Corex cough syrup - no more OTC opioid dependence

Reducing codeine supply forces Corex users to the spiral of change

Corex Cough Syrup opioid dependence

Codeine cough syrup is no longer available over-the-counter (OTC) without a prescription. Record keeping by the dispensing pharmacist is now mandated by a new government notification. This one legislation will aid relapse prevention in abstinent Corex cough syrup addicts. Many former codeine addicts have relapsed after visiting their dispensary for another medication; the pharmacist casually offers opioid containing Corex cough syrup and provides a visual cue to trigger craving and retard their progress through the stages of change.

Codeine cough syrup addiction is fuelled by dispensaries that distribute litres of codeine in the form Corex Cough Syrup and other brands like Mits Linctus. The key ingredient in these ‘cough syrups’, Codeine, is derived from opium and is an addictive substance. Codeine containing cough syrup abuse made its entry to India in the 1990s and since then has contributed to the steadily increasing opioid dependence case-load.The estimated number of opium users in India is well over 5 million with codeine being a major oral source. Opioid dependence in a de-addiction centre increased significantly from 37 to 52% over the last three decades.

Relapse prevention at the pharmacy

Codeine dependent individuals are exposed to visual cues of Corex and other codeine containing cough syrups at every visit to the dispensary. Modification of addictive behaviours involves progression through five stages of change - precontemplation, contemplation, preparation, action, and maintenance. Individuals cycle through these stages many times before termination of the addiction. During relapse individuals regress to an earlier stage of codeine use. Stimulus control - avoiding or countering reminders of codeine use - is a key process for relapse prevention on the spiral of change. Cutting off easy access in the dispensary aids stimulus control and helps prevent relapse to codeine use. The common sight of multiple discarded codeine cough syrup bottle on stairwells would also disappear (see image).

Codeine cough syrup abuse prevention

1. Pharmacy-based approaches help in minimising the harm associated with OTC medicine abuse, and supporting and treating affected individuals.
• Removing products from sight
• Alerting or counselling customers to the abuse potential of products is effective.
• Refusing sales without a prescription
• Suggesting customers contact their doctor
• Supplying only limited amounts.
2. Raising awareness of the addiction potential of codeine cough syrup is necessary for both the public and the prescribers (many doctors are unaware of the ingredients that go into Corex and other cough syrups).
3. Preventing access is the domain of the government.  Regulating and monitoring codeine prescription and dispensing is a welcome step. The finance ministry is now attempting to enable tracing of batches of codeine containing cough syrups  to their suppliers in a bid to control smuggling of Corex and other codeine containing cough syrups.

Nature's vengeance

Unexpected help in relapse prevention by restricting supply has also come in the form of mother nature. Opium growers in Mandsaur, MP are ruing the increasing numbers of nilgai (Boselaphus tragocamelus) that have developed opioid dependence after chance grazing in farms that were once grassland. The nilgai now run amok and destroy swathes of poppy fields in search of their fix.

References

1. Debasish Basu, Munish Aggarwal, Partha Pratim Das, Surendra K. Mattoo, Parmanand Kulhara & Vijoy K. Varma. Changing pattern of substance abuse in patients attending a de-addiction centre in north India (1978-2008). Indian J Med Res 135, June 2012, pp 830-836
2. Richard J. Cooper. J Subst Use. Over-the-counter medicine abuse – a review of the literature. Published online Oct 3, 2011. doi: 10.3109/14659891.2011.615002. Apr 2013; 18(2): 82–107.
3. Gary Reid and Genevieve Costigan. Revisiting ‘The Hidden Epidemic’ A Situation Assessment of Drug Use in Asia in the context of HIV/AIDS. The Centre for Harm Reduction, The Burnet Institute, Australia. 2002. 
4. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. Applications to addictive behaviors. Am Psychol. 1992 Sep;47(9):1102-14.

Whitener Addiction - Death by Inhalant

Whitener (correction fluid) inhalation caused the death of a Pune student recently. Whitener is abused as an inhalant in India. Whitener exerts its effects through trichloroethane, a volatile solvent. Inhalants include other substances such as petrol and toluene. These substances are cheap, accessible and readily available to children and adolescents.

