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How Long Does NyQuil Stay In Your System?

NyQuil is a popular over-the-counter medication sold under the brand “Vicks” utilized to treat symptoms of the common cold, influenza, and allergies – all while simultaneously enhancing sleep and/or without sleep disruption.  The name “NyQuil” is a portmanteau of the words “night” and “tranquil,” effectively reminding consumers that it is intended for nighttime usage and aims to maximize tranquility among those that are sick, thereby offsetting insomnia and/or frequent awakenings associated with illness.  Since NyQuil is marketed specifically for nighttime administration, all formulations contain the chemical sleep aid “doxylamine succinate” to induce and maintain sleep.

In the brain, doxylamine succinate functions as a competitive antagonist of the H1 histamine receptor, which in turn inhibits effects of endogenous histamine.  Modulation of histaminergic transmission leads users to report sedation and somnolence.  Though all NyQuil formulations contain doxylamine succinate, formulations differ in secondary ingredients depending upon the specific symptoms they’re marketed to target (e.g. coughing, fever, pain, sinus blockages, etc.).  Examples of such secondary ingredients within NyQuil formulations include: acetaminophen, dextromethorphan (DXM), phenylephrine, and pseudoephedrine.

While NyQuil is arguably among the most effective over-the-counter agents for the management of common cold and flu-related symptoms at night, it may yield unwanted side effects such as: blurred vision, brain fog, next-day-cognitive impairment, dizziness, drowsiness, and impaired motor skills.  As a result of these unwanted (and potentially dangerous) side effects, many individuals cease NyQuil usage.  Upon cessation, many users wonder how long NyQuil is likely to stay in their system.

How long does NyQuil stay in your system?

After your final dose, you may experience side effects that seem to linger from the NyQuil, leading you to suspect that it may still be in your system.  You may be concerned with the fact that failure to eliminate NyQuil from systemic circulation could increase your risk of a motor vehicle accident, impair your school/work performance, and/or compromise your ability to operate machinery.  For this reason, it is necessary to consider how long NyQuil is likely to remain in your system before its elimination.

To estimate the duration NyQuil stays in your system after your last dose, it is necessary to consider the elimination half-lives of its chemical ingredients.  While all NyQuil formulations contain doxylamine succinate (to induce sleep), other ingredients are subject to variation based on the specific NyQuil subtype (e.g. Flu/Cold).  Other possible NyQuil ingredients include: acetaminophen, doxylamine succinate, dextromethorphan (DXM), phenylephrine, and pseudoephedrine.

Below is a list of potential NyQuil ingredients, their half-lives, and how long they are likely to remain in your plasma.

  • Doxylamine succinate: The ingredient present in all NyQuil formulations is that of doxylamine succinate. Its elimination half-life is approximately 10 hours in healthy adults, meaning that at 10 hours post-ingestion, 50% of the doxylamine within NyQuil will have been eliminated from systemic circulation.  Knowing this half-life, we can estimate that it’ll take approximately 2.29 days to completely eliminate it from your system after you’ve discontinued NyQuil.
  • Acetaminophen: All formulations of NyQuil except “NyQuil Cough” contain acetaminophen. This ingredient has an elimination half-life within the range of 1 to 4 hours, but usually spans between 2 to 3 hours in healthy adults.  With this information we can estimate that it’ll take between 5.5 and 22 hours to clear the acetaminophen component from systemic circulation; in a majority of healthy adults it will be eliminated between 11 and 16.5 hours post-ingestion.
  • Dextromethorphan: This ingredient is included in all NyQuil formulas except “NyQuil Sinus.” Dextromethorphan, also known as “DXM,” has an elimination half-life of 3 to 6 hours, but may narrowed within the range of 2 to 4 hours among those with normative metabolism.  This indicates that for a majority of NyQuil users, DXM should be eliminated from plasma between 11 and 33 hours post-ingestion. (Read: How long does DXM stay in your system?)
  • Phenylephrine: This ingredient is included in formulas of NyQuil marketed to decongest the nasal passages; phenylephrine is a nasal decongestant. Compared to other ingredients, phenylephrine has a short elimination half-life within the range of 2.1 to 3.4 hours.  You should expect the phenylephrine ingredient to be eliminated between 6 and 18.7 hours post-ingestion.
  • Pseudoephedrine: A formerly standard ingredient in NyQuil formulations was pseudoephedrine. This ingredient functions as a nasal decongestant, but is now only attained (in the United States) upon customer request from a pharmacist.  Its elimination half-life, largely contingent upon a user’s age and urinary pH, ranges from 1.9 to 21 hours with an average of 6 hours in healthy adults.  This indicates that pseudoephedrine could be eliminated from a user’s system within the range of 5 hours to 4.8 days.  Most individuals will eliminate pseudoephedrine from systemic circulation in approximately 33 hours (1.38 days) post-ingestion.

