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Hydroxyzine For Dogs: Potential Uses In Canines

Hydroxyzine is a drug that was initially approved by the FDA in the 1950s as an antihistamine.  Most users know hydroxyzine under the brands Vistaril and Atarax, each of which are still popularly prescribed to treat medical conditions such as: allergic skin reactions, generalized anxiety disorders, and nausea resulting from motion sickness.  In some cases, it is used as a pharmacological intervention to decrease the severity of opioid or alcohol withdrawal symptoms.

It should be noted that hydroxyzine’s usage is not limited to humans – it is commonly prescribed to dogs by veterinarians.  In fact, most medical conditions that respond well to hydroxyzine are similar among humans and canines.  Hydroxyzine is considered an effective treatment for canine allergies and allergy-induced symptoms such as: hives, itchiness, and skin rashes.

When ingested by a dog (canine), hydroxyzine exerts its effect by acting as an inverse agonist of the H1 histamine receptor, thereby preventing activity of histamine.  This antihistaminergic effect not only treats allergies, but may decrease anxiety and cases of recurrent nausea.  If your dog happens to be taking hydroxyzine, it may be worth understanding: how the drug works, benefits of the drug, as well as risks associated with its usage.

Hydroxyzine for Dogs (Potential Uses)

There are many potential uses of hydroxyzine among canines such as: to attenuate allergic reactions, minimize anxiety, and decrease nausea.  That said, the anxiolytic and antiemetic efficacy of hydroxyzine in dogs hasn’t been subject to significant investigation.  Evidence provides the most support for using hydroxyzine (and even its cetirizine metabolite) as an intervention for canine atopic dermatitis (CAD).

Allergies: Due to the fact that hydroxyzine functions as an H1 histamine receptor inverse agonist, it effectively mitigates allergic reactions in canines (and humans alike).  By binding to the H1 receptors and preventing activation via histamine, allergic reactions (as generated by histamine) are attenuated.  If your dog is allergic to something in his/her environment, administration of hydroxyzine may reduce these allergies (such as: skin rashes, redness, itchiness, watery eyes, etc.).

Atopic dermatitis: Evidence suggests that among canines, hydroxyzine is most effective when administered as a treatment of canine atopic dermatitis.  Canine atopic dermatitis is a condition characterized by inflammation of the skin, redness, itchiness, and cracking.  Dogs that have been diagnosed with atopic dermatitis may incessantly itch their skin to the point of bleeding and/or fluid release.

Although dietary modifications may prove beneficial for some dogs with this condition, these may only provide partial symptomatic relief.  Hydroxyzine is considered a first-line treatment for canine atopic dermatitis and has a track-record to support its efficacy.  Compared to other antihistamines, hydroxyzine appears to be among the most effective options along with chlorpheniramine.

Anxiety: Treating neuropsychiatric conditions in canines (and other animals) is rather controversial.  Since it is impossible to get direct verbal feedback regarding perceived (subjective) functionality while taking pharmaceuticals, interventions such as hydroxyzine for anxiety should only be administered as a last-resort.  However, among overly anxious dogs, it is likely that hydroxyzine will reduce anxious behaviors.

Assuming that hydroxyzine yields relatively similar effects in canines to humans, its usage as an anxiolytic for canines may be underinvestigated.  Not only does hydroxyzine’s antihistaminergic H1 receptor inverse agonism reduce anxiety, but 5-HT2A antagonism may enhance its anxiolytic effect.  It should be speculated that pet owners of dogs taking hydroxyzine may notice less inhibited behavior.

Itchiness: General itching of the skin [among canines] is referred to as “pruritus” and its causes are often difficult to pinpoint.  Causes of pruritus are typically subject to significant interindividual variation among canines (as well as humans).  For example, some dogs may experience itchy skin as a result of fleas, while others may be allergic to a plant, or volatile organic compounds from furniture (e.g. chemically-infused carpets), etc.

