Cyclizine

Generic Name

Cyclizine

Brand Names

Valoid

Marezine

Cyclivert

Nausicalm

Cinnarizine-Cyclizine combination (in some countries)

Also available in generic formulations

Drug Class

First-generation antihistamine

Histamine H1 receptor antagonist

Classified as an antiemetic and anticholinergic agent

Belongs to the piperazine group of antihistamines

Mechanism of Action

Cyclizine acts primarily by blocking histamine H1 receptors in the central nervous system, particularly in the chemoreceptor trigger zone (CTZ) and the vomiting center in the medulla

Additionally, it exhibits significant anticholinergic and anti-muscarinic properties, contributing to its effectiveness in motion sickness and vertigo

It suppresses the vestibular system and inhibits stimulation of the labyrinth and vomiting center

Also has mild sedative properties due to central H1 antagonism

Indications

Approved Indications

Prevention and treatment of nausea and vomiting associated with:

– Motion sickness

– Post-operative states

– Radiation sickness

– Drug-induced vomiting (e.g., opioids)

– Labyrinthine disorders including Ménière’s disease and vestibular vertigo

– Pregnancy-associated nausea (off-label but commonly used in the UK)

– Palliative care: used to manage nausea related to raised intracranial pressure or opioid use

– Vertigo and dizziness in vestibular disorders

Off-Label Uses

Hyperemesis gravidarum (particularly in first trimester)

Migraine-associated nausea

Nausea secondary to chemotherapy (limited role compared to modern agents)

Supportive care in advanced cancer

Dosage and Administration

Adults and Children Over 12 Years

Oral: 50 mg up to three times daily

IV or IM: 50 mg every 8 hours as needed (used in hospital or hospice settings)

Maximum dose: 150 mg in 24 hours

Children 6–12 Years

Oral: 25 mg up to three times daily

Children under 6 years

Not recommended unless specifically prescribed

Safety and efficacy not well established

Motion Sickness Prophylaxis

Oral 50 mg taken 30 minutes before travel

Repeat after 6–8 hours if needed

Palliative Care (Subcutaneous/IV use)

Often given via syringe driver

Usual dose: 100–150 mg/24 hours via continuous infusion

May be combined with opioids or other antiemetics in palliative regimens

Pregnancy-Related Nausea

Off-label use

25–50 mg every 8 hours orally

Considered low risk in early pregnancy and endorsed by RCOG in the UK when first-line agents (e.g., promethazine, doxylamine) are unavailable or ineffective

Administration Notes

Can be taken with or without food

Oral tablets may be sedating—patients should avoid driving or operating heavy machinery

Injectable form should only be administered by healthcare professionals

Rectal suppositories available in some countries

Pharmacokinetics

Rapid oral absorption

Onset of action: ~30 minutes

Peak plasma concentration: ~2–3 hours

Duration of action: 4–6 hours

Half-life: ~14–15 hours

Metabolized hepatically

Excreted in urine, mainly as metabolites

Crosses the blood-brain barrier

Contraindications

Known hypersensitivity to cyclizine or other piperazine derivatives

Severe liver disease

Closed-angle glaucoma (due to anticholinergic effects)

Urinary retention (especially in prostatic hypertrophy)

Children under 6 years (without specialist guidance)

Porphyria (may trigger attacks)

Use with caution in patients with epilepsy (may lower seizure threshold)

Warnings and Precautions

May cause drowsiness and impair mental alertness

Potentiates the effects of CNS depressants (e.g., alcohol, sedatives, opioids)

Caution in elderly due to risk of anticholinergic side effects (confusion, dry mouth, constipation, urinary retention)

May mask signs of ototoxicity when used with aminoglycosides

Can worsen symptoms of angle-closure glaucoma

Use cautiously in patients with cardiac disease due to potential for tachycardia or palpitations

Risk of delirium or hallucinations in high doses or overdose

Adverse Effects

Common

Drowsiness or sedation

Dry mouth

Blurred vision

Dizziness

Constipation

Headache

Excitability (particularly in children)

Less Common

Nausea

Palpitations

Tachycardia

Hypersensitivity reactions (rash, urticaria)

Urinary retention

Photosensitivity

Rare and Serious

Seizures

Hepatic dysfunction

Hallucinations or confusion (especially in elderly)

Anaphylaxis

Agranulocytosis (extremely rare)

Pregnancy and Lactation

Pregnancy

Classified as Category B (US FDA—discontinued system)

No teratogenic effects observed in animal studies

Widely used in the UK for pregnancy-related nausea

Recommended by the Royal College of Obstetricians and Gynaecologists (RCOG) as an alternative treatment in hyperemesis gravidarum

Preferably avoided in the first trimester unless clinically indicated

Lactation

Excreted in small amounts into breast milk

Use with caution—may cause drowsiness or irritability in infants

Short-term use considered acceptable by some sources

Drug Interactions

CNS Depressants

Additive sedation with alcohol, opioids, benzodiazepines, antipsychotics

Avoid combination unless necessary

Anticholinergic Drugs

Additive anticholinergic effects when combined with tricyclic antidepressants, antihistamines, antipsychotics

May increase risk of dry mouth, constipation, blurred vision, urinary retention

Aminoglycosides

May mask ototoxicity—use with caution

Monoamine Oxidase Inhibitors (MAOIs)

Avoid co-administration—may enhance anticholinergic and CNS effects

Sedating Antihistamines

Additive sedative effect—avoid duplication

Metoclopramide or Domperidone

Pharmacodynamic antagonism when co-administered—cyclizine may reduce the efficacy of dopamine agonist antiemetics

Monitoring Parameters

Mental status, especially in elderly

Signs of CNS depression

Anticholinergic side effects

Response to antiemetic treatment

Glaucoma or urinary retention symptoms in at-risk populations

Counseling Points

Avoid alcohol or sedating drugs while taking cyclizine

Do not drive or operate machinery if drowsy

Take 30–60 minutes before travel if used for motion sickness

Swallow tablets whole with water—can be taken with food to reduce stomach upset

Inform prescriber if vision changes, difficulty urinating, or confusion occur

Store away from light and moisture—especially injectables

Report allergic reactions or worsening nausea

Comparative Notes

Cyclizine vs Promethazine

Both are first-generation antihistamines

Promethazine is more sedating

Cyclizine better tolerated for ambulatory use due to less sedation

Cyclizine has stronger anti-vestibular activity

Cyclizine vs Metoclopramide

Metoclopramide is a prokinetic and dopamine antagonist

Cyclizine is preferred in motion sickness and vestibular disorders

Metoclopramide preferred in gastroparesis or chemotherapy-induced nausea

Cyclizine vs Ondansetron

Ondansetron is a 5-HT3 antagonist used in chemotherapy and post-op nausea

Cyclizine is better for motion sickness, raised intracranial pressure, and palliative care

Ondansetron has less sedation and anticholinergic side effects

Legal and Regulatory Status

Prescription-only in many countries

Available over the counter in low-dose preparations in some regions

Approved by national regulatory bodies including MHRA (UK), FDA (USA – for Valoid), EMA

Widely used in hospital, palliative care, and ambulatory settings