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Antihistamines (Systemic)

This monograph includes information on the following:

1) Azatadine
2) Brompheniramine
3) Cetirizine
4) Chlorpheniramine
5) Clemastine
6) Cyproheptadine
7) Desloratadine
8) Dexchlorpheniramine
9) Dimenhydrinate
10) Diphenhydramine
11) Doxylamine  
12) Fexofenadine
13) Hydroxyzine
14) Loratadine
15) Phenindamine  
16) Tripelennamine

Note: Products listed in this monograph contain single-entity antihistamines. For products containing antihistamines in combination with other medications, refer to Antihistamines and Decongestants (Systemic) , Antihistamines, Decongestants, and Analgesics (Systemic), and Cough/Cold Combinations (Systemic) .



INN:
Chlorpheniramine —Chlorphenamine

VA CLASSIFICATION
Azatadine
Primary: AH109

Brompheniramine
Primary: AH109

Cetirizine
Primary: AH109

Chlorpheniramine
Primary: AH109

Clemastine
Primary: AH109

Cyproheptadine
Primary: AH109

Desloratadine
Primary: AH102

Dexchlorpheniramine
Primary: AH109

Dimenhydrinate
Primary: AH109
Secondary: CN550

Diphenhydramine
Oral
Primary: AH109
Secondary: AU305; CN309; CN550 ; RE302
Parenteral
Primary: CN204



Doxylamine
Primary: AH109
Secondary: CN309

Fexofenadine
Primary: AH102

Hydroxyzine
Primary: AH109
Secondary: CN309

Loratadine
Primary: AH102

Phenindamine
Primary: AH109

Tripelennamine
Primary: AH109


Commonly used brand name(s): Aerius7; Alavert14; Allegra12; Aller-Chlor4; Aller-med10; AllerMax Caplets10; Allerdryl10; Apo-Dimenhydrinate9; Apo-Hydroxyzine13; Atarax13; Banophen10; Banophen Caplets10; Benadryl10; Benadryl Allergy10; Bromphen2; Calm X9; Chlo-Amine4; Chlor-Trimeton4; Chlor-Trimeton Allergy4; Chlor-Trimeton Repetabs4; Chlor-Tripolon4; Chlorate4; Clarinex7; Claritin14; Claritin RediTabs14; Compoz10; Contac 12 Hour Allergy5; Dexchlor8; Dimetane2; Dimetapp Allergy Liqui-Gels2; Dinate9; Diphen Cough10; Diphenhist10; Diphenhist Captabs10; Dormarex 210; Dramamine9; Dramanate9; Gen-Allerate4; Genahist10; Gravol9; Gravol Filmkote9; Gravol I/M9; Gravol I/V9; Gravol L/A9; Gravol Liquid9; Hydrate9; Hyrexin10; Hyzine-5013; Multipax13; Nasahist B2; Nervine Nighttime Sleep-Aid10; Nolahist15; Novo-Hydroxyzin13; Novo-Pheniram4; Nytol QuickCaps10; Nytol QuickGels10; Optimine1; PBZ16; PBZ-SR16; PMS-Dimenhydrinate9; PediaCare Allergy Formula4; Pelamine16; Periactin6; Phenetron4; Polaramine8; Polaramine Repetabs8; Pyribenzamine16; Reactine3; Siladryl10; Sleep-Eze D10; Sleep-Eze D Extra Strength10; Sleep-eze D Extra Strength10; Sominex10; Tavist5; Tavist-15; Telachlor4; Teldrin4; Traveltabs9; Triptone Caplets9; Twilite Caplets10; Unisom Nighttime Sleep Aid11; Unisom SleepGels Maximum Strength10; Vistaril13; Zyrtec3.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antihistaminic (H 1-receptor) — Azatadine; Brompheniramine ; Cetirizine ; Chlorpheniramine ; Clemastine ; Cyproheptadine ; Desloratadine ; Dexchlorpheniramine ; Dimenhydrinate ; Diphenhydramine ; Doxylamine ;  Fexofenadine ; Hydroxyzine ; Loratadine ; Phenindamine ;  Tripelennamine ;

Antianxiety agent—Hydroxyzine;

Antidyskinetic—Diphenhydramine;

Antiemetic—Dimenhydrinate; Diphenhydramine; Hydroxyzine (parenteral);

Antitussive—Diphenhydramine Elixir;

Antivertigo agent—Dimenhydrinate; Diphenhydramine;

Sedative-hypnotic—Diphenhydramine; Doxylamine;  Hydroxyzine;

Appetite stimulant—Cyproheptadine;

Vascular headache suppressant—Cyproheptadine;

Antiasthmatic—Cetirizine; Loratadine;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Rhinitis, perennial and seasonal allergic or vasomotor (prophylaxis and treatment) or
Conjunctivitis, allergic (prophylaxis and treatment)—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.{02} {12} {13}{48}

Pruritus (treatment)
Urticaria (treatment)
Angioedema (treatment)
Dermatographism (treatment) or
Transfusion reactions, urticarial (treatment)— 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. Cyproheptadine may be particularly useful for cold urticaria,{02} {12} {14}dermatitis including neurodermatitis and neurodermatitis circumscripta, eczema, eczematoid dermatitis, mild local allergic reactions to insect bites, angioneurotic edema, drug and serum reactions, anogenital pruritus and pruritus of chickenpox. {48} [Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea.]1

Sneezing (treatment) or
Rhinorrhea (treatment)—Antihistamines are indicated for the relief of sneezing and rhinorrhea associated with the common cold {12}. However, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. Non-sedating (i.e., second-generation) antihistamines are unlikely to be useful in the treatment of the common cold symptoms since they do not have clinically significant anticholinergic effects (e.g., drying effects on nasal mucosa). {15}

Anaphylactic or anaphylactoid reactions (treatment adjunct)—Antihistamines are indicated as adjunctive therapy to epinephrine and other standard measures for anaphylactic reactions after the acute manifestations have been controlled, and to ameliorate the allergic reactions to blood or plasma.{02}{12}{48}

Anxiety (treatment) and
Tension, psychosis-related (treatment)—Hydroxyzine is indicated for the relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. The effectiveness of hydroxyzine as an antianxiety agent for long-term use (for example, more than 4 months) has not been assessed by systematic clinical studies. {12}

Alcohol withdrawal (treatment)—Parenteral hydroxyzine is indicated in the acute or chronic alcoholic with anxiety withdrawal symptoms. {12}

Parkinsonism (treatment)1 or
Extrapyramidal reactions, drug-induced (treatment) 1—Diphenhydramine is indicated for the symptomatic treatment of parkinsonism and drug-induced extrapyramidal reactions in elderly patients unable to tolerate more potent antidyskinetic medications, for mild cases of parkinsonism in other age groups and, in combination with centrally acting anticholinergic agents, for other cases of parkinsonism. {12}

Cough (treatment)—Diphenhydramine hydrochloride syrup is currently indicated as a non-narcotic cough suppressant for control of cough due to colds or allergy. {12}

Motion sickness (prophylaxis and treatment) or
Vertigo (treatment)—Dimenhydrinate and diphenhydramine are indicated for the prevention and treatment of the nausea, vomiting, dizziness, or vertigo of motion sickness. {12}

Nausea or vomiting (prophylaxis and treatment)— Parenteral hydroxyzine is indicated for the control of nausea and vomiting, excluding nausea and vomiting of pregnancy. {12}

Sedation—Diphenhydramine and hydroxyzine are indicated for their sedative and hypnotic effects and as preoperative medications. {12}

Insomnia (treatment)—Diphenhydramine and doxylamine are indicated as nighttime sleep aids to help reduce the time to fall asleep in patients having difficulty falling asleep. {12}

Analgesia adjunct, during surgery
Anesthesia, general, adjunct or
Anesthesia, local, adjunct—Parenteral hydroxyzine is useful as pre- and postoperative, and pre- and postpartum adjunctive medication to allow reduction in narcotic dosage, and to control anxiety and emesis. {12}

[Appetite, lack of (treatment)]—Cyproheptadine is used as an appetite stimulant, in adults and children.

[Headache, vascular (treatment)]—Cyproheptadine is used for treatment of vascular headaches, such as migraine and histamine cephalalgia.
{48}
[Asthma, bronchial (treatment adjunct) ]1—Cetirizine, and loratadine are used as adjunctive treatment to asthma medications to reduce symptoms and improve bronchodilation in patients with mild atopic asthma. {17} {18} {19} {20}

Unaccepted
Cyproheptadine has been used in the treatment of Cushing's disease because of its pronounced antiserotonin properties, which may decrease corticotropin release. Cyproheptadine may also provide antidiarrheal action against intestinal hypermotility associated with the excessive production of serotonin in patients with carcinoid tumors, and in some other conditions involving the release of serotonin. However, there is no conclusive evidence of effectiveness for these uses.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Ethanolamine derivatives: Clemastine; Dimenhydrinate (chlorotheophylline salt of diphenhydramine); Diphenhydramine; Doxylamine
    Ethylenediamine derivatives: Tripelennamine
    Piperidine derivatives:; Azatadine; Cyproheptadine; Desloratadine; Loratadine; Phenindamine;
    Piperazine derivative: Cetirizine (metabolite of hydroxyzine); Hydroxyzine
    Propylamine derivatives (alkylamines): Brompheniramine; Chlorpheniramine; Dexchlorpheniramine
Molecular weight—
    Azatadine maleate: 522.56
    Brompheniramine maleate: 435.32
    Cetirizine hydrochloride: 461.82
    Chlorpheniramine maleate: 390.87
    Clemastine fumarate: 459.97
    Cyproheptadine hydrochloride: 350.89
    Desloratadine: 310.8{51}
    Dexchlorpheniramine maleate: 390.87
    Dimenhydrinate: 469.97
    Diphenhydramine hydrochloride: 291.82
    Doxylamine succinate: 388.46
    Hydroxyzine hydrochloride: 447.83
    Hydroxyzine pamoate: 763.29
    Loratadine: 382.89
    Phenindamine tartrate: 411.45
    Tripelennamine citrate: 447.49
    Tripelennamine hydrochloride: 291.82

pKa—
    Azatadine maleate: 9.3
    Brompheniramine maleate: 3.59 and 9.12
    Chlorpheniramine maleate: 9.2
    Cyproheptadine hydrochloride: 9.3
    Desloratadine: 4.2 and 9.7{51}
    Diphenhydramine hydrochloride: 9
    Doxylamine succinate: 5.8 and 9.3
    Hydroxyzine hydrochloride: 2.6 and 7
    Tripelennamine: 3.9 and 9

Mechanism of action/Effect:

Antihistaminic (H 1-receptor)—Antihistamines used in the treatment of allergy act by competing with histamine for H 1-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.

