Histex I/E

Histex I/E Extended-release Oral Suspension is an H1 receptor antagonist indicated for the symptomatic treatment of:

• Seasonal and perennial allergic rhinitis
• Vasomotor rhinitis
• Allergic conjunctivitis due to inhalant allergens and foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Dermatographism
• As therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled
• Amelioration of the severity of allergic reactions to blood or plasma

The dosage of Histex I/E should be individualized based on the severity of the condition and the response of the patient. Start with lower doses and increase as needed and tolerated.

Administer Histex I/E by the oral route only. Measure Histex I/E with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage. A pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose.

Adults and Adolescents 12 years of age and older:Â 7.5 mL to 20 mL (6 to 16 mg) every 12 hours Children 2 to 11 years of age (approximately 0.2 to 0.4 mg/kg/day):

2 to 3 years: 3.75 mL to 5 mL (3 to 4 mg) every 12 hours

4 to 5 years: 3.75 mL to 10 mL (3 to 8 mg) very 12 hours

6 to 11 years: 7.5 mL to 15 mL (6 to 12 mg) every 12 hours

Children Less Than 2 Years Of Age

Histex I/E is contraindicated in children younger than 2 years of age because deaths have been reported in this age group.

Nursing Mothers

Histex I/E is contraindicated in nursing mothers because of the risk of mortality in infants given carbinoxamine-containing products.

Hypersensitivity

Histex I/E is contraindicated in patients who are hypersensitive to carbinoxamine maleate or any of the inactive ingredients in Histex I/E.

Monoamine Oxidase inhibitors

Histex I/E is contraindicated in patients who are taking monoamine oxidase inhibitors (MAOI).

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Pediatric Mortality

Deaths have been reported in children less than 2 years of age who were taking carbinoxamine containing drug products; therefore, Histex I/E is contraindicated in children younger than 2 years of age.

Activities Requiring Mental Alertness

Histex I/E may produce marked drowsiness and impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Histex I/E. Avoid concurrent use of Karbinal ER with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur.

Concomitant Medical Conditions

Histex I/E has anticholinergic (atropine-like) properties and, therefore, should be used with caution in patients with: increased intraocular pressure, narrow angle glaucoma, hyperthyroidism, cardiovascular disease, hypertension, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, or pyloroduodenal obstruction.

Allergic Reactions Due To Sulfites

Histex I/E contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic individuals.

Dosing

Advise patients to measure Histex I/E with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term studies in animals have been performed to determine the possible effects of carbinoxamine on carcinogenesis, mutagenesis, and fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C. Animal reproductive studies have not been conducted with carbinoxamine maleate. It is also not known whether Histex I/E can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Histex I/E should be given to a pregnant woman only if clearly needed.

Labor And Delivery

The effect of Histex I/E on labor and delivery is not known.

Nursing Mother

Because of the risk of mortality in infants given carbinoxamine-containing drugs, use of Histex I/E is contraindicated in nursing mothers.

Pediatric Use

Deaths have been reported in children younger than 2 years of age who were taking carbinoxaminecontaining drug products. Therefore, Histex I/E is contraindicated in children younger than 2 years of age and in nursing mothers. Carbinoxamine may diminish mental alertness or produce sedation in children. Paradoxical reactions with excitation are more likely in younger children.

Geriatric Use

Histex I/E may cause dizziness, hypotension, confusion, or over-sedation in the elderly. Start elderly patients on lower doses and observe closely.

Use of Histex I/E may result in decreased mental alertness with impaired mental or physical abilities.

The most frequent adverse reactions include: sedation, sleepiness, dizziness, disturbed coordination, epigastric distress, and thickening of bronchial

secretions. In clinical use, younger children and older adults may be particularly sensitive to adverse reactions.

The following adverse reactions, listed by body system, have been identified in case reports and during the use of carbinoxamine in observational studies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose and throat.

Cardiovascular: Hypotension, headache, palpitations, tachycardia, extrasystoles.

Central Nervous System: Fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions.

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, constipation.

Hematologic: Hemolytic anemia, thrombocytopenia, agranulocytosis.

Laboratory: Increase in uric acid levels.

Respiratory: Tightness of chest and wheezing, nasal stuffiness.

Urogenital: Urinary frequency, difficult urination, urinary retention, early menses.

Overdosage with carbinoxamine may cause central nervous system depression or stimulation, hallucinations, convulsions, and death. Atropinelike signs and symptoms – dry mouth; fixed, dilated pupils; flushing; and gastrointestinal symptoms may also occur.

The treatment of overdosage consists of discontinuation of Histex I/E and institution of symptomatic and supportive therapy. Vital signs (including respiration, pulse, blood pressure, and temperature) and EKG should be monitored. Induction of vomiting is not recommended. Activated charcoal should be given and gastric lavage should be considered after ingestion of a potentially life-threatening amount of drug. In the presence of severe anticholinergic effects, physostigmine may be useful. Vasopressors may be used to treat hypotension.

Histex I/E after single-dose administration of 16 mg was bioequivalent to the reference carbinoxamine immediate-release oral solution after the administration of two doses of 8 mg six hours apart under fasting conditions. The carbinoxamine mean (SD) peak plasma concentration (Cmax)Â was 28.7 (5.3) ng/mL at 6.7 hours after Histex I/E administration. The plasma half-life of carbinoxamine was 17.0 hours. There was no effect of food on the pharmacokinetic parameters.

Histex I/E after multiple-dose administration of 16 mg every 12 hours for 8 days was bioequivalent to the reference carbinoxamine immediate-release oral solution after multiple-dose administration of 8 mg every 6 hours. The mean (SD) steady-state Cmax was 72.9 (24.4) ng/mL at 5.6 hours after Histex I/E administration. Carbinoxamine mean (SD) minimum plasma concentration at steady-state was 51.8 (20.3) ng/mL.