GERIATRIC USE SECTION.

GeriatricUse. Carbinoxamine maleateis more likely to cause dizziness, sedation, and hypotension in elderlypatients (approximately 60 years or older). Sedating drugs may alsocause confusion and over sedation in the elderly. Therefore, doseselection for an elderly patient should be cautious, usually startingat the low end of the dosing range, reflecting the greater frequencyof decreased hepatic renal, or cardiac function, and of concomitantdisease or other drug therapy.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Carbinoxamine Maleate Tablets, USP mg are supplied as white, round, scored tablets, debossed CM on one side and scored on the other, and supplied in bottles of 100 tablets, NDC 44523-825-01. Store at 20C to 25C (68F to 77F) [See USP controlled room temperature.]Dispense in tight, light-resistant container with child-resistant closure as defined in the official compendium.Manufactured for: BioComp Pharma(R), Inc. San Antonio, TX 78230 1355 L82501R1017.

INDICATIONS & USAGE SECTION.

INDICATIONSAND USAGE. Carbinoxamine maleateis effective for the symptomatic treatment of:Seasonal and perennial allergic rhinitis.Vasomotorrhinitis.Allergic conjunctivitis due to inhalantallergens and foods.Mild, uncomplicated allergicskin manifestations of urticaria and angio-edema.Dermatographism.As therapy for anaphylacticreactions adjunctiveto epinephrine and other standardmeasures after the acute manifestations have been controlled. Amelioration of the severity of allergic reactions toblood or plasma.

INFORMATION FOR PATIENTS SECTION.

Informationfor Patients. Carbinoxaminemaleate may cause drowsiness; alcohol, sedatives, and tranquilizersmay increase the drowsiness effect. Avoid alcoholic beverages whiletaking this product. Do not take this product if you are taking sedativesor tranquilizers, without first consulting your doctor. Use cautionwhen driving motor vehicle or operating machinery.

MECHANISM OF ACTION SECTION.

Mechanismof Actions. Carbinoxamine maleate,an ethanolamine derivative, is an antihistamine with anticholinergic(drying) and sedative properties. Carbinoxamine appears to competewith histamine (type 1) for receptor siteson effector cells in the gastrointestinal tract, blood vessels andrespiratory tract.

NURSING MOTHERS SECTION.

NursingMothers. Because of the higherrisk of antihistamines for infants generally and for newborns andprematures in particular, use of carbinoxamine maleate is contraindicatedin nursing mothers. (see CONTRAINDICATIONS section).

ADVERSE REACTIONS SECTION.

ADVERSEREACTIONS. The most frequentadverse reactions are underlined:Bodyas Whole: Urticaria, drug rash, anaphylactic shock, photosensitivity,excessive perspiration, chills, dryness of mouth, nose and throat. Cardiovascular: Hypotension, headache,palpitations, tachycardia, extrasystoles. Hematologic: Hemolytic anemia, thrombocytopenia, agranulocytosis. Central Nervous System: Sedation,sleepiness, dizziness, disturbed coordination, fatigue,confusion, restlessness, excitation, nervousness, tremor, irritability,insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo,tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions. Gastrointestinal: Epigastricdistress, anorexia, nausea, vomiting, diarrhea, constipation. Urogenital: Urinary frequency, difficulturination, urinary retention, early menses. Respiratory: Thickening of bronchialsecretions, tightness of chest and wheezing, nasal stuffiness. To report SUSPECTED ADVERSEREACTIONS, contact BioComp Pharma, Inc. at 1-866-762-2365 or FDA at1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis,Mutagenesis, Impairment of Fertility. No long-term studies in animals have been performed to determinethe possible effects of carbinoxamine maleate on carcinogenesis, mutagenesis,and fertility.

CLINICAL PHARMACOLOGY SECTION.

