How Long Does Codeine Stay In Your System?

codeineOpioid analgesics have been used for centuries and are still used to this day as the most potent and reliable analgesic agents. Treatment of acute severe pain following trauma, surgery, and extensive burns are indications in which these drugs are drugs of choice. They are also used in releasing the pain in patients with terminal diseases such as cancer. The efficacy of opiates in these time-limited situations is broadly accepted and extensively documented. The important standard of the patient’s care, required by law in some countries, is adequate pain relief. Thus, causing the usage of opioids to increase nowadays.

Beyond potent analgesia, they produce mild sedation; reduce anxiety and producing a sense of well-being, giving the patient suffering of acute or terminal medical condition an unmitigated benefit. There is no debate over the short term use of opiates but there is growing reluctant among some physicians to prescribe them for chronic, non-malignant, indications knowing they are most liable to cause abuse and addiction.

Mechanism of Action in Opioids

Opioids cause their effects by binding to opioid G-protein coupled receptors (GPCRs) located in our brain. There are four known opioid receptors so far: µ (mu), δ (delta), kappa and nociceptin/orphanin FQ receptor. Potent analgesia is only produced consistently by µ receptor agonists. Drugs activating these (µ) receptors are also most commonly abused (morphine, heroin, oxycodone) as mu receptor stimulation leads users to feel euphoria, pleasure, physical relaxation and pain relief. One additional representative of opioid analgesics binding to the µ receptors is Codeine.


Besides mild to moderate pain, another indication for usage of this morphine derivate (3-methylmorphine) is a severe cough (antitussive) and persistent diarrhea (antidiarrheal).  It is marked as being the second most significant alkaloid and a natural form of methylated morphine. The format of codeine which is mostly manufactured in the United States is codeine sulfate or codeine phosphate. The specifics of its pharmacodynamics are not known well, but it is thought to cause morphine-like effects considering that during metabolism, one part of codeine is converted to morphine. The risk of developing a dependence on codeine and the risk for abuse when using codeine, especially recreationally, is very high which is why it is classified as a Schedule II controlled substance. Chronic codeine usage may cause a deterioration of physical and/or psychological performance and provoke a number of side effects such as sedation, coordination deficits, brain fog and many other. In order to avoid these adverse effects and also to stay negative at the regular drug test, numerous users have stopped using this drug and they are hoping to clear their system completely.

How Long Does It Take to Excrete the Codeine?

Every drug taken has its half-life of elimination, referring to the time needed for blood concentration of a drug to decrease to a half of its prior concentration. That means there is a period between the ingestion of the drug and the actual effects of the codeine and its excretion. This can be measured with the term called the half-time of excretion. The half-time of codeine is somewhere between 2.4 and 2.9 hours. All said leads to the conclusion that 50% of the taken drug will be flushed out of the body after 2 hours and 54 minutes after ingestion. For a complete clearance of codeine, it can take up to 15.97 hours. For someone who metabolizes this opioid at a faster rate (2.4 hours), the complete excretion will be reached after 13.2 hours. Some metabolites of codeine are known to have a longer half-life than the actual drug. This especially refers to codeine-6-gucuronide and morphine-3-glucuronide. Taken this into consideration, it may last up to 24 hours for the complete elimination of both codeine and its metabolites.

Factors Influencing the Time of Elimination

Individual Factors

Age: As in any other drug ingestion, the age of a patient taking the codeine has an important role and can change the metabolism and the half-time of the drug’s excretion. Vascularization of excretion organs can have an impact as well. Kidneys and liver are naturally better in younger person leading to a shorter half-life of a drug. In addition, younger individuals are more likely not using other drugs and their second therapy prescription will not affect the codeine metabolism. For the elderly, that doesn’t count, since they are usually in some kind of therapy and their metabolism is much slower and vascularization lacks in the important organs. This goes for the people at the age of 65 and up.

Body Characteristics: The size of person’s body (height/weight/fat) can influence how quickly the drug is absorbed and eliminated.  Larger the body is in proportion to the dosage of codeine that they ingest, greater the chance for it to metabolize it at a faster rate and vice versa.

Characteristics of Urine: The majority of codeine (and metabolites) is excreted through urine, leading us to the conclusion that excretion may be impacted by a person’s urinary pH. Alkaline urine will likely prolong a half-life of codeine excretion compared to those with a urinary pH of high acidity.  Alkaline urine prevents complete elimination, while acidic urine prevents reabsorption of codeine and results in expedited clearance.

Genetics: Genetic variation is known to have an impact on the excretion and the metabolism of the drug, not just codeine, but any drug in general. It has a different kind of enzymes which can slow down or speed up these processes. The CYP2D6 isoenzyme, located in a liver, is the enzyme involved in the metabolism of a great number of substances. Its regulation may influence the time of codeine excretion. Based on the function of this enzyme we are all divided into two groups – “fast and slow metabolizers”.

