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.
Treatment:
In the management of acute overdosage with Echnatol, 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.
Echnatol should not be given to individuals with known hypersensitivity to cyclizine.
None known.
Blood and lymphatic system disorders
Agranulocytosis
Cardiac disorders
Tachycardia
Eye disorders
Blurred vision, oculogyric crisis
Gastrointestinal system disorders
Dryness of the mouth, nose and throat, constipation
General disorders and administration site conditions
Asthenia
Hepatobiliary disorders
Hepatic dysfunction, 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, headache, dystonia, dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.
Psychiatric disorders
Disorientation, restlessness, nervousness, 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, drug rash, angioedema, allergic skin reactions, fixed drug eruption
Vascular disorders
Hypertension
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. 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. There is no experience of the effect of Echnatol on human fertility.
Echnatol is indicated for the prevention and treatment of nausea and vomiting including:- | |
- Motion sickness. - 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. | |
Echnatol may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance. | |
ATC Code: R60AE03
Pharmacotherapeutic Group: Piperazine derivatives
Mode 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:
Cyclizine produces its antiemetic effect within two hours and last approximately four hours.
H1-blockers are well absorbed from the GI tract. Following oral administration effects develop within 30 minutes, are maximal within 1-2 hours and last, for cyclizine, for 4-6 hours.
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.
The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine. Norcyclizine has little antihistaminic (H1) activity compared to cyclizine. It is widely distributed throughout the tissues and has a plasma elimination half-life of approximately 20 hours.
After a single dose of 50 mg cyclizine given to a single adult male volunteer, urine collected over the following 24 hours contained less than 1% of the total dose administered.
As with other anticholinergic agents, Echnatol may precipitate incipient glaucoma and it should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy.
Cyclizine should be used with caution in patients with severe heart failure. 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.).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Studies designed to detect drowsiness did not reveal sedation in healthy adults who took a single oral therapeutic dose (50 mg) of 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 Echnatol may have additive effects with alcohol and other central nervous system depressants, e.g. hypnotics and tranquillisers.
Route of administration: oral
Adults and Children over 12 Years:
50 mg orally, which may be repeated up to three times a day.
Children 6 - 12 Years:
25 mg orally, which may be repeated up to three times a day.
Children less than 6 years of age:
Echnatol tablets are not recommended for children less than 6 years of age.
Use in the Elderly:
There have been no specific studies of Echnatol in the elderly. Experience has indicated that normal adult dosage is appropriate.
To prevent motion sickness Echnatol should be taken about one to two hours before departure.
No special instructions.
