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IOPANOIC ACID

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Iopanoic acid is an oral iodinated contrast medium used in cholecystography and cholangiography.

Specific Substances

    1) Acidum iopanoicum
    2) Iodopanoic acid
    3) 2-(3-amino-2,4,6-tri-iodobenzyl) butyric acid
    4) CAS 96-83-3

Available Forms Sources

    A) FORMS
    1) Iopanoic acid is available in packets containing six 500 mg tablets.
    B) USES
    1) Iopanoic acid is an iodinated monomeric contrast medium that is used for cholecystography and cholangiography (Prod Info Telepaque(R), 1996).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) The only effects reported in acute overdose have been nausea, vomiting, diarrhea, and slightly elevated serum creatinine.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Hypotension, tachycardia, syncope, shock, and chest pain are rare adverse effects.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) The most commonly reported adverse effects from therapeutic administration are nausea, abdominal pain, and diarrhea.
    B) WITH POISONING/EXPOSURE
    1) Diarrhea and vomiting have been seen in overdose.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) Acute renal insufficiency has been reported with ingestion of large doses, and may be more likely to occur in predisposed individuals (elderly, hepatic disease).
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Thrombocytopenia appears to be a hypersensitivity reaction.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Dermatitis and iododerma have been reported following therapeutic use.
    0.2.19) IMMUNOLOGIC
    A) WITH THERAPEUTIC USE
    1) Anaphylactoid or serum-sickness type hypersensitivity reactions may occur.
    0.2.20) REPRODUCTIVE
    A) Pregnancy Category D
    B) Iopanoic acid is secreted in breast milk, but in such small amounts that harm to the breast-feeding infant is unlikely.
    0.2.22) OTHER
    A) WITH THERAPEUTIC USE
    1) Iopanoic acid is also a potent cholinesterase inhibitor.

Laboratory Monitoring

    A) Monitor renal function tests in significant ingestions or in elderly, renal impaired patients, or patients with hepatic insufficiency.
    B) Monitor blood pressure in patients with cardiovascular disease.
    C) Elevated protein-bound iodine levels may persist for several months.
    D) Iopanoic acid is a radiopaque agent. Abdominal films may be indicated in some cases to confirm history of ingestion.
    E) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Iopanoic acid is an insoluble radiopaque agent that is poorly absorbed in overdose. Gastrointestinal decontamination may not be warranted except after very large and/or symptomatic exposures.
    B) Cholestyramine has a high affinity for iopanoic acid and may prevent absorption.
    C) ACTIVATED CHARCOAL - There are NO data on adsorption to activated charcoal.
    D) Diarrhea is a common effect, therefore cathartics are NOT recommended.
    E) Avoid administration of cholecystagogues which may secrete bile acid into the duodenum and enhance absorption of iopanoic acid.

Range Of Toxicity

    A) Accidental ingestions of 30, 36, and 75 grams in adults has resulted in gastrointestinal symptoms with complete recovery.

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) The only effects reported in acute overdose have been nausea, vomiting, diarrhea, and slightly elevated serum creatinine.

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypotension, tachycardia, syncope, shock, and chest pain are rare adverse effects.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Tachycardia, hypotension, syncope, shock, and chest pain have been rarely reported with therapeutic use, usually in patients with preexisting disease (Prod Info, 1974).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) The most commonly reported adverse effects from therapeutic administration are nausea, abdominal pain, and diarrhea.
    B) WITH POISONING/EXPOSURE
    1) Diarrhea and vomiting have been seen in overdose.
    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORTS - Severe diarrhea was noted in 2 patients who ingested 30 and 76 grams of iopanoic acid, respectively (Hankins, 1971; Gelfand et al, 1978).
    B) VOMITING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Vomiting was present in a patient who ingested 30 grams (Hankins, 1971).
    C) NAUSEA
    1) WITH THERAPEUTIC USE
    a) Nausea, abdominal pain, and diarrhea are common adverse reactions.

