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TRANSCRIPT
AntihistaminesAuthor: Kimberly Mulcahy, PharmD, BCPS
Editor: Claudia Lee, RPh, MD
Learning Objectives■■ Identify current pharmacologic agents that are appropriate for each condition/diagnosis.■■ Recommend optimal pharmacologic interventions based on patient-specific characteristics.■■ Provide appropriate patient-specific counseling points and optimal overall medication management.
Key Terms: antihistamines, histamine, first-generation antihistamines (ethanolamine derivatives, ethylenediamine derivatives, phenothiazine derivatives, piperazine derivatives, propylamine derivatives, miscellaneous), second- generation antihistamines, allergy, anaphylaxis, antibody, anticholinergic, antigen, anxiolytic, central nervous system, congestion, conjunctivitis, dermatoses, drowsiness, gastric acid, hay fever, insomnia, motion sickness, nausea, rhini-tis, rhinorrhea, sedating, somnolence, urticaria, vomiting
Overview of AntihistaminesAntihistamines are commonly utilized, predominantly over-the-counter (OTC) medications for treatment of aller-gic conditions. Histamine is found throughout the body, including within the vesicles of mast cells or basophils, and is abundant in the mast cells in areas particularly susceptible to tissue injury, such as the nose, mouth, feet, internal body surfaces, and blood vessels. While intracellular histamine is inert, it is released and becomes activated when a noxious antigen is detected by sensitized antibodies. Histamine that is not found within mast cells functions as a neurotransmitter in the brain and is involved with neuroendocrine control, cardiovascular functions, thermal and weight regulation, and sleep and arousal balance. The enterochromaffin-like (ECL) cells of the stomach release hista-mine, which is one of the main factors that stimulates the stomach mucosal parietal cells to produce gastric acid for digestion.
Four different histamine receptors have been identified. Each of these receptors is distributed in a different area of the body and elicits a different response to histamine agonism or antagonism. H1 receptors are found on smooth muscle cells, the endothelium, and the brain; H2 receptors are distributed in the gastric mucosa, cardiac muscle, mast cells, and the brain; H3 receptors are located in the brain; and H4 receptors are predominantly found on eosinophils, neutrophils, and T cells. When histamine stimulates the H1 receptor, the reaction produces the allergic response commonly observed with insect stings and contact with other allergens, including symptoms such as bronchoconstriction, pain, and itching. H2 receptors, when exposed to histamine, cause the contraction of gastrointestinal smooth muscles and the release of gastric acid. H3 receptors in the brain are responsible for the release of many neurotransmitters and may also have an effect on satiety. H4 receptors on blood cells produce inflammation and other allergic responses
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when histamine is present. Currently available antihistamine agents affect the H1 and H2 receptors; no antihistamines are approved for use that affect the H3 and H4 receptors, but there is a potential for these receptors to be drug targets in treatments for sleeping disorders, attention-deficit/hyperactivity disorder (ADHD), and obesity, to name a few conditions.
H1 antihistamines are typically the first drugs used to treat the symptoms of an allergic reaction or allergic rhi-nitis, but when used intranasally they are considered secondary agents, to be used after glucocorticoids. These anti-histamines are also the drugs of choice for managing urticaria (itching) associated with an allergic response; they are effective in this indication even if given prior to an anticipated exposure. If allergic rhinitis (hay fever) presents with nasal congestion, antihistamines are not as efficacious as nasal decongestants, such as pseudoephedrine, or combi-nation antihistamine‒decongestants (frequently named with a “D” added after the drug name, such as loratidine-D). H1 antihistamines are not effective for bronchial asthma and antihistamines are used only as adjuvant treatment for patients experiencing systemic anaphylaxis (epinephrine is the mainstay of treatment).
Many antihistamine formulations are also available for topical administration in the eye and nose. When oph-thalmic preparations are used, contact lenses should be removed prior to application, and can be reinserted 10‒15 minutes after administration, unless otherwise specified. Do not reinsert the lenses if the eyes are red, and separate administration of other ophthalmic topical agents by 5 minutes. With nasal preparations, the nasal spray must be primed prior to first use until a fine mist appears. Repriming is necessary when the product is unused for a number of days specified by the certain manufacturer.
1.1 First-Generation AntihistaminesFirst-generation antihistamines are H1 antagonists and are known for their strong sedating properties due to the easy penetration of the central nervous system (CNS). Since the sedating effect is so powerful with some agents, they are commonly used as sleep aids. However, children and some adults (though rare) may experience an excitation effect. Some medications in this class have antinausea and antiemetic effects and can be used to prevent motion sickness (though they are not as effective if used to treat an active episode). Some H1 antagonists—predominantly diphen-hydramine—can suppress extrapyramidal symptoms caused by antipsychotic use. The ethanolamine and ethylenedi-amine agent subgroups have antimuscarinic actions, which may help patients with non-allergic rhinorrhea, but also cause undesirable side effects of urinary retention and blurred vision.
First-generation antihistamines are largely anticholinergic and can cause dry mouth, dry eyes, urinary retention, constipation, and cognitive disturbances. Patients with a diagnosis of closed-angle glaucoma, urinary retention, peptic ulcer disease, or uncontrolled asthma should not use first-generation antihistamines. Anticholinergic side effects can be further exacerbated by other anticholinergic medications, such as tricyclic antidepressants (TCAs). Because monoamine oxidase inhibitors (MAOIs) can also exacerbate anticholinergic side effects, first-generation antihistamines should not be used during treatment or within 2 weeks of MAOI discontinuation.
