Skip to Content

VALOID INJECTION

Active substance(s): CYCLIZINE LACTATE / CYCLIZINE LACTATE / CYCLIZINE LACTATE

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT
Valoid 50 mg/ml Injection
Cyclizine Lactate 50 mg/ml Injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 ml ampoule contains 50 mg cyclizine lactate.

Excipients with known effect:
None

For a full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Clear, colourless solution for injection.
4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications

Valoid is indicated in adults for the prevention and treatment of nausea and vomiting
including:•




Motion sickness when the oral route cannot be used.
Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the
post-operative period.
Vomiting associated with radiotherapy especially for breast cancer since cyclizine
does not elevate prolactin levels.
Valoid injection, by the intravenous route, is also indicated pre-operatively in
patients undergoing emergency surgery in order to reduce the hazard of regurgitation
and aspiration of gastric contents during induction of general anaesthesia.

Valoid may be of value in relieving vomiting and attacks of vertigo associated with Menière’s
disease and other forms of vestibular disturbance when the oral route cannot be used.

4.2.

Posology and method of administration

Posology

For the prevention of postoperative nausea and vomiting, administer the first dose by slow
intravenous injection 20 minutes before the anticipated end of surgery.

Adults
50 mg intramuscularly or intravenously up to three times daily.

When used intravenously, Valoid should be injected slowly into the bloodstream, with only
minimal withdrawal of blood into the syringe.

For the prevention of postoperative nausea and vomiting, administer the first dose by slow
intravenous injection 20 minutes before the anticipated end of surgery.

Cyclizine given intravenously, in half the recommended dose, increases the lower
oesophageal sphincter tone and thereby reduces the hazard of regurgitation and aspiration of
gastric contents if given to patients, undergoing emergency surgery, before induction of
general anaesthesia.

Older people
There have been no specific studies of Valoid in the elderly. Experience has indicated that
normal adult dosage is appropriate.

Paediatric population
Not licensed for use in children.

Method of Administration:

Intramuscularly or intravenously

4.3.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Valoid is contraindicated in the presence of acute alcohol intoxication. The anti-emetic
properties of cyclizine may increase the toxicity of alcohol.

4.4

Special warnings and precautions for use
As with other anticholinergic agents, Valoid may precipitate incipient glaucoma and it should
be used with caution and appropriate monitoring in patients with glaucoma, urinary retention,
obstructive disease of the gastrointestinal tract, 1hepatic disease, pheochromocytoma,
hypertension, epilepsy and in males with possible prostatic hypertrophy. Valoid injection
may have a hypotensive effect.

Cyclizine should be used with caution in patients with severe heart failure or acute
myocardial infarction. In such patients, cyclizine may cause a fall in cardiac output
associated with increases in heart rate, mean arterial pressure and pulmonary wedge
pressure.
Cyclizine should be avoided in porphyria.

There have been reports of abuse of cyclizine, either oral or intravenous, for its
euphoric or hallucinatory effects. The concomitant misuse of Valoid with large
amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine
may increase the toxicity of alcohol 2(see also Section 4.5).
Case reports of paralysis have been received in patients using intravenous cyclizine. Some of
the patients mentioned in these case reports had an underlying neuromuscular disorder. Thus

1
2

PL20072/0010-0006; 05/12/2005
PL 20072/0010-0014; 28/10/2009

intravenous cyclizine, should be used with caution in all patients and with particular care in
patients with underlying neuromuscular disorders.

4.5.

Interactions with other medicinal products and other forms of interaction

Valoid may have additive effects with alcohol and other central nervous system depressants
e.g. hypnotics, tranquillisers, anaesthetics, antipsychotics, barbiturates.

Valoid enhances the soporific effect of pethidine.

Valoid may counteract the haemodynamic benefits of opioid analgesics.

Because of its anticholinergic activity, cyclizine may enhance the side-effects of other
anticholinergic drugs, and may have an additive antimuscarinic action with other
antimuscarinic drugs, such as atropine and some antidepressants (both tricyclics and
MAOIs).
Valoid may mask the warning signs of damage caused by ototoxic drugs such as
aminoglycoside antibacterials.

4.6.

Fertility, pregnancy and lactation

Pregnancy
In the absence of any definitive human data, the use of Valoid in pregnancy is not advised.

Breast-feeding
Cyclizine is excreted in human milk, however, the amount has not been quantified

Fertility:
In a study involving prolonged administration of cyclizine to male and female rats, there was
no evidence of impaired fertility after continuous treatment for 90-100 days at dose levels of
approximately 15 and 25 mg/kg/day. There is no experience of the effect of Valoid on human
fertility.

4.7

Effects on ability to drive and use machines

Studies designed to detect drowsiness did not reveal sedation in healthy adults who took a
single oral therapeutic dose (50 mg) of cyclizine, sedation of short duration was reported by
subjects receiving intravenous cyclizine.

Patients should not drive or operate machinery until they have determined their own response.

Although there are no data available, patients should be cautioned that Valoid may have
additive effects with alcohol and other central nervous system depressants, e.g. hypnotics and
tranquillisers.

4.8

Undesirable effects
Blood and lymphatic system disorders
Agranulocytosis, leucopenia, haemolytic anaemia, thrombocytopenia.

Cardiac disorders
Tachycardia palpitations, arrhythmias (see section 4.4),

Eye disorders
Blurred vision, oculogyric crisis

Gastrointestinal system disorders
Dryness of the mouth, nose and throat, constipation, increased gastric reflux, nausea,
vomiting, diarrhoea, stomach pain, loss of appetite.