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Acute renal insufficiency has been reported with ingestion of large doses, and may be more likely to occur in predisposed individuals (elderly, hepatic disease).
    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) WITH THERAPEUTIC USE
    a) Renal insufficiency or failure has been associated with therapeutic use of iopanoic acid. Most reported cases have been in elderly patients, those with hepatic insufficiency, or those receiving double (6 gram) or repeated doses (Canales et al, 1969; Mudge, 1971).
    b) Large doses of iopanoic acid has also been shown to adversely effect creatinine clearance in normal subjects (Wennberg et al, 1963).
    c) The mechanism of renal injury has not been determined conclusively, but crystalluria, uricosuria, direct cellular toxicity, reduced renal blood flow, and idiosyncrasy have all been suggested.
    d) CASE REPORT - A 66-year-old female with multiple myeloma without previous history of renal dysfunction developed oliguria 2 days after ingesting a single 3 gram dose of iopanoic acid.
    1) She died from progressive myeloma 6 months later without recovery of renal function despite chemotherapy and hemodialysis (Schreiber & Dave, 1989).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Thrombocytopenia appears to be a hypersensitivity reaction.
    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Severe thrombocytopenia without evidence of DIC has been described in patients receiving therapeutic doses of iopanoic acid.
    1) Fever and chills were present in two cases. Platelets normalized within 6 to 9 days with or without corticosteroid therapy.
    2) The mechanism is presumed to be antibody-mediated (Curradi et al, 1981; Hysell et al, 1977; Bishopric, 1964).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Dermatitis and iododerma have been reported following therapeutic use.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - Urticarial and erythematous skin reactions are reported to occur in 1 of 400 patients receiving iopanoic acid prior to oral cholecystogram (Parks, 1974; Personal Communication, 1977).
    b) CASE REPORT - Two days after the second oral 3 gram dose of iopanoic acid, a 45-year-old man with multiple myeloma developed lesions on the face, neck, and trunk consistent with iododerma.
    1) The lesions worsened over the next 2 weeks, and responded rapidly to corticosteroid therapy (Boudoulas et al, 1987).

Immunologic

    3.19.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Anaphylactoid or serum-sickness type hypersensitivity reactions may occur.

Reproductive

    3.20.1) SUMMARY
    A) Pregnancy Category D
    B) Iopanoic acid is secreted in breast milk, but in such small amounts that harm to the breast-feeding infant is unlikely.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    IOPANOIC ACIDD
    Reference: Briggs et al, 1998
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) The amount of iopanoic acid secreted in the milk of lactating mothers is considered to be too small to affect the breast-feeding infant (JEF Reynolds , 1990).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor renal function tests in significant ingestions or in elderly, renal impaired patients, or patients with hepatic insufficiency.
    B) Monitor blood pressure in patients with cardiovascular disease.
    C) Elevated protein-bound iodine levels may persist for several months.
    D) Iopanoic acid is a radiopaque agent. Abdominal films may be indicated in some cases to confirm history of ingestion.
    E) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor renal function tests in significant ingestions or in elderly, renal impaired patients, or patients with hepatic insufficiency.
    2) Elevated protein-bound iodine levels may persist for several months (Perlman et al, 1955).
    3) Monitor fluid and electrolyte status in the presence of significant vomiting or diarrhea.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor blood pressure in patients with cardiovascular disease (1).