Antianxiety agent—Hydroxyzine's sedative action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system (CNS). It is not a cortical depressant.

Antidyskinetic—The actions of diphenhydramine in parkinsonism and in drug-induced dyskinesias appear to be related to a central inhibition of the actions of acetylcholine, which are mediated via muscarinic receptors (anticholinergic action), and to its sedative effects.

Antiemetic; antivertigo agent—The mechanism by which some antihistamines exert their antiemetic, anti–motion sickness, and antivertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect.

Antitussive—Diphenhydramine suppresses the cough reflex by a direct effect on the cough center in the medulla of the brain.

Sedative-hypnotic—Most antihistamines cross the blood-brain barrier and produce sedation due to inhibition of histamine N-methyltransferase and blockage of central histaminergic receptors. Antagonism of other central nervous system receptor sites, such as those for serotonin, acetylcholine, and alpha-adrenergic stimulation, may also be involved. Central depression is not significant with cetirizine (low doses), desloratadine, or loratadine because they do not readily cross the blood-brain barrier. Also, they bind preferentially to peripheral H 1-receptors rather than to central nervous system H 1-receptors.{03}

Appetite stimulant—Cyproheptadine competes with serotonin for receptor sites, thus blocking the responses to serotonin in vascular, intestinal, and other smooth muscles. It is possible that by altering serotonin activity in the appetite center of the hypothalamus, cyproheptadine stimulates appetite.

Vascular headache suppressant—Cyproheptadine's vascular headache suppressant effect is probably due to its antiserotonin action.

Antiasthmatic— Cetirizine, and loratadine have been shown to cause mild bronchodilation and also to block histamine-induced bronchoconstriction in asthmatic patients. Also, loratadine, have been shown to diminish exercise-induced bronchospasm and hyperventilation-induced bronchospasm. Cetirizine has not been shown to be uniformly effective in preventing allergen- or exercise-induced bronchoconstriction; however, due to its inhibition of late-phase eosinophil recruitment after local allergen challenge, it has been shown to be more effective, in higher doses, than other antihistamines in reducing the symptoms of pollen-induced asthma.


Other actions/effects:

Anticholinergic—Antihistamines prevent responses to acetylcholine that are mediated via muscarinic receptors. The ethanolamine derivatives may show greater anticholinergic activity than the other classes of antihistamines. Loratadine, has no significant anticholinergic activity; cetirizine has minimal anticholinergic activity.

Anesthetic, local, dental—Antihistamines are structurally related to local anesthetics and have local anesthetic activity. Local anesthetics prevent the initiation and transmission of nerve impulses by decreasing the permeability of the nerve cell membrane to sodium ions. This action decreases the rate of depolarization of the membrane and prevents the generation of the action potential.

Absorption:

Well absorbed after oral administration.

Note: Ingestion of food may enhance the absorption of loratadine by 40% and of its active metabolite by 15%{03}.
Food may delay the rate, but not the extent of cetirizine absorption.
In one study involving patients 66 to 78 years of age the extent of absorption and peak plasma levels of loratadine and its metabolite were significantly higher (55%) than those in studies with younger patients.{03}
Desloratadine's absorption is not affected by food. Renal impairment and hepatic impairment requires dosage adjustments due to increased AUC (area under the concentration time curve).{51}


Protein binding:

Cetirizine—93%.

Chlorpheniramine—72%.

Desloratadine—82 to 87%.{51}{52} 3-hydroxydesloratadine (active metabolite): 85 to 89%{51}

Diphenhydramine—98 to 99%.

Loratadine—97% (at concentrations of 2.5 to 100 ng/mL). Descarboethoxyloratadine (active metabolite): 73 to 77% (at concentrations of 0.5 to 100 ng/mL).


Biotransformation:

Hepatic (cytochrome P-450 system); some renal. Of the second-generation antihistamine , loratadine is metabolized by the hepatic cytochrome P-450 system and have active metabolites{03}; however, cetirizine is minimally metabolized and excreted unchanged primarily through the kidneys.

Desloratadine is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzymes responsible for the metabolism have not been identified{51}{52}.

Half-life:


Elimination:

Azatadine—12 hours.

Brompheniramine—25 hours.

Cetirizine—8 hours (range, 6.5 to 10 hours).

• In dialysis patients: 20 hours.


• In children: 4.1 to 6 hours.


Chlorpheniramine—14 to 25 hours.

Desloratadine—27 hours.{51}{52}

Diphenhydramine—1 to 4 hours.

Hydroxyzine—20 to 25 hours.

Loratadine—3 to 20 hours (mean, 8.4 hours). Descarboethoxyloratadine (active metabolite): 8.8 to 92 hours (mean, 28 hours).{03}


Note: In children, cetirizine, chlorpheniramine, and hydroxyzine have been found to have shorter elimination half-life values.


Onset of action:


Oral:

Most first-generation antihistamines: 15 to 60 minutes.

Cetirizine: Histamine skin wheal studies—1 and 0.5 hours following 5 and 10 mg doses, respectively {01}.

Desloratadine—Histamine skin wheal studies—within one hour. {51}

Loratadine: Histamine skin wheal studies—1 to 3 hours {03}.



Parenteral:

Dimenhydrinate: Intramuscular, 20 to 30 minutes.



Rectal:

Dimenhydrinate: 30 to 45 minutes.


Time to peak concentration:


Oral:

Azatadine—4 hours.

Brompheniramine—2 to 5 hours.

Cetirizine—1 hour.

Chlorpheniramine—2 to 6 hours.

Clemastine—2 to 4 hours.

Desloratadine—approximately 3 hours. {51}{52}

Diphenhydramine—1 to 4 hours.

Loratadine—1.3 hours {03}.

• Descarboethoxyloratadine (active metabolite)—2.5 hours {03}.



Time to peak effect:


Oral:

Brompheniramine: 3 to 9 hours.

Chlorpheniramine: 6 hours.

Clemastine: 5 to 7 hours.

Loratadine: Histamine skin wheal studies—8 to 12 hours {03}.


Duration of action:


Ethanolamine derivatives:

6 to 8 hours.

• Clemastine: 12 hours.


• Dimenhydrinate: 3 to 6 hours.




Ethylenediamine derivatives:

Tripelennamine: 4 to 6 hours.



Piperazine derivatives:

4 to 6 hours.

• Cetirizine: Up to 24 hours.




Piperidine derivatives:

Azatadine: 12 hours.

Cyproheptadine: 8 hours.

Desloratadine: Histamine skin wheal study—Up to 24 hours. {51}

Loratadine: Histamine skin wheal studies—At least 24 hours {08}.

Phenindamine: 4 to 6 hours.



Propylamine derivatives:

4 to 8 hours.


Elimination:
     Most of the antihistamines studied (except cetirizine) are excreted as metabolites within 24 hours.


Cetirizine—
        Approximately 60% of the total dose administered is excreted unchanged in urine within 24 hours; about 10% is excreted in feces.



Desloratadine—
        Approximately 87% of a 14C-desloratadine dose was equally recovered in urine and feces. {51}{52}



Loratadine—
        Approximately 80% of the total dose administered is excreted equally in urine and feces in the form of metabolic products within 10 days.{03} Twenty-seven percent of the total dose is excreted in the urine in the conjugated form within 24 hours.


Clearance


Cetirizine

The weight-normalized, apparent total body clearance was 33% greater in children aged 7 to 12 years than in adults and 81% to 111% greater in children aged 2 to 5 years than in adults{46}.

Patients with moderate renal impairment had a 70% decrease in clearance compared to normal volunteers{46}.



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to one of the antihistamines may be sensitive to others.

Carcinogenicity/Tumorigenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic, tumorigenic, or mutagenic potential of most antihistamines have not been performed.


Cetirizine

In a 2–year study, cetirizine was not carcinogenic in rats given dietary doses up to 15 times the maximum recommended human daily oral dose for adults and 10 times the maximum recommended human daily oral dose for children on a mg/m2 basis{46}. In another 2–year study in male mice, cetirizine increased the incidence of benign liver tumors at a dose of 6 times the adult maximum recommended daily dose and 4 times the maximum pediatric dose on a mg/m 2 basis{46}. The clinical significance of these findings during long-term use of cetirizine is not known.

Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and the in vivo micronucleus test in rats{46}.



Desloratadine

The carcinogenic potential of desloratadine was assessed using loratadine studies.
{51}


Fexofenadine

The carcinogenic and reproductive toxicity of fexofenadine were assessed using terfenadine# studies with adequate fexofenadine exposure. No evidence of carcinogenicity was observed in an 18 month study in mice and in a 24 month study in rats at oral doses of up to 150 mg/kg of terfenadine# (which led to fexofenadine exposures that were respectively approximately 3 to 5 times the exposure from the maximum recommended daily oral dose of fexofenadine in adults and children).{49}

In in vitro (Bacterial Reverse Mutation, CHO/HGPRT Forward Mutation, and Rat Lymphocyte Chromosomal Aberration assays) and in vivo (Mouse Bone Marrow Micronucleus assay) tests, fexofenadine revealed no evidence of mutagenicity.{49}



Loratadine

In carcinogenicity studies, AUC data demonstrated that the exposure of mice given loratadine 40 mg/kg was 3.6 (loratadine) and 18 (active metabolite) times higher than that for a human given 10 mg/day. Exposure of rats given 25 mg/kg was 28 (loratadine) and 67 (active metabolite) times higher than that for a human given 10 mg/day. Male mice given 40 mg/kg had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg and males and females given 25 mg/kg. The clinical significance of these findings during long-term use of loratadine is not known. {03}



Terfenadine#

Studies in mice and rats have not shown evidence of tumorigenicity when terfenadine# was given in oral doses approximately 5 and 10 times the maximum recommended human daily dose on a mg per square meter of body surface area basis, respectively. Microbial and micronucleus test assays with terfenadine# have not shown evidence of mutagenesis. {08}


Pregnancy/Reproduction

Pregnancy—
Animal studies have suggested that meclizine and cyclizine, chemically related to antihistamines, might have a teratogenic potential


Azatadine, brompheniramine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, dimenhydrinate, and loratadine

Well-controlled studies with azatadine, brompheniramine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, dimenhydrinate, and loratadine in humans have not been done.

Studies in animals have not shown that these medicines cause adverse effects on the fetus.

FDA Pregnancy Category B.



Cetirizine

Adequate and well-controlled studies in humans have not been done. Cetirizine was not teratogenic in mice, rats, and rabbits {01}.

FDA Pregnancy Category B {01}.



Desloratadine

Adequate and well-controlled studies in humans have not been done.