Regardless of the cause of pruritus for any particular canine, symptoms can be attenuated via administration of hydroxyzine.  Nearly all published research supports the efficacy of hydroxyzine as an intervention for pruritus among canines.  It significantly reduces

Many studies support the efficacy of hydroxyzine for the treatment of pruritus.  It significantly reduces scratching, licking, and chewing behaviors in attempt to combat the itch – suggesting that the itch itself is reduced.  If your dog is excessively itchy, regardless of whether the itchiness is transient (short-term) or protracted (long-term), hydroxyzine is considered a viable intervention.

Nausea: It is known that hydroxyzine can have antiemetic effects in humans and is effective for reducing nausea as a result of motion sickness.  It could be that hydroxyzine also attenuates nausea among dogs.  If you notice that your dog is seemingly less nauseous after administration of hydroxyzine, it may be necessary to consider that it’s exerting an antiemetic effect.  Further investigation is necessary before hydroxyzine can be considered an effective antiemetic agent among canines.

Skin rash: Studies have documented that severity of skin rashes in canines as characterized by lesions, bumps, etc. – are reduced following administration of hydroxyzine.  Administration of hydroxyzine to canines prior to a rash-provoking stimuli decreases lesion size and redness to a greater extent than administration after exposure to the stimuli.  That said, regardless of when administered (pre- or post-exposure to the allergy-provoking stimuli), hydroxyzine decreases severity of skin rashes.

Not only does it decrease redness and bump size, but it also mitigates most of the pruritus (itching).  Dogs with severe skin rashes are often able to reduce symptoms of the rash – to a significant extent – with hydroxyzine administration.  Even after discontinuation of hydroxyzine, the therapeutic effect may linger for an additional 3 to 9 days (in canines).

Hydroxyzine for Dogs (Pharmacokinetics)

The pharmacokinetics (absorption, metabolism, and excretion) of hydroxyzine have been investigated in healthy canines when administered at oral and intravenous dosages of 2 mg/kg.  When administered in the form of an oral dose, the hydroxyzine exhibited a bioavailability of 72%.  Regardless of whether administered orally or intravenously, hydroxyzine was quickly absorbed and metabolized to form cetirizine – its primary metabolite.

Duration of exposure to the cetirizine metabolite (as evidenced by plasma concentrations) exceeded that of the parent chemical (hydroxyzine) by nearly 8-fold (when administered orally) and 10-fold (when administered intravenously).  Following oral administration of hydroxyzine to canines, peak plasma concentrations of the cetirizine metabolite reached 2.2 micrograms per milliliter, whereas peak plasma concentrations of hydroxyzine reached just 0.16 micrograms per milliliter.  Elimination half-life of the cetirizine metabolite in canines ranges from 10 to 11 hours after dosing, regardless of modality of administration (oral vs. intravenous).

Antihistaminergic effects of hydroxyzine peak within the first 8 hours of administration and correlated to plasma concentrations of the cetirizine metabolite exceeding 1.5 micrograms per milliliter.  Evidence suggests that increasing hydroxyzine dosage and/or frequency does not elicit superior antihistaminergic efficacy to twice-daily (b.i.d.) administration of hydroxyzine at 2 mg per kg.  Therefore, it is likely that many veterinarians follow this specific dosing protocol.

It is important to consider that serum half life and clearance may be subject to alteration from regular, long-term hydroxyzine usage.  A study testing the effects of intramuscular hydroxyzine in dogs, noted that after 30, 60, and 120 days – the serum half-lives significantly increased and clearance values were much slower than in early days of treatment.  In other words, the longer a dog has been regularly receiving hydroxyzine (intramuscularly), the longer it’ll take to eliminate from systemic circulation upon discontinuation.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18980631
  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/hydroxyzine

Hydroxyzine for Dogs (The Research)

To determine the therapeutic value of hydroxyzine as a pharmaceutical agent for dogs (canines), it is necessary to assess its efficacy in available clinical research.  Studies evaluating the efficacy of hydroxyzine as an antihistaminergic intervention for dogs date back to the 1980s.  Most published research suggests that hydroxyzine is a highly effective treatment for allergic skin conditions such as atopic dermatitis in canines.

2013: Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial.

