Previous changes

December 2022 — minor update.  Added information relating to phenothiazine derivatives potentiating QT interval prolongation based on an updated manufacturer’s SPC.

November 2017 — reviewed. A literature search was conducted in August 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. Minor changes have been made to the sections on diagnosis and symptomatic treatment and a link to patient information has been added. The prescribing information section now includes more detailed information on dosage, contraindications, cautions, adverse effects, and interactions for the recommended drugs.

December 2016 — minor update. The contraindications and adverse effects of prochlorperazine have been updated in line with the manufacturer's Summary of Product Characteristics.

July 2013 — minor update. Links to the DVLA website have been updated.

November 2010 to February 2011 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 November 2022.

HTAs (Health Technology Assessments)

No new HTAs since 1 November 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 November 2022.

Systematic reviews and meta-analyses

No new systematic reviews published since 1 November 2022.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 November 2022.

New policies

No new national policies or guidelines since 1 November 2022.

New safety alerts

No new safety alerts since 1 November 2022.

Changes in product availability

No changes in product availability since 1 November 2022.

Head impulse test

• Use caution if the person has neck pathology (for example, cervical spine disease), as the head impulse test involves rapid repositioning of the head. Always start by asking the person to rotate their neck themselves to assess for any limitation of neck movement. If in doubt about the safety of the manoeuvre, seek specialist advice or refer the person to a balance specialist.
• To carry out the head impulse test:
  • Advise the person to sit upright and to fix their gaze on the examiner.
  • Then rapidly turn the head 10–20 degrees to one side and watch the person's eyes. In a normal response (indicating a normal peripheral vestibular system), the eyes stay fixed on the examiner. If the eyes are dragged off target by the head turn, a corrective abnormal movement (saccade) occurs as the eyes move back to fix on the examiner.
  • Repeat several times to the same or opposite side, randomly and unpredictably, until satisfied as to the consistent presence or absence of the corrective saccade.
    • A corrective saccade represents a positive test (disrupted vestibulo-ocular reflex) and implies moderate to severe loss of function of the horizontal semi-circular canal on the side to which the test is positive.

Basis for recommendation

Enquire about symptoms indicative of vestibular neuronitis

• This recommendation is derived from information on the symptoms of vestibular neuronitis in review articles [Dommaraju and Perera, 2016; Johns, 2020; BMJ Best Practice, 2021; Bae, 2022; BMJ Best Practice, 2022b; Strupp, 2022].  

Enquire about recent viral illness

• This recommendation is based on expert opinion in review articles that many people with vestibular neuronitis experience a viral prodrome before the onset of symptoms, and contacts may have the same symptoms [Dommaraju and Perera, 2016; Smith, 2022]. 

Look for signs of vestibular neuronitis

• The characteristic features of nystagmus and the results of otoscopy in a person with vestibular neuronitis are based on information in review articles [Dommaraju and Perera, 2016; Johns, 2020; BMJ Best Practice, 2021; Bae, 2022; BMJ Best Practice, 2022b; Strupp, 2022].  
• The head impulse test is also recommended on the basis of expert opinion in review articles [Jacobson, 2020; Johns, 2020; Bae, 2022], which include details of the procedure. An ocular tilt reaction (which is a combination of a skew deviation, head tilt, and ocular counter-roll) may be a subtle finding in many cases of vestibular neuronitis [Green, 2021]. 
• Experts note that the head impulse test demonstrates the presence or absence of the vestibulo-ocular reflex; therefore, can be used to assess peripheral vestibular function [Hogue, 2015; BMJ Best Practice, 2021].

Vestibular neuronitis is a clinical diagnosis

• In review articles, experts advise that the diagnosis of vestibular neuronitis is usually made on clinical grounds, without the need for further investigation [Bae, 2022; BMJ Best Practice, 2021].

Basis for recommendation

This information is based on expert opinion in review articles [Dommaraju and Perera, 2016; Johns, 2020; BMJ Best Practice, 2021; Bae, 2022; Smith, 2022]. 

Further sources of information are discussed in the CKS topic on Vertigo.

What should I advise a person with vestibular neuronitis?

