Codelac Phyto: codeine, children aged two years and older, and the price of a suppressed cough
A clinical-pharmacological examination of the non-prescription elixir manufactured by OJSC Pharmstandard-Leksredstva, its advertising, the business behind it, corporate governance and state oversight.
One consumer scenario combined an opioid, a prolonged symptom and unrestricted purchase for use at home
The state-approved instruction and corporate advertising combined, within a single consumer scenario, codeine, a child from two years of age, a cough that naturally lasts for days or weeks, and dispensing without a mandatory medical examination. A bottle kept at home contained 10–25 labelled daily codeine doses for the youngest age group stated in the instruction.
Codeine does not treat a viral infection, influenza, pneumonia, Mycoplasma infection or bronchial inflammation. It suppresses the cough response and could be metabolised by CYP2D6 into morphine; the extent of that conversion varied substantially between patients. Morphine activates μ-opioid receptors, reduces respiratory drive and can cause somnolence, bradypnoea, hypoventilation, hypoxia, coma and death.
These outcomes do not occur in every child and do not form an inevitable sequence. Their probability at a daily dose of 4.5 mg specifically in children aged two to five was not established in the product-specific studies available to this review; the severity of risk depended on metabolism, respiratory reserve, concomitant medicines, duration of use and dosing errors.
A twofold assault on breathing
In lower-respiratory-tract disease, codeine can simultaneously impair mechanical clearance of the bronchi and, through morphine, reduce central respiratory drive.
mucus, inflammation and narrowing of the airways
secretions are cleared less effectively
individually variable CYP2D6 bioactivation
hypoventilation, rising CO₂ and oxygen deficiency
apnoea, hypoxic brain injury, death
What cough suppression means in acute viral respiratory infection, influenza, pneumonia and bronchitis
What matters is not only the name of the illness, but also the presence of secretions, respiratory reserve, age, concomitant medicines and the ability to recognise deterioration in time.
| Condition | Children | Adults | Consequence of suppression |
|---|---|---|---|
| Acute respiratory viral infection (ARVI) / common cold | Codeine does not treat the virus. In children, cough is often associated with mucus, post-nasal drip and inflammation; opioid risk is added to limited benefit. | Short-term symptomatic relief should be considered only after the cause and contraindications have been assessed; codeine does not shorten the infection. | When secretions are present, coughing clears the airways. Sedation can mask increasing lethargy and respiratory impairment. |
| Influenza | Cough may persist after the fever has resolved. Suppression neither treats the virus nor prevents viral or secondary bacterial pneumonia. | The symptom can persist for more than two weeks; central suppression changes the observable symptom but not oxygenation or inflammation. | Recurrent fever, shortness of breath, cyanosis, chest pain, marked lethargy or reduced fluid intake require medical assessment, not another dose. |
| Typical (non-atypical) pneumonia | Inflammatory exudate and narrow airways reduce respiratory reserve. Cough helps mobilise secretions; morphine can simultaneously reduce respiratory drive. | An opioid is not routine treatment for pneumonia; risk increases with hypoxaemia, COPD, sleep apnoea, older age and combinations with sedatives. | Retained secretions, mucus plugging, atelectasis, impaired ventilation and hypoxia form a clinically significant chain of risk. |
| Atypical pneumonia / Mycoplasma | Persistent cough requires diagnosis. Codeine does not act against the pathogen and does not prevent bronchial obstruction or extrapulmonary complications. | A cough that is initially dry may later become productive; an outwardly mild course does not exclude pneumonia. | Apparent symptomatic ‘quietening’ can delay reassessment; once sputum develops, suppression reduces clearance. |
| Acute bronchitis | Routine cough suppressants are not recommended for children. When mucus is being produced, coughing provides clearance, while codeine adds sedative and respiratory risk. | Cough and mucus may persist for up to three weeks. Codeine has not shown an advantage over placebo for acute cough. | In a productive cough, central suppression creates a risk of retained secretions and does not address the inflammation. |
The sequence of codeine intoxication
- 01
Administration
The elixir is absorbed from the gastrointestinal tract.
- 02
Bioactivation
CYP2D6 converts some codeine to morphine; the rate is determined by genotype and drug interactions.
- 03
μ-receptors
Morphine reduces the respiratory centre’s sensitivity to carbon dioxide and causes somnolence and miosis.