A study published by Eichenseer, Johansen, and Mueller (2013) sought to determine the efficacy of dimetinden, as well as a combination of “hydroxyzine plus chlorpheniramine” in 19 dogs with atopic dermatitis.  Prior to their study, researchers noted that antihistamines were often administered to dogs for the treatment of atopic dermatitis.  However, despite being commonly utilized, their efficacy wasn’t fully supported by research.

To further evaluate the therapeutic value of dimetinden, hydroxyzine, and chlorpheniramine, researchers devised a placebo-controlled, double-blinded, cross-over trial.  The study involved administration of a pharmaceutical agent or a placebo for 14 days, followed by a washout period of equal duration (14 days).  Before and after each 14-day period of receiving either the pharmaceutical antihistamine or a placebo, all dogs were assessed with the CADESI (Canine Atopic Dermatitis Extent and Severity Index).

Measures of the CADESI were interpreted by a professional, whereas dog owners also reported severity of pruritus and general health of their respective dogs.  Results of the study indicated that the combination of hydroxyzine plus chlorpheniramine significantly reduced CADESI measures and pruritus, whereas the dimetinden was deemed insignificant in reduction of CADESI scores.  Researchers concluded that antihistamines such as hydroxyzine can significantly improve symptoms of atopic dermatitis in dogs.

That said, they also noted that although efficacy of antihistamines such as hydroxyzine are significant, they may not alleviate symptoms significant enough for optimal relief.  In these cases, administration of an adjunctive agent may be of additional benefit.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24114734

2012: Owner assessment of therapeutic interventions for canine atopic dermatitis: a long-term retrospective analysis.

A study published by Dell et al. (2012) documented the efficacy of pharmacologic interventions for canine atopic dermatitis – as perceived by owners.  In this study, the goal of researchers was to compare various pharmaceuticals prescribed to multiple groups of canines over extended durations of 5 or 10 years.  They identified canines using a privately owned veterinarian medical records database.

Researchers then contacted pet owners to take part in a survey that included 28 questions and could be taken online.  Results of the survey were then assessed, regardless of whether the owner completed the entire survey; questions were analyzed on an individual basis.  The goal of researchers was to determine whether any of the pets were suffering from atopic dermatitis, and if they were, whether they responded well to any particular interventions.

A total of 136 surveys were compiled by researchers, 39 of which were from a 10-year period, and 97 of which were from a 5-year period.  Of the 135 owners, 85 documented that their pet had received medicinal therapy for atopic dermatitis at the time of survey administration.  Authors concluded that antihistamines (e.g. hydroxyzine) can be a useful intervention for canine atopic dermatitis.

However, other modalities such as dietary modifications may work equally as well as an agent like hydroxyzine.  Furthermore, most noticeable improvement was reported among dogs receiving allergen-specific immunotherapy.  While hydroxyzine (and other antihistamines) may provide some therapeutic value, other treatments may warrant prior experimentation.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22575021

2004: Treatment of canine atopic dermatitis with cetirizine, a second generation antihistamine: a single-blinded, placebo-controlled study.

A study published by Cook et al. (2004) investigated the efficacy of cetirizine, the primary metabolite of hydroxyzine for the treatment of canine atopic dermatitis.  For the study, researchers implemented a placebo-controlled, single-blinded design and recruited 23 dogs to participate.  During the first 2 weeks of the trial, dogs were administered cetirizine hydrochloride (brand name “Zyrtec”) at a dosage of 1 mg/kg (with or without food).

For the next 2 weeks of the trial, dogs were administered a placebo tablet.  All pet owners were blinded to the treatment that their pets were receiving and evaluated efficacy of the treatments after 2 weeks, and then again after 4 weeks.  Outcomes were determined based on reduction of pruritus (scratching, licking, chewing).  If owners perceived either the cetirizine or the placebo as managing symptoms, they were instructed to administer it for an extra 30 days to note whether responses were sustained.

Results indicated that pruritus was substantially decreased among 18% of dogs that were administered cetirizine; 4 out of 22 dogs.  Among the dogs that were responsive to cetirizine, all had been previously diagnosed with non-seasonal pruritus and had attempted dietary modifications with no clinical benefit.  The remaining dogs (a total of 18) received no significant benefit from the cetirizine or the placebo.