General disorders and administration site conditions
Asthenia
Injection site reactions including vein tracking, erythema, pain, thrombophlebitis and blisters.
A sensation of heaviness, chills, and pruritus have been reported rarely.
Anaphylaxis has been recorded following intravenous administration of cyclizine coadministered with propanidid in the same syringe.

Hepatobiliary disorders
Hepatic dysfunction (see section 4.4), hypersensitivity hepatitis, cholestatic jaundice and
cholestatic hepatitis have occurred in association with cyclizine.

Immune system disorders
Hypersensitivity reactions, including anaphylaxis have occurred.

Musculoskeletal and connective tissue disorders
Twitching, muscle spasms

Nervous system disorders
Effects on the central nervous system have been reported with cyclizine these include
somnolence, drowsiness, incoordination, headache, dystonia, dyskinesia, extrapyramidal
motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech
disorders, paraesthesia, paralysis* and generalised chorea.
*Case reports of paralysis have been received in patients using intravenous cyclizine. Some of
the patients mentioned in these case reports had an underlying neuromuscular disorder. (see
section 4.4)

Ear and labyrinth disorders
Tinnitus.
There have been rare case reports of patients experiencing depressed levels of
consciousness/loss of consciousness.

Psychiatric disorders
Disorientation, restlessness or agitation, nervousness, euphoria, insomnia and auditory and
visual hallucinations have been reported, particularly when dosage recommendations have
been exceeded.

Renal and urinary disorders
Urinary retention

Respiratory, thoracic and mediastinal disorders
Bronchospasm, apnoea

Skin and subcutaneous tissue disorders
Urticaria, pruritus, drug rash, angioedema, allergic skin reactions, fixed drug eruption,
photosensitivity

Vascular disorders
Hypertension, hypotension

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via the
Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.
4.9.

Overdose

Symptoms
Symptoms of acute toxicity from cyclizine arise from peripheral anticholinergic effects and
effects on the central nervous system.

Peripheral anticholinergic symptoms include, dry mouth, nose and throat, blurred
vision, tachycardia and urinary retention. Central nervous system effects include
drowsiness, dizziness, incoordination, ataxia, weakness, hyperexcitability,
disorientation, impaired judgement, hallucinations, hyperkinesia, extrapyramidal
motor disturbances, convulsions, hyperpyrexia and respiratory depression.
An oral dose of 5 mg/kg is likely to be associated with at least one of the clinical symptoms
stated above. Younger children are more susceptible to convulsions. The incidence of
convulsions, in children less than 5 years, is about 60% when the oral dose ingested exceeds
40 mg/kg.

Management
In the management of acute overdosage with Valoid, gastric lavage and supportive measures
for respiration and circulation should be performed if necessary. Convulsions should be
controlled in the usual way with parenteral anticonvulsant therapy.
5.1.

Pharmacodynamic properties

ATC Code: R06AE

Pharmacotherapeutic Group: Piperazine derivatives

Mechanism of action:
Cyclizine is a histamine H1 receptor antagonist of the piperazine class which is characterised
by a low incidence of drowsiness. It possesses anticholinergic and antiemetic properties. The
exact mechanism by which cyclizine can prevent or suppress both nausea and vomiting from
various causes is unknown. Cyclizine increases lower oesophageal sphincter tone and reduces
the sensitivity of the labyrinthine apparatus. It may inhibit the part of the midbrain known
collectively as the emetic centre.

Pharmacodynamics effects:
Cyclizine produces its antiemetic effect within two hours and lasts approximately four hours.
5.2.

Pharmacokinetic properties

Distribution
In healthy adult volunteers the administration of a single oral dose of 50 mg cyclizine resulted
in a peak plasma concentration of approximately 70 ng/mL occurring at about two hours after
drug administration. The plasma elimination half-life was approximately 20 hours.

Biotransformation
The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine.
Norcyclizine has little antihistaminic (H1) activity compared to cyclizine and has a plasma
elimination half life of approximately 20 hours.

Elimination
After a single dose of 50mg cyclizine given to a single adult male volunteer, urine collected
over the following 24 hours contained less than 1% of the total dose administered.
5.3.

Preclinical safety data

A. Mutagenicity
Cyclizine was not mutagenic in a full Ames test, including use of S9-microsomes but can
nitrosate in vitro to form mutagenic products.

B. Carcinogenicity
No long term studies have been conducted in animals to determine whether cyclizine has a
potential for carcinogenesis. However, long-term studies with cyclizine administered with
nitrate have indicated no carcinogenicity.

C. Teratogenicity
Some animal studies are interpreted as indicating that cyclizine may be teratogenic at dose
levels up to 25 times the clinical dose level. In another study, cyclizine was negative at oral
dose levels up to 65 mg/kg in rats and 75 mg/kg in rabbits. The relevance of these studies to
the human situation is not known.

D. Fertility
In a study involving prolonged administration of cyclizine to male and female rats there was
no evidence of impaired fertility after continuous treatment for 90-100 days at dose levels of
approximately 15 and 25 mg/kg/day. There is no experience of the effect of Valoid on human
fertility.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactic Acid
Water for Injections

6.2.

Incompatibilities

None known. In the absence of compatibility studies, this medicinal product must not be
mixed with other medicinal products.

6.3

Shelf life

Two years

6.4.

Special Precautions for Storage

Store below 25ºC
Protect from light, keep the ampoule in the outer carton.

6.5

Nature and contents of container

1ml neutral glass ampoules. Five ampoules in a carton.

6.6

Special precautions for disposal
No special instructions.

7

MARKETING AUTHORISATION HOLDER
Amdipharm UK Limited
Capital House, 85 King William Street,
London EC4N 7BL, UK

8.

MARKETING AUTHORISATION NUMBER

PL 20072/0010

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/12/2005

10

DATE OF REVISION OF THE TEXT

21/12/2016

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide