Iomeron 350 (iomeprol)

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Iomeprol/Neuroleptics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Neuroleptics may lower seizure threshold.(1)

CLINICAL EFFECTS: Use of iomeprol in a patient receiving a neuroleptic may increase the risk of seizure.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of iomeprol states that neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1)

DISCUSSION: Because neuroleptics may lower seizure threshold, neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1)

Iomeprol/Selected Antidepressants

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both iomeprol and selected antidepressants may lower the seizure threshold.(1)

CLINICAL EFFECTS: Use of iomeprol in a patient receiving selected antidepressants may increase the risk of seizure.(1) Antidepressants included in this monograph are tricyclic antidepressants (except formulations which also include benzodiazepines), bupropion, and oral monoamine oxidase(MAO) inhibitors used to treat depression.

PREDISPOSING FACTORS: Iomeprol associated seizures are more likely in patients with intracranial tumors or epilepsy.(1)

PATIENT MANAGEMENT: The manufacturer of iomeprol states that tricyclic antidepressants and MAO inhibitors should be discontinued 48 hours before iomeprol use. Treatment with an antidepressant should not be resumed until 24 hours post-procedure.(1) The UK manufacturer of bupropion states that it must not be used in the presence of predisposing risk factors such as medicinals which are known to lower the seizure threshold unless there is a compelling clinical justification that concurrent use outweighs the potential increased risk of seizure.(2)

DISCUSSION: Because selected antidepressants may lower seizure threshold, antidepressants should be discontinued 48 hours before iomeprol use. Treatment with an antidepressant should not be resumed until 24 hours post-procedure.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Affect Iodide/Radioactive Iodide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)

Agents That Affect Iodide/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)

Iodinated Contrast Materials/Metformin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Use of iodinated contrast materials may result in acute changes in renal function, resulting in a decrease in metformin clearance.(1-3)

CLINICAL EFFECTS: Use of iodinated contrast materials may increase levels of metformin, which may result in lactic acidosis.(1-3)

PREDISPOSING FACTORS: Pre-existing renal dysfunction may contribute to decreased clearance of metformin. Other factors which may increase the risk for lactic acidosis include age greater than 65 years, dehydration, metabolic acidosis, sepsis, a history of hepatic impairment, alcoholism, or heart failure.(1-4)

PATIENT MANAGEMENT: Evaluate renal function prior to contrast procedure. According to manufacturer recommendations, discontinue metformin at the time of, or prior to, the contrast imaging procedure in patients with a history of liver disease, alcoholism, heart failure, or if contrast is to be administered intra-arterially. When contrast is to be administered by other routes, discontinue metformin at the time of, or prior to, the procedure for patients with an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Re-evaluate eGFR 48 hours after the imaging procedure and restart metformin if renal function is stable. Discontinuation of metformin is not required if eGFR is > 60 mL/min/1.73 m2.(4) According to American College of Radiology guidelines, discontinue metformin at the time of, or prior to, the contrast imaging procedure in patients with acute kidney injury or chronic kidney disease (Stage IV or V or eGFR < 30 mL/min/1.73 m2), or who are undergoing arterial catheter studies that might result in emboli (atheromatous or other) to the renal arteries. Re-evaluate eGFR 48 hours after the imaging procedure and restart metformin if renal function is normal. Discontinuation of metformin is not required in patients with no evidence of acute kidney injury and with eGFR >= 30 mL/min/m2.(5)

DISCUSSION: An FDA review of the medical literature showed that metformin may be safely used in patients with mild or moderate renal impairment, resulting in modifications of prescribing recommendations and method for evaluation of renal function.(4) A clinical review of 33 patients on metformin who had received contrast media showed elevations in serum creatinine of the four patients with baseline elevations. The 29 patients with normal baseline renal function showed no elevations after administration of contrast media. The authors recommend that a baseline serum creatinine is obtained for all patients and that metformin should only be discontinued in patients with baseline elevations.(6) A retrospective study of ninety-seven patients currently taking metformin underwent a radiologic procedure with contrast media. Of these patients, 4 developed contrast material associated nephropathy and eight patients had an increased risk of lactic acidosis, with a baseline serum creatinine <1.5mg/dl.(7) A prospective clinical trial with 50 diabetic patients on metformin with baseline serum creatinine <1.47mg/dl showed no statistical difference in renal function before and 48 hours after administration of contrast media. The authors recommend a baseline serum creatinine for all patients and suggest that temporary discontinuation of metformin may not be necessary when baseline renal function is <1.47mg/dl.(8) A systematic review of the literature reveals that 17 of 18 case reports of metformin-induced lactic acidosis involved patients with renal dysfunction prior to administration of contrast media. The authors recommend a baseline serum creatinine in all patients and if renal dysfunction is present, metformin should be discontinued for 48 hours before and after administration of contrast media. The authors recommend follow-up creatinine measurement in patients with prior renal impairment or known comorbidities affecting lactate levels.(9)

Iodinated Contrast Media/Methotrexate (Oncology-Injection)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: One possible mechanism is renal dysfunction caused by the nephrotoxicity of both agents.

CLINICAL EFFECTS: Concurrent use of iodinated contrast media may result in methotrexate toxicity, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia.

PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions

PATIENT MANAGEMENT: It is recommended that the use of iodinated contrast media in patients receiving high dose methotrexate therapy be avoided until the serum methotrexate level is 0.1 mcmol/L or lower. With lower dose methotrexate therapy, iodinated contrast media should be used with caution and preventative measures should be considered.(1)

DISCUSSION: There are three case reports of patients receiving concurrent iodinated contrast agents and methotrexate therapy developing methotrexate toxicity. One patient received iodinated contrast media the day after receiving a methotrexate infusion while the other two patients received contrast media 30 hours and 4.5 hours after methotrexate therapy.(1,2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Iodinated Contrast Med/Methotrexate (Low Strength Inj, Oral)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: One possible mechanism is renal dysfunction caused by the nephrotoxicity of both agents.

CLINICAL EFFECTS: Concurrent use of iodinated contrast media may result in methotrexate toxicity, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia.

PREDISPOSING FACTORS: Renal impairment

PATIENT MANAGEMENT: It is recommended that the use of iodinated contrast media in patients receiving high dose methotrexate therapy be avoided until the serum methotrexate level is 0.1 mcmol/L or lower. With lower dose methotrexate therapy, iodinated contrast media should be used with caution and preventative measures should be considered.(1)

DISCUSSION: There are three case reports of patients receiving concurrent iodinated contrast agents and methotrexate therapy developing methotrexate toxicity. One patient received iodinated contrast media the day after receiving a methotrexate infusion while the other two patients received contrast media 30 hours and 4.5 hours after methotrexate therapy.(1,2)

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There are no contraindication contraindications for this drug.

• Chronic heart failure
• Dehydration
• Hyperthyroidism
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Pheochromocytoma
• Sickle cell disease

• Diabetes mellitus
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Myasthenia gravis
• Peripheral vascular disease

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Less Frequent

• Dyspnea

Rare or Very Rare

• Acute myocardial infarction
• Acute respiratory failure
• Anaphylaxis
• Angina
• Angioedema
• Bronchospastic pulmonary disease
• Cardiac arrhythmia
• CNS toxicity
• Cyanosis
• DRESS syndrome
• Edema
• Erythema multiforme
• Hemolytic anemia
• Paresthesia
• Seizure disorder
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis

Less Frequent

• Chest pain
• Dizziness
• Erythema
• Headache disorder
• Injection site sequelae
• Nausea
• Pruritus of skin
• Vomiting

Rare or Very Rare

• Acute abdominal pain
• Acute cognitive impairment
• Agitation
• Back pain
• Bradycardia
• Chills
• Diarrhea
• Fever
• Flushing
• General weakness
• Hyperhidrosis
• Hypertension
• Hyperthyroidism
• Hypotension
• Sensation of warmth
• Skin rash
• Symptoms of anxiety
• Syncope
• Tachycardia
• Urticaria
• Vasodilation of blood vessels
• Wheezing

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