Desloratadine was not teratogenic in rats at doses up to 48 mg/kg/day, or in rabbits at doses up to 60 mg/kg/day.{51}

In a separate study, an increase in pre-implantation loss and a decreased number of implantations and fetuses were noted in female rats at 24 mg/kg. Reduced body weight and slow righting reflex were reported in pups at doses of 9 mg/kg/day or greater. Desloratadine had no effect on pup development at an oral dose of 3 mg/kg/day.{51}

FDA Pregnancy Category C {51}



Diphenhydramine

Adequate and well-controlled studies in humans have not been done.

Studies in rats and rabbits at doses up to 5 times the human dose have revealed no evidence of impaired fertility or harm to the fetus.

FDA Pregnancy Category B.



Doxylamine

The Food and Drug Administration has stated that human epidemiologic data have not produced convincing evidence that the doxylamine and pyridoxine combination, a medication previously prescribed to treat nausea and vomiting during pregnancy, causes diaphragmatic hernias or other birth defects.

FDA Pregnancy Category B {21}.



Fexofenadine

Adequate and well-controlled studies in humans have not been done.{49}

Studies done in rats and rabbits showed no evidence of teratogenicity. Oral doses of terfenadine# up to 300 mg/kg (which led to fexofenadine exposures that were approximately 3 times the maximum recommended daily oral dose of fexofenadine in adults.{49}

Nonteratogenic effects were seen as dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of 150 mg/kg of terfenadine# (approximately 3 times the maximum daily oral dose of fexofenadine in adults based on comparison of fexofenadine AUCs). {49}

FDA Pregnancy Category C{49}



Hydroxyzine

Adequate and well-controlled studies in humans have not been done. However, hydroxyzine is not recommended for use in the early months of pregnancy since studies in rats have shown that it causes fetal abnormalities when given in doses substantially above the human therapeutic range.

FDA Pregnancy Category C {12}.



Tripelennamine

Adequate and well-controlled studies in humans have not been done. However, there is no evidence linking the use of tripelennamine with congenital defects {21}.

Limited animal reproduction studies have not shown that tripelennamine causes adverse effects in the fetus.

FDA Pregnancy Category B {21}.


Breast-feeding

First-generation antihistamines may inhibit lactation because of their anticholinergic actions.

Small amounts of antihistamines are distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants.


Desloratadine:

Desloratadine is distributed into breast milk{51}



Cetirizine:

The extent of distribution into human breast milk is unknown. Studies in dogs indicated that approximately 3% of the dose is distributed into milk {01}.



Loratadine:

Loratadine and its metabolite descarboethoxyloratadine are distributed into breast milk, achieving concentrations equivalent to plasma levels. In one study, approximately 0.03% of the administered dose was distributed into breast milk over 48 hours after maternal ingestion of a single oral dose of 40 mg.


Pediatrics

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 (CNS) excitation, and an increased tendency toward convulsions.

A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines.


Cetirizine, and loratadine:

Although adequate and well-controlled studies have not been done in the pediatric population, loratadine, is not likely, and cetirizine is less likely than first-generation antihistamines, to cause anticholinergic or significant CNS effects in children.



Desloratadine:

No information is available on the relationship of age to the effects of desloratadine in children under 12 years of age. Safety and efficacy have not been established.



Fexofenadine:

In two placebo controlled trials, the safety of fexofenadine in 6 to 11 year old pediatric patients was established for treatment of seasonal allergic rhinitis and was found to significantly reduce total symptom scores.{49}

Based on a extrapolation of the demonstrated efficacy in adults, the safety of fexofenadine in 6 to 11 year old pediatric patients for the treatment of chronic idiopathic urticaria is established.{49}




Adolescents


Desloratadine

Desloratadine is approved for use in adolescents 12 years of age and older.{51}



Geriatrics


Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines.

A paradoxical reaction characterized by hyperexcitability may 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.


Desloratadine, cetirizine, and loratadine:

Desloratadine, and Loratadine are not likely, and cetirizine is less likely than first-generation antihistamines, to cause anticholinergic or significant CNS effects in geriatric patients {14}{51}. However, because elderly patients are more likely to have age-related renal function impairment, cetirizine and loratadine may accumulate and cause anticholinergic or CNS effects when given in such patients at the usual adult dose {01} {03}.



Pharmacogenetics

Desloratadine has higher peak plasma concentration and area under the curve values in females compared with males and in African-Americans compared with Caucasian patients. However, no dosage adjustments are recommended in either case.{51}


Dental

Prolonged use of antihistamines (except cetirizine, desloratadine, or loratadine) may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.
# Products containing terfenadine were withdrawn from the U.S. market by the Food and Drug Administration in February 1998 and from the Canadian market by the Health Protection Branch, Health Canada in August 1998

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: It is not likely that cetirizine, desloratadine, or loratadine will interact with most of the following medications because they lack significant anticholinergic and CNS actions. However, cetirizine and loratadine have been shown to cause dose-related CNS effects (e.g., sedation); and cetirizine has minimal anticholinergic effects.{01}{03}{14}{51}
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antacids, magnesium or aluminum containing    (administration of fexofenadine within 15 minutes of an aluminum or magnesium containing antacid decreased fexofenadine AUC by 41% and C max by 43%.{49})


» Alcohol or
» CNS depression–producing medications, other (see Appendix II )    (concurrent use 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)


» Anticholinergics or other medications with anticholinergic activity (see Appendix II )    (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy)


Apomorphine    (prior administration of dimenhydrinate, diphenhydramine, doxylamine, or hydroxyzine may decrease the emetic response to apomorphine in the treatment of poisoning)


Potent inhibitors of the cytochrome P450 enzyme system such as:
Erythromycin
Fluconazole
Itraconazole
Ketoconazole
Metronidazole
Miconazole     (concurrent use of these medications may increase plasma levels of loratadine; there are no reports to date of serious ventricular arrhythmias associated with increased plasma levels of loratadine)

    (concurrent use of fexofenadine with co-administered ketoconazole and erythromycin may lead to increased plasma levels of fexofenadine, and may also enhance fexofenadine gastrointestinal absorption and decrease fexofenadine gastrointestinal excretion{49})


» Monoamine oxidase (MAO) inhibitors, including furazolidone and procarbazine    (concurrent use of MAO inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended)

{48}
Ototoxic medications (see Appendix II )    (concurrent use with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo)


Photosensitizing medications, other    (concurrent use of these medications with antihistamines may cause additive photosensitizing effects)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results

For all antihistamines:
Skin tests using allergen extracts    (antihistamines may inhibit the cutaneous histamine response, thus producing false-negative results; it is recommended that antihistamines be discontinued at least 72 hours before testing begins [at least 1 week with loratadine ] {05} {06} {07} {09} {11})


For hydroxyzine (in addition to those listed for all antihistamines) :
Urine 17-hydroxycorticosteroid determinations    (false increases have been reported with concurrent use of hydroxyzine)

With physiology/laboratory test values

For cyproheptadine
Amylase and
Prolactin    (serum concentrations may be increased when cyproheptadine is administered with thyrotropin-releasing hormone)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Hepatic function impairment    (desloratadine dosage adjustment recommended due to increases in bioavailability, half-life, and area under the curve.{51})


» Renal function impairment    (Desloratadine dosage adjustment is recommended due to increases in plasma concentration and area under the curve{51})


Risk-benefit should be considered when the following medical problems exist
» Bladder neck obstruction{48} or
» Prostatic hypertrophy, symptomatic{48} or
» Urinary retention, predisposition to{48}    (anticholinergic effects may precipitate or aggravate urinary retention )


» Glaucoma, angle-closure,{02}{48} or predisposition to    (anticholinergic mydriatic effect resulting in increased intraocular pressure may precipitate an attack of angle-closure glaucoma)


Glaucoma, open-angle    (anticholinergic mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted)


Hypersensitivity to the antihistamine used
Caution is recommended when dimenhydrinate, diphenhydramine, or hydroxyzine is used, since their antiemetic action may impede diagnosis of such conditions as appendicitis and obscure signs of toxicity from overdosage of other drugs.
For cyproheptadine:
» Peptic ulcer, stenosing{02}
» Pyloroduodenal obstruction{02}{48}    (anticholinergic effects of cyproheptadine may exacerbate these conditions )


For desloratadine:
Metabolism of desloratadine, impaired    (slow metabolizers of desloratadine may be more susceptible to dose-related adverse events {51})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Anaphylaxis (cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue ; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness ; wheezing){48}
    
blood dyscrasias ( sore throat; fever; unusual bleeding or bruising; unusual tiredness or weakness)— with azatadine, brompheniramine, cyproheptadine, and dexchlorpheniramine{12}{35}{36}{37}{45}
    
cardiac arrhythmias/palpitations/tachycardia (fast pounding or irregular heartbeat or pulse)— less frequent or rare with azatadine, cetirizine, clemastine, cyproheptadine, desloratadine, dexchlorpheniramine, diphenhydramine, or loratadine{03}{04}{12}{26}{28}{35}{37}{39}{40}{41}{45}
    
cholestasis, hepatitis or other hepatic function abnormalities (abdominal or stomach pain; chills; clay-colored stools or dark urine; diarrhea; dizziness; fever; headache; itching){02}
    
convulsions or seizures {48}
    
edema (swelling )
    
paresthesia or neuritis (burning; prickly sensations ; tingling){48}—with cyproheptadine
    
urticaria (hives or welts; itching; redness of skin; skin rash)—with desloratadine{51}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness
    
dryness of mouth, nose, or throat
    
gastrointestinal upset, stomach pain, or nausea —with azatadine, diphenhydramine, , and tripelennamine
    
headache —with desloratadine{51}
    
increased appetite or weight gain —with , cyproheptadine
    
pharyngitis (body aches or pain ; congestion ; cough; dryness or soreness of throat; fever; hoarseness; runny nose; tender, swollen glands in neck; trouble in swallowing ; voice changes)— with desloratadine. {51}
    
thickening of mucus —with azatadine and cyproheptadine{02}{03}{04}{08}{10}{12}{26}{28}{30}{33}{34}{35}{36}{37}{38}{39}{40}{41}{42}{43}{44}{45}
Note: Tolerance to central nervous system effects may develop quickly with some antihistamines, so that sedation is no longer troublesome after a few days.
Incidence of sedation may increase when the recommended doses of loratadine are exceeded.