Based on the above elimination half-lives of each NyQuil ingredient, we can see that the chemical doxylamine succinate has the longest half-life of ~10 hours, taking around 2.29 days for complete systemic elimination.  Since all NyQuil formulations contain this ingredient, and it is this ingredient that makes you drowsy, most users can expect NyQuil to be out of their systems within 3 days of their final dose.

In the event that you ingested NyQuil with pseudoephedrine, it is possible that the pseudoephedrine component could take longer than that of doxylamine succinate.  In the event that a user’s urinary pH is highly alkaline, it may take up to 4.8 days to completely eliminate pseudoephedrine.  That said, most NyQuil formulations no longer contain pseudoephedrine, and therefore shouldn’t stay in a user’s plasma for a longer duration than doxylamine succinate.

  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/acetaminophen
  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/dextromethorphan
  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/doxylamine
  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/phenylephrine
  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/pseudoephedrine
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7507589

Variables that influence how long NyQuil stays in your system

Though most users will have eliminated all chemical constituents of NyQuil from their plasma in less than 2.5 days after a final dose, elimination times are often subject to individual variation.  Some users may eliminate certain chemical constituents of NyQuil in less than 2.5 days, while others may take considerably longer than 2.5 days for elimination.  Differences in elimination times can be accounted for by considering variables such as: attributes of the user (e.g. metabolism), dosage ingested, frequency/term of administration, and co-administered drugs.

  1. Individual factors

Two individuals could simultaneously ingest the same NyQuil formulation (e.g. NyQuil Cough) at the same dose, yet one user may eliminate the ingredients from his/her plasma quicker than the other.  Since ingestion was simultaneous, formulations were the same, and dosage was equipotent – what explains the difference in elimination speed?  Differences in elimination speed often result from interindividual factors such as: a user’s age, body mass, genetics, glutathione levels, hepatic function, renal function, and urinary pH.

Age + Sex: The age of a NyQuil user may significantly alter the pharmacokinetics of certain ingredients.  Specifically, elderly individuals (over the age of 65) are known to exhibit decreased levels of plasma proteins/glutathione, poorer hepatic function, diminishing renal function, and overall, less efficient physiologic function.  As a result of these age-related changes, it should be expected that standard doses of NyQuil require a longer duration to be eliminated from the plasma of an elderly individual.

Furthermore, it is necessary to consider that elderly NyQuil users are often plagued with various other health conditions, and as a result, may be more likely to co-ingest drugs that interfere with the metabolism of NyQuil ingredients.  This interference may spike plasma levels of certain chemicals, alter their respective volumes of distribution, and prolong systemic circulation.  On the other hand, a young healthy adult should exhibit normative hepatic/renal function, efficient physiologic function, and is unlikely to be on a slew of medications that interfere with NyQuil metabolism.

One study documented that doxylamine succinate, an ingredient present in all formulations of NyQuil, exhibits a longer elimination half-life among elderly men (at 15.5 hours) – compared to just 10.2 hours in younger adults.  This implies that NyQuil is likely to remain in the plasma of elderly men for 3.55 days after a final dose; this is over 24 hours longer than elimination in younger adults (2.34 days).  Reduced oxidative capacity associated with old-age could be responsible for this protracted half-life.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/2743704

Body mass + Fat (%): The ubiquitous NyQuil ingredient, doxylamine succinate, is considered lipophilic, meaning it is soluble in fat.  For this reason, individuals with a high percentage of body fat may be susceptible to doxylamine succinate accumulation prior to elimination.  Specifically, with consistent administration of NyQuil (e.g. daily, several times per day), doxylamine succinate may accumulate within a user’s adipose tissue.