This suggests that cetirizine, a metabolite of hydroxyzine, may provide significant therapeutic benefit to a subset of dogs diagnosed with atopic dermatitis.  It appears particularly effective among cases in which pruritus is non-seasonal.  That said, it remains unclear as to whether the efficacy of cetirizine is greater or lesser than that of its parent compound, hydroxyzine.

Authors documented that responses to antihistamines (in general) among dogs with canine atopic dermatitis should be considered individualized.  Since cetirizine is considered well-tolerated with only mild or transient side effects, it may be worth testing for dogs with atopic dermatitis.  Additionally, since it only requires once-daily administration, it may be preferred over other agents that require more frequent dosing.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15206590

2002: Antihistamines in the management of canine atopic dermatitis: a retrospective study of 171 dogs (1992-1998).

A study published by Zur et al. (2002) aimed to determine the efficacy of antihistamines for the treatment of atopic dermatitis in canines.  Researchers compiled data from the Veterinary Medical Teaching Hospital and noted that antihistamines were prescribed to 178 of 271 dogs that had been diagnosed with atopic dermatitis over a 6-year term (1992 to 1998).  They also documented that of the 166 of the dogs administered administered antihistamines, 54% attained significant benefit from these agents.

Of the 54% that attained significant benefit, half (27%) of the responses were considered “good,” and the other half (27%) were considered “moderate.”  Upon evaluation of specific antihistaminergic agents prescribed, it appeared as though hydroxyzine and diphenhydramine were the most effective (compared to others), and were the most popularly administered.  Agents such as chlorpheniramine and clemastine exhibited poorer efficacy and were (perhaps justifiably) administered less frequently.

Authors mentioned that antihistamines provided most therapeutic value when administered to younger-aged dogs compared to older ones.  Based on results from this retrospective study, we can conclude that hydroxyzine remains among the most effective antihistamines for the management of canine atopic dermatitis.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12050832

1999: Antihistamines in the management of allergic pruritus in dogs and cats.

A study published by Scott and Miller (1999) evaluated antihistamines for the management of allergic pruritus in dogs (and cats).  Researchers noted that therapeutic efficacy of antihistamines may be contingent upon adherence to professionally recommended dosages and frequencies of administration.  Furthermore, they mentioned that antihistamines are often best utilized as a preventative agent for allergic pruritus rather than a treatment.

In cases of canine atopic dermatitis, efficacy of antihistaminergics chlorpheniramine, diphenhydramine, and hydroxyzine – were subject to comparison.  Specifically, researchers wanted to determine how effective these agents were for controlling pruritus.  Approximately 8.9 to 10% of dogs receiving chlorpheniramine exhibit a reduction of pruritus symptoms, whereas 6.7% benefit from diphenhydramine.

Hydroxyzine appears to reduce symptoms of pruritus in 6.7% to 10% of dogs – making it among the most effective agents.  It should be noted that a 2013 study found that a combination of hydroxyzine plus chlorpheniramine significantly reduces atopic dermatitis symptoms (e.g. pruritus) compared to other interventions.  This provides more evidence to support hydroxyzine’s usage as an antihistamine among canines for allergic pruritus.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10476522/

1995: Additive benefits of EFAs in dogs with atopic dermatitis after partial response to antihistamine therapy.

A study published by Patterson (1995) documented that treatment of canine atopic dermatitis with antihistamines often attenuates symptoms in 20% to 70% of cases.  Although antihistamines are an effective intervention, they may only provide partial symptomatic relief.  Therefore, another intervention may be necessary to improve functional outcomes for dogs diagnosed with canine atopic dermatitis.

Patterson provides evidence to support the idea of combining EFAs (essential fatty acids) with antihistamines for additional therapeutic benefit.  His study assesses a combination of antihistamines (hydroxyzine, chlorpheniramine, cyproheptadine and clemastine) with EFAs and a combination of antihistamines with a placebo (olive oil).  Results indicate that utilization of EFAs as an antihistamine adjunct appears to be more efficacious than standalone antihistamine interventions.