Incidence less frequent or rare
    
Blurred vision or any change in vision —with azatadine, cetirizine, cyproheptadine, diphenhydramine, and loratadine,
    
confusion —with azatadine, cetirizine, cyproheptadine, diphenhydramine, and loratadine, ; not reported with diphenhydramine
    
difficult or painful urination —with azatadine, cetirizine, chlorpheniramine, cyproheptadine, dexclorpheniramine, loratadine, and tripelennamine
    
dizziness — except with brompheniramine, hydroxyzine, and tripelennamine
    
drowsiness —with brompheniramine, chlorpheniramine; reported with high doses of desloratadine and loratadine{51}
    
dryness of mouth, nose, or throat —with cetirizine and loratadine
    
dysmenorrhea ( difficult or painful menstruation)— with desloratadine
    
dyspepsia ( acid or sour stomach; belching; heartburn; indigestion; stomach discomfort upset or pain)—with desloratadine
    
increased appetite or weight gain —with cetirizine and loratadine
    
increased sweating —with azatadine, cetirizine, chlorpheniramine, cyproheptadine, loratadine, and
    
fatigue ( unusual tiredness or weakness)— with desloratadine{51}
    
loss of appetite —with cetirizine, chlorpheniramine, cyproheptadine, and loratadine
    
myalgia ( joint pain; swollen joints; muscle aching or cramping; muscle pains or stiffness; difficulty in moving)— with desloratadine{51}
    
nausea — with desloratadine
    
paradoxical reaction (nightmares; unusual excitement, nervousness, restlessness, or irritability)—except with azatadine, chlorpheniramine, cyproheptadine, desloratadine, hydroxyzine, and loratadine
    
photosensitivity (increased sensitivity of skin to sun)—with azatadine, cetirizine, cyproheptadine, and loratadine, {03}
    
ringing or buzzing in ears —with azatadine, cetirizine, cyproheptadine, and loratadine {03}
    
skin rash — with azatadine, brompheniramine, cetirizine, clemastine, cyproheptadine, loratadine,{03} and tripelennamine
    
gastrointestinal upset, stomach pain, or nausea —with cetirizine, clemastine, cyproheptadine, and loratadine
    
tachycardia (fast heartbeat)—with azatadine, cetirizine, cyproheptadine, and loratadine,{03}
    
thickening of mucus — with cyproheptadine, dexchlorpheniramine and diphenhydramine
    
abnormal coordination (clumsiness or unsteadiness)
    
constipation
    
diarrhea
    
early menses
    
fatigue
    
tremor
    
vomiting —with cyproheptadine

Note: Confusion; difficult or painful urination; drowsiness; dizziness; and dryness of mouth, nose, or throat are more likely to occur in the elderly.
Nightmares, unusual excitement, nervousness, restlessness, or irritability is more likely to occur in children and elderly patients.






Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).

Clinical effects of overdose
Symptoms of overdose
    
Anticholinergic effects (clumsiness or unsteadiness; severe drowsiness; severe dryness of mouth, nose, or throat ; flushing or redness of face; shortness of breath or troubled breathing)— especially with azatadine and clemastine
{35}{39}    
cardiac arrhythmias (fast or irregular heartbeat){04} {34} {42} ; less frequent with azatadine and clemastine
    
CNS depression (severe drowsiness)
    
CNS stimulation (hallucinations, seizures, trouble in sleeping)
    
hypotension (feeling faint)
Note: Anticholinergic and CNS stimulant effects are more likely to occur in children with overdose. Hypotension may also occur in the elderly at usual doses.
Anticholinergic and CNS effects may be less likely to occur with , cetirizine, desloratadine or, loratadine, than with the first-generation antihistamines.


    
somnolence (sleepiness or unusual drowsiness)—especially with desloratadine


Treatment of overdose
Since there is no specific antidote for overdose with antihistamines, treatment is symptomatic and supportive.


To decrease absorption:
Induction of emesis (syrup of ipecac recommended); however, precaution against aspiration is necessary, especially in infants and children.

Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within 3 hours of ingestion.



To enhance elimination:
Saline cathartics (milk of magnesia) are sometimes used.



Specific treatment:
Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure.

Oxygen and intravenous fluids.

Precaution against use of stimulants (analeptic agents) because they may cause seizures.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antihistamines (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to any antihistamine

Pregnancy—Not taking during early months of pregnancy because of fetal abnormalities in studies in animals (for hydroxyzine only)





Breast-feeding—Use not recommended; may cause unusual excitement or irritability in nursing infant




Use in children——Increased susceptibility to anticholinergic side effects in newborn or premature infants; hyperexcitability (paradoxical reaction) may occur in children





Use in the elderly—— Increased susceptibility to anticholinergic side effects; hyperexcitability (paradoxical reaction) may occur




Dental——Increased risk of dental problems because of decrease or inhibition of salivary flow
Other medications, especially alcohol or other CNS depressants, anticholinergics or other medications with anticholinergic activity, or MAO inhibitors
Other medical problems, especially angle closure glaucoma, bladder neck obstruction, hepatic or renal impairment (with desloratadine), prostatic hypertrophy, pyloroduodenal obstruction (with cyproheptadine), stenosing peptic ulcer (with cyproheptadine) or urinary retention.

Proper use of this medication
» Importance of not taking more medication than the amount recommended

» Proper dosing
If on scheduled dosing regimen—Using as soon as possible; not using if almost time for next dose; not doubling doses

» Proper storage

For oral dosage forms
Taking with food, water, or milk to minimize gastric irritation

Swallowing extended-release dosage forms whole

For injection dosage forms
Knowing correct administration technique for self-administration; checking with physician if necessary

For rectal dosage forms
Proper administration technique

For dimenhydrinate and diphenhydramine when used as antivertigo agent
Taking at least 30 minutes (preferably 1 to 2 hours) before traveling

Precautions while using this medication
Possible interference with skin tests using allergens; need to inform physician if using medication

May mask ototoxic effects of large doses of salicylates

» Avoiding use of alcohol or other CNS depressants

» Caution if drowsiness occurs

Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

For dimenhydrinate, diphenhydramine, or hydroxyzine
Need to inform physician of use: Possible interference with diagnosis of appendicitis; may mask signs of toxicity from overdosage of other drugs

For diphenhydramine and doxylamine when used in the treatment of insomnia
» Not using concurrently with other sedatives or tranquilizers


Side/adverse effects
Signs of potential side effects, especially anaphylaxis; blood dyscrasias, cardiac arrhythmias/palpitations/tachycardia, cholestasis, convulsions or seizures, dyspnea, edema, hepatitis or other hepatic function abnormalities, convulsions or seizures, paresthesia or neuritis; pruritis, rash, or urticaria)


General Dosing Information

For oral dosage forms only
Most antihistamines may be taken with food, water, or milk to lessen gastric irritation.

For parenteral dosage forms only
Intramuscular injections should be administered deeply into the muscle.

Intravenous injections should be administered slowly, preferably with the patient in a recumbent position.


For hydroxyzine:
Administration should be by deep intramuscular injection into a large muscle mass, preferably the upper outer quadrant of the buttock or the mid-lateral thigh.

Intramuscular injections should not be made into the lower or mid-third of the upper arm.

When used preoperatively or prepartum, narcotic requirements may be decreased as much as 50%.


Note: Products containing terfenadine were withdrawn from the U.S. market by the Food and Drug Administration in February 1998 and from the Canadian market by the Health Protection Branch, Health Canada in August 1998.


Note: Products containing astemizole were withdrawn from the U.S. and Canadian markets by the manufacturer in June 1999.


AZATADINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Piperidine derivative.

pKa—9.3.

Half-life—12 hours.

Time to peak concentration—4 hours.

Duration of action—12 hours.



Side/adverse effects:
Potential for blood dyscrasias; more frequent gastrointestinal upset; no paradoxical reaction.



Oral Dosage Forms

AZATADINE MALEATE TABLETS USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 1 to 2 mg every eight to twelve hours as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Use is not recommended.

Children 12 years of age and over: Oral, 500 mcg (0.5 mg) to 1 mg two times a day as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


1 mg (Rx) [Optimine (scored)]

Canada—


1 mg (Rx) [Optimine (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


BROMPHENIRAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Propylamine derivative.

pKa—3.59 and 9.12.

Half-life—25 hours.

Time to peak concentration—2 to 5 hours.

Time to peak effect—3 to 9 hours.

Duration of action—4 to 8 hours.



Side/adverse effects:
Sedative effects less pronounced.

Potential for blood dyscrasias.



Oral Dosage Forms

BROMPHENIRAMINE MALEATE CAPSULES

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 4 mg every four to six hours as needed.


Usual adult prescribing limits
Up to 24 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)


• Children younger than 12 years of age: See Brompheniramine Maleate Elixir USP .


• Children 12 years of age and over: Oral, 4 mg every four to six hours as needed.


Note: The available strength of the capsule may not conform to some of the recommended pediatric dosages.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg (Rx) [Dimetapp Allergy Liqui-Gels]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


BROMPHENIRAMINE MALEATE ELIXIR USP

Usual adult and adolescent dose
See Brompheniramine Maleate Capsules .

Usual adult prescribing limits
See Brompheniramine Maleate Capsules .

Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface per day, in three or four divided doses, as needed; or for

• Children 2 to 6 years of age: Oral, 1 mg every four to six hours as needed.


• Children 6 to 12 years of age: Oral, 2 mg every four to six hours as needed.


• Children 12 years of age and over: Oral, 4 mg every four to six hours as needed.



Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Brompheniramine Maleate Capsules .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2 mg per 5 mL (Rx/OTC) [Bromphen][Generic]


2 mg per 5 mL (OTC)[Generic]

Canada—


2 mg per 5 mL (OTC) [Dimetane (alcohol 3%)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


BROMPHENIRAMINE MALEATE TABLETS USP

Usual adult and adolescent dose
See Brompheniramine Maleate Capsules .

Usual pediatric dose
See Brompheniramine Maleate Elixir USP .

Note: The available strength of the tablet may not conform to some of the recommended pediatric dosages.


Usual geriatric dose
See Brompheniramine Maleate Capsules .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


4 mg (OTC) [Dimetane]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

BROMPHENIRAMINE MALEATE INJECTION USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Intramuscular, intravenous, or subcutaneous, 10 mg every eight to twelve hours as needed.


Usual adult prescribing limits
Up to 40 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Intramuscular, intravenous, or subcutaneous, 125 mcg (0.125 mg) per kg of body weight or 3.75 mg per square meter of body surface three or four times a day as needed.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


10 mg per mL (Rx) [Nasahist B][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
Crystallization may occur if cooled below 0 °C (32 °F); but on warming to 30 °C (86 °F), the crystals will redissolve.

Additional information:
The period of protection provided by a single dose ranges from three to twelve hours.


CETIRIZINE

Summary of Differences


Indications:
Used as treatment adjunct in asthma.



Pharmacology/pharmacokinetics:
Chemical group—Hydroxyzine metabolite.

Absorption—Decreased absorption rate, but not extent, with food.

Protein binding—93%.

Half-life—8 hours.

Time to peak concentration—1 hour.



Side/adverse effects:
Minimal sedative effects.



Oral Dosage Forms

CETIRIZINE HYDROCHLORIDE SYRUP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 5 to 10 mg once a day {01}.


Note: In patients with reduced creatinine clearance (< 31 mL per min) and with hepatic impairment, a dose of 5 mg once a day is recommended {01}.