As a result of this adipose tissue accumulation, NyQuil may remain within a user’s system for a longer duration after their final dose.  Among users with a low percentage of body fat, there’s less overall adipose tissue for doxylamine succinate accumulation, likely leading to faster elimination.  It is also necessary to note that obese individuals are known to exhibit altered levels of plasma proteins, volumes of chemical distribution, and renal function.

Since NyQuil formulations consist primarily of lipophilic ingredients, a longer elimination half-life should be expected among long-term users with a high BMI and/or body fat percentage.  Also consider that the NyQuil ingredient “DXM” (present in select formulations) is highly lipophilic, meaning that it may also accumulate in fat stores (along with doxylamine).  If you have a high percentage of body fat, know that NyQuil ingredients may remain in your system for a protracted term (compared to average).

  • Source: http://www.medsafe.govt.nz/profs/datasheet/p/PharmacistsOwnPainReliefPlustab.pdf

Genetics: The doxylamine succinate within NyQuil, as well as the “DXM” in certain formulations, are subject to metabolism via CYP450 enzymes within the liver.  Enzymatic function is largely dictated by allelic expression of certain CYP-genes.  NyQuil users that exhibit non-functional or reduced function alleles for respective CYP-pathways necessary for metabolizing NyQuil ingredients should expect a prolonged elimination half-life.

Specifically, it may be necessary to analyze your allelic expression of the CYP2D6 gene.  CYP2D6 is speculated to facilitate metabolism of doxylamine succinate (an ingredient in all NyQuil formulations) and DXM (an ingredient in some NyQuil formulations).  If you are considered a CYP2D6 “poor metabolizer,” you’re likely to retain doxylamine (and DXM) for longer than usual.  This is due to the fact that you have non-functional CYP2D6 alleles and the NyQuil doesn’t get properly metabolized.

Improper metabolism as a result of poor CYP2D6 isoenzyme function leads to spikes in plasma concentrations of NyQuil.  Approximately 3-10% of the population are considered CYP2D6 “poor metabolizers.”  Among poor metabolizers, doxylamine succinate exhibits an elimination half-life of approximately 19.1 hours, suggesting that it’ll take 4.38 days until it is no longer in the plasma.

If you are like a majority of users and exhibit normative CYP2D6 expression, you’ll be considered an “extensive metabolizer” and should clear NyQuil from systemic circulation within just 3 days of cessation.  A small percentage of users may metabolize NyQuil ingredients like doxylamine succinate at a much faster pace than others.  These individuals usually exhibit two functional CYP2D6 alleles and are classified as “ultrarapid metabolizers” – eliminating NyQuil ingredients at a faster pace than average.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8841152

Glutathione levels: Nearly all NyQuil formulations (with a couple exceptions) contain acetaminophen in varying amounts.  It is understood that upon absorption, acetaminophen undergoes glucuronidation and sulfation via various pathways within the liver.  While most of an acetaminophen dosage forms APAP-GLUC (acetaminophen glucuronide) and APAP-SULF (acetaminophen sulfate) metabolites, a small percentage (5-10%) may form a toxic metabolite known as “NAPQI.”  In most cases, this toxic metabolite is bound to glutathione (GSH), detoxified, and eliminated.

However, among those with abnormally low levels of glutathione and/or depleted glutathione, it is possible that a substantial percentage of NAPQI may accumulate and wreak internal havoc.  It may also stay in systemic circulation for a prolonged term among those with low glutathione (GSH) compared to those with sufficient levels.  Therefore, when considering how long the acetaminophen within NyQuil may stay in your system, realize that its elimination may be contingent upon your glutathione levels.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/3829578

Hepatic function: Individuals with compromised hepatic function are likely to retain NyQuil ingredients (and their respective metabolites) in systemic circulation for a longer duration than those with normative hepatic health.  Nearly all major ingredients within NyQuil (e.g. doxylamine succinate, acetaminophen, DXM, etc.) undergo biotransformation through hepatic pathways, usually via CYP450 isoenzymes.  Hepatic impairment is known to decrease function of these pathways, thereby prolonging elimination half-life of NyQuil.