• Reassure the person that symptoms will usually settle over several weeks, even if no treatment is given. Advise that factors such as alcohol, tiredness, or intercurrent illness may have a greater than usual effect on their balance. Explain that there may be periods during their recovery when their symptoms appear to be worsening again.
• Advise that bed rest may be necessary if symptoms are particularly severe during the acute phase, but that activity should be resumed as soon as possible (even if vertigo becomes more prominent during movement).
• Advise on safety issues.
  • Advise the person not to drive when they are dizzy, or if they are likely to experience an episode of vertigo while driving.
    • The Driver and Vehicle Licensing Agency (DVLA) states that people with 'liability to sudden and unprovoked or unprecipitated episodes of disabling dizziness' should stop driving and inform the DVLA. For more information, see the DVLA publication Assessing fitness to drive: a guide for medical professionals.
  • Workplace — the person should inform their employer if their vertigo poses a risk in the workplace (for example, people using ladders, operating heavy machinery, or driving).
  • Falls in the home — discuss the risk of falling in the home during an episode of vertigo, and suggest measures to reduce this.
• Offer the person written information, such as that provided by NHS on Vestibular neuronitis.

How should I treat the symptom of vertigo?

• If symptoms are severe, offer short-term symptomatic drug treatment.
• To rapidly relieve severe nausea or vomiting associated with vertigo, consider giving buccal prochlorperazine, or an intramuscular injection of prochlorperazine or cyclizine. 
• To alleviate less severe nausea, vomiting, and vertigo, consider prescribing a short oral course of prochlorperazine, or an antihistamine (cinnarizine, cyclizine, or promethazine teoclate). 
  • Advise the person to take medication regularly for up to 3 days. Explain that medication should be taken for the minimum amount of time possible, as it may delay recovery by affecting the body's compensatory mechanisms.
  • Advise that this medication may make them drowsy, and that their ability to drive or operate machinery may be impaired whilst taking it.
  • For more information, see Prescribing information.
• Treatment with antiviral drugs, corticosteroids, or benzodiazepines is not recommended.
• Advise the person to return if their symptoms deteriorate or have not fully resolved after 1 week.

When should I admit or refer a person with vestibular neuronitis?

• Admit the person to hospital if they have severe nausea and vomiting and cannot tolerate oral fluids or symptomatic drug treatment.
• Refer the person to a balance specialist (audiovestibular physician or neurologist — depending on local protocol) for further assessment or consideration of vestibular rehabilitation, (involving exercises to promote central nervous system compensation) if:
  • Symptoms are not typical of vestibular neuronitis (for example, additional neurological symptoms).
  • Symptoms persist without improvement for more than 1 week despite treatment (urgently refer).
  • Symptoms persist for longer than 6 weeks — investigation to exclude other causes, or vestibular rehabilitation may be required.

What dosage of cinnarizine should I prescribe?

• For vestibular symptoms, prescribe oral cinnarizine 30 mg three times a day.

[ABPI, 2021a; BNF, 2022]. 

What are the contraindications and cautions when prescribing cinnarizine?

• Do not prescribe cinnarizine if the person:
  • Is hypersensitive to cinnarizine or any of its excipients.
  • Has porphyria.
  • Has severe liver disease (there is an increased risk of coma).
• Prescribe cinnarizine with caution if the person has:
  • Parkinson’s disease – give only if the advantages outweigh the risk of disease exacerbation.
  • Hepatic or renal impairment.
  • Epilepsy.
  • Prostatic hypertrophy.
  • Pyloroduodenal obstruction.
  • Susceptibility to angle closure glaucoma.
  • Urinary retention.

 [ABPI, 2021a; BNF, 2022]

What are the adverse effects of cinnarizine?

• Adverse effects of cinnarizine are more common in older people and include drowsiness, nausea, dyspepsia, and weight gain.
• Less common adverse effects include:
  • Anaphylaxis and angio-oedema.
  • Dyskinesia, extrapyramidal disorder, Parkinsonism, tremor, and convulsions.
  • Cholestatic jaundice.
  • Palpitations.
  • Bronchospasm.
  • Subacute cutaneous lupus erythematosus, lichen planus, photosensitivity reactions, and rashes.
  • Angle-closure glaucoma.
  • Confusion and depression.