Usual adult prescribing limits
10 mg a day {01}.

Usual pediatric dose
Antihistaminic (H 1-receptor)1
Children up to 2 years of age: Safety and efficacy have not been established. {26}{46}

Children 2 to 6 years of age: Oral, 2.5 mg once a day. The dosage may be increased to a maximum daily dose of 5 mg, given as 5 mg once a day or 2.5 mg every 12 hours. {26}{46}

Children 6 years of age and older: Oral, 5 or 10 mg once a day. {01} {26}{46}

Note: The dosage should be decreased in patients who have reduced renal function (creatinine clearance of 11–31 mL per minute) or hepatic function impairment. In patients up to 6 years of age with renal or hepatic dysfunction, cetirizine use is not recommended. For children 6 years of age and older, the lower dosage of 5 mg once a day should be used. {26}{46}



Usual geriatric dose
See Usual adult and adolescent dose {01} {26}.

Strength(s) usually available
U.S.—


5 mg per 5 mL (Rx) [Zyrtec (alcohol and dye free)]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by the manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CETIRIZINE HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
See Cetirizine Syrup .


Usual pediatric dose
Antihistaminic (H 1-receptor)
See Cetirizine Syrup .


Usual geriatric dose
See Cetirizine Syrup .

Strength(s) usually available
U.S.—


5 mg (Rx) [Zyrtec (dye free)]


10 mg (Rx) [Zyrtec (dye free)]

Canada—


10 mg (OTC) [Reactine{29}] [Zyrtec{28}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENIRAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Propylamine derivative.

pKa—9.2.

Protein binding—72%.

Half-life—14 to 25 hours.

Time to peak concentration—2 to 6 hours.

Time to peak effect—6 hours.

Duration of action—4 to 8 hours.



Side/adverse effects:
Sedative effects less pronounced; no paradoxical reaction.



Oral Dosage Forms

CHLORPHENIRAMINE MALEATE EXTENDED-RELEASE CAPSULES USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 8 or 12 mg every eight to twelve hours as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Use is not recommended.

Children 12 years of age and over: Oral, 8 mg every twelve hours as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


8 mg (Rx) [Telachlor][Generic]


8 mg (OTC)[Generic]


12 mg (Rx) [Telachlor][Generic]


12 mg (OTC) [Teldrin][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Swallow capsules whole.
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENIRAMINE MALEATE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 4 mg every four to six hours as needed.


Usual adult prescribing limits
Up to 24 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, 87.5 mcg (0.0875 mg) per kg of body weight or 2.5 mg per square meter of body surface every six hours as needed; or for

• Children up to 6 years of age: Use is not recommended.


• Children 6 to 12 years of age: Oral, 2 mg three or four times a day as needed, not to exceed 12 mg per day.



Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


1 mg per 5 mL (OTC) [PediaCare Allergy Formula]


2 mg per 5 mL (OTC) [Aller-Chlor (alcohol 7%)] [Chlor-Trimeton ( alcohol 5%)][Generic]

Canada—


2.5 mg per 5 mL (OTC) [Chlor-Tripolon (alcohol 7%)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENIRAMINE MALEATE TABLETS USP

Usual adult and adolescent dose
See Chlorpheniramine Maleate Syrup USP .

Usual pediatric dose
See Chlorpheniramine Maleate Syrup USP .

Usual geriatric dose
See Chlorpheniramine Maleate Syrup USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg (Rx) [Phenetron (scored)][Generic]


4 mg (OTC) [Aller-Chlor] [Chlorate] [Chlor-Trimeton ( scored)] [Chlor-Trimeton Allergy] [Gen-Allerate][Generic]

Canada—


4 mg (OTC) [Chlor-Tripolon (scored)] [Novo-Pheniram (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENIRAMINE MALEATE TABLETS (CHEWABLE) USP

Usual adult and adolescent dose
See Chlorpheniramine Maleate Syrup USP .

Usual pediatric dose
See Chlorpheniramine Maleate Syrup USP .

Usual geriatric dose
See Chlorpheniramine Maleate Syrup USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2 mg (OTC) [Chlo-Amine]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Chew before swallowing.
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENIRAMINE MALEATE EXTENDED-RELEASE TABLETS

Usual adult and adolescent dose
See Chlorpheniramine Maleate Extended-release Capsules USP .

Usual pediatric dose
See Chlorpheniramine Maleate Extended-release Capsules USP .

Usual geriatric dose
See Chlorpheniramine Maleate Extended-release Capsules USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


8 mg (Rx) [Phenetron][Generic]


8 mg (OTC) [Chlor-Trimeton Repetabs][Generic]


12 mg (Rx) [Phenetron (sugar-coated)][Generic]


12 mg (OTC) [Chlor-Trimeton Repetabs (sugar-coated)][Generic]

Canada—


12 mg (OTC) [Chlor-Tripolon]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Swallow tablets whole.
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

CHLORPHENIRAMINE MALEATE INJECTION USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Intramuscular, intravenous, or subcutaneous, 5 to 40 mg administered as a single dose as needed.


Usual adult prescribing limits
Up to 40 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Subcutaneous, 87.5 mcg (0.0875 mg) per kg of body weight or 2.5 mg per square meter of body surface every six hours as needed.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


10 mg per mL (Rx)[Generic]

Canada—


10 mg per mL (Rx) [Chlor-Tripolon]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Additional information:
The 10-mg-per-mL solution may be administered intravenously, intramuscularly, or subcutaneously.


CLEMASTINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Ethanolamine derivative.

Other actions/effects—Greater anticholinergic activity.

Time to peak concentration—2 to 4 hours.

Time to peak effect—5 to 7 hours.

Duration of action—12 hours.



Oral Dosage Forms

CLEMASTINE FUMARATE SYRUP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 1.34 mg two times a day or 2.68 mg one to three times a day as needed.


Note: Clemastine is indicated for dermatologic conditions at the 2.68-mg dosage level only.


Usual adult prescribing limits
Up to 8.04 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 6 years of age: Dosage has not been established.

Children 6 to 12 years of age: Oral, 670 mcg (0.67 mg) to 1.34 mg two times a day, not to exceed 4.02 mg per day.


Note: Clemastine is indicated for dermatologic conditions at the 1.34-mg dosage level only.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


0.67 mg per 5 mL (Rx) [Tavist (alcohol 5.5%)][Generic]

Canada—


0.67 mg per 5 mL (OTC) [Tavist (alcohol 6.1%)]

Packaging and storage:
Store below 25 °C (77 °F), preferably between 15 and 25 °C (59 and 77 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CLEMASTINE FUMARATE TABLETS USP

Usual adult and adolescent dose
See Clemastine Fumarate Syrup .

Note: Clemastine is indicated for dermatologic conditions at the 2.68-mg dosage level only.


Usual pediatric dose
See Clemastine Fumarate Syrup.

Note: Clemastine is indicated for dermatologic conditions at the 1.34-mg dosage level only.


Usual geriatric dose
See Clemastine Fumarate Syrup .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


1.34 mg (OTC) [Contac 12 Hour Allergy] [Tavist-1 (scored)][Generic]


2.68 mg (Rx) [Tavist (scored)][Generic]

Canada—


1 mg (base) (OTC) [Tavist (scored)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CYPROHEPTADINE

Summary of Differences


Indications:
Also indicated in cold urticaria and used as an appetite stimulant in adults and children.



Pharmacology/pharmacokinetics:
Chemical group—Piperidine derivative.

pKa—9.3.

Other actions/effects—Serotonin antagonist.

Duration of action—8 hours.



Precautions:



Laboratory value alterations:
May increase serum amylase and serum prolactin concentrations when administered with thyrotropin-releasing hormone.



Side/adverse effects:
Potential for blood dyscrasias; no paradoxical reaction.



Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CYPROHEPTADINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, initially 4 mg every eight hours, the dosage being increased as needed. For most patients the therapeutic range is 4 to 20 mg a day. However, doses up to 32 mg a day have been used occasionally. {48}

[Vascular headache suppressant ]
Initial: Oral, 4 mg at the start of the attack, repeated after thirty minutes if necessary.{48}

Maintenance: Oral, 4 mg every four to six hours.{48}


Usual adult prescribing limits
32 mg per day
{48}
Usual pediatric dose
Antihistaminic (H 1-receptor)


• Children 2 to 6 years of age: Oral, 2 mg every eight to twelve hours as needed, not to exceed 12 mg per day {48}.


• Children 7 to 14 years of age: Oral, 2 mg every six to eight hours as needed, not to exceed 16 mg per day {48}.



Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


2 mg per 5 mL (OTC) [Periactin (alcohol 5%){48}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F),{48} unless otherwise specified by manufacturer. Store in a tight container.{48} Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CYPROHEPTADINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, initially 4 mg every eight hours, the dosage being increased as needed. For most patients the therapeutic range is 4 to 20 mg a day. However, doses up to 32 mg a day have been used occasionally. {02}

[Appetite stimulant]
Oral, 4 mg three times a day with meals.

Note: Treatment period to promote weight gain should not exceed six months.


[Vascular headache suppressant ]
Initial: Oral, 4 mg at the start of the attack, repeated after thirty minutes if necessary.

Maintenance: Oral, 4 mg every four to six hours.


Usual adult prescribing limits
500 mcg (0.5 mg) per kg of body weight daily {02}.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, 125 mcg (0.125 mg) per kg of body weight or 4 mg per square meter of body surface, every eight to twelve hours as needed or for

• Children 2 to 6 years of age: Oral, 2 mg every eight to twelve hours as needed, not to exceed 12 mg per day {02}.


• Children 7 to 14 years of age: Oral, 4 mg every eight to twelve hours as needed, not to exceed 16 mg per day {02}.


[Appetite stimulant]
Children 2 to 6 years of age: Oral, initially 2 mg two or three times a day with meals. The dosage may be increased, if necessary, but not to exceed 8 mg a day.

Children 7 to 14 years of age: Oral, initially 2 mg three or four times a day with meals. The usual maintenance dose is 4 mg two or three times a day. The dosage may be increased, if necessary, but not to exceed 16 mg a day.


