Hydroxyzine

Registered South African indications:

• Short-term management of anxiety, tension and psychomotor agitation in conditions of emotional stress
• Alleviation of the manifestations of anxiety and tension in situations in which the causative stress is temporary, as in the preparation for dental and other minor surgical procedures and in acute emotional problems
• Allergic conditions with strong emotional overlay, as in urticaria and pruritus
• As adjunctive pre- and postoperative sedative medication
  - To allay anxiety, control emesis, and reduce the amount of opioid analgesic required
• Symptomatic treatment of vertigo, nausea and vomiting of Meniere's disease and related disorders

Contraindications

Injection

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other piperazine derivatives
• May not be administered by the subcutaneous, intravenous or intra-arterial route
• Pregnancy
• Breastfeeding
• Porphyria
• Respiratory failure
• Patients who have blood transfusion reactions caused by ABO blood group incompatibilities
• Premature infants or neonates as this group of patients have an increased susceptibility to antimuscarinic effects

Tablet & syrup

• Hypersensitivity to the active ingredient or any of its excipients
• Acute intermittent porphyria
• Respiratory failure
• Pregnancy

Cautions

• Breastfeeding (syr, tab)
• Moderate to severe renal impairment (eGFR≤49ml/min/1.73m²) and patients on dialysis
• Mild to moderate hepatic impairment
• Elderly
• Children
• Glaucoma (including angle closure glaucoma)
• Hypertension
• Cardiac arrhythmias
• Urinary retention
• Increased intraocular pressure
• Prostatic hyperplasia
• Pyroduodenal obstruction
• Seizures disorders
• Epilepsy
• Myasthenia gravis
• Dementia
• Decreased gastrointestinal motility
• Bladder outflow obstruction
• Stenosing peptic ulcer
• Breathing problems
• Emphysema
• Chronic bronchitis
• Hyperthyroidism
• Cardiovascular disease
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct, tab, syr, inj

South African registered indications and dosages

Injection

Usual dose range

• IM: 25-100mg

Symptomatic treatment of vertigo, nausea and vomiting of Meniere's disease and related disorders

• IM: 25-100mg

As a pre- and postoperative sedative for the control of nausea, vomiting and anxiety

• IM: 50-100mg

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Administration should be by deep intramuscular injection into a large muscle mass, preferably the upper outer quadrant of the buttock (gluteus maximus) or the mid-lateral thigh

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The deltoid area should only be used if well developed in the adult and only when extreme caution to avoid radial nerve injury. Intramuscular injections should not be made in the lower and mid-third of the upper arm. Aspiration is necessary to avoid inadvertent injection into a blood vessel

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Tablet & syrup

Usual dose range

• Oral (fct, tab, syr): 25mg, 3 times daily to 100mg, 4 times daily

Anxiety
- Short-term management of anxiety, tension and psychomotor agitation in conditions of emotional stress
- Alleviation of the manifestations of anxiety and tension in situations in which the causative stress is temporary, as in the preparation for dental and other minor surgical procedures and in acute emotional problems

• Oral (fct. tab, syr): 50-100mg, 4 times daily

Other indications
- Allergic conditions with strong emotional overlay, as in urticaria

• Oral (fct, tab, syr): 25-100mg, 4 times daily

- Pruritis

• Oral (fct, tab, syr): Initial: 25mg, given at night; Increase to 25mg, 3-4 times daily

As adjunctive pre- and postoperative sedative medication
- To allay anxiety, control emesis, and reduce the amount of opioid analgesic required

• Oral (fct, tab, syr): 50 -100mg

Paed. forms avail. in SA and covered in this monograph: fct, tab, syr, inj

South African registered indications and dosages

Injection

Usual dose range

• IM: 1.1mg/kg body weight

Symptomatic treatment of vertigo, nausea and vomiting of Meniere's disease and related disorders

Younger than 6 years

• IM: 5-15mg, daily; Increase to 50mg, daily in divided doses if necessary

Older than 6 years

• IM: 15-25mg, daily; Increase to 50-100mg, daily in divided doses if necessary

As a pre- and postoperative sedative for the control of nausea, vomiting and anxiety

• IM: 0.6mg/kg body weight

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Not for use in premature infants and neonates (see contraindications)

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It is recommended that intramuscular injection should be given preferably in the mid-lateral muscles of the thigh. In infants and small children, the periphery of the upper outer quadrant of the gluteal region should be used only when necessary, such as in burn patients, in order to minimise the possibility of damage to the sciatic nerve

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The deltoid area should only be used if well developed in older children and only when extreme caution to avoid radial nerve injury. Intramuscular injections should not be made in the lower and mid-third of the upper arm. Aspiration is necessary to avoid inadvertent injection into a blood vessel

---

Tablet & syrup

Anxiety
- Short-term management of anxiety, tension and psychomotor agitation in conditions of emotional stress
- Alleviation of the manifestations of anxiety and tension in situations in which the causative stress is temporary, as in the preparation for dental and other minor surgical procedures and in acute emotional problems
Other indications
- Allergic conditions with strong emotional overlay, as in urticaria and pruritus

Younger than 6 years

• Oral (fct, tab, syr): 5-15mg, daily; Increase to 50mg, daily in divided doses if necessary

Older than 6 years

• Oral (fct, tab, syr): 15-25mg, daily; Increase to 50-100mg, daily in divided doses if necessary

