SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml solution (34 drops) contains 19 mg of pentoxyverine (as pentoxyverine citrate).
Excipients with known effect For the full list of excipients, see section 6.1. 1 ml solution (34 drops) contains 566.26 mg propylene glycol (E1520) and 0.002 mg methyl benzoate.
3. PHARMACEUTICAL FORM
Oral drops, solution
Clear, colourless to yellowish solution
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
For the symptomatic treatment of dry cough.
4.2 Posology and method of administration
Posology In adults and adolescents from the age of 14 years, the single dose is 20 to 30 mg of pentoxyverine. This dose may be repeated every 6 to 8 hours. The maximum daily dose is 120 mg of pentoxyverine.
In children aged 6 to 13 years, the daily dose is 1 to 2 mg of pentoxyverine per kg of body weight. In younger children aged 2 to 5 years, the daily dose is 0.5 to 1 mg of pentoxyverine per kg of body weight; this dose should not be exceeded.
This results in the following dosage recommendations:
Paediatric population Children from the age of 2 to 5 years Pentoxyverine oral drops are to be taken according to body weight. The single doses should be spread evenly throughout the day. See Table 1.
Table 1 Children from the age of 2 to 5 years Body weight of Daily number of drops Corresponding daily the child dose of pentoxyverine 11 to 13 kg 3 times 4 drops 7 to 11 mg to 4 times 5 drops 13 to 15 kg 3 times 4 drops 8 to 13 mg Body weight of Daily number of drops Corresponding daily the child dose of pentoxyverine to 4 times 6 drops 15 to 17 kg 3 times 5 drops 9 to 15 mg to 4 times 6 drops 17 to 19 kg 3 times 6 drops 10 to 16 mg to 4 times 7 drops 19 to 21 kg 3 times 6 drops 11 to 19 mg to 4 times 8 drops 21 to 23 kg 3 times 7 drops 12 to 21 mg to 4 times 9 drops 23 to 25 kg 3 times 8 drops 13 to 23 mg to 4 times 10 drops
Children from the age of 6 to 13 years Pentoxyverine oral drops are to be taken according to body weight. The single doses should be spread evenly throughout the day (see Table 2). With a body weight of less than 25 kg, the dosage table for 2 to 5-year-olds is to be used (see Table 1).
Table 2 Children from the age of 6 to 13 years Body weight of Daily number of drops Corresponding daily the child dose of pentoxyverine 25 to 28 kg 3 times 16 drops 28 to 51 mg to 4 times 22 drops 28 to 30 kg 3 times 17 drops 30 to 56 mg to 4 times 25 drops 30 to 32 kg 3 times 19 drops 32 to 58 mg to 4 times 26 drops 32 to 34 kg 3 times 20 drops 34 to 63 mg to 4 times 28 drops 34 to 36 kg 3 times 21 drops 36 to 66 mg to 4 times 29 drops 36 to 38 kg 3 times 22 drops 38 to 71 mg to 4 times 31 drops 38 to 40 kg 3 times 25 drops 42 to 76 mg to 4 times 34 drops
Adolescents aged 14 years and over and adults 34 to 51 drops 3 to 4 times a day (equivalent to 57 to 114 mg of pentoxyverine).
In general, this medicinal product must not be taken for longer than 2 weeks. If the cough persists for more than 2 weeks, a diagnostic evaluation is required. Method of administration
Oral use
The bottle must always be vertical when removing the drops in order to ensure the correct dosage.
Pentoxyverine is taken with a spoon in undiluted form or with a little liquid.
4.3 Contraindications
hypersensitivity to the active substance or to any of the excipients listed in section 6.1 respiratory failure or CNS depression hepatic insufficiency pregnancy and lactation children in the first two years of life
4.4 Special warnings and precautions for use
The combined use of secretolytics and cough suppressants may improve the treatment of the cough, with secretolysis recommended during the day and cough suppression during the night. However, in the case of a productive cough with considerable mucus production, a cough suppressant such as pentoxyverine should only be used after a careful assessment of the benefits and risks and with particular caution, since under these circumstances, suppression of the cough reflex is undesirable.
In patients with asthma, cough suppressants such as pentoxyverine can be used in addition to the standard therapy, if the cough does not respond – or only responds inadequately – to the anti-asthmatic therapy. However, other causes must be clarified in advance.
Because of the very rare occurrence of seizures and respiratory depression in infants, these must be particularly closely observed during treatment with pentoxyverine (see also section 4.8).
Caution is advised in patients with renal insufficiency and in elderly patients, since for these patient groups there is not enough data available concerning the use of this medicinal product.
Particular caution is required with respect to use in patients with increased sensitivity to anticholinergic effects, such as patients with glaucoma or benign prostatic hyperplasia.
Excipients Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce adverse effects in children less than 5 years old.
Medical monitoring is required in patients with impaired renal function because various adverse events attributed to propylene glycol have been reported such as renal dysfunction (acute tubular necrosis) and acute renal failure. This medicinal product contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
The use of medicinal products which have a depressant effect on the central nervous system can lead to an intensification of the sedative and respiratory depressant effect. When taken together with alcohol, pentoxyverine reduces psychomotor performance to a greater extent than would be expected based on the effect of the individual components.
Interactions with medicinal products which result in the induction or inhibition of the cytochrome P450 – 2D6 enzyme system are possible, since pentoxyverine is primarily metabolised via this pathway (see also section 5.2). These substances include, among others, active substances from the group of antidepressants (e.g. paroxetine, fluoxetine) and antiarrhythmics (e.g. propafenone).