Toxicities of the first-generation antihistamines include convulsions, postural hypotension (increasing the risk of falls in patients, especially the elderly), and cardiac arrhythmias. Central nervous system depression can be additive if first-generation antihistamines are combined with other medications with sedative properties or alcohol. Patients should be cautioned about driving and operating machinery while using these medications. There is also a potential for sedative properties to still be present the following morning if these agents are used for sleep. First-generation an-tihistamines are on the Beers list and are considered potentially harmful in elderly patients; other medication options should be explored if possible.
First-Generation Antihistamines
BrompheniramineCarbinoxamineChlorpheniramineClemastineCyproheptadine
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DiphenhydramineDoxylaminePromethazineTriprolidineDimenhydrinate (See also the Antiemetics section in the Gastrointestinal Agents chapter)Hydroxyzine (See also the Anxiolytics, Sedatives, and Hypnotics section in the Central Nervous System chapter)Meclizine (See also the Antiemetics section in the Gastrointestinal Agents chapter)
Case Studies and Conclusions
Joanne was doing yard work over the weekend and is now covered in an itchy rash on both arms. She states she has not been able to sleep at night because she cannot stop scratching.
1. Which of the following would be the best option to manage Joanne’s allergic reaction?
a. Fexofenadineb. Epinephrinec. Diphenhydramined. Ranitidine
Answer C is correct. Fexofenadine is a nonsedating second-generation antihistamine; this patient would benefit from a first-generation antihistamine to increase sedation at night. Epinephrine is used in cases of anaphylaxis, but this patient presents with a local rash. Ranitidine is an H2 antihistamine that is used for gastrointestinal disorders, not allergies.
It has been a few days, and Joanne’s rash has improved and has almost disappeared. She states that she is going on a cruise next week and is afraid she will get motion sickness. She wants a recommendation for an OTC product.
2. What is an OTC formulation of an antihistamine that can be used to prevent nausea?
a. Doxylamineb. Promethazinec. Diphenhydramined. Cetirizine
Answer C is correct. Doxylamine and cetirizine are not indicated for the treatment of nausea. Promethazine is a prescrip-tion-only medication. Diphenhydramine is OTC and has indications for nausea and vomiting as well as helping with the uti-caria and insomnia.
Joanne returned from her cruise and came home just in time for allergy season. She states that she would like to take a first-generation antihistamine to manage her seasonal allergies.
3. Which of the following statements is FALSE?
a. Counsel the patient about the morning “hangover” that may occur if she takes a first-generation antihis-tamine at bedtime.
b. A common side effect with frequent use of a first-generation antihistamine is diarrhea.c. Many of the first-generation antihistamines should be used with caution in geriatric patients.d. First-generation antihistamines should not be used within 2 weeks of use of an MAOI.
Answer B is correct. First-generation antihistamines can cause daytime sleepiness, so patients should be warned about driving or operating machinery. The most common side effects with these drugs are anticholinergic, such as constipation, urinary retention, dry eyes, and dry mouth. First-generation antihistamines are on the Beers list, so second-generation antihistamines should be used instead if possible. The combination of MAOIs and first- generation antihistamines has the potential to cause hypertensive crisis due to the antihistamine’s concurrent effects on neurotransmitters.
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George is a 68-year-old patient being seen for his annual physical examination appointment. He mentions that he experiences seasonal allergies and in the past had success with diphenhydramine. His medical history includes depression, hypertension, dyslipidemia, and type 2 diabetes mellitus.
1. What is a concern with using a first-generation antihistamine in George?
a. Many first-generation antihistamines are Beers list medications and may not be safe for all patients.b. First-generation antihistamines may cause excitation in geriatric patients instead of sedation.c. Use of antihistamines may exacerbate George’s diabetes.d. All of the above are true.
Answer A is correct. First-generation antihistamines are on the Beers list, and alternative options for therapy should be explored if possible. In George’s case, it would be appropriate to try a second-generation antihistamine first. Excitation—as opposed to sedation—is a possible side effect when first-generation antihistamines are used in pediatric patients. These antihistamines have anticholinergic properties and could exacerbate closed-angle glaucoma, urinary retention, and prostatic hypertrophy.
Despite your suggestion that a first-generation antihistamine may not be the best option, George says that he is used to these products and would rather take something with which he has had prior experience. George is currently being treated with fluoxetine (a selective serotonin reuptake inhibitor [SSRI]) for his depression.
2. Which of the following statements is true regarding possible drug interactions between the SSRI and first-generation antihistamines?
a. George must wait 2 weeks between his last dose of fluoxetine and brompheniramine.b. Fluoxetine will exacerbate the anticholinergic side effects of the first-generation antihistamines.c. Fluoxetine may worsen the drowsiness/sedative effects of the first-generation antihistamines.d. Use of antidepressants is contraindicated with the first-generation antihistamines.
Answer C is correct. Use of MAOIs should be avoided when a patient is taking brompheniramine, with a 2-week washout period being recommended. TCAs have the potential to exacerbate anticholinergic side effects of the first-generation antihistamines; some SSRIs have the potential to cause anticholinergic effects, although this is not a common side effect of fluoxetine. Medications that have the potential to lead to CNS depression (including antidepressants) may also worsen the drowsiness and sedative effects of the first-generation antihistamines. Although use of antidepressants is not contraindicated with the first- generation antihistamines, MAOIs, TCAs, and other antidepressants with anticholinergic side effects should be used with caution.