- 04
Hypoventilation
Carbon dioxide rises and oxygen falls; coughing and airway-protective reflexes weaken.
- 05
Decompensation
Slow shallow breathing, unusual snoring, cyanosis, stupor, apnoea and cardiac arrest.
- 06
Emergency care
Stop administration, call emergency services and support breathing; naloxone requires medical monitoring.
Foreseeable system errors
Without a mandatory medical examination, the non-prescription model left parents and pharmacists to perform the initial recognition of contraindications, divide a liquid dose and decide how long to continue treatment. This characterises the model’s risk; it does not assert that any particular error occurred in every user.
| Scenario | Why it could occur | Medical consequence |
|---|---|---|
| Giving the entire daily dose at once | 5 mL instead of 2.5 mL or approximately 1.67 mL in a single administration | a higher single-dose peak |
| Repeating the dose too soon | the cough did not disappear after the first dose | an increase in total morphine exposure |
| Extending the course | cough naturally persists for 10–25 days | an increase in total opioid exposure and in the risk of tolerance, physical dependence and withdrawal |
| Combining it with a sedative | an antihistamine, sleeping pill, benzodiazepine, alcohol or another opioid | additive somnolence and respiratory depression |
| Giving it for a productive cough | the parent did not distinguish a dry cough from a wet/productive one | reduced secretion clearance plus hypoventilation |
| Accidental ingestion | the bottle remains accessible to the child | immediate access to 10–25 labelled daily doses |
Tolerance, physiological dependence and withdrawal
The historical instruction expressly warned that prolonged use could lead to drug dependence on codeine. Risk increases with duration, regularity and cumulative exposure; the available data do not allow its frequency to be calculated for this product at 4.5 mg per day.
Regular exposure
repeated activation of μ-receptors
somnolence, constipation and nausea; the antitussive effect may diminish
Neuroadaptation
tolerance and physiological dependence
the same dose is perceived as less effective
Abrupt discontinuation
a drop in opioid stimulation
crying, irritability, insomnia, tremor, sweating, tachycardia, vomiting or diarrhoea
Misinterpretation
withdrawal symptoms resemble illness
an adult may restart the medicine, temporarily relieving the symptoms
A child’s age became a commercial selling point
The strip above the article contains 15 records from a private television archive, with the dates and channels stated by that archive. For the reviewed items, the modal window shows a short locally stored excerpt; a link to the complete source recording remains alongside it. Dates and channels are attributed to the archive, not to official broadcast logs maintained by the broadcasters.
2005 audio track‘Tablets for adults and syrup for children aged two years and older.’
Open all 15 broadcasts
Documented roles and professional assessment
The assessments are tied to disclosed positions, education, corporate functions and signed legal instruments. A position or ownership interest justifies scrutiny of the corresponding function, but does not by itself prove personal approval of the instruction, registration or advertisement.
Igor Krylov
chief executive of OJSC Pharmstandard from 2003; medically qualified
As chief executive, Igor Krylov led the company’s day-to-day operations; his medical education raised the professional standard against which paediatric risk should have been assessed. Maintaining a mass-market, non-prescription model for a paediatric opioid product during his tenure warrants an exceptionally severe adverse assessment of corporate governance. Open sources do not establish that he personally approved the specific instruction or advertisement.
Olga Mednikova
Chief Sales & Marketing Officer from 2004; physician and Candidate of Medical Sciences
This is the most direct documented functional link to sales and promotion. At the level of the function she headed, positioning the product for children without equally prominent disclosure of its opioid nature, dependence potential and respiratory risk warrants an exceptionally severe professional and ethical assessment. The open record does not establish her personal signature on a particular advertisement.
Viktor Kharitonin
largest beneficial owner disclosed before the IPO; chairman of the board of directors and executive director during the relevant period
The combination of the largest disclosed interest, chairmanship of the board and an executive position justifies the most exacting personal question about the strategic system of risk control. The public record reviewed contains no published independent paediatric review commensurate with the scale of commercial promotion; it does not establish that Kharitonin personally approved the instruction or advertisement.