The Function of Organs: Based on what we previously said, the liver impairment will lead to decreased function of liver enzymes (for codeine metabolism most important isoenzyme CYP2D6) thus, causing a slower breakdown and excretion of codeine comparing to those with a healthy liver. The time of the excretion in these patients will depend on the organ state since the healthy cells will do the job faster or slower, depending on the damage. Another thing which should be taken into consideration is the dosage that these organs have to manage. Kidney conditions may also slow clearance rate, taking into consideration their role in excretion of drugs and metabolites.

Metabolic Rate: Individuals with faster BMR (basal metabolic rate) are more likely to get the drug faster out of the system and not just the codeine, but other ingredients as well. On the other hand, the ones having a slow baseline metabolism will slowly breakdown and excretion of the drug. This will have a huge impact on the codeine excretion from the body.

Codeine Ingestion

When consumed frequently, codeine accumulates within the body, which leads to longer excretion of the same in those taking it regularly (on a daily basis) comparing to those who use codeine rarely. Enzymes in the liver and the transport proteins in kidneys have their own limit in the amount of substance that can be metabolized and excreted in a unit of time. This is more likely to happen to patients who are regular codeine users since there is no time for the first dose to metabolize before the second one is ingested. Once the limit is reached, the excretion might not go that fast since the drug will have a greater accumulated amount in the system which the metabolism won’t be able to excrete. The metabolism can slow down and also affect the time of elimination.

Our metabolism naturally tends to slow down at later times in the day, which is exactly the time when frequent users may ingest codeine. This, in addition, leads to the accumulation of the codeine in the system. This will be emphasized among frequent users and their system may not be that efficient in codeine elimination. The ones that use codeine less frequently will be more efficient at drug excretion since their metabolism hasn’t reached the maximum of its function and the amount of the drug isn’t that high in their system.

Codeine Dosage

After all the previous information, it is easy to conclude that higher dosage of codeine ingested leads to the greater effects on the individual’s physiology – this is specifically associated with the organs required for drug excretion which are kidneys and the liver.

When indication for codeine usage is the therapy for a chronic pain, the doctor may opt for different options. It can go from 15 mg up to 60 mg every 4 hours if the pain is present.  The daily maximum dosage of codeine that can be ingested is 360 mg. Since the higher dosages are usually associated with the adverse effects, the doctors usually prescribe less than 60 mg for a treatment. The greater therapy might not reduce the pain, but will cause side effects, so it is advised not to use a higher dosage of the drug.

Drug Interaction

Co-administration of a higher number of drugs can affect metabolism and clearance rates of one another. Drugs altering CYP2D6 isoenzyme can either induce or inhibit its function.  CYP2D6 inducers will enhance metabolism and clearance of codeine, opposite to the inhibitors whose effects will prolong codeine metabolism. Such CYP2D6 inhibitors include Amiodarone, Celecoxib, Clomipramine, Diltiazem, Haldol, Perphenazine, and various SSRIs.

Codeine is also metabolized by the liver’s CYP3A4 enzyme, therefore, drugs that act as inducers/inhibitors of CYP3A4 may also affect clearance rates.  CYP3A4 inducers include Carbamazepine, Dexamethasone, Glucocorticoids, and Progesterone. CYP3A4 inhibitors are Amiodarone, Cannabinoids, Danazol.

How to Improve the Elimination of Codeine?


Regular hydration, healthy diet, and supplements may be helpful when attempting to detoxify. Hydration ensures excretion of a normative amount of codeine and its metabolites through urine, whereas dehydration may cause the retention of these substances. In order for metabolic processes to run properly, the body needs the nutrients provided by the healthy balanced diet. Supplements may support liver and kidney function – leading to optimal clearance times.

Therapy Interruption

The complete body clearance can’t be expected if the ingestion isn’t interrupted. For the full sobriety to be reached (without codeine in your system), no amount of codeine intake can be tolerated.

Other Drugs

A variety of drugs and supplements can enhance the metabolism of codeine, causing a half-time of clearance to decrease. Activity inducers of CYP2D6, CYP3A4 liver enzymes, and other liver-based enzymes may reduce total excretion time. Enzymatic inducers may have contraindications with codeine and other substances present in the body, thus, they should never be ingested without medical consent.

Urine pH

Increasing the acidity of your urine will likely lead to faster overall clearance, especially if your urine is of high alkalinity.

Body Movement

Daily exercise (especially in the form of cardio) can ramp up metabolism; improve circulation to certain regions, thus improving drug clearance. Though the degree to which exercise will speed up codeine clearance isn’t known, it may help. If anything, exercise can help your body produce natural endorphins that replace the effect of codeine.


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