George states that his biggest complaint about his allergies occurs when he is working in his garden. On top of the typical “hay fever”‒like symptoms, he says that he almost always manages to come in contact with poison ivy or poison oak and breaks out in a rash.
3. Which product would be best to manage this patient’s allergic rhinitis and the contact allergic reaction?
a. Meclizineb. Chlorpheniraminec. Doxylamined. Diphenhydramine
Answer D is correct. Meclizine is approved as an antiemetic drug. Chlorpheniramine will treat the allergic rhinitis but does not have contact allergic reactions as a labeled indication. Doxylamine is used for insomnia or allergic rhinitis. Diphenhydramine would manage both allergic rhinitis and the contact allergic reaction.
1.2 Second-Generation AntihistaminesBoth first and second generations of antihistamines have been found to have equal efficacy in the treatment of allergic responses. Unlike the first-generation antihistamines, however, the second-generation products do not cross the blood‒brain barrier to the same extent and, therefore, do not have the same sedative properties; in addition, they have fewer antimuscarinic and anticholinergic effects. Nevertheless, the second-generation antihistamines may still cause drowsiness in some patients, especially if used concurrently with medications that cause CNS depression or
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alcohol. The second-generation products are most commonly used for chronic allergy symptoms due to their lack of sedation and amenability to daily use. This class is the preferred treatment in geriatric patients and children due to the favorable side-effect profile and minimal CNS penetration.
Second-Generation Antihistamines
AcrivastineCetirizineDesloratadineFexofenadineLevocetirizineLoratadineAzelastine (See also the Antiallergic Agents section in the Eye, Ears, Nose, and Throat Preparations chapter)
Case Studies and Conclusions
Ray is a construction worker and has complaints of seasonal allergies. He says that whenever the pollen level is high, he gets watery and itchy eyes, a runny nose, and persistent sneezing.
1. Which of the following would be the best first-choice option for managing Ray’s allergies?
a. Diphenhydramine by mouthb. Azelastine intranasallyc. Loratadine by mouthd. Cimetidine by mouth
Answer C is correct. Ray is a construction worker, so he presumably operates machinery that requires full attention. Thus di-phenhydramine would be too sedating for him. Azelastine intranasally is not a first-choice option; instead, intranasal antihis-tamines are used after the patient has tried an intranasal glucocorticoid. Cimetidine is an H2 antihistamine and used to treat gastrointestinal upset.
Ray later adds that he typically is very congested, during especially bad pollen days.
2. What would the best advice be for the patient?
a. An antihistamine is sufficient alone to manage nasal congestion.b. Use a combination antihistamine and decongestant.c. Use a decongestant alone.d. Use a combination oral and nasal antihistamine when symptoms are worse.
Answer B is correct. Antihistamines alone are not sufficient to manage nasal congestion with allergy symptoms; combination products with a decongestant, such as pseudoephedrine, are more effective. A decongestant alone would manage Ray’s nasal symptoms, but the antihistamine would be required to help treat his other symptoms, such as watery eyes. While nasal antihistamines are effective for symptom management in patients with nasal congestion, they are not a first-line option and need to be used regularly to achieve their greatest efficacy.
Ray asks whether his medications might also be safe for his 72-year old father, who is having similar reactions.
3. Which of the following statements best summarizes the recommended use of antihistamines in older adults?
a. First-generation antihistamines are a good option for geriatric patients with seasonal allergies because they can cause CNS excitation, which can help give them more energy.
b. Second-generation antihistamines are the best option for geriatric patients with seasonal allergies be-cause of their minimal CNS penetration.
c. Geriatric patients should be offered only intranasal or ophthalmic preparations; oral medications are not recommended in older adults.
d. No antihistamines are safe in geriatric patients under any circumstances.
Answer B is correct. Second-generation antihistamines have less CNS penetration and a safer side-effect profile for geriatric patients.
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Sam presents to his doctor’s appointment with complaints of a runny nose, watery eyes, and nasal congestion. He says that these symptoms occur every year around this time, but he usually just muddles his way through the allergy season without any medications. This year, however, his symptoms are worse than ever, and he would like to explore possible medication options.
1. Which of the following is NOT a benefit of Sam using a second-generation antihistamine as opposed to a first-generation antihistamine?
a. The risk of sedation is less with the first-generation antihistamines, so using the second-generation products could help him sleep better at night.
b. Many second-generation products come in combination products with a decongestant.c. Most second-generation medications are dosed once a day.d. All of the above are true.
Answer A is correct. Second-generation antihistamines are less sedating than the first-generation products. Second- generation antihistamines are available in many different combinations, including with pseudoephedrine, ibuprofen, or acetaminophen. Another appealing aspect of second-generation products is that most require only once-daily dosing, whereas most first-generation antihistamines are dosed multiple times a day.
Sam’s medical history includes hypertension, and he has an extensive family history of cardiovascular disease. His blood pressure at the beginning of this visit was elevated, and he says he often forgets to take his blood pressure medication.
2. Which of the following products would be the least appropriate to recommend to Sam?
a. Acrivastineb. Cetirizinec. Fexofenadined. Loratadine
Answer A is correct. Acrivastine should be avoided in patients with severe hypertension or coronary artery disease. Cetirizine, fexofenadine, and loratidine do not have cardiovascular concerns and would be better recommendations for Sam to use.
Sam states that he frequently consumes alcoholic beverages and would like to avoid an allergy agent that is metabolized via the liver.