 [ABPI, 2021a; BNF, 2022]

What drug interactions occur with cinnarizine?

• Concurrent use of cinnarizine and alcohol, CNS depressants, or tricyclic antidepressants may result in increased sedative effects. Advise that this may influence the ability to perform skilled tasks such as driving.
• The use of phenelzine in conjunction with cinnarizine increases the risk of antimuscarinic adverse effects. 
• Avoid using cinnarizine within 4 days of skin testing as it may influence the results 

[ABPI, 2021a; BNF, 2022]

What dosage of cyclizine should I prescribe?

• For nausea, vomiting, vertigo, or labyrinthine disorders, prescribe cyclizine 50 mg orally up to three times a day.
• If the oral route is not appropriate, cyclizine 50 mg by intramuscular injection can be given up to three times a day.

[ABPI, 2018b; BNF, 2022].

What are the contraindications and cautions when prescribing cyclizine?

• Do not prescribe cyclizine to people with:
  • Hypersensitivity to cyclizine or its excipients.
  • Severe liver disease — increased risk of coma.
  • Porphyria.
• Prescribe cyclizine with caution to people with:
  • Prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, and pyloroduodenal obstruction.
  • Hepatic disease.
  • Epilepsy.
  • Severe heart failure or acute myocardial infarction — cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure, and pulmonary wedge pressure.
  • Phaeochromocytoma.

[ABPI, 2018a; BNF, 2022]

What are the adverse effects of cyclizine?

• Drowsiness is a significant adverse effect with most of the older antihistamines (such as cyclizine), especially with high doses or in the elderly.
• Other adverse effects include:
  • Psychiatric — restlessness, nervousness, euphoria, disorientation, insomnia, and auditory and visual hallucinations.
  • Neurological — headache, dystonia, dyskinesia, extrapyramidal motor disturbances, tremor, seizures, dizziness, somnolence and decreased consciousness, speech disorders (transient), paraesthesia, and generalized chorea.
  • Cardiovascular — tachycardia, palpitations, arrhythmias, hypertension, and hypotension.
  • Respiratory — bronchospasm and apnoea.
  • Gastrointestinal and hepatic — dry mouth, nose and throat; constipation; increased gastric reflux; nausea, vomiting, and diarrhoea; stomach pain; loss of appetite; hepatic dysfunction; cholestatic jaundice and hepatitis.
  • Skin — rashes, urticaria, angio-oedema, allergic skin reactions, and fixed drug eruption photosensitivity.
  • Musculoskeletal — twitching and muscle spasms.
  • Immune system — hypersensitivity reactions, including anaphylaxis.
  • Blood and lymphatic system — agranulocytosis, haemolytic anaemia, leucopenia, and thrombocytopenia.
  • Others — tinnitus, blurred vision and oculogyric crisis, and urinary retention.

[ABPI, 2018a; BNF, 2022]

What drug interactions occur with cyclizine?

• Important drug interactions with cyclizine include:
  • Alcohol — the anti-emetic effect of cyclizine may increase the toxic effects of alcohol.
  • Antimuscarinic drugs — there is a risk of increased antimuscarinic adverse effects when cyclizine is given with other antimuscarinic drugs. 
  • Central nervous system (CNS) depressant drugs — cyclizine may have additive effects with other CNS depressants, such as opioid analgesics.
  • Ototoxic drugs — cyclizine may disguise signs indicating the onset of damage caused by ototoxic drugs (such as aminoglycoside antibiotics).

[ABPI, 2018a; BNF, 2022]

What dosage of prochlorperazine should I prescribe?

• For vertigo, prescribe prochlorperazine 5 mg orally three times a day (maximum dose 30 mg daily). 
• If the oral route is not appropriate, consider prescribing either:
  • Prochlorperazine buccal tablets 3–6 mg twice a day (to be placed high in the buccal cavity and allowed to dissolve), or 
  • A one-off dose of prochlorperazine 12.5 mg by deep intramuscular injection followed by oral medication after an interval of 6 hours, if required.