Epidemiology

Solvent abuse is prevalent among street children and working kids. Teenagers start using solvents to gain entry into a gang, and occasionally as experimentation. Its use in a college student is unusual. But this may be a developing pattern indicating spread of the habit into middle class homes. (Kumar S 2008). Most adolescents are one-time or short-term users. Those who abuse inhalants persistently usually have conduct disorders.

Methods of inhalant abuse

1. Sniffing - direct inhalation from a container or piece of clothing sprayed with the substance.
2. Huffing - holding a soaked cloth over the nose or mouth to increase the concentration of vapours.
3. Bagging - breathing from a paper or plastic bag containing the volatile substance to further increase the concentration (Henretig, 1996).

Mechanism of action

Young people abuse volatile solventsby deliberately inhaling available vapours 15–20 times over 10-15 minutes. This results in concentrations of up to 10000ppm as against the industrial standard of 50-100ppm (Bowen et al., 2006).

Inhaled organic solvents like toluene cross from the blood into the brain within minutes. In the brain cells solvents act on specific receptors (NMDA and GABA) to produce effects similar to those of alcohol. Toluene, a common solvent in thinner and paint, increases opiate receptors in the Nucleus Accumbens - a key brain area associated with the reward system and the experience of pleasure. Toluene enhances dopamine release in the Nucleus Accumbens.

Effects on the body

(Lubman 2008)

• At low concentration (500-4000ppm) transient euphoria and disinhibition make abusers prone to risk taking and accidents.
• At higher concentrations (6000-15000ppm) dizziness, sleepiness, slurred speech, blurred vision and headaches appear. Users appear confused, unbalanced, or begin responding to hallucinations.
• Higher doses result in seizures, coma and cardiopulmonary arrest .

Death by inhalant

• Sudden sniffing death is the most common cause. Even first-time experimental users are at risk of sudden sniffing death as a result of heart rhythm abnormalities especially if the user is startled or agitated. 
• Suffocation and burns from exploding solvents
• Accidental injury as a result of impulsive risk taking and impaired motor skills while intoxicated. 
• Suicide accounts for up to 40% of inhalant-related deaths
• First-time users are also likely to die, perhaps because they are inexperienced at this dangerous pastime.

Recognition

Inhalant abuse should be suspected in teenagers showing intermittent intoxication,and signs of recent inhalant abuse including paint or oil stains on clothing or skin, spots or sores around the mouth, red eyes, runny nose, chemical odor on the breath, and a dazed appearance (Anderson, 2003).

Mass screening in schools could be undertaken as part of the annual health check. The mental health component for middle and high schoolers should include the CRAFFT. The CRAFFT is a validated short screening instrument for substance abuse in teenagers.

Laboratory diagnosis is not reliable as these volatile substances

• Do not persist in the body beyond a few hours
• They are undetectable in urine samples because of their volatility
• Hippuric acid, a long lasting toluene metabolite is also produced by foods and  raises the question of false positives. Also, it is usually not available for testing in emergency

Outcome

For most adolescents inhalant use should be regarded as a passing phase or fad. A few persistent users have antisocial personality disorder and abuse other substances. Chronic users develop damage to all organ systems - heart, lungs, brain, kidneys, and liver. The good news (Cairney et al., 2005) -

Damage to the brain is reversible with abstinence

Treatment

There is no specific medication to treat intoxication or for abstinence.

If you suspect a child is intoxicated with an inhalant stay calm and do not alarm him or her. Startling or frightening the child precipitates hallucinations and can also lead to ‘sudden sniffing death’ due to the effect on heart rhythm. Initiate cardio-pulmonary resuscitation (CPR) until help arrives if there is no heart beat or breathing.

When the child or adolescent recovers the incident should be discussed non-confrontationally. Remember, even a single inhalation can kill the child. Also abuse of other substances is frequent with regular whitener abusers. After talking it over commit to seeking psychiatric help. Social, environmental and recreational opportunities need to be addressed.