3. Which of the following medications requires dose adjustment or dose consideration with hepatic impairment?
a. Cetirizineb. Desloratadinec. Levocetirizined. Loratadine
Answer B is correct. Desloratadine requires dose adjustment for both hepatic and renal impairment (5 mg every other day). Cetirizine, levocetirizine, and loratadine require dose adjustment for renal impairment.
1.3 Other AntihistaminesH2 antihistamines (cimetidine, famotidine, nizatidine, and ranitidine) are used to inhibit the secretion of gastric acid in patients with gastrointestinal (GI) disorders. Intranasal products should be used after a patient has tried an intranasal glucocorticoid. Intranasal antihistamines are most effective when used regularly and do not cause rebound effects as nasal decongestants do.
Bepotastine (See also the Antiallergic Agents section in the Eye, Ears, Nose, and Throat Preparations chapter)Cimetidine (See also the Antiulcer Agents and Suppressants section in the Gastrointestinal Agents chapter)Emedastine (See also the Antiallergic Agents section in the Eye, Ears, Nose, and Throat Preparations chapter)
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Famotidine (See also the Antiulcer Agents and Suppressants section in the Gastrointestinal Agents chapter)Ketotifen (See also the Antiallergic Agents section in the Eye, Ears, Nose, and Throat Preparations chapter)Nizatidine (See also the Antiulcer Agents and Suppressants section in the Gastrointestinal Agents chapter)Olopatadine (See also the Antiallergic Agents section in the Eye, Ear, Nose, and Throat Preparations chapter)Ranitidine (See also the Antiulcer Agents and Suppressants section in the Gastrointestinal Agents chapter)
Common Class Considerations
Anaphylaxis: A life-threatening allergic reaction. Signs and symptoms include an itchy rash, swelling of the tongue, bronchoconstriction, hypotension, and facial edema. Anaphylaxis presents suddenly, typically over a few minutes. Antihistamines alone are not a sufficient treatment, and patients should immediately receive epinephrine. Antihistamines and steroids are added as adjuvant treatments.
Excitation: In children, normal doses of first-generation antihistamines often result in an excitatory effect instead of a sedative effect. This phenomenon has also been infrequently reported in some adult cases at ther-apeutic doses, but is more common in overdose and toxic situations.
Sedation/somnolence: Increased sedation and somnolence are frequently reported with use of the first- generation antihistamines. When taken at bedtime, these drugs may also lead to a daytime “hangover” of drowsiness and somnolence. Second-generation antihistamines are referred to as “nonsedating” and have similar incidence of sedation as placebo in studies.
Toxicity: Toxicity of antihistamines has been reported in incidents of overdose or interactions with liver metabolism enzymes (CYP)-inhibiting medications (predominately macrolides and azole a ntifungal drugs), with patients experiencing higher than intended circulating antihistamine levels. Signs and symptoms of toxicity include hallucinations, incoordination, convulsions, cardiac arrhythmias, and fever.
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Tips from the Field
1. Make sure your patients understand the difference between antihistamines and decongestants. Decongestants constrict nasal blood vessels, resulting in an improvement in nasal stuffiness but they do not affect histamine and won’t impact any of the other symptoms associated with hay fever, such as sneezing, runny nose, and itching. Caution patients that if they use nasal spray deconges-tants for more than a few days, these agents can produce a rebound swelling of the nasal tissues, resulting in even greater congestion.
2. Suggest use of OTC products, such as Claritin D, which contain both an antihistamine and a decon-gestant if symptoms warrant use. Make sure they understand the side effects associated with this combination.
3. Help patients determine the right antihistamine for them, for example, daytime use avoid s edating agents like diphenhydramine (Benadryl). Newer generation antihistamines, such as loratadine (Claritin), fexofenadine (Allegra), and cetirizine (Zyrtec), are generally a better choice since they are less sedating.
4. Note that even the newer nonsedating generation antihistamines can cause drowsiness and other symptoms in some people, especially older adults, particularly if they take them at higher doses. Make sure they understand importance of starting the drug at the lowest dose and evaluate its effectiveness.
5. Most of these agents can be purchased OTC and there is no difference between the generic brand ver-sus the name brand.
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6. Explain to your elderly patients that antihistamines can cause other central nervous system effects, in-cluding coordination problems, fatigue, and temporary cognitive impairment. Research has shown an increased risk of long-term cognitive decline in older people who take the drugs regularly.
7. First-generation antihistamines are also more likely than the newer products to cause serious side ef-fects, such as a rapid heart rate or urinary retention (which can be especially problematic in men who have BPH).
8. Several first-generation antihistamines can reduce motion sickness such as diphenhydramine, doxyl-amine, dimenhydrinate (as found in Dramamine), and meclizine (the active ingredient in Bonine) These are all OTC and are the most commonly used motion sickness medications. Make sure they understand that it can take at least 30 minutes for them to take effect.
9. People suffering closed or narrow-angle glaucoma, COPD (chronic obstructive pulmonary disease), kidney disease, prostate problems, hypertension, heart disease, and thyroid problems should not take any OTC antihistamines without first consulting with their provider.
10. The FDA Nonprescription Drug Advisory Committee and the Pediatric Advisory Committee has recommended that nonprescription cough and cold products should not be used in children less than 2 years of age and an official ruling regarding the use of these products in children older than 2 has not yet been announced. Refer to pediatric drug references for additional information (FDA, 2008).
References
American Geriatrics Society. Updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227-2246.
Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88:1183-1241.
Holgate ST, Canonica GW, Simons FE, et al. Consensus Group on New-Generation Antihistamines (CONGA): present status and recom-mendations. Clin Exp Allergy. 2003;33:1305-1324.