Radiographic Studies

    A) ABDOMINAL RADIOGRAPH
    1) Iopanoic acid is a radiopaque agent. Abdominal films may be indicated in some cases to confirm history of ingestion.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor renal function tests in significant ingestions or in elderly, renal impaired patients, or patients with hepatic insufficiency.
    B) Monitor blood pressure in patients with cardiovascular disease.
    C) Elevated protein-bound iodine levels may persist for several months.
    D) Iopanoic acid is a radiopaque agent. Abdominal films may be indicated in some cases to confirm history of ingestion.
    E) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Three adult patients ingesting large amounts of iopanoic acid (30, 36, and 75 grams) developed minimal adverse effects (Gelfand et al, 1978; Hankins, 1971). Gastrointestinal decontamination may not be warranted except after very large and/or symptomatic exposures.
    B) GASTRIC LAVAGE
    1) Gastric lavage performed more than 16 hours after ingestion of a massive amount removed a significant amount from the stomach (Gelfand et al, 1978).
    2) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    3) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    4) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    5) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    6) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    C) ACTIVATED CHARCOAL
    1) There are NO data on adsorption to activated charcoal.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    D) CHOLESTYRAMINE
    1) Has been recommended to chelate bile acids, which are necessary for absorption of iopanoic acid. It also has a high affinity for iopanoic acid, and interferes with its absorption (Nelson, 1974).
    2) Three adult patients ingesting large amounts of iopanoic acid (30, 36, and 75 grams) have developed minimal adverse effects without this intervention (Gelfand et al, 1978; Hankins, 1971).
    3) Cholestyramine has not been compared with activated charcoal. Usual dose of cholestyramine is one packet (9 grams of powder containing 4 grams of anhydrous cholestyramine) one to six times daily.
    E) ENEMA
    1) Enemas have been successful in removing iopanoic acid after overdose (Gelfand et al, 1978).
    6.5.3) TREATMENT
    A) ALKALINE DIURESIS
    1) Iopanoic acid is a potent uricosuric agent, with an effect about equal to that of probenecid. Intravenous fluid administration has been recommended to prevent precipitation of uric acid in the kidneys (Mudge, 1971).
    a) Alkalinization of the urine is also reported to increase the solubility of the iopanoic acid glucuronide metabolite, and thus prevent precipitation in the renal tubules (Gelfand et al, 1978).
    b) This modality has not been studied and demonstrated to be effective or necessary and is not routinely recommended.
    2) SODIUM BICARBONATE/INITIAL DOSE
    a) Administer 1 to 2 milliequivalents/kilogram of sodium bicarbonate as an intravenous bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. In patients with underlying dehydration additional administration of 0.9% saline may be needed to maintain adequate urine output (1 to 2 milliliters/kilogram/hour). Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5.
    3) SODIUM BICARBONATE/REPEAT DOSES
    a) Additional sodium bicarbonate (1 to 2 milliequivalents per kilogram) and potassium chloride (20 to 40 milliequivalents per liter) may be needed to achieve an alkaline urine.
    4) CAUTION
    a) Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalinization. Do not administer potassium to an oliguric or anuric patient. Monitor fluid and electrolyte balance carefully. Monitor blood pH, especially in intubated patients, to avoid severe alkalemia.
    B) CONTRAINDICATED TREATMENT
    1) Avoid administration of cholecystagogues which may secrete bile acid into the duodenum and enhance absorption of iopanoic acid.
    C) MONITORING OF PATIENT
    1) Monitor renal function and blood pressure.

Case Reports

    A) ADVERSE EFFECTS
    1) Gelfand et al (1978) report a 42-year-old man who ingested 75 grams of iopanoic acid. Severe diarrhea persisted for 16 hours. The patient received gastric lavage, enemas, and forced alkaline diuresis.
    2) A minor elevation of serum creatinine on the first and second day were the only biochemical abnormalities noted.
    B) ADULT
    1) A 50-year-old woman who ingested 30 grams developed extreme nausea, diarrhea, and vomiting. No other effects were noted, but laboratory data were not presented. Another patient reportedly took 36 grams with recovery (Hankins, 1971).

Summary

    A) Accidental ingestions of 30, 36, and 75 grams in adults has resulted in gastrointestinal symptoms with complete recovery.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) The usual dose is 3 grams orally as a single dose. Up to 6 grams have been used (S Sweetman , 2001).
    7.2.2) PEDIATRIC
    A) GENERAL
    1) Less than 13 kilograms - 150 milligrams/kilogram orally (USPDI , 2001)
    2) 13 to 23 kilograms - 2 grams orally (USPDI , 2001)
    3) Greater than 23 kilograms - 3 grams orally (USPDI , 2001)

Maximum Tolerated Exposure

    A) ACUTE
    1) Accidental ingestions of 30, 36, and 75 grams in adults has resulted in gastrointestinal symptoms with complete recovery (Hankins, 1971; Gelfand et al, 1978).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)MOUSE:
    a) 1540 mg/kg
    2) LD50- (ORAL)RAT:
    a) 2870 mg/kg

Pharmacologic Mechanism

    A) The use of iopanoic acid is based not on its pharmacologic actions, but on its metabolism and distribution in the body.
    B) Its most important characteristic is its iodine content; the relatively high atomic weight of iodine contributes sufficient radiodensity for radiographic contrast with surrounding tissues.

Physical Characteristics

    A) White or cream tasteless powder

Molecular Weight

    A) 570.93

General Bibliography

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