References

1. Carrie E. Anderson, and Glenn A. Loomis. Recognition and Prevention of Inhalant Abuse. Am Fam Physician. 2003 Sep 1;68(5):869-874. (Also gives good links for information on inhalant abuse and prevention)
2. Bowen SE, Batis JC, Paez-Martinez N, Cruz SL. The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies. Neurotoxicol Teratol. 2006;28:636–647.
3. Cairney S, Maruff P, Burns CB, Currie J, Currie BJ. Neurological and cognitive recovery following abstinence from petrol sniffing. Neuropsychopharmacology. 2005 May;30(5):1019-27.
4. Henretig F. Inhalant abuse in children and adolescents. Pediatr Ann. 1996 Jan;25(1):47-52.
5. Kumar S, Grover S, Kulhara P, Mattoo SK, Basu D, Biswas P, Shah R. Inhalant abuse: A clinic-based study. Indian J Psychiatry. 2008 Apr;50(2):117-20.
6. D I Lubman, M Yücel and A J Lawrence. Inhalant abuse among adolescents: neurobiological considerations. Br J Pharmacol. 2008 May; 154(2): 316–326. Published online 2008 March 10. doi: 10.1038/bjp.2008.76.

Corex Cough Syrup - Opioid Addiction Over-the-Counter

Codeine is methyl-morphine

Corex Cough Syrup contains codeine – an addiction causing opioid. One 100ml bottle of codeine containing Corex cough syrup has the same effect as a 30mg tablet of morphine. The drug belongs to the same class of substances as heroin. Medicines are routinely purchased over-the-counter at most pharmacies in Pune and cough syrups very frequently so. Always read the fine print.

Codeine suppresses the cough reflex through a direct effect on the cough centre in the brain stem. However, there is little evidence in the medical literature to support its use as a cough suppressant. Several studies show that codeine does not reduce cough frequency, intensity, or duration (Herbert & Brewster, 2000).

Patients who are prescribed Corex cough syrup or those who buy it over-the-counter are not warned of its addiction potential. They subsequently continue using it as they 'feel restless and anxious' without it. These feelings are part of the spectrum of withdrawal symptoms associated with all opioids, and are another sign of addiction. A 36 year old woman who came to me for treatment of lethargy and lack of interest was consuming a bottle of Corex cough syrup every day for more than two years. Patients and parents should be educated about the lack of benefit and the addiction risk of codeine cough syrups (American Academy of Pediatrics, 1997).

Pharmacists dispensing Corex cough syrup know its potential for addiction. They have their 'regulars' who buy litres of Corex cough syrup over the month. The bottles are handed over in a paper bag without the exchange of a word, leave alone a prescription.

Corex is the top selling medication in India earning Pfizer, the drug manufacturer, Rs 1,820,000,000 during the year 2009. U.S.-based Pfizer and Abbott Laboratories are leading players in India's $103-million market for codeine-based cough syrups. The ministry of finance is now pressuring the companies to enable tracking of each batch produced. The sheer malevolence of this entire chain is brought home by the patient who relapses repeatedly during treatment. Every time he tries to fill his prescription for deaddiction the pharmacist takes advantage of his craving cues to resupply him with codeine containing Corex cough syrup.

So it was with a certain joy that I read

Store employee nabbed for selling drugs without prescription

That was the Indian FDA (Food and Drug Administration) in action in Pune. Their sting on a reputed chain of pharmacies gives us new hope for control of over-the-counter codeine opioid addiction. 

Codeine prescription restrictions - Update

Ministry of Health (2016)
Bans codeine containing cough syrups. Ban upheld by Drugs Technical Advisory Board in July 2018

EMA-CMDh (2015)
(European Medicines Agency – Coordination Group for Mutual Recognition and Decentralised Procedures - Human)
Use of codeine for cough and cold

• contraindicated in children below 12 years. This means it must not be used in this patient group.
• not recommended in children and adolescents between 12 and 18 years who have breathing problems

Govt of India Notification 2014

• Codeine cough syrup is not available over-the-counter (OTC) without a prescription
• Record keeping by the dispensing pharmacist is now mandated

References

1. Committee on Drugs, American Academy of Pediatrics. Use of codeine-and dextromethorphan-containing cough remedies in children. Pediatrics 1997;99:918-20
2. EMA-CMDh. Codeine Article-31 referral - Codeine not to be used in children below 12 years for cough and cold. EMA/249413/2015. 24 April 2015
3. Herbert ME, Brewster GS. Myth: codeine is an effective cough suppressant for upper respiratory tract infections. West J Med 2000;173:283.