Roman Abramovich and Eugene Shvidler
beneficial interests of 17% and 6%, respectively, disclosed before the IPO
A substantial economic interest in a portfolio in which codeine brands were material to revenue raises a serious question about responsible-ownership standards: what safeguards, independent medical review and risk controls did the major beneficial owners require? Operational positions and any involvement by these individuals in registration or advertising have not been established.
OJSC Pharmstandard-Leksredstva
manufacturer named in the official instruction
As manufacturer, the company was responsible for manufacturing in accordance with the registration dossier and for reporting safety signals as required by law. Supplying a liquid opioid formulation through the non-prescription home-use channel for children aged two years and older required the highest level of consumer protection and transparent pharmacovigilance; the open record does not permit this function to be attributed to a specific production employee.
Mikhail Zurabov and the federal regulator
minister who signed Orders Nos. 578 and 823; Order No. 823 placed the exact liquid formulation on the OTC list
The signature connects the minister to the federal instrument that placed the relevant liquid codeine formulation on the OTC list. Choosing that dispensing status for a product indicated for children should be assessed as a serious failure of the precautionary principle and public accountability; the relevant line of the instrument does not name the trade brand and does not prove that the signatory personally conducted a clinical assessment.
Vladimir Starodubov
physician and Doctor of Medical Sciences; as acting minister, signed Order No. 109 imposing a two-pack limit
For a physician and health-services specialist, a quantitative limit in place of mandatory clinical assessment was a professionally inadequate measure for managing opioid risk.
Roszdravnadzor and the Ministry of Health and Social Development
registration, oversight and maintenance of the dispensing status; prescription-only status for low-dose combinations took effect only on 1 June 2012
The open record reviewed contains no published product-specific rationale for the combination ‘codeine + liquid formulation + children aged two years and older + non-prescription’. This is a serious defect in regulatory transparency, although the absence of a published document does not prove that no internal assessment existed. Public materials concerning the 2012 transition did not explain why the previous status had been maintained for so long.
Formal registration does not exhaust the duty to protect a child’s health
Russian regulation
Codeine and codeine phosphate were included in List II. Order No. 823 placed the exact low-dose liquid formulation on the OTC list; from 1 June 2012, Resolution No. 599 made a prescription mandatory for such combinations.
Advertising after 1 July 2006
Article 24(9) of the Advertising Law restricted mass advertising of medicines containing permitted narcotic substances in Lists II and III. If a date after 1 July 2006, identification of the codeine-containing formulation and dissemination to an indefinite audience are established, the materials provide a strong, direct basis for scrutiny under that provision. No published decision of the Federal Antimonopoly Service or a court specifically concerning the broadcast copies presented here was found.
Convention on the Rights of the Child
Articles 3 and 24 establish the best interests of the child as a primary consideration and the right to the highest attainable standard of health. The Convention did not prescribe a particular dispensing status for this medicine, but it supplied a human-rights framework that the state was required to apply in decision-making.
International practice, 2000–2013
Use from two years of age was not wholly unique, but the combination ‘children from two years + OTC + federal advertising + a bottle kept at home’ lay at the exceptionally permissive edge of practice. Comparable countries used prescription-only status, mandatory pharmacist involvement, age restrictions or recorded sales.
From product launch to mandatory prescription
Prospective cohort of children aged 0–4: half had stopped coughing by day ten and 90% by day twenty-five.
The company prospectus later reports the launch of Codelac Phyto for the treatment of cough symptoms in children.
A corporate report records an advertising campaign; two archived copies catalogued by the television archive as dating from 2005 state ‘syrup for children aged two years and older’.
The Advertising Law enters into force with specific restrictions for medicines containing substances in Lists II and III.
In response to increasing misuse, Sverdlovsk Region limits dispensing of Codelac Phyto to one pack and recommends sale to adults only.
The federal inclusion of the exact 4.5 mg/5 mL formulation in the non-prescription list takes effect.
The State Register records instruction R N002419/01: elixir, codeine, children aged two years and older, dependence, ‘Available without prescription’.
The Federal Drug Control Service publicly describes the spread of desomorphine made from pharmacy medicines and proposes restricting advertising and introducing prescription-only status.
The Government adopts Resolution No. 599 but postpones prescription-only status for codeine until 1 June 2012.
Low-dose codeine combinations become subject to a mandatory prescription.
