Chlorpheniramine maleate

390.86

390.134644

205-054-0

DTXSID0022804

OILY LIQUID

R06AB54|R - Respiratory system

2933399090

90.7

3.53040

Chlorpheniramine maleate appears as odorless white crystalline solid or white powder with a bitter taste. pH (2% aqueous solution) 5. pH (1% aqueous solution) 4-5. (NTP, 1992)

1.1±0.1 g/cm3

130-135 °C

579.3°C at 760 mmHg

9℃

1.565

H2O: 1-5 g/100 mL at 21 ºC

-20°C Freezer

2.9E-14mmHg at 25°C

9.13 (at 25 °C)

164.5 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

WHITE CRYSTALLINE POWDER; ODORLESS; SOLN ARE ACID TO LITMUS HAVING PH BETWEEN 4 & 5; MP:BETWEEN 130 °C & 135 °C; SLIGHTLY SOL IN ETHER & BENZENE /MALEATE/

Water soluble.

Hydrocarbons, Aliphatic Unsaturated

An acidic salt of an organic amine. Materials in this group are generally soluble in water, though some also may react with water. The resulting solutions contain moderate concentrations of hydrogen ions and have pHs of less than 7.0. Compounds in this group react as weak acids to neutralize bases. These neutralizations generate heat, but less than is generated by neutralization of inorganic acids, inorganic oxoacids, or carboxylic acids. Many of these compounds catalyze organic reactions.

III

6.1(b)

UN 2811 6.1/PG 3

3

25-39/23/24/25-23/24/25-11

36/37/39-45-36/37-16

US6504000

T,F

SENSITIVE TO LIGHT. /MALEATE/

P301 + P312 + P330

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

DHHS/NTP; Toxicology & Carcinogenesis Studies of Chlorpheniramine maleate in F344/N Rats and B6C3F1 Mice Technical Report Series No. 317 (1986) NIH Publication No. 86-2573

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H301 (89.08%): Toxic if swallowed [Danger Acute toxicity, oral]|P260, P261, P264, P270, P271, P280, P301+P310, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P314, P321, P322, P330, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 240 companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P281, P301+P312, P307+P311, P308+P313, P314, P321, P330, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material under ambient temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

Despite widespread use, the first generation antihistamines such as brompheniramine and chlorpheniramine have rarely been linked to liver test abnormalities or to clinically apparent liver injury. A single case report of clinically apparent liver injury with jaundice attributed to dexchlorpheniramine was reported from France. The time to onset was 10 days, and the clinical presentation resembled acute viral hepatitis, with marked elevations in serum aminotransferase levels and jaundice. Recovery was rapid and complete, but jaundice and hepatitis recurred within 10 days of restarting. Immunoallergic features (rash, fever, eosinophilia) were absent as were autoantibodies. Interestingly, the patient tolerated other antihistamines (cetirizine) without difficulty.

Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/|Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/|Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/|Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/|Concurrent use /of other photosensitizing medications/ with antihistamines may cause additive photosensitizing effects. /Antihistamines/

Toxicology and carcinogenesis studies of chlorpheniramine maleate (99% pure) ... were conducted by administering this chemical in deionized water by gavage to 50 male and 50 female F344/N rats and B6C3F1 mice, 5 days/wk for 103 wk. The doses used were: male rats: 0, 15, or 30 mg/kg; female rats: 0, 30, or 60 mg/kg; male mice: 0, 25, or 50 mg/kg; female mice: 0, 100, or 200 mg/kg. ... Under the conditions of these two yr studies, there was no evidence of carcinogenicity for F344/N rats or B6C3F1 mice administered chlorpheniramine maleate in deionized water, 5 days/wk for two yr. Due to high mortality in high dose female rats and high dose male mice, the sensitivity of these groups to detect carcinogenic response was reduced. /The cmpd/ had a proliferative effect on the thyroid gland of female mice, as shown by the increased evidences of follicular cell cysts and hyperplasia in both low dose and high dose groups. /Chlorpheniramine maleate/

Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system excitation, and an increased tendency toward convulsions. A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/|Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/

72%

For the treatment of rhinitis, urticaria, allergy, common cold, asthma and hay fever.

Brompheniramine and chlorpheniramine maleate are first generation antihistamines that are widely used to treat symptoms of allergic rhinitis and the common cold. Clinically apparent liver injury from brompheniramine or chlorpheniramine must be exceeding rare, if it occurs at all.

Antihistamines

Anti-Allergic Agents; Antipruritics; Histamine H1 Antagonists|Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines; Included in US product labeling/|Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. /Antihistamines; Included in US product labeling/|Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea. /Antihistamines; NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for CHLORPHENIRAMINE (10 total), please visit the HSDB record page.

Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system excitation, and an increased tendency toward convulsions. A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/|Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/|Prolonged use of antihistamines ... may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort. /Antihistamines/|ANTIHISTAMINE DRUGS MAY BE OF SOME USE IN MINIMIZING SERUM REACTIONS BUT ARE OF NO THERAPEUTIC VALUE...& MAY EVEN POTENTIATE TOXIC ACTION OF VENOM... /ANTIHISTAMINES/|For more Drug Warnings (Complete) data for CHLORPHENIRAMINE (14 total), please visit the HSDB record page.