Note: Premature and full-term neonates—Use is not recommended.
Treatment period to promote weight gain should not exceed 3 months.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg (Rx) [Periactin (scored){02}][Generic]

Canada—


4 mg (OTC) [Periactin (scored){48}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F),{48} unless otherwise specified by manufacturer. Store in a well-closed container.{02}

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DESLORATADINE

Summary of Differences


Indications:
Used for treatment of allergic rhinitis and chronic idiopathic urticaria.{51}{52}



Pharmacology/pharmacokinetics:
Chemical group—Piperidine derivative; metabolite of loratadine.{51}{52}

Molecular weight—310.8 {51}{52}

pKa—Pyridine functional group; 4.2{52}

pKa—Piperidine functional group; 9.7{52}

Protein binding—desloratadine 82 to 87% ; 3-hydroxydesloratadine (active metabolite): 85 to 89%{51}

Half-life—27 hours. {51}{52}

Onset of action—Histamine skin wheal studies—within one hour.{51}

Time to peak concentration—approximately 3 hours. {51}{52}

Duration of action—Histamine skin wheal studies—up to 24 hours. {51}



Precautions:
Medical considerations/contraindications—hepatic and renal impairment cause increases in pharmacokinetic parameters requiring dosage adjustments.{51}



Side/adverse effects:
May cause anaphylaxis, dry mouth, dysmenorrhea, dyspepsia, dyspnea, fatigue, edema, headache, myalgia, nausea, pharyngitis, pruritus, rash, somnolence, tachycardia or urticaria.{51}



Oral Dosage Forms

DESLORATADINE TABLETS

Usual adult and adolescent dose
Rhinitis, allergic (treatment)
Oral, 5 mg once daily. {51}{52}

Urticaria, idiopathic, chronic (treatment)
Oral, 5 mg once daily. {51}{52}


Note: In patients with liver or renal impairment, U.S. prescribing information recommends a starting dose of Oral, 5 mg every other day.{51}


Usual Pediatric Dose
Safety and efficacy have not been established.
{51}{52}
Geriatric Dose
SeeUsual adult and adolescent dose.
{51}{52}
Strength(s) usually available
U.S.—


5 mg (Rx) [Clarinex]{51}

Canada—


5 mg (Rx) [Aerius]{52}

Packaging and storage:
Store between 2 and 25 °C (36 and 77 °F). Avoid exposure at or above 30 °C (86 °F). Heat sensitive. Protect from moisture. {51}

Note: Canadian product information states to store between 15 and 30 °C. {52}


Auxiliary labeling:
   • Do not use if you are breast-feeding. Contact your doctor or pharmacist.


DEXCHLORPHENIRAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Propylamine derivative.

Duration of action—4 to 8 hours.



Side/adverse effects:
Potential for blood dyscrasias; thickening of mucus less pronounced.



Oral Dosage Forms

DEXCHLORPHENIRAMINE MALEATE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 2 mg every four to six hours as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Oral, 150 mcg (0.15 mg) per kg of body weight or 4.5 mg per square meter of body surface per day, in four divided doses or for

• Children 2 to 5 years of age: Oral, 500 mcg (0.5 mg) every four to six hours as needed.


• Children 5 to 12 years of age: Oral, 1 mg every four to six hours as needed.



Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2 mg per 5 mL (Rx) [Polaramine (alcohol 6%)]

Canada—


2 mg per 5 mL (OTC) [Polaramine (alcohol 5%)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DEXCHLORPHENIRAMINE MALEATE TABLETS USP

Usual adult and adolescent dose
See Dexchlorpheniramine Maleate Syrup USP .

Usual pediatric dose
See Dexchlorpheniramine Maleate Syrup USP .

Usual geriatric dose
See Dexchlorpheniramine Maleate Syrup USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2 mg (Rx) [Polaramine]

Canada—


2 mg (OTC) [Polaramine]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DEXCHLORPHENIRAMINE MALEATE EXTENDED-RELEASE TABLETS

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 4 or 6 mg every eight to twelve hours as needed.


Usual pediatric dose
Use is not recommended.

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg (Rx) [Dexchlor] [Polaramine Repetabs (sugar-coated)][Generic]


6 mg (Rx) [Dexchlor] [Polaramine Repetabs (sugar-coated)][Generic]

Canada—


6 mg (OTC) [Polaramine Repetabs]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Swallow tablets whole.
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIMENHYDRINATE

Summary of Differences


Category:
Also indicated as an antiemetic and antivertigo agent.



Pharmacology/pharmacokinetics:
Chemical group—Ethanolamine derivative.

Other actions/effects—Greater anticholinergic activity.

Duration of action—3 to 6 hours.



Precautions:
Drug interactions and/or related problems—May decrease emetic response to apomorphine.

Medical considerations/contraindications—May impede diagnosis of appendicitis; may obscure signs of overdose.



Additional Dosing Information
See also General Dosing Information .

When dimenhydrinate is used for prophylaxis of motion sickness, it should be taken at least 30 minutes, and preferably 1 or 2 hours, before exposure to conditions that may precipitate motion sickness.
For parenteral dosage form only

   • Do not administer intra-arterially.


Oral Dosage Forms

DIMENHYDRINATE EXTENDED-RELEASE CAPSULES

Usual adult and adolescent dose
Antiemetic or
Antivertigo agent
Oral, 1 capsule every twelve hours.


Usual pediatric dose
Use is not recommended.

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


75 mg (25 mg for immediate release and 50 mg for extended release) (OTC) [Gravol L/A{27}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIMENHYDRINATE ORAL SOLUTION

Usual adult and adolescent dose
Antiemetic or
Antivertigo agent
Oral, 50 to 100 mg every four to six hours. {10} {27}


Usual adult prescribing limits
400 mg per 24 hours. {10} {27}

Usual pediatric dose
Antiemetic or
Antivertigo agent
Children 2 to 6 years of age: Oral, 12.5 to 25 mg every six to eight hours as needed, not to exceed 75 mg per day {10} {27}.

Children 6 to 12 years of age: Oral, 25 to 50 mg every six to eight hours as needed, not to exceed 150 mg per day {10} {27}.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


12.5 mg per 5 mL (OTC)[Generic]{31}

Canada—


15 mg per 5 mL (OTC) [Gravol Liquid{27} ( alcohol-free)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIMENHYDRINATE SYRUP USP

Usual adult and adolescent dose
See Dimenhydrinate Oral Solution .

Usual adult prescribing limits
See Dimenhydrinate Oral Solution .

Usual pediatric dose
See Dimenhydrinate Oral Solution .

Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Dimenhydrinate Oral Solution .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


12.5 mg per 5 mL (OTC) [Dramamine][Generic]

Canada—


15 mg per 5 mL (OTC) [PMS-Dimenhydrinate{32}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIMENHYDRINATE TABLETS USP

Usual adult and adolescent dose
See Dimenhydrinate Oral Solution .

Usual adult prescribing limits
See Dimenhydrinate Oral Solution .

Usual pediatric dose
See Dimenhydrinate Oral Solution .

Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Dimenhydrinate Oral Solution .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


50 mg (OTC) [Calm X (scored)] [Dramamine (scored)] [Triptone Caplets][Generic]

Canada—


15 mg (OTC) [Gravol Filmkote{27}]


25 mg (OTC) [Gravol Filmkote{27} (Junior Strength )]


50 mg (OTC) [Apo-Dimenhydrinate] [Gravol Filmkote{27}] [PMS-Dimenhydrinate] [Traveltabs]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIMENHYDRINATE TABLETS (CHEWABLE) USP

Usual adult and adolescent dose
See Dimenhydrinate Oral Solution .

Usual adult prescribing limits
See Dimenhydrinate Oral Solution .

Usual pediatric dose
See Dimenhydrinate Oral Solution .

Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Dimenhydrinate Oral Solution .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


50 mg (OTC) [Dramamine (scored)]

Canada—


15 mg (OTC) [Gravol{27}]


50 mg (OTC) [Gravol{27}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

DIMENHYDRINATE INJECTION USP

Usual adult and adolescent dose
Antiemetic or
Antivertigo agent
Intramuscular, 50 mg repeated every four hours as needed.

Intravenous, 50 mg in 10 mL of 0.9% sodium chloride injection, administered slowly over a period of at least two minutes, repeated every four hours as needed.


Usual pediatric dose
Antiemetic or
Antivertigo agent
Intramuscular, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, every six hours as needed, not to exceed 300 mg per day.

Intravenous, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, in 10 mL of 0.9% sodium chloride injection, administered slowly over a period of at least two minutes, every six hours as needed, not to exceed 300 mg per day.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


50 mg per mL (Rx) [Dinate] [Dramanate] [Hydrate][Generic]

Canada—


10 mg per mL (Rx) [Gravol I/V{27}{30} (for intravenous administration only) ( ethyl alcohol)]


50 mg per mL (Rx) [Gravol I/M{27}{30} (for intramuscular administration) ( methylparaben) (propylene glycol) (propylparaben {27})]

Note: The 50-mg-per-mL concentration is intended for intramuscular use. To use this concentration for intravenous administration, the solution must be further diluted at a ratio of at least 1:10 (10 mL of diluent for each 1 mL of dimenhydrinate) with a compatible intravenous solution, such as sterile saline or 5% dextrose in water. {27}


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.



Rectal Dosage Forms

DIMENHYDRINATE SUPPOSITORIES

Usual adult and adolescent dose
Antiemetic or
Antivertigo agent
Rectal, 50 to 100 mg every six to eight hours as needed.


Usual pediatric dose
Antiemetic or
Antivertigo agent
Children up to 6 years of age: Dosage has not been established.

Children 6 to 8 years of age: Rectal, 12.5 to 25 mg every eight to twelve hours as needed.

Children 8 to 12 years of age: Rectal, 25 to 50 mg every eight to twelve hours as needed.

Children 12 years of age and over: Rectal, 50 mg every eight to twelve hours as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


25 mg (OTC) [Gravol]

Packaging and storage:
Store between 8 and 15 °C (46 and 59 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.

Note: When dispensing, include patient instructions.



DIPHENHYDRAMINE

Summary of Differences


Category:
Also indicated as an antidyskinetic, antiemetic, antitussive (syrup only), antivertigo agent, and a sedative-hypnotic.



Pharmacology/pharmacokinetics:
Chemical group—Ethanolamine derivative.

pKa—9.

Other actions/effects—Greater anticholinergic activity.

Protein binding—98 to 99%.

Half-life—1 to 4 hours.

Time to peak concentration—1 to 4 hours.

Duration of action—6 to 8 hours.



Precautions:
Drug interactions and/or related problems—May decrease emetic response to apomorphine.

Medical considerations/contraindications—May impede diagnosis of appendicitis; may obscure signs of overdose.



Side/adverse effects:
No confusion; sedative effects and gastrointestinal upset are more pronounced; thickening of mucus less pronounced.



Additional Dosing Information
See also General Dosing Information .

When diphenhydramine is used for prophylaxis of motion sickness, it should be taken at least 30 minutes, and preferably 1 or 2 hours, before exposure to conditions that may precipitate motion sickness.


Oral Dosage Forms

DIPHENHYDRAMINE HYDROCHLORIDE CAPSULES USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 25 to 50 mg every four to six hours as needed.

Antidyskinetic1
For idiopathic and postencephalitic parkinsonism: Oral, 25 mg three times a day initially, the dose then being gradually increased to 50 mg four times a day if needed.