Opioid risk was built into a permitted consumer scenario
A parent saw a television advertisement, purchased the elixir without a mandatory medical examination and received an official dosage for children aged two years and older. Yet the cough could have been a manifestation of lower-respiratory-tract infection, morphine exposure was individually variable, and the bottle kept at home contained dozens of children’s daily doses.
The company scaled the product model; state authorities permitted it by regulation, and the open record does not show commensurate safeguards before the transition to prescription-only status in 2012. From the standpoint of evidence-based paediatrics, medication safety, corporate ethics and the primary consideration of the child’s best interests, this model was unacceptable.
The three-page Russian instruction, preserved and translated in full
The Russian original remains available as an unchanged scan and as a complete transcription. The ordered sections below provide a faithful English rendering of that historical text.
Product identification
- Registration number: R N002419/01-130808.
- Trade (proprietary) name: Codelac® Phyto.
- International non-proprietary name: none.
- Dosage form: elixir.
Composition per 5 mL of elixir
- Active ingredients: codeine phosphate hemihydrate — 4.5 mg; dry thermopsis extract — 10 mg; liquid thyme extract — 1,000 mg; thick liquorice extract — 200 mg.
- Excipients: methyl parahydroxybenzoate (Nipagin), propyl parahydroxybenzoate (Nipazol), sorbitol, purified water.
Description
A brown liquid with a characteristic aromatic odour. Sediment may form during storage.
Pharmacotherapeutic group and ATC code
Combined antitussive (opioid antitussive + expectorant). ATC code: R05FA.
Pharmacological properties
A cough medicine containing components of plant origin. A combination product.
Codeine reduces the excitability of the cough centre, thereby reducing cough intensity. At the recommended therapeutic doses, it does not cause depression of the respiratory or cough centre, does not impair ciliated-epithelium function and does not reduce bronchial secretion.
Thermopsis herb has an expectorant action manifested by increased secretory function of the bronchial glands, increased activity of the ciliated epithelium and accelerated removal of secretions, and increased bronchial smooth-muscle tone through a central vagotropic effect.
Liquorice root has expectorant, anti-inflammatory and antispasmodic actions. It contains glycyrrhizin, which has antiviral action and potentiates the action of endogenous glucocorticosteroids, producing anti-inflammatory and antiallergic effects. Owing to its pronounced anti-inflammatory activity, glycyrrhizin promotes more rapid resolution of the infectious-inflammatory process in the respiratory tract.
Thyme-herb extract contains a mixture of essential oils with expectorant, anti-inflammatory and bactericidal actions, through increased activity of the ciliated epithelium of the upper-airway mucosa, an increase in bronchial mucosal secretions, thinning of sputum, accelerated evacuation of sputum and loosening of inflammatory deposits. Thyme also has mild antispasmodic and reparative properties.
Indications for use
Symptomatic treatment of dry cough of any aetiology in bronchopulmonary diseases.
Contraindications
- Hypersensitivity to any component of the product.
- Respiratory failure.
- Bronchial asthma.
- Pregnancy and breastfeeding.
- Children under 2 years of age.
- Use of morphine-like medicines (buprenorphine, nalbuphine, pentazocine).
- Consumption of alcohol.
Method of administration and dosage
For adults and children over 2 years of age. Oral use, according to age: children aged 2 to 5 years — 5 mL per day; children aged 5 to 8 years — 10 mL per day; children aged 8 to 12 years — 10–15 mL per day; children aged 12 to 15 years and adults — 15–20 mL per day. The daily dose should be divided into 2–3 administrations.
Shake before use. It is recommended that the elixir be taken between meals. Symptomatic treatment should be brief (several days).
Textual point preserved from the source: the instruction states both ‘children over 2 years of age’ and a first dosage band for ‘children aged 2 to 5 years’. This translation does not harmonise those formulations.
Adverse effects
Allergic reactions (itching of the skin, urticaria) may develop when therapeutic doses are taken. Nausea, vomiting, constipation, headache and somnolence are possible. Prolonged use may lead to the development of codeine dependence.
Overdose
Symptoms: somnolence, vomiting, headache, itching, miosis, depression of the respiratory centre, bradypnoea, arrhythmias, bradycardia, urinary retention and bladder atony.
Treatment is symptomatic and includes restoration of respiratory and cardiovascular function, gastric lavage, administration of respiratory analeptics, atropine and naloxone, described in the source as a competitive physiological antagonist of codeine.