4.6 Fertility, pregnancy and lactation
Pregnancy Pentoxyverine is contraindicated during pregnancy (see section 4.3). There are no adequate experimental animal studies available with respect to reproductive toxicity (see section 5.3). The potential risk to humans is unknown. For this reason, pentoxyverine must not be taken during pregnancy. In the case of accidental ingestion during pregnancy, no harmful effects are to be expected on the foetus. Nevertheless, treatment should be discontinued immediately.
Breastfeeding Pentoxyverine is excreted in the mother's milk. Use during breastfeeding is contraindicated due to the risk of adverse reactions in the infant.
Fertility No preclinical studies have been carried out with pentoxyverine with regard to fertility. The effect on human fertility has not been evaluated in studies.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. This medicinal product may occasionally lead to tiredness even when used in accordance with instructions. Since tiredness can alter the ability to react, it is possible that the ability to drive or use machines may be impaired.
4.8 Undesirable effects
The following frequency categories are used for the evaluation of undesirable effects:
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) Not known (cannot be estimated from the available data)
Immune system disorders Very rare: hypersensitivity reactions, including anaphylactic reactions
Nervous system disorders Uncommon: somnolence Very rare: seizures (especially in infants)
Respiratory, thoracic and mediastinal disorders Very rare: dyspnoea (usually reported in association with allergic reactions), respiratory depression (especially in infants)
Gastrointestinal disorders Common: epigastric pain, diarrhoea, nausea, vomiting
Skin and subcutaneous tissue disorders Very rare: angioedema, urticaria, exanthema
General disorders and administration site conditions Uncommon: fatigue
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 national reporting system listed in Appendix V.
4.9 Overdose
Signs of intoxication are central nervous and gastrointestinal symptoms such as respiratory depression, sedation and vomiting, as well as anticholinergic effects (e.g. urinary retention, glaucoma, tachycardia, blurred vision, agitation, hallucinations).
After general measures such as primary poison removal, the vital parameters must be monitored in intensive care.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Cough and cold preparations, Other cough suppressants ATC code: R05DB05
Pentoxyverine is a non-narcotic, centrally acting cough suppressant which has a specific effect on the cough reflex. It reduces the overstimulation of the cough centre and normalises its function.
A small, local anaesthetic effect on the tongue and throat has also been described. When given orally, the antitussive effect begins to appear after 10 to 20 minutes and lasts for 4 to 6 hours. Pulmonary function tests have shown that pentoxyverine has a slight bronchodilatory effect. Moreover, pentoxyverine has slight spasmolytic and anticholinergic properties. Compared with codeine, no decrease in respiratory volume has been observed. No symptoms of addiction or withdrawal have been reported.
5.2 Pharmacokinetic properties
The following pharmacokinetic data come from healthy adults; there is insufficient data available from individuals who are sick.
Absorption Following an oral dose, pentoxyverine is absorbed relatively quickly from liquid preparations in conjunction with a rapid onset of effect after 10 to 20 minutes. The peak plasma concentration is achieved within 2 hours (tmax between 0.5 and 2 hours). The absorption from liquid formulations is slightly faster than from tablets (mean tmax 0.9 vs. 1.2 h).
Distribution There is no human data available on tissue distribution. The distribution volume is approximately 10 l/kg. The extent of protein binding is unknown.
Biotransformation In vitro studies have shown that pentoxyverine is primarily metabolised via cytochrome P450 2D6, and to a lesser extent via P450 3A4, as well as hepatic esterases. A relevant effect on the CYP enzyme catalysed metabolism of simultaneously administered drugs is unlikely. The main metabolites that have been detected are N-desethyl pentoxyverine and 1- phenyl-cyclopentane carboxylic acid.
Elimination The elimination half-life in adults is 2 hours (mean half-life t1/2 = 2.3 hours). The half-life found for adults corresponds to that of the estimated value of approximately 2 to 3 hours deduced from the duration of action (5 to 6 hours), while in neonates the elimination appears to be greatly delayed.
5.3 Preclinical safety data
Acute toxicity In acute toxicity studies in rodents, the LD50 after intravenous administration was 18-30 mg/kg of body weight. In an ECG study in anaesthetised dogs, the intravenous administration of 10 mg/kg of body weight of pentoxyverine (base) resulted in a lowering of blood pressure, while 30 mg/kg of body weight resulted in circulatory failure.
Chronic and subchronic toxicity Subchronic toxicity studies in mice have not revealed any evidence of toxic effects.
Mutagenic and tumorigenic potential Pentoxyverine has not undergone any detailed mutagenicity investigation; a bacterial gene mutation assay was negative. Long-term studies involving animals with respect to a tumorigenic potential are not available.
Reproductive toxicity Pentoxyverine has been insufficiently studied with respect to its reproductive toxicity properties. It is not possible to make reliable statements about any teratogenic potential because the available studies do not include any corresponding investigations. Based on the most sensitive species (mouse), a no-effect level dose for other embryotoxic effects of 10 mg/kg of body weight per day can be assumed.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients propylene glycol saccharin sodium strawberry flavour purified water
6.2 Incompatibilities
Not applicable. 6.3 Shelf life
36 months
After the first opening of the bottle: 1 year.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Amber glass bottle with vertical dropper manufactured of LDPE, screw cap and originality ring (one part, consisting of PP).
Pack size 30 ml of oral drops, solution
6.6 Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
[to be completed nationally]
8. MARKETING AUTHORISATION NUMBER
[to be completed nationally]
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
[to be completed nationally]
10. DATE OF REVISION OF THE TEXT
02/10/2020