Studies have confirmed that the elimination half-life of NyQuil ingredient “acetaminophen,” is increased to 4.25 hours (+/- 1.15 hours) among those with severe liver disease, compared to just 2.43 hours in healthy adults.  In other words, healthy individuals should eliminate acetaminophen ingested via NyQuil in around 13.37 hours, whereas someone with severe hepatic impairment would take around 23.34 hours; nearly double the time.  Other reports indicate elimination half-lives of H1 receptor antagonists like doxylamine succinate are likely to increase among users with severe hepatic impairment (e.g. cirrhosis).

Usually the extent of hepatic impairment dictates how long NyQuil is likely to remain in a user’s system.  If the impairment is considered “severe,” NyQuil elimination may take considerably longer (specifically elimination of doxylamine succinate) than average.  In cases of mild hepatic impairment, elimination of NyQuil ingredients may be prolonged, but not to the same extent as cases of severe impairment.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/499292

Metabolic rate: A user’s BMR (basal metabolic rate) may affect how long NyQuil remains in systemic circulation after discontinuation.  Individuals with high BMRs are known to utilize and burn more energy in a resting state than persons with low BMRs.  There is some evidence to suggest that a high BMR may increase the speed of drug metabolism and ultimately systemic elimination, whereas a low BMR may decrease speed of drug metabolism.

If you have a high BMR, it is plausible to consider that it may expedite the plasma elimination of NyQuil, likely to a minor extent.  If you have a low BMR, you may want to consider that it could slightly slower the elimination of NyQuil (ingredients) from circulation.  BMR may also indirectly influence NyQuil ingredient elimination speed via its affect on body fat percentage; users with greater fat may eliminate certain lipophilic ingredients at a slower rate.

  • Source: https://books.google.com/books?id=az8uSDkB0mgC

Renal function: After NyQuil ingredients such as acetaminophen, doxylamine succinate, and/or dextromethorphan are hepatically metabolized, their metabolites are subject to excretion from the body via the liver.  Individuals with renal impairment (compromised kidney function) may not excrete NyQuil metabolites as efficiently as someone with normative renal function.  When renal function is compromised, metabolites may accumulate in detoxification pathways prior to their elimination.

As a result of this accumulation, some metabolites may be reabsorbed and recirculate throughout a user’s system before excretion – inevitably increasing elimination half-life.  If you have any form of renal impairment, expect elimination of NyQuil to be prolonged.  The extent to which elimination of NyQuil (ingredients) is prolonged as a result of renal impairment is usually reflective upon its severity; severe impairment likely protracts elimination to a greater extent than mild impairment.

Urinary flow rate: Elimination speed of various NyQuil ingredients may be altered by a user’s urinary flow rate.  Generally, the greater a user’s urinary flow rate, the quicker they can expect to eliminate metabolites formed via NyQuil ingestion.  On the other hand, someone with a slow urinary flow rate may take longer than usual to eliminate NyQuil metabolites.

It may be possible to modify urinary flow rate based on fluid intake.  The greater the amount of fluid consumed and the more hydrated you’re staying, the greater your urinary flow rate is likely to be.  If you are dehydrated, your urinary flow rate may be reduced, leading to less efficient excretion of NyQuil.  Though elimination speed of all NyQuil ingredients may be impacted by urinary flow rate, there is evidence to support that urinary flow rate especially influences elimination of the ingredient “pseudoephedrine.”

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7438686

Urinary pH: Certain NyQuil ingredients may be eliminated at a faster or slower pace based on a user’s urinary pH.  Particularly, the greater the acidity of an individual’s urine, the faster they are likely to excrete NyQuil metabolites, whereas the greater the alkalinity of a user’s urine, the slower they are likely to excrete NyQuil metabolites.  Acidic urine usually results from consumption of foods that lower pH including: meat, fish, poultry, and grains.

Alkaline urine results from consumption of foods that increase pH such as: avocados, berries, broccoli, and cucumber.  If your urine is alkaline, certain metabolites may get reabsorbed and recirculated throughout your system prior to their elimination, thereby extending elimination time (perhaps to a slight extent).  Urinary pH is known to have a major impact on elimination of the NyQuil ingredient pseudoephedrine.