This study provides evidence to support the idea the hydroxyzine is effective for the management of pruritus in dogs.  Moreover, hydroxyzine’s efficacy is bolstered with augmentation of essential fatty acids (EFAs).  Essential fatty acids (EFAs) should be recommended for the treatment of atopic dermatitis among canines exhibiting partial symptomatic relief from antihistamines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8583767

1989: Duration of inhibition of immediate skin test reactivity by hydroxyzine hydrochloride in dogs.

A study published by Barbet and Halliwell (1989) tested skin reactivity of dogs following administration of hydroxyzine.  They intradermally administered histamine phosphate and aqueous flea antigen to 18 dogs that were reportedly allergic to fleas.  The purpose was to provoke an allergic, hypersensitive skin reaction – then immediately administer hydroxyzine to determine its efficacy.

Following administration of the allergens (histamine phosphate and aqueous flea antigen), and thereafter, the hydroxyzine – researchers documented significance of allergic reactions as measured by wheal diameters and scores.  In most dogs, inhibition of allergies spanned for 3 to 5 days after discontinuation of treatment.  This suggests that hydroxyzine is capable of attenuating allergic skin reactions in dogs and that the effect may be sustained for 3 to 5 days after cessation.

Researchers also noted that a subset of dogs took up to 9 days for their pretreatment allergies to reemerge following administration of hydroxyzine.  Although this was an early study, it demonstrates that hydroxyzine is an effective intervention for allergic skin responses in canines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/2753775

Risks of Hydroxyzine for Dogs (Possibilities)

Despite the fact that hydroxyzine is considered a safe, effective treatment for canine atopic dermatitis and pruritus, it is not devoid of risk.  As with any pharmaceutical intervention, it may be helpful to assess potential risks associated with administration of hydroxyzine to canines.  Risks should be assessed and weighed in respect to the potential therapeutic benefits associated with hydroxyzine administration.  In most cases, risks of hydroxyzine administration are minimal and significantly outweighed by its therapeutic value.

Adverse effects: Although the likelihood of adverse reactions from hydroxyzine is relatively low compared to other medications, adverse effects have been noted in the literature.  Examples of some adverse reactions include: aggression, breathing abnormalities, heart rate increases, twitching and vomiting.  It should be noted that adverse reactions may be more likely in certain breeds of dogs and/or among those administered supratherapeutic (high) doses.

  • Aggression: There is a case report of a terrier that ate 450 mg of hydroxyzine and exhibited significant aggression. This aggression may have been caused by alterations in histaminergic and serotonergic transmission.  That said, it could’ve been that hydroxyzine reduced anxiety to such an extent, that an underlying propensity to act aggressively (among this particular terrier) may have overridden learned regulatory mechanisms.
  • Apnea: Another adverse effect documented in the aforestated terrier example was that of apnea. This effect is characterized by interruptions in normative breathing during sleep.  Some dogs taking hydroxyzine, especially at larger-than-necessary dosages may exhibit signs of apnea.  If your dog’s breathing appears to temporarily stop during sleep, you may want to consider that hydroxyzine may have induced apnea.
  • Coma: In rare cases, a dog may go into a coma after taking hydroxyzine. A coma is likely triggered by unnecessarily high dosing of hydroxyzine and/or an interaction with another pharmaceutical medication.  A dog may be able to recover from the hydroxyzine-induced coma if rushed to an emergency veterinarian.
  • Rapid pulse: Some dogs may exhibit an abnormally rapid pulse after taking hydroxyzine. Pulse changes should be monitored closely by a professional while a dog is taking hydroxyzine to ensure that they aren’t serious.  Since hydroxyzine is a CNS depressant, a slowing of pulse may be more common.
  • Twitching: It is known that humans taking high doses of hydroxyzine are prone to involuntary tremors. Reports indicate that some dogs may exhibit involuntary muscle twitching as an adverse reaction to hydroxyzine.  Obviously if your dog starts to twitch after hydroxyzine administration, immediate attention from a veterinarian is advised.
  • Vomiting: In clinical research, one study reported that 2 dogs vomited after hydroxyzine administration. It is unclear as to whether hydroxyzine specifically prompted the vomiting though.  That said, it should be speculated that some dogs may not tolerate hydroxyzine as well as others, and vomit as a result.