Antiemetic or
Antivertigo agent
Oral, 25 to 50 mg every four to six hours as needed.

Sedative-hypnotic
Oral, 50 mg twenty to thirty minutes before bedtime if needed.


Usual adult prescribing limits
Up to 300 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 6 years of age: Oral, 6.25 to 12.5 mg every four to six hours.

Children 6 to 12 years of age: Oral, 12.5 to 25 mg every four to six hours, not to exceed 150 mg per day.

Antiemetic or
Antivertigo agent
Oral, 1 to 1.5 mg per kg of body weight every four to six hours as needed, not to exceed 300 mg per day.


Note: The available strength of the capsule may not conform to some of the recommended pediatric dosages.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg (Rx)[Generic]


25 mg (OTC) [Banophen] [Benadryl Allergy] [Genahist] [Nytol QuickCaps][Generic]


50 mg (Rx)[Generic]


50 mg (OTC) [Nytol QuickGels] [Sleep-eze D Extra Strength] [Unisom SleepGels Maximum Strength][Generic]

Canada—


25 mg (Rx) [Allerdryl]


25 mg (OTC) [Benadryl]


50 mg (Rx) [Allerdryl]


50 mg (OTC) [Benadryl]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


DIPHENHYDRAMINE HYDROCHLORIDE ELIXIR USP

Usual adult and adolescent dose
See Diphenhydramine Hydrochloride Capsules USP .

Usual adult prescribing limits
See Diphenhydramine Hydrochloride Capsules USP .

Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, every four to six hours, not to exceed 300 mg a day or for

• Children weighing up to 9.1 kg: Oral, 6.25 to 12.5 mg every four to six hours.


• Children weighing 9.1 kg and over: Oral, 12.5 to 25 mg every four to six hours.


Antiemetic or
Antivertigo agent
Oral, 1 to 1.5 mg per kg of body weight every four to six hours as needed, not to exceed 300 mg per day.

Antitussive
Children up to 2 years of age: Dosage must be individualized by physician.

Children 2 to 6 years of age: Oral, 6.25 mg every four to six hours as needed, not to exceed 25 mg per day.

Children 6 to 12 years of age: Oral, 12.5 mg every four to six hours as needed, not to exceed 75 mg per day.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


12.5 mg per 5 mL (Rx)[Generic]


12.5 mg per 5 mL (OTC) [Diphen Cough (alcohol 5%)] [Diphenhist] [Genahist (alcohol 14%)] [Siladryl (alcohol 5.6%)][Generic]

Canada—


12.5 mg per 5 mL (OTC) [Benadryl (alcohol 14%)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


DIPHENHYDRAMINE HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
See Diphenhydramine Hydrochloride Capsules USP .

Usual adult prescribing limits
See Diphenhydramine Hydrochloride Capsules USP .

Usual pediatric dose
See Diphenhydramine Hydrochloride Elixir USP .

Usual geriatric dose
See Diphenhydramine Hydrochloride Capsules USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg (Rx)[Generic]


25 mg (OTC) [Aller-med] [Banophen Caplets] [Benadryl] [Diphenhist Captabs] [Nervine Nighttime Sleep-Aid] [Sleep-Eze D] [Sominex]


50 mg (Rx)[Generic]


50 mg (OTC) [AllerMax Caplets] [Compoz] [Dormarex 2] [Sleep-Eze D Extra Strength] [Twilite Caplets]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

DIPHENHYDRAMINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor) or
Antidyskinetic1
Intramuscular or intravenous, 10 to 50 mg.

Antiemetic or
Antivertigo agent
Intramuscular or intravenous, 10 mg initially, may be increased to 20 to 50 mg every two to three hours.


Usual adult prescribing limits
Up to 100 mg per dose or 400 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor) or
Antidyskinetic
Intramuscular, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, four times a day, not to exceed 300 mg per day.

Antiemetic or
Antivertigo agent
Intramuscular, 1 to 1.5 mg per kg of body weight every six hours, not to exceed 300 mg per day.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


10 mg per mL (Rx)[Generic]


50 mg per mL (Rx) [Benadryl] [Hyrexin][Generic]

Canada—


50 mg per mL (Rx) [Benadryl][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.


DOXYLAMINE

Summary of Differences


Category:
Also indicated as a sedative-hypnotic.



Pharmacology/pharmacokinetics:
Chemical group—Ethanolamine derivative.

pKa—5.8 and 9.3.

Other actions/effects—Greater anticholinergic activity.

Duration of action—6 to 8 hours.



Precautions:



Drug interactions and/or related problems:
May decrease emetic response to apomorphine.



Oral Dosage Forms

DOXYLAMINE SUCCINATE TABLETS USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 12.5 to 25 mg every four to six hours as needed.

Sedative-hypnotic
Oral, 25 mg thirty minutes before bedtime if needed.


Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 6 years of age: Use is not recommended.

Children 6 to 12 years of age: Oral, 6.25 to 12.5 mg every four to six hours as needed.

Sedative-hypnotic
Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg (OTC) [Unisom Nighttime Sleep Aid (scored)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. Protect from light.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


FEXOFENADINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Metabolite of terfenadine{49}

Half-life—14.4 hours.{49}

Time to peak concentration— 2.6 hours{49}.



Oral Dosage Forms

FEXOFENADINE HYDROCHLORIDE CAPSULES

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 60 mg twice daily, or 180 mg once daily.{49}{50}

Urticaria, chronic idiopathic 1
Oral, 60 mg twice daily.
{49}{50}

Note: For patients with decreased renal function, an initial dose of 60 mg once a day is recommended {49}{50}.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Urticaria (treatment)1
Children 12 years of age and older: SeeUsual adult and adolescent dose

Children 6 to 11 years of age: Oral, 30 mg twice daily.{49}{50}

Note: Capsules are not available in a 30 mg dose.


Children up to 6 years of age: Safety and efficacy have not been established.{49}

Note:  In Canada, not indicated for children younger than 12 years of age{50}


Note: For pediatric patients with decreased renal function, an initial dose of 30 mg once a day is recommended{49}{50}



Strength(s) usually available
U.S.—


60 mg (Rx) [Allegra (croscarmellose sodium) ( magnesium stearate) (gelatin) ( lactose) (microcrystalline cellulose) (pregelatinized starch)]{49}

Canada—


60 mg (Rx) [Allegra]

Packaging and storage:
Store at controlled room temperature 20– 25°C (68– 77 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from excessive moisture.
{49}{50}

FEXOFENADINE HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Urticaria (treatment)1
See Fexofenadine Hydrochloride Capsules

{49}{50}
Usual pediatric dose
Antihistaminic (H 1-receptor)
Urticaria (treatment)1
See Fexofenadine Hydrochloride Capsules

Note:  In Canada, not indicated for children younger than 12 years of age

{49}{50}

Strength(s) usually available
U.S.—


30 mg (Rx) [Allegra (croscarmellose sodium) ( magnesium stearate) (microcrystalline cellulose ) (pregelatinized starch)]{49}


60 mg (Rx) [Allegra (croscarmellose sodium) ( magnesium stearate) (microcrystalline cellulose ) (pregelatinized starch)]{49}


180 mg (Rx) [Allegra (croscarmellose sodium) ( magnesium stearate) (microcrystalline cellulose ) (pregelatinized starch)]{49}

Canada—


60 mg (Rx) [Allegra (croscarmellose sodium) ( hydroxypropyl methylcellulose) (iron oxide) (lactose) (magnesium stearate) (microcrystalline cellulose) (povidone ) (polyethylene glycol) ( silicon dioxide) (starch) ( titanium dioxide)]{50}

Packaging and storage:
Store at controlled room temperature 20– 25°C (68– 77 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from excessive moisture.
{49}{50}

HYDROXYZINE

Summary of Differences


Category:
Also indicated in the treatment of anxiety and psychosis-related tension; antiemetic agent and sedative-hypnotic.



Pharmacology/pharmacokinetics:
Chemical group—Piperazine derivative.

pKa—Hydroxyzine hydrochloride: 2.6 and 7.

Half-life (elimination)—20 to 25 hours.

Duration of action—4 to 6 hours.



Precautions:
Pregnancy—Not taking during early months of pregnancy because of fetal abnormalities in studies in animals.

Drug interactions and/or related problems—May decrease emetic response to apomorphine.

Laboratory value alterations—False increases in urine 17-hydroxycorticosteroid determinations.

Medical considerations/contraindications—May impede diagnosis of appendicitis; may obscure signs of overdose.



Side/adverse effects:
No dizziness; no paradoxical reaction.



Oral Dosage Forms

HYDROXYZINE HYDROCHLORIDE CAPSULES

Usual adult and adolescent dose
Antianxiety agent or
Sedative-hypnotic
Oral, 50 to 100 mg as a single dose.

Antihistaminic (H 1-receptor) or
Antiemetic
Oral, 25 to 100 mg three or four times a day as needed.


Usual pediatric dose
Antianxiety agent or
Sedative-hypnotic
Oral, 600 mcg (0.6 mg) per kg of body weight as a single dose.

Antihistaminic (H 1-receptor) or
Antiemetic
Oral, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface every six hours as needed; or for

Children up to 6 years of age: Oral, 30 to 50 mg a day in divided doses, or 12.5 mg every six hours as needed.

Children 6 to 12 years of age: Oral, 50 to 100 mg a day in divided doses, or 12.5 to 25 mg every six hours as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


10 mg (Rx) [Apo-Hydroxyzine] [Novo-Hydroxyzin]


25 mg (Rx) [Apo-Hydroxyzine] [Atarax] [Multipax] [Novo-Hydroxyzin]


50 mg (Rx) [Apo-Hydroxyzine] [Multipax] [Novo-Hydroxyzin]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


HYDROXYZINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
See Hydroxyzine Hydrochloride Capsules .

Usual pediatric dose
See Hydroxyzine Hydrochloride Capsules .

Usual geriatric dose
See Hydroxyzine Hydrochloride Capsules .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


10 mg per 5 mL (Rx) [Atarax (alcohol 0.5%)][Generic]

Canada—


10 mg per 5 mL (Rx) [Atarax]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


HYDROXYZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Hydroxyzine Hydrochloride Capsules .

Usual pediatric dose
See Hydroxyzine Hydrochloride Capsules .

Usual geriatric dose
See Hydroxyzine Hydrochloride Capsules .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


10 mg (Rx) [Atarax][Generic]


25 mg (Rx) [Atarax][Generic]


50 mg (Rx) [Atarax][Generic]


100 mg (Rx) [Atarax][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


HYDROXYZINE PAMOATE CAPSULES USP

Usual adult and adolescent dose
Antianxiety agent or
Sedative-hypnotic
Oral, 50 to 100 mg as a single dose.

Antihistaminic (H 1-receptor) or
Antiemetic
Oral, 25 to 100 mg three to four times a day as needed.