[ABPI, 2019; ABPI, 2020; ABPI, 2021b]

What are the contraindications and cautions when prescribing prochlorperazine?

• Do not prescribe prochlorperazine to people with:
  • Hypersensitivity to prochlorperazine or its excipients.
  • Agranulocytosis.
  • A history of angle closure glaucoma.
  • Prostate hypertrophy.
  • Myasthenia gravis.
  • Heart failure.
  • Hypothyroidism.
  • Parkinson's disease.
  • History of jaundice.
  • Liver or renal dysfunction.
  • Phaeochromocytoma.
• Prescribe prochlorperazine with caution to:
  • People with epilepsy or a history of seizures — close monitoring is required in this group of people as prochlorperazine may lower the seizure threshold.
  • Elderly people — use with caution, especially during very hot or cold weather due to the risk of hyper- or hypothermia.
  • People with cardiovascular disease or family history of QT prolongation — cases of QT interval prolongation have been very rarely reported with prochlorperazine. An alternative anti-emetic should be considered for people with predisposing factors for ventricular arrhythmias, or they should be carefully monitored (check electrolytes and ECG), particularly during the initial phase of treatment.
    • Cardiac disease; metabolic abnormalities such as hypokalaemia, hypocalcaemia, or hypomagnesaemia; starvation; alcohol misuse; and concurrent treatment with other drugs known to prolong the QT interval may predispose people to ventricular arrhythmias.

[ABPI, 2020; BNF, 2022]

What are the adverse effects of prochlorperazine?

• Extrapyramidal symptoms
  • These depend on the dose and the susceptibility of the individual person.
    • Parkinsonian symptoms (including tremor) may occur more commonly in adults or the elderly, and may appear gradually.
    • Dystonia (abnormal face and body movements) and dyskinesia are more common in young people, and can occur after only a few doses.
    • Akathisia (restlessness) characteristically occurs after large initial doses.
    • Tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw) usually develops on long-term treatment or with high doses.
• Endocrine disorders
  • Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, impotence, and amenorrhoea has been reported following treatment with prochlorperazine.
• Cardiac disorders
  • Cardiac arrhythmias including atrial arrhythmia, atrioventricular block, ventricular fibrillation, and ventricular tachycardia (rare), have been reported. QT prolongation, sudden death, cardiac arrest, and Torsades de points have also occurred following treatment with prochlorperazine.
  • Pre-existing cardiac disease, family history of QT prolongation, increasing age, hypokalaemia, and concurrent use of other drugs known to prolong the QT interval may increase the likelihood of these effects.
• Blood and lymphatic system disorders
  • Mild leucopenia occurs in up to 30% of people on high doses of prochlorperazine for a prolonged period of time.
  • Agranulocytosis may occur rarely, but it is not related to the dose. If unexplained infections or fever occur, immediate haematological investigation is required.
  • Cases of venous thromboembolism have also been reported with prochlorperazine.
• Other adverse effects include:
  • Neurological disorders — drowsiness, apathy, agitation, excitement, insomnia, convulsions, dizziness, headache, and confusion.
  • Antimuscarinic effects — dry mouth, constipation, difficulty with micturition, blurred vision, and precipitation of angle-closure glaucoma (very rare).
  • Skin and tissue disorders — photosensitization, contact sensitization, rashes, and purplish pigmentation of the skin.
  • Hepatobiliary disorders — jaundice (including cholestatic).
  • Eye disorders — corneal and lens opacities and purplish pigmentation of the cornea, conjunctiva, and retina.
  • Neuroleptic malignant syndrome (potentially fatal) — symptoms include changes in conscious level and mental status, unexplained fever, hyperthermia, autonomic dysfunction, and muscle rigidity.

[ABPI, 2020; BNF, 2022]

What drug interactions occur with prochlorperazine?