Balance / coordination loss: Since hydroxyzine depresses activity in the CNS, and has been noted to impair fine motor skills in humans, it may cause balance and/or coordination difficulties in dogs.  If your dog appears unable to balance, is walking into furniture, and appears similar to a drunken human – the effects of hydroxyzine may be too potent for your dog to handle.  Perhaps an easy solution to balance and/or coordination problems is to simply talk to your veterinarian and work with him/her to reduce the dosage.

Depression: Some dogs may appear depressed while taking hydroxyzine, but whether they are actually in a state of emotional depression is subject to debate. Since antihistaminergics are capable of causing depressive symptoms in some humans, it could be speculated that dogs may experience a subdued mood after hydroxyzine administration.  Owners should be cognizant of dog depression resulting from medications, but should avoid jumping to the conclusion that their dog is depressed without considering side effects such as drowsiness and fatigue – each of which may lead to similar behaviors.

Drowsiness: The most commonly reported hydroxyzine side effect in canines (as well as humans) is drowsiness.  Don’t be surprised if your dog appears sleepy, less energetic, fatigued, or lethargic after administration of hydroxyzine.  Evidence from human studies suggests that drowsiness is typically most severe within the first week of hydroxyzine administration and usually improves thereafter (in consecutive weeks).

Interactions: If your dog is receiving multiple medications simultaneously, it is necessary to consider that they may interact with hydroxyzine – leading to contraindications.  Discuss all potential contraindications with your veterinarian and ensure that your dog isn’t taking another CNS depressant that may increase risk of serious adverse reactions (e.g. coma).  Due to hydroxyzine’s unique mechanism of action, contraindication risk is generally considered low in humans, however, this may differ in canines.

Ineffective: While hydroxyzine is considered an effective treatment for conditions such as atopic dermatitis and pruritus, it is not universally effective.  Some studies document that just over 50% of dogs derive benefit from its administration, while others have documented it as being effective in fewer than 20% of dogs.  Although lack of efficacy may not be considered a large “risk” per se, if your dog fails to derive therapeutic benefit, he/she may suffer for a longer period without symptomatic relief.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11824769
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15206590

How do the effects of Hydroxyzine differ between dogs and humans?

The effects of hydroxyzine are thought to be similar among dogs and humans.  In both dogs and humans, hydroxyzine is an effective treatment for atopic dermatitis and functions as an H1 receptor inverse agonist.  Dogs and humans tend to derive similar antihistaminergic value from hydroxyzine, which results in a reduction of allergies and decreases symptoms of pruritus (itching).

The pharmacokinetics are also very similar in both humans and dogs.  Exact pharmacokinetic data is subject to individual variation in humans based on hepatic function and CYP2D6 isoenzyme expression.  Among dogs, it is possible that pharmacokinetics may differ based on the particular breed of dog and/or additional factors such as adjuvant medications.

Due to neurophysiologic differences between dogs and humans, effects cannot be considered the “exact same.”  However, there are clearly parallels, including the formation of cetirizine metabolites as a result of hepatic metabolism.  Moreover, the safety and efficacy of hydroxyzine as a medical intervention is well-documented within each species.

Does your dog take Hydroxyzine?

If your dog is prescribed hydroxyzine, share whether you believe it has improved the quality of your pet’s life and/or ability to function.  To help others get a better understanding of your pet’s situation, mention: the condition for which your dog was prescribed hydroxyzine, breed of your dog (and its age), as well as the total duration over which he/she has been using hydroxyzine.  Also document whether your dog has experienced unwanted hydroxyzine side effects and whether these side effects are outweighed by the therapeutic effects.

For those that are administering hydroxyzine to their dog for the treatment of atopic dermatitis, have you tried dietary modifications and/or augmentation with EFAs (essential fatty acids)?  Realize that for many cases, hydroxyzine is a safe antihistaminergic intervention for the management of canine atopic dermatitis.  Further investigation is necessary to determine its therapeutic value for the treatment of other conditions.

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