Usual pediatric dose
Antianxiety agent or
Sedative-hypnotic
Oral, 600 mcg (0.6 mg) per kg of body weight as a single dose.

Antihistaminic (H 1-receptor) or
Antiemetic
Oral, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface every six hours as needed; or for

Children 6 years of age and over: Oral, 12.5 to 25 mg every six hours as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—



The equivalent of hydroxyzine hydrochloride


25 mg (Rx) [Vistaril][Generic]


50 mg (Rx) [Vistaril][Generic]


100 mg (Rx) [Vistaril][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


HYDROXYZINE PAMOATE ORAL SUSPENSION USP

Usual adult and adolescent dose
See Hydroxyzine Pamoate Capsules USP .

Usual pediatric dose
Antianxiety agent or
Sedative-hypnotic
Oral, 600 mcg (0.6 mg) per kg of body weight as a single dose.

Antihistaminic (H 1-receptor) or
Antiemetic
Oral, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface every six hours as needed; or for

Children up to 6 years of age: Oral, 12.5 mg every six hours as needed.

Children 6 years of age and over: Oral, 12.5 to 25 mg every six hours as needed.


Usual geriatric dose
See Hydroxyzine Pamoate Capsules USP .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—



The equivalent of hydroxyzine hydrochloride


25 mg per 5 mL (Rx) [Vistaril]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Shake well.
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

HYDROXYZINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Antianxiety agent
Intramuscular, 50 to 100 mg, repeated as needed every four to six hours.

Sedative-hypnotic
Intramuscular, 50 mg as a single dose.

Adjunct to narcotic medication: Intramuscular, 25 to 100 mg.

Antiemetic
Intramuscular, 25 to 100 mg.


Usual pediatric dose
Adjunct to narcotic medication or
Antiemetic
Intramuscular, 1 mg per kg of body weight, or 30 mg per square meter of body surface, as a single dose.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg per mL (Rx) [Vistaril][Generic]


50 mg per mL (Rx) [Hyzine-50] [Vistaril][Generic]

Canada—


50 mg per mL (Rx) [Atarax][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.


LORATADINE

Summary of Differences


Indications:
Used as treatment adjunct in asthma.



Pharmacology/pharmacokinetics:
Chemical group—Piperidine derivative.

Other actions/effects—No significant anticholinergic activity. Mild bronchodilator.

Protein binding—97%.

Half-life—3 to 20 hours.

Onset of action—Histamine skin wheal studies—1 to 3 hours.

Time to peak concentration—1 to 2 hours.

Time to peak effect—Histamine skin wheal studies—8 to 12 hours.

Duration of action—Histamine skin wheal studies—At least 24 hours.



Side/adverse effects:
No paradoxical reaction; sedation more pronounced with large doses.



Oral Dosage Forms

LORATADINE SYRUP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)—Oral, 10 mg once a day {03}.

Note: In patients with hepatic failure or decreased renal function (creatinine clearance < 30 mL per minute), the initial dose should be 10 mg every other day {03}.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children 2 to 6 years of age: Oral, 5 mg once a day.

Children 6 years of age and over: See Usual adult and adolescent dose {03}.


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


5 mg per 5 mL (OTC) [Claritin]

Canada—


5 mg per 5 mL (OTC) [Claritin]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.


LORATADINE TABLETS

Usual adult and adolescent dose
See Loratadine Syrup .

Usual pediatric dose
See Loratadine Syrup .

Usual geriatric dose
See Loratadine Syrup .

Strength(s) usually available
U.S.—


10 mg (OTC) [Claritin (scored)] [Claritin RediTabs (rapidly-disintegrating )]


10 mg (OTC) [Alavert (orally disintegrating)]

Canada—


10 mg (OTC) [Claritin (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.


PHENINDAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Piperidine derivative.

Duration of action—4 to 6 hours.



Oral Dosage Forms

PHENINDAMINE TARTRATE TABLETS

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 25 mg every four to six hours as needed.


Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 6 years of age: Dosage must be individualized by physician.

Children 6 to 12 years of age: Oral, 12.5 mg every four to six hours as needed, not to exceed 75 mg per day.

Children 12 years of age and over: See Usual adult and adolescent dose .


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg (OTC) [Nolahist (scored)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


TRIPELENNAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Ethylenediamine derivative.

pKa—3.9 and 9.

Duration of action—4 to 6 hours.



Side/adverse effects:
Gastrointestinal effects more pronounced; no dizziness.



Oral Dosage Forms

TRIPELENNAMINE CITRATE ELIXIR USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, the equivalent of tripelennamine hydrochloride: 25 to 50 mg every four to six hours as needed.


Usual adult prescribing limits
Up to the equivalent of 600 mg of tripelennamine hydrochloride daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, the equivalent of tripelennamine hydrochloride, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface every six hours as needed, not to exceed 300 mg per day.


Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


37.5 mg of tripelennamine citrate (equivalent to 25 mg of tripelennamine hydrochloride) per 5 mL (Rx) [PBZ (alcohol 12%)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


TRIPELENNAMINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)—Oral, 25 to 50 mg every four to six hours as needed.

Usual adult prescribing limits
Up to 600 mg daily.

Usual pediatric dose
Antihistaminic (H 1-receptor)—Oral, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface every six hours as needed, not to exceed 300 mg per day.

Note: Premature and full-term neonates—Use is not recommended.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg (Rx) [PBZ (scored)]


50 mg (Rx) [PBZ (scored)] [Pelamine (scored)][Generic]

Canada—


50 mg (OTC) [Pyribenzamine (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


TRIPELENNAMINE HYDROCHLORIDE EXTENDED-RELEASE TABLETS

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)—Oral, 100 mg every eight to twelve hours as needed.

Usual adult prescribing limits
Up to 600 mg daily.

Usual pediatric dose
Use is not recommended.

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


100 mg (Rx) [PBZ-SR]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from light.

Auxiliary labeling:
   • Swallow tablets whole.
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Revised: 03/03/2003



References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

  1. Cetirizine product monograph (Zyrtec, Pfizer—US), Rev 9/96.
  1. Product Information: Periactin®, cyproheptadine hydrochloride. Merck & Co, West Point, PA, (PI revised 9/1999) reviewed 10/2000.
  1. Product Information: Claratin®, loratadine tablets, syrup, and rapidly-disintegrating tablets. Schering, Kenilworth, NJ (PI revised 1/99) reviewed 6/2000.
  1. Astemizole package insert (Hismanal, Janssen—US), Rev 2/98, Rec 4/99.
  1. Reviewers' responses on monograph revision of 11/16/93.
  1. Tyolathi J, Lathi A. Start and end of effects of terfenadine and astemizole on histamine-induced wheals in human skin. Acta Derm Venereol (Stockholm) 1989; 69: 269-71.
  1. Davies R, Brook M, Griffiths J. Skin test recovery after astemizole therapy [abstract]. Rev Esp Alergol Immunol Clin 1987; 2: 79.
  1. Terfenadine product labeling, (Seldane, Hoechst Marion Roussel—US), Rev 9/97, Rec 2/98.
  1. Hedrick CL. DIAS Rounds. Astemizole effects on skin testing [letter]. Ann Pharmacother 1992; 26: 1389.
  1. Dimenhydrinate product labeling (Dramamine, Upjohn—US).
  1. Reviewers' responses on monograph revision of 1/28/91.
  1. Dexchlorpheniramine package insert (Polaramine repetabs, Schering—US), Rev 1/91, Rec 4/99.
  1. Davies BH. Prophylactic treatment of seasonal allergic rhinitis. Clin Ther 1991; 13: 87-91.
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  1. West S, Brandon B, Stolley P, et al. A review of antihistamines and the common cold. Pediatr 1975; 56: 100-7.
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  1. Rafferty P. Antihistamines in the treatment of clinical asthma. J Allergy Clin Immunol 1990; 46: 647-50.
  1. Howarth PH. Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy 1990; 20 Suppl 2: 31-41.
  1. Dirksen A, Engel T, Frülund L, et al. Effect of a non-sedative antihistamine (loratadine) in moderate asthma. A double-blind controlled clinical crossover trial. Allergy 1989; 44: 556-71.
  1. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins. 1994.
  1. Reviewers' responses to Allergy and Immunology Panel Ballot, 7/8/92.
  1. Brown MW, Maldonado AL, Meredith CG, et al. Effect of ketoconazole on hepatic oxidative drug metabolism. Clin Pharmacol Ther 1985; 37: 290-7.
  1. Itraconazole package insert (Sporonox, Janssen—US), Rev 1992.
  1. FDA talk paper. Important new safety information about Hismanal. Rockville, MD: Food and Drug Administration; February 1998. Report No.: T98-5.
  1. Cetirizine package insert (Zyrtec, Pfizer—US), Rev 1/97, Rec 4/99.
  1. Dimenhydrinate product monograph (Gravol, Carter-Horner—Canada), Rev 8/97, Rec 1/98.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1920-1.
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  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 677.
  1. Dimenhydrinate. In: Drug topics red book 1998. Montvale, NJ: Medical Economics Company; 1998. p. 696.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1323-4.
  1. Hydroxyzine package insert (Atarax, Pfizer—US), Rev 12/93, Rec 4/99.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 706-7.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1219.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 500.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1297-8.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 308-9.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1633.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 182.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 326-7.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1516-8.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1406-7.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 150-1.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1331.
  1. Product Information: Zyrtec®, cetirizine hydrochloride tablets and syrup. Pfizer Labs, New York, NY (PI revised 3/2000) reviewed 6/2000.
  1. Parfitt K, editor. Martindale: the extra pharmacopeia. 32nd ed. London: The Pharmaceutical Press; 1999. p. 402, 419.
  1. Product Information: Periactin®, cyproheptadine hydrochloride. Johnson & Johnson—Merck, Canada. Compendium of Pharmaceuticals and Specialties, 34th ed, Canadian Pharmacists Association, Ottawa, Ontario, Canada, 2000. p. 1215–6.
  1. Product Information: Allegra®, fexofenadine. Aventis Pharmaceuticals, Kansas City, MO. (PI revised 11/2000) PI reviewed 10/2001.
  1. Product Information: Allegra™, fexofenadine. Aventis Pharma, Laval, Quebec (PI revised 05/2000) PI reviewed 10/2001.
  1. Product Information: Clarinex®, desloratadine. Schering, Kenilworth, NJ, (PI issued 2/2002) reviewed 10/2002.
  1. Product Information: Aerius™, desloratadine. Schering Canada,.Pointe-Claire, Quebec, (PI revised 2/2002) reviewed 10/2002.
  1. Alavert™, loratadine. (12/20/2002). Wyeth. Retrieved February 26, 2003, from The World Wide Web: http://www.wyeth.com/news
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