of pregnancy. Iohexol was not embryotoxic or teratogenic in either species at the dose levels tested.
(PLLR conversion)
Risk Summary
The literature reports that breast feeding after iohexol administration to the mother would result in the infant receiving an oral dose of approximately 0.7% of the maternal intravenous dose. There is no information on the effects of the drug on milk production. Iodinated contrast agents are excreted unchanged in human milk in very low amounts with poor absorption from the gastrointestinal tract of a breastfed infant. Exposure to iohexol to a breastfed infant can be minimized by temporary discontinuation of breastfeeding (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OMNIPAQUE and any potential adverse effects on the breastfed infant from OMNIPAQUE or from the underlying maternal condition.
Clinical Considerations
Interruption of breastfeeding after exposure to iodinated contrast agents is not necessary because the potential exposure of the breastfed infant to iodine is small. However, a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 10 hours (approximately 5 elimination half-lives) after OMNIPAQUE administration to minimize drug exposure to a breastfed infant.
(subsection revised, additions underlined)
The safety and efficacy of OMNIPAQUE 300 mg iodine/mL have been established in pediatric patients birth to 17 years of age for CT imaging of the head and body. Use of OMNIPAQUE 300 mg iodine/mL is supported by controlled clinical trials in pediatric patients undergoing head CT and evidence of effectiveness from well-controlled studies of Omnipaque in adults for head and body CT. The safety and efficacy of OMNIPAQUE 350 mg iodine/mL have not been established in pediatric patients birth to 17 years of age for CT imaging of the head and body.
(new subsection added)
In clinical studies of OMNIPAQUE in computed tomography, 52/299 (17%) of patients were 70 years and older. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(new section added)
Hypersensitivity Reactions
Advise the patient concerning the risk of hypersensitivity reactions that can occur both during and after OMNIPAQUE administration. Advise the patient to report any signs or symptoms of hypersensitivity reactions during the procedure and to seek immediate medical attention for any signs or symptoms experienced after discharge.
Advise patients to inform their physician if they develop a rash after receiving OMNIPAQUE.
Contrast Induced Acute Kidney Injury
Advise the patient concerning appropriate hydration to decrease the risk of contrast induced acute kidney injury.
Extravasation
If extravasation occurs during injection, advise patients to seek medical care for progression of symptoms.
Lactation
Advise a lactating woman that interruption of breastfeeding is not necessary, however, to avoid any exposure a lactating woman may consider pumping and discarding breast milk for 10 hours after OMNIPAQUE administration.
Other
Extensively changed by Physician Labeling Rule (PLR) conversion, please refer to label.
04/05/2017 (SUPPL-36)
5 Warnings and Precautions
PRECAUTIONS(additions underlined)
Diagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out under the direction of personnel with the prerequisite…Dehydration in these patients seems to be enhanced by the osmotic diuretic action of urographic agents. It is believed that overnight fluid restriction prior to excretory urography generally does not provide better visualization in normal patients. Patients should be well hydrated prior to and following administration of any contrast medium, including iohexol.
Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible non-diabetic patients (often elderly with preexisting renal disease) following excretory urography. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients.
…
(additions underlined)
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions(SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Omnipaque to patients with a history of a severe cutaneous adverse reaction to Omnipaque.
6 Adverse Reactions
General Adverse Reactions to Contrast Media
(additions underlined)
Physicians should remain alert for the occurrence of adverse effects in addition to those
discussed above.
The following reactions have been reported after administration… Skin and Subcutaneous Tissue Disorders: Reactions range from mild (rash, erythema, pruritus, urticaria, skin discoloration) to severe: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).
...
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATIONInformation for Patients
(addition underlined)
Patients receiving injectable radiopaque diagnostic agents should be instructed to:
1. Inform your physician if you are pregnant (see CLINICAL PHARMACOLOGY— Intravascular).
2. Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease, or known thyroid disorder (see WARNINGS).
3. Inform your physician if you are allergic to any drugs, food, or if you had any reactions to previous injections of dyes used for x-ray procedures (see PRECAUTIONS—General).
4. Inform your physician about any other medications you are currently taking, including non- prescription drugs, before you are administered this drug.
5. Advise patients to inform their physician if they develop a rash after receiving
Omnipaque.
04/05/2017 (SUPPL-37)
5 Warnings and Precautions
PRECAUTIONS(additions underlined)
Diagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out under the direction of personnel with the prerequisite…Dehydration in these patients seems to be enhanced by the osmotic diuretic action of urographic agents. It is believed that overnight fluid restriction prior to excretory urography generally does not provide better visualization in normal patients. Patients should be well hydrated prior to and following administration of any contrast medium, including iohexol.
Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible non-diabetic patients (often elderly with preexisting renal disease) following excretory urography. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients.
…
(additions underlined)
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions(SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Omnipaque to patients with a history of a severe cutaneous adverse reaction to Omnipaque.
6 Adverse Reactions
General Adverse Reactions to Contrast Media(additions underlined)
Physicians should remain alert for the occurrence of adverse effects in addition to those
discussed above.
The following reactions have been reported after administration… Skin and Subcutaneous Tissue Disorders: Reactions range from mild (rash, erythema, pruritus, urticaria, skin discoloration) to severe: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).
...
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Information for Patients(addition underlined)
Patients receiving injectable radiopaque diagnostic agents should be instructed to:
1. Inform your physician if you are pregnant (see CLINICAL PHARMACOLOGY— Intravascular).
2. Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease, or known thyroid disorder (see WARNINGS).
3. Inform your physician if you are allergic to any drugs, food, or if you had any reactions to previous injections of dyes used for x-ray procedures (see PRECAUTIONS—General).
4. Inform your physician about any other medications you are currently taking, including non- prescription drugs, before you are administered this drug.
5. Advise patients to inform their physician if they develop a rash after receiving
Omnipaque.