CLINICALPHARMACOLOGY. Mechanismof Actions. Carbinoxamine maleate,an ethanolamine derivative, is an antihistamine with anticholinergic(drying) and sedative properties. Carbinoxamine appears to competewith histamine (type 1) for receptor siteson effector cells in the gastrointestinal tract, blood vessels andrespiratory tract. Pharmacokineticsand Metabolism. Carbinoxamineis well absorbed from the GI tract and appears to be extensively metabolizedby the liver, and excreted in the urine as inactive metabolites within24 hours. Virtually no intact drug is extended in the urine.In study comparing controlled-release suspension anda solution of carbinoxamine, healthy volunteers were administereda single dose of mg carbinoxamine. time to maximum concentration(Tmax) was between 1.5 hours to hours, peak plasma concentration(Cmax) of about 24 ng/mL was observed, and extent of exposure (AUC)was about 286 ng hr/mL. The serum half-life is reported to be 10 to20 hours.. Drug/FoodInteractions. Carbinoxamineshould not be used in patients with hypersensitivity to carbinoxamine.Carbinoxaminemay increase the effects of other drugs such as barbiturates, TCAs,MAO inhibitors such as Phenelzine (Nardil), Tranylcypromine (Parnate),or Selegiline (Eldepryl), alcohol, other antihistamines, and CNS depressants.Carbinoxamine can be taken with or without food.. CardiovascularEffects. Cardiac effects, includingprolongation of QT interval have not been adequately studied. Unlikeother newer antihistamines, severe adverse cardiovascular effectsare uncommon, and usually limited to over dosage situations.. SpecialPopulations. Pediatric PatientsCarbinoxamineshould not be used in newborn or premature infants. Neonates havean increased susceptibility to anticholinergic side effects, suchas CNS excitation, which may lead to convulsions.Pregnancy and LactationSafe use of carbinoxamine during pregnancy has not beenestablished. Therefore, carbinoxamine should not be used in womenwho are, or may become pregnant. Carbinoxamine is in the FDA pregnancyCategory C.Women who are breastfeeding shouldavoid use of carbinoxamine, since small amounts appear to be distributedinto breast milk.Geriatric PatientsCarbinoxamine is more likely to causedizziness, sedation, and hypotension in elderly patients. The incidenceof adverse reactions is higher in the elderly; therefore, dosingadjustment may be necessary in this sub-population.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Carbinoxamine maleate is contraindicated in childrenyounger than years of age.Carbinoxamine maleateis contraindicated in nursing mothers.Carbinoxaminemaleate is contraindicated in patients who are hypersensitive to thedrug or on monoamine oxidase inhibitor therapy. (See Drug Interactionssection).

DESCRIPTION SECTION.

DESCRIPTION. Carbinoxamine maleate is histamine-H1 receptor blockingagent.Each tablet contains mg carbinoxaminemaleate and the following inactive ingredients: anhydrous lactose,magnesium stearate, microcrystalline cellulose, and sodium starchglycolate.Carbinoxamine maleate is freely solublein water. Its structure is:2-[(4-chlorophenyl)-2-pyridinylmethoxy]- N, N- dimethylethanamine (Z)-2-butenedioate(1:1) 16H 19CIN 2OoC 4H 4O MW=406.86 Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGEAND ADMINISTRATION. Carbinoxaminemaleate is contraindicated in children younger than years of age(see CONTRAINDICATIONS).Carbinoxamine maleateshould be taken on an empty stomach with water.DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSEOF THE PATIENT.Carbinoxamine maleate dosageshould bebased on the severity of the condition and the response ofthe patient. The drug is well tolerated in adults in doses as highas 24 mg daily, in divided doses, over prolonged periods. On the otherhand, some patients respond to as little as mg daily.Clinical experience suggests the followingdosage schedules:TabletsUsual Adult Dosage: or tablets (4 to mg) to times daily. Usual Childs Dosage: Six to eleven years 1/2 to tablet (2 to mg) to times daily.

DRUG INTERACTIONS SECTION.

Drug Interactions. Monoamine oxidase inhibitors prolong and intensifythe anticholinergic (drying) effects of antihistamines.Carbinoxamine maleate has additive effects with alcoholand other CNS depressants (hypnotics, sedatives, tranquilizers, etc.).

GENERAL PRECAUTIONS SECTION.

General. As many other antihistamines, carbinoxamine maleatehas an atropine-like action and, therefore, should be used with cautionin patients with: increased intraocular pressure, hyperthyroidism,cardiovascular disease, hypertension.Antihistaminessuch as carbinoxamine maleate should not be used to treat lower respiratorytract symptoms, including asthma.

OVERDOSAGE SECTION.

OVERDOSAGE. Manifestations: Antihistamine overdosagereactions may vary from central nervous system depression to stimulation.Stimulation is particularly likely in children. Atropine-like signsand symptoms dry mouth; fixed, dilated pupils; flushing; and gastrointestinalsymptoms may also occur. Especially in infantsand children, antihistamine overdosage may cause hallucinations, convulsions,or death.The oral LD 50 of carbinoxamine maleate in guinea pigs is 411 mg/kg. Treatment: The treatmentof overdosage with carbinoxamine maleate is essentially symptomaticand supportive. Vital signs (including respiration, pulse, blood pressure,and temperature) and EKG should be monitored. Induction of vomitingis not recommended. Activated charcoal should be given and gastriclavage should be considered after ingestion of potentially life-threateningamount of drug. In the presence of severe anticholinergic effects,physostigmine may be useful. Vasopressors may be used to treat hypotension.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Carton mg. Label mg.

PEDIATRIC USE SECTION.

PediatricUse. Carbinoxamine maleateis contraindicated in children younger than years of age (see CONTRAINDICATIONS).Neonates have an increased susceptibility to anticholinergicside effects, such as CNS excitation, which may lead to convulsions.Carbinoxamine maleate may diminish mental alertness inchildren. In the young child, particularly, they may produce excitation.

PHARMACOKINETICS SECTION.

