Symptoms
The signs and symptoms are mainly due to the anticholinergic (atropine-like) activity of Cinedile.
Acute Cinedile overdoses have been reported with doses ranging from 90 to 2,250 mg. Vomiting, alterations in consciousness ranging from somnolence to stupor and coma, extrapyramidal symptoms and hypotonia are the most commonly reported signs and symptoms associated with a Cinedile overdose. In a small number of young children, seizures developed. Clinical consequences were not severe in most cases, but deaths have been reported after single and polydrug overdoses involving Cinedile.
Treatment
There is no specific antidote to Cinedile and in the event of overdosage, treatment is symptomatic and supportive care. The administration of activated charcoal should only be considered in patients presenting within one hour of taking a potentially toxic overdose (i.e. more than 15 mg/kg).
Not applicable
The safety of Cinedile was evaluated in 372 Cinedile-treated subjects who participated in 7 placebo-controlled trials for the indications peripheral circulatory disorders, cerebral circulatory disorders, vertigo and seasickness; and in 668 Cinedile treated subjects who participated in six comparator and thirteen open label clinical trials for the indications peripheral circulatory disorders, cerebral circulatory disorders and vertigo. Based on pooled safety data from these clinical trials, the most commonly reported (>2% incidence) adverse drug reactions (ADRs) were: somnolence (8.3) and weight increased (2.1).
Including the above mentioned ADRs, the following ADRs have been observed from clinical trials and post-marketing experiences reported with the use of Cinedile. Frequencies displayed use the following convention:
Very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
| System organ class | Adverse drug reactions | ||
| Frequency category | |||
| Common | Uncommon | Not known | |
| Nervous system disorders | Somnolence | Lethargy | Dyskinesia, extrapyramidal disorder (sometimes associated with depressive feelings), Parkinsonism, tremor |
| Gastrointestinal disorders | Nausea, dyspepsia | Vomiting, upper abdominal pain | |
| Hepatobiliary disorders | Cholestatic jaundice | ||
| Skin and subcutaneous tissue disorders | Hyperhidrolysis, Lichenoid keratosis including lichen planus | Subacute cutaneous lupus erythematosus | |
| Musculoskeletal and connective tissue disorders | Muscle rigidity | ||
| General disorders and administrative site conditions | Fatigue | ||
| Investigations | Weight increased | ||
Cases of hypersensitivity, headache and dry mouth have also been reported.
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 at: www.mhra.gov.uk/yellowcard.
Nonclinical safety studies showed that effects were observed only after chronic exposures from approximately 7 to 35 times the recommended maximum daily human dose of 90 mg/day calculated on a body surface area basis. Cinedile blocked the cardiac hERG channel in vitro, however in isolated cardiac tissue and following intravenous application in guinea-pigs, no QTc prolongation or proarrhythmic effects were observed at substantially higher exposures than those expected clinically.
In reproductive studies in the rat, rabbit, and dog, there was no evidence of adverse effects on fertility and no teratogenicity. At high doses associated with maternal toxicity in the rat there was a decreased litter size, an increase in resorptions and a decrease in foetal birth weight.
In vitro mutagenicity studies indicated that the parent compound is not mutagenic however, after reacting with nitrite and forming the nitrosation product, a weak mutagenic activity was observed. Carcinogenicity studies have not been conducted however, no pre-neoplastic changes were evident during chronic 18-month oral administration in rats up to approximately 35 times the maximum human dose level.
Cinedile is used for the control of vestibular disorders such as vertigo, tinnitus, nausea and vomiting such as that seen in Meniere's disease.
Cinedile is also effective in the control of motion sickness.
Pharmacotherapeutic group: Antivertigo preparations, ATC code: N07CA02.
Mechanism of action
Cinedile is a piperazine derivative with the actions and uses of the antihistamines.
Cinedile has been shown to be a non-competitive antagonist of the smooth muscle contractions caused by various vasoactive agents including histamine. It acts on smooth muscle by selectively inhibiting the transport of calcium ions across cell membranes into depolarised cells, therefore reducing the availability of free Ca+ ions for the induction and maintenance of contraction.
Pharmacodynamic effects
Vestibular eye reflexes induced by caloric stimulation of the labyrinth in guinea pigs are markedly depressed by Cinedile.
Cinedile has been shown to inhibit nystagmus.
Absorption
In man, after oral administration, absorption is relatively slow, peak serum concentrations occurring after 2.5 to 4 hours.
Distribution
The plasma protein binding of Cinedile is 91%
Biotransformation
In animals, Cinedile is extensively metabolised, N-dealkylation being the major pathway.
Cinedile undergoes extensive metabolism mainly via CYP2D6 but there is considerable interindividual variation in the extent of metabolism.
Elimination
Approximately two thirds of the metabolites are excreted with the faeces, the rest in the urine (unchanged as metabolites and glucuronide conjugates), mainly during the first five days after a single dose.
The reported elimination half-life for Cinedile ranges from 4 to 24 hours.
As with other antihistamines, Cinedile may cause epigastric discomfort; taking it after meals may diminish gastric irritation. Cinedile should only be given to patients with Parkinson's disease if the advantages outweigh the possible risk of aggravating this disease.
Use of Cinedile should be avoided in porphyria.
There have been no specific studies in hepatic or renal dysfunction. Cinedile should be used with care in patients with hepatic or renal insufficiency.
Cinedile Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Cinedile may cause drowsiness, especially at the start of treatment; patients affected in this way should not drive or operate machinery.
Posology
Vestibular symptoms:
Adults, elderly and children over 12 years:
Two tablets three times a day.
Children 5-12 years:
One tablet three times a day.
The stated doses should not be exceeded.
Motion sickness:
Adults, elderly and children over 12 years:
Two tablets two hours before travel and one tablet every eight hours during journey if necessary.
Children 5-12 years:
One tablet two hours before travel and half a tablet every eight hours during journey if necessary.
Method of administration
For oral use.
Cinedile should preferably be taken after meals. The tablets may be sucked, chewed or swallowed whole with water.
No special requirements