McEvoy GK, ed. AHFS: Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2016.
Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of H1 antihistamines. J Clin Psychopharmacol. 2002;22:511-515.
Skidgel RA, Kaplan AP, Erdös EG. Histamine, bradykinin, and their antagonists. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011:911-936.
U.S. Food and Drug Administration (FDA). Public health advisory: FDA recommends that over-the-counter (OTC) cough and cold products not be used for infants and children under 2 years of age 2008. http://www.fda.gov/NewsEvents/Newsroom / PressAnnouncements/2008/ucm051137.htm
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(PI)
for m
ore
info
rmat
ion.
Clin
icia
ns s
houl
d co
ntin
ue to
pro
vide
edu
catio
n ab
out t
he re
pro
duct
ive
risks
of a
ny m
edic
atio
n us
e an
d of
fer r
isk-
redu
ctio
n st
rate
gies
(whi
ch m
ay
incl
ude
cont
race
ptiv
e us
e) to
wom
en o
f chi
ldb
earin
g ag
e an
d un
ders
tand
that
thes
e re
pro
duct
ive
risks
may
als
o ex
tend
to m
ales
.
•Br
and
nam
es a
re p
rovi
ded
for t
hose
age
nts
still
ava
ilab
le o
n th
e m
arke
t. D
ue to
the
ever
-cha
ngin
g p
rodu
ct a
vaila
bili
ty, r
efer
to F
ood
and
Dru
g A
dmin
istr
atio
n (F
DA
) res
ourc
es to
con
firm
the
actu
al b
rand
s av
aila
ble
Thi
s dr
ug s
umm
ary
is fo
r edu
catio
nal p
urp
oses
onl
y. P
resc
ribin
g de
cisi
ons
shou
ld b
e b
ased
on
real
-tim
e co
mp
rehe
nsiv
e dr
ug d
atab
ases
that
are
up
date
d on
a re
gula
r bas
is.
Firs
t-G
ener
atio
n A
ntih
ista
min
esU
nive
rsal
pre
scrib
ing
aler
ts:
•C
entr
al n
ervo
us d
epre
ssio
n ca
n b
e ad
ditiv
e if
first
-gen
erat
ion
antih
ista
min
es a
re c
omb
ined
with
oth
er m
edic
atio
ns w
ith s
edat
ive
pro
per
ties
or a
lcoh
ol; p
atie
nts
shou
ld b
e ca
utio
ned
abou
t driv
ing
and
oper
atin
g m
achi
nery
whi
le u
sing
thes
e m
edic
atio
ns.
•Fi
rst-
gene
ratio
n an
tihis
tam
ines
are
larg
ely
antic
holin
ergi
c ag
ents
and
can
cau
se d
ry m
outh
, dry
eye
s, u
rinar
y re
tent
ion,
con
stip
atio
n, a
nd c
ogni
tive
dist
urb
ance
s;
thei
r use
sho
uld
be
avoi
ded
in p
atie
nts
with
und
erly
ing
clos
ed-a
ngle
gla
ucom
a, u
rinar
y re
tent
ion,
pep
tic u
lcer
dis
ease
, and
unc
ontr
olle
d as
thm
a. A
ntic
holin
ergi
c si
de e
ffec
ts c
an b
e fu
rthe
r exa
cerb
ated
by
othe
r ant
icho
liner
gic
med
icat
ions
, suc
h as
tric
yclic
ant
idep
ress
ants
and
mon
oam
ine
oxid
ase
inhi
bito
rs (M
AO
Is).
•Fi
rst-
gene
ratio
n an
tihis
tam
ines
sho
uld
not b
e us
ed w
ithin
2 w
eeks
of M
AO
Is.
•Th
ere
is a
pot
entia
l for
sed
ativ
e p
rop
ertie
s to
stil
l be
pre
sent
the
follo
win
g m
orni
ng if
thes
e ag
ents
are
use
d fo
r sle
ep.
•Fi
rst-
gene
ratio
n an
tihis
tam
ines
are
on
the
Beer
s lis
t and
are
con
side
red
pote
ntia
lly h
arm
ful i
n el
derly
pat
ient
s; ot
her m
edic
atio
n op
tions
shou
ld b
e ex
plor
ed if
pos
sibl
e.
ChAPter 1 Antihistamines 9
9781284110562_CH01_Pass01.indd 9 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Dru
g N
ame
FDA
-Ap
pro
ved
Ind
icat
ion
sD
osa
ge
Ran
ge
Prec
auti
on
s an
d C
linic
al P
earl
s
Gen
eric
Nam
e
Brom
phe
nira
min
e m
alea
te
Bra
nd
Nam
e
J-Ta
n PD
Resp
a-BR
Brom
ax
LoH
ist
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis
Com
mon
col
d
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se
(mal
eate
):
6 to
12
mg
ever
y
12 h
ours
•Ta
ke w
ith fo
od, w
ater
, or m
ilk to
min
imiz
e ga
stric
irrit
atio
n
•D
exb
rom
phe
nira
min
e m
alea
te is
a c
hem
ical
ly re
late
d in
gred
ient
•U
se is
gen
eral
ly “a
s ne
eded
”
•So
me
bro
mp
heni
ram
ine
cont
aini
ng p
rodu
cts
are
OTC
and
oth
ers
requ
ire a
pre
scrip
tion
•D
iffer
ent s
alt f
orm
s ar
e av
aila
ble
(mal
eate
and
tann
ate)
requ
iring
di
ffer
ent d
ose
sche
dule
s.
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Car
bin
oxam
ine
mal
eate
Bra
nd
Nam
e
Arb
inox
a
Karb
inal
ER
QT BL PD GD
QT BL PD GD
Alle
rgie
s an
d re
late
d sy
mp
tom
s su
ch a
s rh
initi
s,
pru
ritus
, rhi
norr
hea
and
urtic
aria
Usu
al o
ral d
ose
:
IR: 4
to 8
mg
3 to
4
times
dai
ly
ER: 6
to 1
6 m
g ev
ery
12
hou
rs (n
ot to
exc
eed
32 m
g da
ily)
•Ta
ke o
n an
em
pty
sto
mac
h w
ith w
ater
•A
vaila
ble
by
pre
scrip
tion
only
•Ex
tend
ed re
leas
e an
d im
med
iate
rele
ase
pro
duct
dos
ing
sche
dule
s ar
e di
ffer
ent,
revi
ew d
irect
ions
prio
r to
use
Gen
eric
Nam
e
Chl
orp
heni
ram
ine
mal
eate
Bra
nd
Nam
e
Alle
r-C
hlor
Chl
or-T
rimet
on A
llerg
y
Chl
or-T
rimet
on
Chl
orp
hen
Ed C
hlor
Ped
Ed-C
hlor
tan
Phar
bec
hlor
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis,
pru
ritus
, rh
inor
rhea
, and
urt
icar
iaD
ose
varie
s de
pen
ding
on
pro
duct
sel
ecte
d
Illu
stra
tive
ora
l do
se
imm
edia
te r
elea
se:
4 m
g ev
ery
4 to
6 h
ours
(m
axim
um d
aily
dos
e [M
DD
]: 24
mg)
•D
exch
lorp
heni
ram
ine
mal
eate
is a
che
mic
ally
rela
ted
ingr
edie
nt
•O
TC a
nd p
resc
riptio
n (h
ighe
r dos
es) a
re a
vaila
ble
•Ex
tend
ed re
leas
e an
d im
med
iate
rele
ase
pro
duct
dos
ing
sche
dule
s ar
e di
ffer
ent,
revi
ew d
irect
ions
prio
r to
use
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
10 Pharmacotherapeutics for Advanced Nursing Practice
9781284110562_CH01_Pass01.indd 10 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Gen
eric
Nam
e
Cle
mas
tine
fum
arat
e
Bra
nd
Nam
e
Day
hist
Alle
rgy
12 H
our
Relie
f
Tavi
st A
llerg
yQT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis,
pru
ritus
, ur
ticar
ia, s
ymp
tom
s of
th
e co
mm
on c
old
and
angi
oede
ma
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
OTC
ora
l d
ose
: 1.3
4 m
g tw
ice
daily
(MD
D 8
.04
mg
incl
udin
g p
resc
riptio
n do
sing
)
•Ta
ke w
ith fo
od o
r milk
if p
atie
nt e
xper
ienc
es s
tom
ach
upse
t
•Pr
escr
iptio
n p
rodu
cts
avai
lab
le fo
r use
at h
ighe
r dos
es
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Cyp
rohe
pta
dine
hy
droc
hlor
ide
QT BL PD GD
QT BL PD GD
Illu
stra
tive
ind
icat
ion
s fo
r u
se:
Alle
rgic
rhin
itis,
pru
ritus
, ur
ticar
ia, a
nd a
ngio
edem
a
Usu
al o
ral d
ose
:
4 to
20
mg
daily
in
divi
ded
dose
s (M
DD
0.
5 m
g/kg
per
day
or
32 m
g w
hich
ever
is le
ss)
•H
epat
ic im
pai
rmen
t dos
e ad
just
men
t rec
omm
ende
d, h
owev
er, n
o sp
ecifi
c do
se s
ugge
stio
n p
rovi
ded
by m
anuf
actu
rer
Gen
eric
Nam
e
Dip
henh
ydra
min
e hy
droc
hlor
ide
Bra
nd
Nam
e
Bena
dryl
and
var
ious
ot
hers
QT BL PD GD
QT BL PD GD
QT BL PD GD
QT BL PD GD
QT BL PD GD
Illu
stra
tive
ind
icat
ion
s fo
r u
se:
Alle
rgic
rhin
itis,
con
tact
de
rmat
itis,
ant
ituss
ive,
dru
g-in
duce
d EP
S, P
arki
nson
ian
synd
rom
es, i
nsom
nia,
mot
ion
sick
ness
, adj
unct
trea
tmen
t of
anap
hyla
xis
Dos
e va
ries
dep
endi
ng
on c
omb
inat
ion
pro
duct
sel
ecte
d
Illu
stra
tive
ora
l do
se:
25 to
50
mg
ever
y 4
to 8
ho
urs
(max
300
mg
per
24
hou
rs)
Usu
al p
aren
tera
l do
se:
IM/I
V:1
0 to
50
mg
per
do
se
(max
100
mg
per
dos
e;
max
400
mg
per
day
)
•To
pic
al a
pp
licat
ion
can
caus
e an
alle
rgic
-typ
e co
ntac
t der
mat
itis
•D
rug
inte
ract
ions
may
requ
ire d
ose
adju
stm
ents
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Dox
ylam
ine
succ
inat
e
Bra
nd
Nam
e
Dox
ytex
Nite
time
Slee
p-A
id
Slee
p A
id
Uni
som
QT BL PD GD
