CYP3A4 produces norcodeine, and UGT2B7 conjugates codeine, norcodeine, and morphine to the corresponding 3- and 6-glucuronides. Srinivasan, Wielbo and Tebbett speculate that codeine-6-glucuronide is responsible for a large percentage of the analgesia of codeine, and thus these patients should experience some analgesia. Many of the adverse effects will still be experienced in poor metabolizers. Conversely, between 0.5% and 2% of the population are "extensive metabolizers"; multiple copies of the gene for 2D6 produce high levels of CYP2D6 and will metabolize drugs through that pathway more quickly than others. Some medications are CYP2D6 inhibitors and reduce or even completely block the conversion of codeine to morphine. The best-known of these are two of the selective serotonin reuptake inhibitors, paroxetine (Paxil) and fluoxetine (Prozac) as well as the antihistamine diphenhydramine (Benadryl) and the antidepressant bupropion (Wellbutrin, also known as Zyban). Other drugs, such as rifampicin and dexamethasone, induce CYP450 isozymes and thus increase the conversion rate. CYP2D6 converts codeine into morphine, which then undergoes glucuronidation. Life-threatening intoxication, including respiratory depression requiring intubation, can develop over a matter of days in patients who have multiple functional alleles of CYP2D6, resulting in ultrarapid metabolism of opioids such as codeine into morphine.Studies on codeines analgesic effect are consistent with the idea that metabolism by CYP2D6 to morphine is important, but some studies show no major differences between those who are poor metabolizers and extensive metabolizers.
The most common preparation is Panadeine, which contains 500 mg of Paracetamol and 8 mg of Codeine. But cough syrup containing codeine and promethazine is banned, even with a prescription. United Arab Emirates
The UAE takes an exceptionally strict line on medicines, with many common drugs, notably anything containing codeine being banned unless one has a notarized and authenticated doctors prescription. Visitors breaking the rules, even inadvertently, have been deported or imprisoned. The US Embassy to the UAE maintains an unofficial list of what may not be imported. United Kingdom
In the United Kingdom, the sale and possession of codeine are restricted separately under law. Neat codeine and higher-strength codeine formulations are generally prescription-only medicines (POM) meaning that the sale of such products is restricted under the Medicines Act 1968. Lower-strength products containing combinations of up to 12.8 mg of codeine per dosage unit, combined with paracetamol, ibuprofen or aspirin are available over the counter at pharmacies. Codeine linctus of 15 mg per 5 ml is also available at some pharmacies, although a purchaser would have to request it specifically from the pharmacist.Under the Misuse of Drugs Act 1971 codeine is a Class B controlled substance or a Class A drug when prepared for injection. The possession of controlled substances without a prescription is a criminal offence. However, certain preparations of codeine are exempt from this restriction under Schedule 5 of the Misuse of Drugs Regulations 2001.