CHLORPHENIRAMINE MALEATE
Chemistry - A propylamine (alkylamine) antihistaminic agent, chlorpheniramine maleate occurs asan odorless, white, crystalline powder with a melting point between 130 - 135° C and a pKa of 9.2.
One gram is soluble in about 4 ml of water, or 10 ml of alcohol. The pH of the commerciallyavailable injection is between 4 - 5.2.
Chlorpheniramine for injection is reportedly compatible with most commonly used IV solutionsand the following drugs: amikacin sulfate, diatrizoate meglumine 52%/diatrizoate sodium 8%(Renografin-60®), diatrizoate meglumine 34.3%/diatrizoate sodium 35% (Renovist®), diatrizoatesodium 75% (Hypaque®), iothalamate meglumine 60% (Conray®), and iothalamate sodium 80%(Angio-Conray®).
Chlorpheniramine is reportedly incompatible with: calcium chloride, kanamycin sulfate, norepinephrine bitartrate, pentobarbital sodium, and iodipamide meglumine 52% (Cholographin®).
Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents usedand it is suggested to consult specialized references for more specific information.
Chlorpheniramine is well distributed after IV injection, the highest distribution of the drug (inrabbits) occurs in the lungs, heart, kidneys, brain, small intestine and spleen. In humans, the apparent steady-state volume of distribution is 2.5 - 3.2 L/kg and it is about 70% bound to plasmaproteins. It is unknown if chlorpheniramine is excreted into the milk.
Chlorpheniramine is metabolized in the liver and practically all the drug (as metabolites and unchanged drug) is excreted in the urine. In human patients with normal renal and hepatic function, the terminal serum half-life the drug ranges from 13.2-43 hours.
Contraindications/Precautions - Chlorpheniramine is contraindicated in patients who are hypersensitive to it or other antihistamines in its class. Because of their anticholinergic activity, antihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be cautiously used in patients with hyperthyroidism, cardiovascular disease or hypertension.
The sedative effects of antihistamines may adversely affect the performance of working dogs.
Overdosage - Overdosage may cause CNS stimulation (excitement to seizures) or depression(lethargy to coma), anticholinergic effects, respiratory depression, and death. Treatment consists ofemptying the gut if the ingestion was oral using standard protocols. Induce emesis if the patient isalert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may begiven after emesis or gastric lavage. Treatment of other symptoms should be performed usingsymptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizurescaused by antihistamine overdose in humans; barbiturates and diazepam are avoided.
CNS depressant drugs.
Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin.
Laboratory Interactions - Antihistamines can decrease the wheal and flare response to antigenskin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days beforetesting.
One gram is soluble in about 4 ml of water, or 10 ml of alcohol. The pH of the commerciallyavailable injection is between 4 - 5.2.
Storage, Stability, Compatibility
Chlorpheniramine tablets and sustained-release tablets shouldbe store in tight containers. The sustained-release capsules should be stored in well-closed containers. The oral solution and injectable products should be stored in light-resistant containers;avoid freezing. All chlorpheniramine products should be stored at room temperature (15-30°C).Chlorpheniramine for injection is reportedly compatible with most commonly used IV solutionsand the following drugs: amikacin sulfate, diatrizoate meglumine 52%/diatrizoate sodium 8%(Renografin-60®), diatrizoate meglumine 34.3%/diatrizoate sodium 35% (Renovist®), diatrizoatesodium 75% (Hypaque®), iothalamate meglumine 60% (Conray®), and iothalamate sodium 80%(Angio-Conray®).
Chlorpheniramine is reportedly incompatible with: calcium chloride, kanamycin sulfate, norepinephrine bitartrate, pentobarbital sodium, and iodipamide meglumine 52% (Cholographin®).
Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents usedand it is suggested to consult specialized references for more specific information.
Pharmacology - CHLORPHENIRAMINE MALEATE
Antihistamines (H1-receptor antagonists) competitively inhibit histamine at H1receptor sites. They do not inactivate or prevent the release of histamine, but can prevent histamine'saction on the cell. Besides their antihistaminic activity, these agents all have varying degrees ofanticholinergic and CNS activity (sedation). Some antihistamines have antiemetic activity (e.g., diphenhydramine) or antiseritonin activity (e.g., cyproheptadine, azatadine).Uses, Indications
Antihistamines are used in veterinary medicine to reduce or help preventhistamine mediated adverse effects.Pharmacokinetics - CHLORPHENIRAMINE MALEATE
Chlorpheniramine pharmacokinetics have not been described in domesticspecies. In humans, the drug is well absorbed after oral administration, but because of a relativelyhigh degree of metabolism in the GI mucosa and the liver, only about 25-60% of the drug isavailable to the systemic circulation.Chlorpheniramine is well distributed after IV injection, the highest distribution of the drug (inrabbits) occurs in the lungs, heart, kidneys, brain, small intestine and spleen. In humans, the apparent steady-state volume of distribution is 2.5 - 3.2 L/kg and it is about 70% bound to plasmaproteins. It is unknown if chlorpheniramine is excreted into the milk.
Chlorpheniramine is metabolized in the liver and practically all the drug (as metabolites and unchanged drug) is excreted in the urine. In human patients with normal renal and hepatic function, the terminal serum half-life the drug ranges from 13.2-43 hours.
Contraindications/Precautions - Chlorpheniramine is contraindicated in patients who are hypersensitive to it or other antihistamines in its class. Because of their anticholinergic activity, antihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be cautiously used in patients with hyperthyroidism, cardiovascular disease or hypertension.
Adverse Effects, Warnings
Most commonly seen adverse effects are CNS depression (lethargy, somnolence) and GI effects (diarrhea, vomiting, anorexia). The sedative effects of antihistaminesmay diminish with time. Anticholinergic effects (dry mouth, urinary retention) are a possibility.The sedative effects of antihistamines may adversely affect the performance of working dogs.
Overdosage - Overdosage may cause CNS stimulation (excitement to seizures) or depression(lethargy to coma), anticholinergic effects, respiratory depression, and death. Treatment consists ofemptying the gut if the ingestion was oral using standard protocols. Induce emesis if the patient isalert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may begiven after emesis or gastric lavage. Treatment of other symptoms should be performed usingsymptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizurescaused by antihistamine overdose in humans; barbiturates and diazepam are avoided.
Drug Interactions
Increased sedation can occur if chlorpheniramine is combined with otherCNS depressant drugs.
Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin.
Laboratory Interactions - Antihistamines can decrease the wheal and flare response to antigenskin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days beforetesting.