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis,
inso
mni
aD
ose
varie
s de
pen
ding
on
pro
duct
sel
ecte
d
Illu
stra
tive
ora
l do
se:
25 m
g da
ily o
r at
bed
time
•O
ptim
al d
ose
sche
dule
for i
nsom
nia
is ta
ke d
ose
30 m
inut
es p
rior t
o p
lann
ed 8
-hou
r sle
ep (b
edtim
e)
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
ChAPter 1 Antihistamines 11
9781284110562_CH01_Pass01.indd 11 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Gen
eric
Nam
e
Prom
etha
zine
hy
droc
hlor
ide
Bra
nd
Nam
e
Phen
adoz
Phen
erga
n
Prom
ethe
gan
QT BL PD GD
QT BL PD GD
QT BL PD GD
QT BL PD GD
Alle
rgic
con
ditio
ns, m
otio
n si
ckne
ss, a
ntie
met
ic, s
edat
ive
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se
for
nau
sea/
vom
itin
g:
12.5
mg
bef
ore
mea
ls
and
HS
Illu
stra
tive
rec
tal d
ose
fo
r n
ause
a/vo
mit
ing
:
12.5
to 2
5 m
g ev
ery
4 to
6
hour
s as
nee
ded
Illu
stra
tive
IM d
ose
for
nau
sea/
vom
itin
g:
12.5
to 2
5 m
g ev
ery
4 to
6
hour
s as
nee
ded
•M
ild to
mod
erat
e ak
athi
sia
and
extr
apyr
amid
al s
ymp
tom
s p
ossi
ble
aft
er
inje
ctio
n or
long
-ter
m u
se
•U
se is
ass
ocia
ted
with
QT
pro
long
atio
n
•D
rug
inte
ract
ions
may
requ
ire d
ose
adju
stm
ent
•W
hen
trea
ting
naus
ea/v
omiti
ng; a
dmin
iste
r bef
ore
mea
ls o
r sna
ck
•D
eep
IM in
ject
ion
pre
ferr
ed ro
ute
of p
aren
tera
l adm
inis
trat
ion
Ass
ocia
ted
with
:
•In
ject
ion
can
caus
e se
vere
tiss
ue in
jury
•Su
bcu
tane
ous
and
intr
a-ar
teria
l adm
inis
trat
ion
•U
se in
pat
ient
s in
a c
oma
•U
se in
pat
ient
s w
ith a
sthm
a
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Trip
rolid
ine
hydr
ochl
orid
e
Bra
nd
Nam
e
His
tex
PD
His
tex
QT BL PD GD
QT BL PD GD
Alle
rgie
s, rh
initi
s, u
rtic
aria
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se:
2.5
mg
ever
y 4
to 6
ho
urs
(max
10
mg
per
24
hou
rs)
•M
ay b
e ad
min
iste
red
with
out r
egar
d to
mea
ls, h
owev
er m
ay ta
ke w
ith
food
or m
ilk to
min
imiz
e st
omac
h up
set
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Dim
enhy
drin
ate
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
Hyd
roxy
zine
QT BL PD GD
Refe
r to
the
Cent
ral N
ervo
us S
yste
m c
hapt
er.
Mec
lizin
e
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
12 Pharmacotherapeutics for Advanced Nursing Practice
9781284110562_CH01_Pass01.indd 12 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Seco
nd
-Gen
erat
ion
Ant
ihis
tam
ines
•U
nive
rsal
pre
scrib
ing
aler
ts:
Man
y of
thes
e se
cond
-gen
erat
ion
agen
ts c
ause
CN
S de
pre
ssio
n (a
lbei
t not
to th
e sa
me
exte
nt a
s th
e fir
st-g
ener
atio
n an
tihis
tam
ines
). Pa
tient
s sh
ould
use
cau
tion
whe
n p
erfo
rmin
g ta
sks
that
requ
ire m
enta
l ale
rtne
ss.
Dru
g N
ame
FDA
-Ap
pro
ved
Ind
icat
ion
sD
osa
ge
Ran
ge
Prec
auti
on
s an
d C
linic
al P
earl
s
Gen
eric
Nam
e
Acr
ivas
tine
Bra
nd
Nam
e
Sem
pre
x-D
Alle
rgic
rhin
itis,
nas
al
cong
estio
nU
sual
ora
l do
se:
8 m
g ev
ery
4 to
6 h
ours
(32
mg
max
imum
per
da
y)
•A
void
use
in p
atie
nts
with
CrC
l les
s th
an 4
8 m
L/m
in
•U
se in
cau
tion
in p
atie
nts
with
dia
bet
es o
r thy
roid
dys
func
tion
•A
vaila
ble
in c
omb
inat
ion
with
pse
udoe
phe
drin
e on
ly
•8
mg
acriv
astin
e ta
ble
ts a
lso
cont
ain
60 m
g p
seud
oep
hedr
ine
•Re
com
men
ded
for u
se a
s ne
eded
up
to 1
4 da
ys
Con
trai
ndic
atio
ns:
•C
oron
ary
arte
ry d
isea
se
•U
ncon
trol
led
hyp
erte
nsio
n
•D
rug
inte
ract
ions
may
pre
clud
e us
e (i.