5. 5= EXTREMELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-50 MG/KG, BETWEEN 7 DROPS & 1 TEASPOONFUL FOR 70 KG PERSON (150 LB). /ANTIHISTAMINICS/

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H₁-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. (See all compounds classified as Histamine H1 Antagonists.)|Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475) (See all compounds classified as Anti-Allergic Agents.)|Agents, usually topical, that relieve itching (pruritus). (See all compounds classified as Antipruritics.)

Well absorbed in the gastrointestinal tract.|STUDIES IN MAN & EXPTL ANIMALS INDICATE THAT (3)H-CHLORPHENIRAMINE MALEATE IS RAPIDLY & QUANT ABSORBED FROM GUT. ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED, PLASMA T/2 OF CHLORPHENIRAMINE IS ONLY 12-15 HR IN MAN & 3 HR IN DOG. T/2 IN MAN IS ABOUT 3 TIMES LONGER THAN THERAPEUTIC EFFECT...|The H1 antagonists are well absorbed from the GI tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/|H1 blockers are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /Histamine Antagonists: H1 Antagonists/

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.|MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/

21-27 hours|IN MAN...PLASMA T/2 OF CHLORPHENIRAMINE IS...12-15 HR...ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED...|Elimination: 14 to 25 hours

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.|Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/|H1 antagonists inhibit most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/|H1 antagonists strongly block the action of histamine that results in increased permeability and formation of edema and wheal. /Histamine Antagonists: H1 Antagonists/|Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine induced changes in systemic blood pressure parallel these vascular effects. /Histamine Antagonists: H1 Antagonists/|Many of the H1 antagonists tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. These atropine like actions are sufficiently prominent in some of the drugs to be manifest during clinical usage ... . /Histamine Antagonists: H1 Antagonists/

SYMPTOMS: Symptoms of exposure to this compound may include drowsiness, dizziness, sleeplessness, nervousness and excitability. Other symptoms may include sensitivity reactions, dry mouth, weakness, anorexia, nausea, vomiting headache, hypotension, polyuria, heartburn, diplopia, dysuria, blurred vision and dermatitis. Exposure to large amounts may lead to hallucinations, convulsions or death, especially in infants and children. There has been one report of left-sided blepharospasm and dyskinesia on the left side of the face. Other symptoms may include central nervous system depression, local anesthesia, skin sensitization, dryness of the nose and throat, abdominal pain and diarrhea. A dulling of mental alertness may also occur. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits very toxic fumes of chlorine and nitrogen oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

There is no specific therapy for antihistamine poisoning, and treatment is along general symptomatic and supportive lines. ... Should breathing fail, mech support of ventilation offer safer and ... effective means of maintaining resp than use of analeptics which are prone to initiative or intensify convulsive phase. /Antihistamine/

SYMPTOMATOLOGY: 1. CENTRAL NERVOUS DEPRESSION IS USUALLY DOMINANT REACTION IN ADULTS; IT IS EVIDENCED BY DROWSINESS, LETHARGY, FATIGUE, HYPNOSIS, & COMA. RELATED NERVOUS SYMPTOMS INCL VERTIGO, ATAXIA, TINNITUS, & BLURRED VISION. /ANTIHISTAMINICS/|SYMPTOMATOLOGY: 2. CENTRAL NERVOUS HYPEREXCITABILITY OFTEN FOLLOWS INITIAL SEDATION; IN CHILDREN EXCITEMENT IS OFTEN FIRST EVIDENCE OF POISONING. STIMULANT PHASE BRINGS TREMORS, ANXIETY, INSOMNIA, EXCITEMENT, HALLUCINATIONS, DELIRIUM, TOXIC PSYCHOSIS & CONVULSIONS... /ANTIHISTAMINICS/|SYMPTOMATOLOGY: 3. DANGEROUS HYPERPYREXIA MAY OCCUR IN POISONED CHILDREN... 4. GASTROINTESTINAL REACTIONS INCL DRY MOUTH, ANOREXIA, NAUSEA, VOMITING, ABDOMINAL DISTRESS, CONSTIPATION, &/OR DIARRHEA. /ANTIHISTAMINICS/|SYMPTOMATOLOGY: 5. TERMINAL PHASE IS ONE OF SEVERE CENTRAL NERVOUS DEPRESSION, WITH DEATH FROM RESP ARREST OR CARDIOVASCULAR COLLAPSE. /ANTIHISTAMINICS/|For more Human Toxicity Excerpts (Complete) data for CHLORPHENIRAMINE (10 total), please visit the HSDB record page.

Aller-Chlor

TABLETS, 4 MG; REPEAT-ACTION TABLETS, 8 & 12 MG, INJECTION; SYRUP /FROM TABLE/|GRADE: USP /MALEATE/

2-Pyridinepropanamine, .gamma.-(4-chlorophenyl)-N,N-dimethyl-: INACTIVE|TREATMENT OF BASE WITH EQUIMOLAR PORTION OF MALEIC ACID RESULTS IN FORMATION OF MALEATE. /MALEATE/

HIGH PERFORMANCE LIQUID CHORMATOGRAPHIC ANALYSIS OF CHLORPHENIRAMINE IN OINTMENT.

RAPID QUANTITATIVE ANALYSIS OF CHLORPHEN IN PLASMA, SALIVA, AND URINE BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY.

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