Drug Safety-related Labeling Changes (SrLC)
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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 70 (NDA-018956)
(IOHEXOL)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/08/2024 (SUPPL-119)
04/25/2023 (SUPPL-116)
02/18/2022 (SUPPL-113)
08/05/2021 (SUPPL-112)
04/17/2018 (SUPPL-101)
4 Contraindications
(additions underlined)
OMNIPAQUE 140 and OMNIPAQUE 350 are contraindicated for intrathecal use.
OMNIPAQUE oral solution 9 and 12 are contraindicated for parenteral administration.
5 Warnings and Precautions
(PLR conversion: subsections created as below, see label for complete information)
5.1 Risks Associated with Inadvertent Intrathecal Administration
5.2 Risks with Associated with Inadvertent Parenteral Administration
5.3 Hypersensitivity Reactions
5.4 Contrast Induced Acute Kidney Injury
5.5 Cardiovascular Adverse Reactions
5.6 Thromboembolic Events
5.7 Extravasation and Injection Site Reactions
5.8 Thyroid Storm in Patients with Hyperthyroidism
5.9 Hypertensive Crisis in Patients with Pheochromocytoma
5.10 Sickle Cell Crisis in Patients with Sickle Cell Disease
5.11 Severe Cutaneous Adverse Reactions
6 Adverse Reactions
(PLR conversion)The following clinically significant adverse reactions are described elsewhere in the labeling:
(new subsection added, please refer to label)
(new subsection added)
The following additional reactions listed by indication have been identified during post-approval use of OMNIPAQUE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
General
Immune system Disorders: Hypersensitivity reactions, anaphylactic or anaphylactoid reactions, anaphylactic or anaphylactoid shock including life-threatening or fatal anaphylaxis.
General disorders and Administration Site Conditions: Pyrexia, chills, pain and discomfort, asthenia, administration site conditions including extravasation.
Intrathecal Administration
Nervous System Disorders: Meningism, aseptic meningitis, seizures or status epilepticus, disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia,
hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia.
Musculoskeletal and Connective Tissue Disorders: Pain, muscle spasms or spasticity.
Psychiatric Disorders: Confusional state, agitation, anxiety.
Eye Disorders: Transient visual impairment including cortical blindness.
Renal reactions: Acute kidney injury. Intravascular Administration
Cardiovascular Disorders: Severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), shock, peripheral vasodilatation, palpitations, vasospasm including spasm of coronary arteries, myocardial infarction, syncope, cyanosis, pallor, flushing, chest pain.
Hemodynamic reactions: Vasospasm and thrombophlebitis following intravenous injection.
Blood and lymphatic system disorders: Neutropenia.
Nervous System Disorders: Disorientation, coma, depressed or loss of consciousness, transient contrast-induced toxic encephalopathy (including amnesia, hallucination, paralysis, paresis, speech disorder, aphasia, dysarthria), restlessness, tremors, hypoesthesia.
Psychiatric Disorders: Confusional state, agitation.
Eye Disorders: Eye irritation or itchiness, periorbital edema, ocular or conjunctival hyperemia, lacrimation.
Renal reactions: Acute kidney injury, nephropathy toxic (CIN), transient proteinuria, oliguria or anuria, increased serum creatinine.
Gastrointestinal disorders: Abdominal pain, pancreatitis aggravated, salivary gland enlargement.
Endocrine reactions: Hyperthyroidism. Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to adult and pediatric patients, including infants. Some patients were treated for hypothyroidism.
Respiratory; Thoracic, and Mediastinal Disorders: Respiratory Distress, respiratory failure, pulmonary edema, bronchospasm, laryngospasm, throat irritation, throat tightness, laryngeal edema, wheezing, chest discomfort, asthmatic attack.
Skin and Subcutaneous Tissue Disorders: Contrast media reactions range from mild (e.g. pleomorphic rashes, drug eruption, erythema and skin discoloration, blisters, hyperhidrosis, angioedema, localized areas of edema) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), bullous or exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)].
Oral Administration
Gastrointestinal disorders: Dysphagia, abdominal pain. Body Cavity Administration
Gastrointestinal disorders: Pancreatitis.
Musculoskeletal and Connective Tissue Disorders: Arthritis (arthrography).
7 Drug Interactions
7.1 Drug-Drug Interactions(new subsection added)
Metformin
In patients with renal impairment, metformin can cause lactic acidosis. Iodinated contrast agents appear to increase the risk of metformin-induced lactic acidosis, possibly as a result of worsening renal function. Stop metformin at the time of, or prior to, OMNIPAQUE administration in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and reinstitute metformin only after renal function is stable.
Radioactive Iodine
Administration of iodinated contrast agents may interfere with thyroid uptake of radioactive iodine (I-131 and I-123) and decrease therapeutic and diagnostic efficacy in patients with carcinoma of the thyroid. The decrease in efficacy lasts for 6-8 weeks.
Beta-adrenergic Blocking Agents
The use of beta-adrenergic blocking agents lowers the threshold for and increases the severity of contrast reactions and reduces the responsiveness of treatment of hypersensitivity reactions with epinephrine. Because of the risk of hypersensitivity reactions, use caution when administering OMNIPAQUE to patients taking beta-blockers.
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.
(new subsection added)
Effect on Thyroid tests
If iodine-containing isotopes are to be administered for the diagnosis of thyroid disease, the iodine-binding capacity of thyroid tissue may be reduced for up to 2 weeks after contrast medium administration. 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
8.1 Pregnancy(PLLR conversion)
Risk Summary
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).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, 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 DataLiterature 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.
(PLLR conversion)
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 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 updated, new information added; please refer to label)
(new subsection added)
In clinical studies of OMNIPAQUE for CT, 52/299 (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 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.