One study found that increasing the alkalinity of urinary pH can increase the elimination half-life of pseudoephedrine from 1.9 to 21 hours.  If your urine is on the acidic end of the pH spectrum, expect pseudoephedrine (and its metabolites) to be eliminated in around 10.5 hours, whereas if your urine is highly alkaline, elimination could take up to 4.81 days.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7438686
  1. Dosage

The dosage of NyQuil that you take may also affect how long it remains in your system after your last dose.  As a general rule of thumb, most users should assume that the greater the dosage of NyQuil ingested, the longer it’ll likely remain in systemic circulation.  This rule should be considered commonsense in that elimination half-lives of NyQuil ingredients are often protracted among individuals that “overdose” and/or that ingest supratherapeutic amounts.

There are numerous reasons as to why high NyQuil doses take longer to get out of your system than lower does.  At high doses, a greater burden is placed on isoenzymes within your liver to metabolize various ingredients.  In other words, these isoenzymes need to work harder to process a high quantity of an exogenous compound, but are only capable of metabolizing a set amount at once.

Once enzymes are maximally taxed beyond a certain threshold, their efficiency is compromised.  As a result, large doses aren’t as likely to get metabolized as quickly as smaller ones.  Also, after NyQuil ingredients are metabolized, a larger dosage yields greater number of metabolites, all of which end up circulating throughout a user’s system.  A greater number of metabolites suggests heightened plasma concentrations and an increased propensity of accumulation within bodily tissues.

Furthermore, as a high dose and its metabolites are eliminated from the plasma, they are subject to renal excretion.  Like hepatic pathways, renal pathways are only capable of excreting a threshold amount of a substance at once.  If a high dose exceeds the threshold, some of these metabolites may be subject to reabsorption and recirculation – each of which may prolong NyQuil’s half-life.

If you’re taking a low dose of NyQuil, expect its ingredients to be efficiently metabolized, subject to less accumulation within fat stores, and to be efficiently excreted via the kidneys.  Should you take a high dose and/or a dosage that exceeds recommended guidelines, understand that elimination may be protracted.  Finally, realize that dosages of ingredients may be subject to variation based on the specific NyQuil formulation (e.g. the acetaminophen content in NyQuil D differs from that of NyQuil Cold/Flu).

  1. Frequency/Term of administration

The frequency at which you administer NyQuil (how often you take it), as well as the cumulative duration over which you’ve consistently taken it can affect how long it stays in your system.  If you frequently administer NyQuil (e.g. 3 times per day), you’ll likely have ingested a greater total daily dosage than a less frequent user.  In addition to the likelihood of an increased total daily dosage among a frequent NyQuil user, it is necessary to consider that frequent administration may compromise elimination efficiency.

In other words, administering a secondary or tertiary dose after an initial dose may tax hepatic and renal processes to such an extent that efficiency is compromised.  An unmetabolized initial dose may be circulating in your system when an additional one is administered; this is like adding more fuel to a fire before the initial fuel was done burning (metabolizing).  For these reasons, we’d expect a frequent NyQuil user to exhibit a prolonged elimination half-life.

That said, a frequent short-term user may eliminate NyQuil ingredients quicker than a frequent long-term user.  Over a long-term (assuming someone is addicted or constantly administers NyQuil), accumulation of ingredients (and their metabolites) within fat stores (e.g. adipose tissue) is likely to occur to a greater extent than over a short-term.  Additionally, long-term users may have built-up tolerance to low doses of NyQuil, and as a result, regularly ingest abnormally high doses (which were already mentioned to increase half-life).

If you use NyQuil on an infrequent basis and/or for an extremely short-term, don’t expect to accumulate a significant amount of the drug in your system.  Furthermore, you may be taking lower-than-average doses due to the fact that you haven’t developed tolerance.  As a result, we’d expect an infrequent or single-dose NyQuil user to eliminate ingredients from systemic circulation quicker than a frequent, long-term user.

