Chemistry - A propylamine (alkylamine) antihistaminic agent, chlorpheniramine maleate occurs as an 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 commercially available injection is between 4 - 5.2.
Storage/Stability/Compatibility - Chlorpheniramine tablets and sustained-release tablets should be 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 solutions and the following drugs: amikacin sulfate, diatrizoate meglumine 52%/diatrizoate sodium 8% (Renografin-60®), diatrizoate meglumine 34.3%/diatrizoate sodium 35% (Renovist®), diatrizoate sodium 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 used and it is suggested to consult specialized references for more specific information.
Pharmacology - Antihistamines (H1-receptor antagonists) competitively inhibit histamine at H1 receptor sites. They do not inactivate or prevent the release of histamine, but can prevent histamine’s action on the cell. Besides their antihistaminic activity, these agents all have varying degrees of anticholinergic 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 prevent histamine mediated adverse effects.
Pharmacokinetics - Chlorpheniramine pharmacokinetics have not been described in domestic species. In humans, the drug is well absorbed after oral administration, but because of a relatively high degree of metabolism in the GI mucosa and the liver, only about 25-60% of the drug is available to the systemic circulation.
Chlorpheniramine is well distributed after IV injection, the highest distribution of the drug (in rabbits) 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 plasma proteins. 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 antihistamines may 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 of emptying the gut if the ingestion was oral using standard protocols. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other symptoms should be performed using symptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans; barbiturates and diazepam are avoided.
Drug Interactions - Increased sedation can occur if chlorpheniramine is combined with other 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 antigen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing.
Doses - Note: Contents of sustained-release capsules may be placed on food, but should not be allowed to dissolve before ingestion.
a) 4 - 8 mg PO q12h (Kirk 1986)
b) 2 - 4 mg PO bid-tid (Morgan 1988)
As an antihistamine:
a) Pheniramine: 1700-2300 mg/animal in Asian elephants; author’s personal experience (Cheeran, 1995).
Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and
Practice of Fixing Dose of Drugs for Elephants. In: Daniel,J.C. (Editor), A Week with
Elephants; Proceedings of the International Seminar on Asian Elephants.
Bombay Natural History Society; Oxford University Press, Bombay, India pp.
Monitoring Parameters -
1) Clinical efficacy and adverse effects
Client Information/FDA Approval Status - Except in the combination products listed below, no veterinary-approved product is available. Chlorpheniramine is approved for use in humans; the oral dosage forms are either prescription or non-prescription agents, depending on the product’s labeling. The injectable products are prescription only.
Dosage Forms/Preparations -
Veterinary-Approved Products:. None None as a single entity. This compound is also found in the veterinary-approved (dogs, cats, horses) products Diathal® (Schering) and Azimycin® (Schering). Diathal® contains: chlorpheniramine maleate 10 mg/ml, procaine penicillin G 200,000 U/ml, dihydrostreptomycin sulfate 250 mg/ml and diphemanil methylsulfate 25 mg/ml. Azimycin® contains: chlorpheniramine maleate 10 mg/ml, procaine penicillin G 200,000 U/ml, dihydrostreptomycin sulfate 250 mg/ml, dexamethasone 0.5 mg/ml, and procaine HCl 20 mg/ml.
Chlorpheniramine Maleate Oral Tablets 2 mg (chewable), 4 mg, 8 mg (timed release), 12 mg (timed release) (OTC)
Chlorpheniramine Maleate Oral Syrup 2 mg/5 ml in 118 ml btls (OTC)
Chlorpheniramine Maleate Injection 10 mg/ml in 30 ml vials & 100 mg/ml in 10 ml vials; (Rx)
There are many registered trade names for chlorpheniramine; a commonly known product is Chlor-Trimeton® (Schering). Many combination products are available that combine chlorpheniramine with decongestants, analgesics, and/or antitussives.
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