Pharmacokineticsand Metabolism. Carbinoxamineis well absorbed from the GI tract and appears to be extensively metabolizedby the liver, and excreted in the urine as inactive metabolites within24 hours. Virtually no intact drug is extended in the urine.In study comparing controlled-release suspension anda solution of carbinoxamine, healthy volunteers were administereda single dose of mg carbinoxamine. time to maximum concentration(Tmax) was between 1.5 hours to hours, peak plasma concentration(Cmax) of about 24 ng/mL was observed, and extent of exposure (AUC)was about 286 ng hr/mL. The serum half-life is reported to be 10 to20 hours.. Drug/FoodInteractions. Carbinoxamineshould not be used in patients with hypersensitivity to carbinoxamine.Carbinoxaminemay increase the effects of other drugs such as barbiturates, TCAs,MAO inhibitors such as Phenelzine (Nardil), Tranylcypromine (Parnate),or Selegiline (Eldepryl), alcohol, other antihistamines, and CNS depressants.Carbinoxamine can be taken with or without food.. CardiovascularEffects. Cardiac effects, includingprolongation of QT interval have not been adequately studied. Unlikeother newer antihistamines, severe adverse cardiovascular effectsare uncommon, and usually limited to over dosage situations.

PRECAUTIONS SECTION.

PRECAUTIONS. General. As many other antihistamines, carbinoxamine maleatehas an atropine-like action and, therefore, should be used with cautionin patients with: increased intraocular pressure, hyperthyroidism,cardiovascular disease, hypertension.Antihistaminessuch as carbinoxamine maleate should not be used to treat lower respiratorytract symptoms, including asthma.. Informationfor Patients. Carbinoxaminemaleate may cause drowsiness; alcohol, sedatives, and tranquilizersmay increase the drowsiness effect. Avoid alcoholic beverages whiletaking this product. Do not take this product if you are taking sedativesor tranquilizers, without first consulting your doctor. Use cautionwhen driving motor vehicle or operating machinery.. Drug Interactions. Monoamine oxidase inhibitors prolong and intensifythe anticholinergic (drying) effects of antihistamines.Carbinoxamine maleate has additive effects with alcoholand other CNS depressants (hypnotics, sedatives, tranquilizers, etc.).. Carcinogenesis,Mutagenesis, Impairment of Fertility. No long-term studies in animals have been performed to determinethe possible effects of carbinoxamine maleate on carcinogenesis, mutagenesis,and fertility.. Pregnancy. Pregnancy Category C:Animalreproductive studies have not been conducted with carbinoxamine maleate.It is also not known whether carbinoxamine maleate can cause fetalharm when administered to pregnant woman or can affect reproductivecapacity. Carbinoxamine maleate should be given to pregnant womanonly if clearly needed. NursingMothers. Because of the higherrisk of antihistamines for infants generally and for newborns andprematures in particular, use of carbinoxamine maleate is contraindicatedin nursing mothers. (see CONTRAINDICATIONS section).. PediatricUse. Carbinoxamine maleateis contraindicated in children younger than years of age (see CONTRAINDICATIONS).Neonates have an increased susceptibility to anticholinergicside effects, such as CNS excitation, which may lead to convulsions.Carbinoxamine maleate may diminish mental alertness inchildren. In the young child, particularly, they may produce excitation.. GeriatricUse. Carbinoxamine maleateis more likely to cause dizziness, sedation, and hypotension in elderlypatients (approximately 60 years or older). Sedating drugs may alsocause confusion and over sedation in the elderly. Therefore, doseselection for an elderly patient should be cautious, usually startingat the low end of the dosing range, reflecting the greater frequencyof decreased hepatic renal, or cardiac function, and of concomitantdisease or other drug therapy.

PREGNANCY SECTION.

Pregnancy. Pregnancy Category C:Animalreproductive studies have not been conducted with carbinoxamine maleate.It is also not known whether carbinoxamine maleate can cause fetalharm when administered to pregnant woman or can affect reproductivecapacity. Carbinoxamine maleate should be given to pregnant womanonly if clearly needed.

SPL UNCLASSIFIED SECTION.

Drug/FoodInteractions. Carbinoxamineshould not be used in patients with hypersensitivity to carbinoxamine.Carbinoxaminemay increase the effects of other drugs such as barbiturates, TCAs,MAO inhibitors such as Phenelzine (Nardil), Tranylcypromine (Parnate),or Selegiline (Eldepryl), alcohol, other antihistamines, and CNS depressants.Carbinoxamine can be taken with or without food.

WARNINGS SECTION.

WARNINGS. Deaths have been reported in children less than2 years of age who were taking antihistamines, including carbinoxamine-containingdrug products, therefore, carbinoxamine maleate is contraindicatedin children younger than years of age (see CONTRAINDICATIONS).Antihistamines should be used with considerable cautionin patients with: narrow angle glaucoma, stenosing peptic ulcer, symptomaticprostatic hypertrophy, bladder neck obstruction, pyloroduodenald obstruction.