  1. Co-administration of drugs (CYP2D6)

It is important to consider the combination of potential ingredients within NyQuil and how they may interact with a co-administered drug or supplement.  Certain components of NyQuil such as doxylamine succinate and DXM are hepatically metabolized via CYP450 isoenzymes.  Should any co-administered drug or supplement affect the function of these CYP450 isoenzymes, particularly CYP2D6, it may expedite or prolong elimination of NyQuil from your system.

Some drugs are classified as “CYP2D6 inhibitors” due to their interference with CYP2D6 isoenzyme function.  As a result of CYP2D6 interference, elimination half-lives of ingredients such as doxylamine succinate and DXM are thought to increase, sometimes significantly.  Examples of CYP2D6 inhibitors include: Bupropion, Cinacalcet, Fluoxetine, Paroxetine, Quinidine, and Ritonavir.

Other drugs are classified as “CYP2D6 inducers” due to their induction of CYP2D6 isoenzyme function.  As a result of CYP2D6 induction, elimination half-lives of ingredients such as doxylamine succinate and DXM are thought to be reduced.  Examples of CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin.

Note: The degree of CYP2D6 inhibition/induction as a result of a co-administered agent may be subject to variation based on the specific drug and the dosage at which it is ingested.

NyQuil: Absorption, Metabolism, Excretion (Details)

Due to the fact that NyQuil formulations are subject to variation based on their ingredients, the pharmacokinetics of each respective ingredient should be discussed.  Below is information regarding the absorption, metabolism, elimination/excretion of each potential chemical within NyQuil.  Ingredients include: doxylamine succinate, acetaminophen, phenylephrine, DXM, and pseudoephedrine.

Doxylamine Succinate

Upon oral administration of NyQuil, the ingredient doxylamine succinate is absorbed by the jejunum within the gastrointestinal (GI) tract.  Administration just 25 mg doxylamine succinate to healthy adults yields peak plasma concentrations (of ~100 ng/ml) within 2.4 hours post-ingestion.  Doxylamine succinate is distributed at a volume of 2.5 L/kg and is lipophilic, meaning it has an affinity for fat tissue.

This component of NyQuil functions as an antihistamine/hypnotic and also elicits anticholinergic and antimuscarinic effects. Effects of doxylamine succinate span between 6 and 8 hours and plasma concentrations dwindle to just 28 ng/ml after 24 hours.  Nearly 36 hours after administration, plasma concentrations will have dipped to a level of 10 ng/ml.

Doxylamine succinate is thought to undergo hepatic CYP450 metabolism, a majority of which may be facilitated by CYP2D6 isoenzymes.  In any regard, it is known that CYP450 enzymes convert doxylamine to metabolites nordoxylamine and dinordoxylamine.  These metabolites are formed through N-demethylation, N-oxidation, hydroxylation, N-acetylation, and ether cleavage.

The half-life of doxylamine succinate is around 10 hours, making its elimination the slowest among all NyQuil ingredients.  Furthermore, since it is present in all NyQuil formulations, we can usually assume that when doxylamine succinate is out of your system, other ingredients are likely to have also been eliminated.  The drug is eliminated from the plasma (along with its metabolites) in around 2.29 days.

Upon elimination from the plasma, the parent drug (doxylamine) and its metabolites are excreted via the urine.  Urinary elimination consists of roughly 60% unchanged doxylamine succinate and 40% as “nor” and/or “dinor” metabolites.

  • Source: http://www.medsafe.govt.nz/profs/datasheet/d/dozilecap.pdf
  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/doxylamine


Most NyQuil formulations contain acetaminophen to address symptoms such as aches, pains, and fevers.  Upon administration of NyQuil, the acetaminophen ingredient is quickly absorbed through the gastrointestinal (GI) tract.  After its absorption, it is metabolized within the liver via glucuronidation and sulfation pathways, converting the parent compound acetaminophen to form metabolites: APAP-GLUC (acetaminophen glucuronide) and APAP-SULF (acetaminophen sulfate).

In the event that a NyQuil user has insufficient and/or depleted glutathione, a third metabolite known as “NAPQI” may form.  NAPQI is toxic, but can be readily detoxified with sufficient glutathione.  Most NyQuil users will not experience NAPQI toxicity unless they administer an extremely large dosage and/or are aware that they have suboptimal glutathione levels.