e., M
AO
Is)
Gen
eric
Nam
e
Cet
irizi
ne h
ydro
chlo
ride
Bra
nd
Nam
e
All
Day
Alle
rgy
Zyrt
ec
QT BL PD GD
QT BL PD GD
QT BL PD GD
Alle
rgie
s, rh
initi
s, u
rtic
aria
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se:
5 to
10
mg
daily
•C
etiri
zine
is n
ot re
mov
ed w
ith h
emod
ialy
sis
•IS
MP
safe
ty a
lert
(may
sou
nd li
ke o
r loo
k lik
e ot
her m
edic
atio
ns, t
hus
mis
take
s m
ay b
e m
ore
com
mon
with
this
dru
g)
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Des
lora
tadi
ne
Bra
nd
Nam
e
Cla
rinex
QT BL PD GD
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis,
chr
onic
id
iop
athi
c ur
ticar
ia, p
rurit
usD
ose
varie
s de
pen
ding
on
pro
duct
sel
ecte
d
Illu
stra
tive
ora
l do
se:
5 m
g da
ily
•D
eslo
rata
dine
is n
ot re
mov
ed b
y he
mod
ialy
sis
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
ChAPter 1 Antihistamines 13
9781284110562_CH01_Pass01.indd 13 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Gen
eric
Nam
e
Fexo
fena
dine
hy
droc
hlor
ide
Bra
nd
Nam
e
Alle
gra
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis
Chr
onic
idio
pat
hic
urtic
aria
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se:
60 m
g tw
ice
daily
or
180
mg
once
dai
ly
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Levo
cetir
izin
e di
hydr
ochl
orid
e
Bra
nd
Nam
e
Xyza
l
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis
Chr
onic
idio
pat
hic
urtic
aria
Usu
al o
ral d
ose
:
5 m
g on
ce d
aily
•D
iarr
hea
and
cons
tipat
ion
com
mon
adv
erse
eff
ects
Con
trai
ndic
atio
ns:
•En
d-st
age
rena
l dis
ease
•U
se o
f lev
ocet
irizi
ne in
pat
ient
s un
derg
oing
dia
lysi
s
Gen
eric
Nam
e
Lora
tadi
ne
Bra
nd
Nam
e A
lave
rt
Alle
rgy
Cla
ritin
Lora
dam
ed
QT BL PD GD
QT BL PD GD
QT BL PD GD
QT BL PD GD
Alle
rgic
rhin
itis,
urt
icar
ia,
pru
ritus
Dos
e va
ries
dep
endi
ng
on p
rodu
ct s
elec
ted
Illu
stra
tive
ora
l do
se:
10 m
g on
ce d
aily
or
5 m
g tw
ice
daily
•H
eada
che
is th
e m
ost c
omm
on s
ide
effe
ct
•O
rally
dis
solv
able
tab
lets
are
ava
ilab
le (t
able
t dis
inte
grat
es w
ith o
r w
ithou
t wat
er)
•Lo
rata
dine
is n
ot re
mov
ed b
y he
mod
ialy
sis
•Br
and
nam
e C
larit
in o
ral p
rodu
cts
do n
ot c
onta
in th
e sa
me
ingr
edie
nt a
s C
larit
in e
ye p
rodu
cts
(ket
otife
n fu
mar
ate)
—us
e ca
re w
hen
pre
scrib
ing
Ava
ilab
le in
mul
tiple
com
bin
atio
n p
rodu
cts.
Ple
ase
see
indi
vidu
al p
rodu
ct
for i
ndic
atio
ns, d
osin
g, a
nd n
ame
bra
nd.
Gen
eric
Nam
e
Aze
last
ine
Bra
nd
Nam
e
Vario
us b
ased
on
pro
duct
se
lect
ed a
nd a
rea
of
app
licat
ion
QT BL PD GD
Refe
r to
the
Eye,
Ear
s, N
ose,
and
Thr
oat P
repa
ratio
ns c
hapt
er.
14 Pharmacotherapeutics for Advanced Nursing Practice
9781284110562_CH01_Pass01.indd 14 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
Oth
er A
ntih
ista
min
esU
nive
rsal
pre
scrib
ing
aler
ts:
•In
tran
asal
ant
ihis
tam
ines
are
mos
t eff
ectiv
e w
hen
used
regu
larl
y an
d do
not
cau
se re
bou
nd e
ffec
ts a
s na
sal d
econ
gest
ants
do.
Dru
g N
ame
FDA
-Ap
pro
ved
Ind
icat
ion
sD
osa
ge
Ran
ge
Prec
auti
on
s an
d C
linic
al P
earl
s
Bep
otas
tine
QT BL PD GD
Refe
r to
the
Eye,
Ear
s, N
ose,
and
Thr
oat P
repa
ratio
ns c
hapt
er.
Cim
etid
ine
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
Emed
astin
e
QT BL PD GD
Refe
r to
the
Eye,
Ear
s, N
ose,
and
Thr
oat P
repa
ratio
ns c
hapt
er.
Fam
otid
ine
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
Keto
tifen
QT BL PD GD
Refe
r to
the
Eye,
Ear
s, N
ose,
and
Thr
oat P
repa
ratio
ns c
hapt
er.
Niz
atid
ine
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
Olo
pat
adin
e
QT BL PD GD
Refe
r to
the
Eye,
Ear
s, N
ose,
and
Thr
oat P
repa
ratio
ns c
hapt
er.
Rani
tidin
e
QT BL PD GD
Refe
r to
the
Gas
troi
ntes
tinal
Age
nts c
hapt
er.
ChAPter 1 Antihistamines 15
9781284110562_CH01_Pass01.indd 15 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.
9781284110562_CH01_Pass01.indd 16 25/11/16 8:03 PM
© Jones & Bartlett Learning, LLC, An Ascend Learning Company. Not for sale or distribution.