ISOPROPAMIDE IODIDE

Also see the Prochlorperazine monograph for information on the product Darbazine®.
Chemistry - A synthetic quaternary ammonium anticholinergic agent, isopropamide iodide occursas a bitter-tasting, odorless, white to pale yellow, crystalline powder. It has a melting point of 183°and is sparingly soluble in water at 25° (freely soluble at 100°) and soluble in alcohol. One mg ofisopropamide is equivalent to 1.36 mg of isopropamide iodide.

Storage, Stability, Compatibility

Store isopropamide tablets in well-closed, light-resistant containers.

Pharmacology - ISOPROPAMIDE IODIDE

An antimuscarinic with actions similar to atropine, isopropamide is a quaternaryammonium compound, however, and does not cross appreciably into the CNS. It, therefore, shouldnot exhibit the same extent of CNS adverse effects that atropine possesses. For further information, refer to the atropine monograph.
Uses, Indications - Isopropamide is used in small animal medicine for its antiemetic, antidiarrhealand anticholinergic antiarrhythmic effects. It is often used in a fixed-dose combination withprochlorperazine for the treatment of vomiting and/or diarrhea.

Pharmacokinetics - ISOPROPAMIDE IODIDE

Quaternary anticholinergic agents are not completely absorbed after oraladministration, but quantitative data reporting the rate and extent of absorption of isopropamide isnot available. After oral administration, the anticholinergic effects of isopropamide may persist for8-12 hours.
Little information is available regarding the distributory aspects of isopropamide. Being a quaternary ammonium compound, isopropamide is completely ionized. Therefore, it has poor lipid solubility and does not readily penetrate into the CNS or eye. It is unknown if it is excreted into milk or crosses the placenta.
Isopropamide is excreted in the urine as both unchanged drug and metabolites. Much of the drugis eliminated unchanged in the feces because of its poor absorption.
Contraindications/Precautions - Isopropamide should be considered contraindicated if the patient has a history of hypersensitivity to anticholinergic drugs, tachycardias secondary to thyrotoxicosis or cardiac insufficiency, myocardial ischemia, unstable cardiac status during acute hemorrhage, GI obstructive disease, paralytic ileus, severe ulcerative colitis, obstructive uropathy or myasthenia gravis (unless used to reverse adverse muscarinic effects secondary to therapy).
Antimuscarinic agents should be used with extreme caution in patients with known or suspected
GI infections. Atropine or other antimuscarinic agents can decrease GI motility and prolong retention of the causative agent(s) or toxin(s) resulting in prolonged symptoms. Antimuscarinic agents must also be used with extreme caution in patients with autonomic neuropathy.
Antimuscarinic agents should be used with caution in patients with hepatic disease, renal disease, hyperthyroidism, hypertension, CHF, tachyarrhythmias, prostatic hypertrophy, esophogeal reflux, and geriatric or pediatric patients.

Adverse Effects, Warnings

With the exception of fewer effects on the eye and the CNS, isopropamide can be expected to have a similar adverse reaction profile as atropine (dry mouth, dry eyes, urinary hesitancy, tachycardia, constipation, etc.). High doses may lead to the development of ileus in susceptible animals. For more information refer to the atropine monograph.
Overdosage - Because of its quaternary structure, it would be expected that minimal CNS effectswould occur after an overdose of isopropamide when compared to atropine. See the informationlisted in the atropine monograph for more information.
If a recent oral ingestion, emptying of gut contents and administration of activated charcoal andsaline cathartics may be warranted. Treat symptoms supportively and symptomatically. Do not usephenothiazines as they may contribute to the anticholinergic effects. Fluid therapy and standardtreatments for shock may be instituted.
The use of physostigmine is controversial and should probably be reserved for cases where thepatient exhibits either extreme agitation and is at risk of injuring themselves or others, or for caseswhere supraventricular tachycardias and sinus tachycardias are severe or life-threatening. The usualdose for physostigmine (human) is 2 mg IV slowly (for average sized adult); if no response mayrepeat every 20 minutes until reversal of toxic antimuscarinic effects or cholinergic effects takesplace. The human pediatric dose is 0.02 mg/kg slow IV (repeat q10 minutes as above) and may be areasonable choice for treatment of small animals. Physostigmine adverse effects(bronchoconstriction, bradycardia, seizures) may be treated with small doses of IV atropine.

Drug Interactions

The following drugs may enhance the activity of isopropamide and its derivatives: antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines.
The following drugs may potentiate the adverse effects of isopropamide and its derivatives:primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocularpressure).
Isopropamide and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics.
Isopropamide and its derivatives may antagonize the actions of metoclopramide.
Drug/Laboratory Interactions - Isopropamide iodide may alter thyroid function tests (due tothe iodine component) and will suppress iodine131 uptake. It is recommended that the drug bediscontinued one week prior to testing or treatment.