• Alcohol — advise the person to avoid taking alcohol whilst taking prochlorperazine.
  • The sedative effects of alcohol on driving and operating heavy machinery may be enhanced by prochlorperazine.
• Antimuscarinic drugs — there is a risk of increased antimuscarinic adverse effects when prochlorperazine is given with other antimuscarinic drugs.
• Antiepileptic drugs — concurrent use of prochlorperazine and antiepileptic drugs may lower the seizure threshold because of liver enzyme induction. 
• Antihypertensive drugs — the hypotensive effect of most antihypertensive drugs (particularly alpha-adrenoceptor blockers and calcium channel blockers) may be increased by prochlorperazine.
• Cimetidine — plasma concentrations of prochlorperazine may be increased or decreased by cimetidine. Excessive sedation may occur, and it may be necessary to reduce the dose of prochlorperazine.
• Central nervous system (CNS) depressants— the CNS depressant actions of prochlorperazine may be increased by barbiturates, opioid analgesics, anxiolytics, and hypnotics, raising the risk of respiratory depression.
• Drugs that prolong the QT interval — there is an increased risk of ventricular arrhythmias when prochlorperazine is used concurrently with drugs that prolong the QT interval, for example, antiarrhythmics, sotalol, antidepressants (tricyclics, citalopram, and escitalopram), antihistamines (terfenadine), methadone, and risperidone.
• Lithium — there is an increased risk of extrapyramidal adverse effects and possibly neurotoxicity when prochlorperazine is given with lithium. 
• Sulphonylureas — the hypoglycaemic effect of sulfonylureas (such as gliclazide) may be antagonized by prochlorperazine. Dose adjustment of the sulfonylurea may be required.

[ABPI, 2020; BNF, 2022; Preston, 2023]

What dosage of promethazine teoclate should I prescribe?

• Prescribe promethazine teoclate 25 mg orally at night. The dose may be increased to 100 mg daily.

[ABPI, 2022; BNF, 2022]

What are the contraindications and cautions when prescribing promethazine teoclate?

• Promethazine teoclate should not be used in people with:
  • Hypersensitivity to promethazine, its excipients, or other phenothiazines.
  • Central nervous system (CNS) depression of any cause.
  • Exposure to monoamine oxidase inhibitors within the previous 14 days.
  • Severe liver disease — increased risk of coma.
• Promethazine teoclate should be used with caution in people with:
  • Hepatic or renal impairment.
  • Severe coronary artery disease.
  • Urinary retention or prostatic hypertrophy.
  • Angle-closure glaucoma.
  • Pyloroduodenal obstruction.
  • Epilepsy.
  • Asthma, bronchitis, or bronchiectasis — promethazine teoclate may thicken or dry lung secretions and impair expectoration.
  • In addition phenothiazine derivatives may potentiate QT interval prolongation increases the risk of ventricular arrhythmias including Torsade de pointes. QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalaemia, and drug induced QT prolongation. The manufacturer suggests that if the clinical situation permits, medical and laboratory evaluations should be performed to rule out possible risk factors before initiating treatment with a phenothiazine derivative and when necessary during treatment.

[ABPI, 2022; BNF, 2022]

What are the adverse effects of promethazine teoclate?

Adverse effects of promethazine include:

• Neurological — dizziness, confusion, restlessness, headaches, nightmares, sedation (affected people should not drive or operate heavy machinery), tremor, muscle spasms and tic-like movements of the head and face, and extrapyramidal effects.
• Antimuscarinic effects — blurred vision, dry mouth, and urinary retention.
• Skin — rash and photosensitivity.
• Gastrointestinal — anorexia, gastric irritation, and jaundice (rare).
• Cardiovascular — palpitations, hypotension, and arrhythmias.

 [ABPI, 2022; BNF, 2022]

What drug interactions occur with promethazine?

• Drug interactions with promethazine include:
  • Opioid analgesics — sedative effects may be enhanced when promethazine is given with opioid analgesics.
  • Alcohol — sedative effects may be increased by the combination of promethazine and alcohol.
  • Antimuscarinic drugs, tricyclic antidepressants, sedatives, and hypnotics — concomitant use with promethazine enhances the antimuscarinic and/or sedative action of these drugs.
• Promethazine has the potential to interact with immunological pregnancy tests (may give false-positive or false-negative results). It may also give a false negative result with skin tests by inhibiting the cutaneous histamine response — discontinue 72 hours in advance.

[ABPI, 2022; BNF, 2022; Preston, 2023]