Interactions with other medicinal products
Use with other products that depress the central nervous system is inadvisable because of increased sedation and depression of the respiratory centre: hypnotics, sedatives, antihistamines, narcotic analgesics derived from morphine, anxiolytics and antipsychotic medicines.
Codeine enhances the effect of ethanol on psychomotor function.
Chloramphenicol inhibits the biotransformation of codeine in the liver and thereby enhances its effect.
When codeine is used in high doses, the effects of cardiac glycosides (digoxin and others) may be increased because reduced peristalsis increases their absorption.
Adsorbents, astringents and coating agents may reduce gastrointestinal absorption of the codeine contained in the product.
Special warnings and precautions
- Prolonged treatment with high doses may lead to dependence on the product.
- Codelac® Phyto should not be prescribed concurrently with mucolytic and expectorant medicines.
- Before an antitussive is prescribed, the cause of the cough should be established because specific treatment may be necessary.
- Because sedation may occur, activities requiring heightened attention and rapid mental and motor responses are not recommended during treatment.
- Athletes should remember that the product contains codeine and constitutes doping.
- Caution is required in the presence of increased intracranial pressure.
- Codeine elimination is delayed in patients with impaired renal function; longer intervals between doses are therefore recommended.
- Consumption of alcoholic beverages while taking Codelac® Phyto is prohibited.
Presentation
Elixir. 50, 100 and 125 mL in dark-glass bottles. One bottle with the instruction for use and a measuring spoon, or one bottle with a multi-page label and a measuring spoon, is packed in a cardboard carton.
Storage conditions
List B. Store protected from light at 8–15 °C. Keep out of the reach of children.
Shelf life
1 year 6 months. Do not use after the expiry date stated on the packaging.
Pharmacy dispensing status
Available without prescription.
Manufacturer and organisation receiving complaints
OJSC Pharmstandard-Leksredstva, 1a/18, 2nd Agregatnaya Street, Kursk 305022, Russia. Tel./fax: +7 (4712) 34-03-13.
The original names E. V. Tolstova as representative of OJSC Pharmstandard-Leksredstva and A. N. Vasiliev; the document contains signatures and a seal.
Full article and primary sources
The web edition and the downloadable PDF and Word files are in English. The complete English translation of the historical instruction appears below; its unchanged official Russian scan remains available beside it.
- 01State Register of Medicinal Products (GRLS): official scan of instruction R N002419/01-130808
- 02State Register of Medicinal Products (GRLS): historical Codelac Phyto record
- 03OJSC Pharmstandard: Annual Report 2007
- 04OJSC Pharmstandard: Offering Memorandum / Prospectus 2007
- 05OJSC Pharmstandard: Annual Report 2012
- 06Federal Law No. 38-FZ ‘On Advertising’
- 07Order No. 823 of the Ministry of Health and Social Development
- 08Russian Government Resolution No. 681: List II
- 09Russian Government Resolution No. 599
- 10Ministry of Health and Social Development: transition of codeine combinations to prescription-only status
- 11WHO, 2001: cough and cold remedies in young children
- 12Taylor et al., 1993: placebo-controlled trial
- 13AAP, 1978: the protective role of cough
- 14AAP, 1997: codeine-containing cough remedies in children
- 15CHEST/ACCP, 2006: cough suppressants in children
- 16Hay et al., 2003: duration of acute cough in preschool children
- 17BMJ, 2013: duration of respiratory symptoms in children
- 18CDC: clinical signs and symptoms of influenza
- 19CDC: acute bronchitis
- 20NICE: evidence summary for acute cough
- 21AAP HealthyChildren: pneumonia in children
- 22Health Canada: paediatric respiratory events with codeine for cough
- 23EMA: codeine for cough/cold in paediatric patients
- 24DailyMed: opioid antitussive warnings
- 25Yin et al.: liquid-medication dosing errors
- 26CDC: emergency visits involving cough and cold medicines
- 27UN Convention on the Rights of the Child
- 28Order No. 801-p of the Sverdlovsk Region Ministry of Health
- 29Rossiyskaya Gazeta: position of the Federal Drug Control Service, 23 April 2010
- 30CPIC: CYP2D6 genotype and codeine therapy