As adjunctive pre- and postoperative sedative medication
- To allay anxiety, control emesis, and reduce the amount of opioid analgesic required

• Oral (fct, tab, syr): 0.6mg/kg body weight

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For indications where oral administration is not practical, the intramuscular dose in children is 1.1mg/kg body weight

Pregnancy

• Contraindicated
• Safety in pregnancy has not been established
• Hypotonic syndrome in infants may occur with chronic use of hydroxyzine during late pregnancy

Breastfeeding

Injection

• Contraindicated
• Safety in lactation has not been established

Tablet & syrup

• Caution; no information available

Renal Impairment

• eGFR ≥50ml/min/1.73m²: No dose adjustment recommended
• eGFR ≤49ml/min/1.73m² OR on dialysis: Caution; dose adjustment recommended 
  Reduce dose by 50%
  Discontinue therapy if further deterioration in CrCl was observed

Hepatic Impairment

• Mild to moderate: (Child-Pugh Classes A & B): Caution; dose adjustment recommended
  Reduce dose by 33%
  Discontinue therapy if an increase in ALT and/or bilirubin >X3 ULN
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• Caution; dose adjustment recommended
  Max: 50mg/24hrs 

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dyskinesia
• Insomnia
• Sedation
• Drowsiness
• Dizziness
• Lassitude
• Weakness
• Headache
• Tremor
• Psychomotor impairment
• Paraesthesias
• Extrapyramidal effects
• Seizures
• Coma
• Disturbance in attention
• Ataxia
• Slurred speech
• Agitation
• Confusion
• Disorientation
• Hallucinations
• Sleep disturbances
• Somnolence
• Depression
• Nightmares
• Increased anxiety
• Faintness
• Fatigue
• Irritability
• Incoordination
• Headache
• Involuntary motor activity

Cardiovascular Disorders

• Ventricular arrhythmias
• Torsade de Pointes
• QT prolongation
• Tachycardia
• Palpitation
• Hypotension
• Flushing

Respiratory Disorders

• Bronchospasm
• Thickened respiratory tract secretions
• Wheezing
• Nasal stuffiness
• Dryness of throat
• Tightness of chest

Gastrointestinal Disorders

• Constipation
• Dry mouth
• Nausea and vomiting
• Increased gastric reflux
• Diarrhoea
• Epigastric pain
• Increased gastrointestinal peristalsis

Hepatobiliary Disorders

• Hepatic dysfunction
• Abnormal liver function tests

Genitourinary Disorders

• Urinary retention
• Dysuria
• Priapism
• Impotence
• Early menses

Endocrine and Metabolic Disorders

• Anorexia

Musculoskeletal Disorders 

• Myalgia

Skin and Subcutaneous Tissue Disorders

• Dermatitis
• Fixed drug eruption
• Pruritis
• Erythema
• Maculo­papular rash
• Angioneurotic oedema
• Increased sweating
• Urticaria
• Hair loss
• Eczema
• Acute generalised exanthematous pustulosis
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Injection site reactions (inj)

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylaxis
• Angioedema
• Porphyria
• Blood disorders
• Agranulocytosis
• Leukopaenia
• Haemolytic anaemia
• Thrombocytopaenia
• Fever

Sensory Disorders

• Accommodation disorder
• Tinnitus
• Labrynthitis
• Vertigo
• Blurred vision
• Bitter taste in mouth

• QT prolonging agents
• Class IA antiarrhythmics
• Quinidine
• Disopyramide
• Class III antiarrhythmics
• Amiodarone
• Sotalol
• Antihistamines
• Antipsychotics
• Haloperidol
• Citalopram
• Escitalopram
• Antimalarial agents
• Mefloquine
• Antibiotics
• Erythromycin
• Levofloxacin
• Moxifloxacin
• Antifungal agents
• Pentamidine
• Gastrointestinal agents
• Prucalopride
• Antineoplastics
• Toremifene
• Vandetanib
• Methadone
• Hypokalaemia-inducing agents
• CYP3A4/5 inhibitors
• Central nervous system depressants
• Anticholinergics
• Antimuscarinic agents 
• Methocoline
• Betahistine
• Anticholinesterase agents
• Monoamine oxidase inhibitors
• Adrenaline
• Cimetidine
• Phenytoin
• Aminoglycosides
• CYP2D6 substrates
• Agents which have effects on the brain
• Agents that affect the hepatic microsomal enzyme system
• Ototoxic agents
• Alcohol

• Blood pressure 
• Mental status

Hydroxyzine is a first generation antihistamine with antimuscarinic and sedative properties. It acts as a competitive antagonist of histamine at histamine H1-receptors, thus inhibiting H1-receptor mediated reactions, such as vasodilation, flare and itch reactions and sneezing. It crosses the blood-brain barrier, producing sedative and anticholinergic effects. First-generation antihistamines also have affinity for 5-HT receptors, alpha-adrenoreceptors, and muscarinic receptors. They also reduce cyclic GMP concentrations, increase atrioventricular nodal conduction, and inhibit activation of airway vagal afferent nerves.

Tablet 25mg

• Aterax (AHN Pharma) originator

Tablet 100mg

• Aterax (AHN Pharma) originator

Syrup (per ml) 2mg

• Aterax  (AHN Pharma) originator

Injection (per 2ml) 100mg

• Pharma-Q Hydroxyzine (Pharma-Q)