After acetaminophen metabolites form, it is distributed throughout your system with an elimination half-life of 2 to 3 hours in healthy adults.  This implies that acetaminophen and its metabolites should be out of systemic circulation within 11 to 16.5 hours post-ingestion.  Nearly 90% of acetaminophen within NyQuil will have been excreted via urine in under 24 hours, a majority of which will consist of acetaminophen glucuronide and acetaminophen sulfate; only a small percentage will be excreted as unchanged acetaminophen.

  • Source: Source: https://pubchem.ncbi.nlm.nih.gov/compound/acetaminophen


Many formulations of NyQuil contain “DXM” (dextromethorphan) as an active ingredient.  DXM aids in the suppression of coughs and is thought to reduce throat irritation.  When NyQuil is administered, the DXM ingredient is rapidly absorbed within the gastrointestinal (GI) tract and thereafter, it undergoes extensive hepatic metabolism.

Its hepatic metabolism is catalyzed by CYP2D6 isoenzymes, converting dextromethorphan to the metabolite “dextrorphan.”  After administration, plasma concentrations of DXM peak within 2.5 hours and concentrations of its dextrorphan metabolites peak within 1.7 hours. Since the drug is metabolized by CYP2D6 isoenzymes, and CYP2D6 is considered polymorphic, those with non-functional CYP2D6 alleles may exhibit more DXM and less dextrorphan metabolites than those with functional CYP2D6 alleles.

Other isoenzymes such as CYP3A4 and CYP3A5 convert DXM to form minor metabolites: 3-methoxymorphinan and 3-hydroxymorphinan.  Among extensive CYP2D6 metabolizers, DXM’s elimination half-life is reported within the range of 3 to 6 hours, whereas among poor CYP2D6 metabolizers, its elimination half-life may increase to around 19.1 hours.  Since most of the population are extensive metabolizers, DXM should be eliminated from the plasma in 16.5 hours to 1.38 days.

In the event that you happen to be a poor DXM metabolizer, expect to retain it in systemic circulation for up to 4.38 days after your NyQuil dose.  It should be considered that DXM may linger in systemic circulation for a longer term than doxylamine succinate if taken by a poor CYP2D6 metabolizer.  Quantities of DXM and its metabolites excreted within urine will be contingent upon CYP2D6 metabolism; better metabolizers will excrete mostly metabolites, whereas poor metabolizers will excrete more unchanged DXM.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/dextromethorphan
  • Source: http://www.nhtsa.gov/people/injury/research/job185drugs/dextromethorphan.htm


Phenylephrine was added to NyQuil Sinus formulations to act as a decongestant.  Upon ingestion of NyQuil Sinus, phenylephrine is fully absorbed and subject to first pass metabolism via the intestinal wall and liver.  Phenylephrine exhibits a bioavailability of 38% and is quickly circulated throughout the body to peripheral tissues.

Metabolism of phenylephrine is facilitated principally within the intestinal wall via sulfate conjugation and by monoamine oxidase enzymes via oxidative deamination.  Only a small percentage of phenylephrine is metabolized via conjugation with glucuronic acid.  The elimination half-life of phenylephrine ranges between 2.1 and 3.4 hours, suggesting that it should be eliminated from the plasma within 18.7 hours post-ingestion.

Within 48 hours, most NyQuil users will have excreted over 80% of phenylephrine within urine.  A majority of urinary excretion consists of metabolites (<95%) and approximately 2.5% consists of unchanged phenylephrine.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/phenylephrine


Select NyQuil formulations contain the nasal/sinus decongestant pseudoephedrine.  Upon its ingestion, pseudoephedrine (within NyQuil) is efficiently and nearly fully absorbed via the gastrointestinal (GI) tract.  It is not subject to first-pass hepatic metabolism and reaches peak plasma concentrations (of 180-300 ng/ml) when administered at an oral dose of 60 mg.

Peak plasma concentrations are attained within 2 hours of administration, but absorption may be delayed when administered with food and/or after a meal.  Nasal decongestant effects are believed to span for 4 to 6 hours after pseudoephedrine’s ingestion.  Renal clearance rates of pseudoephedrine in healthy adults reportedly range between 7.3 and 7.6 ml/min/kg.

The half-life of pseudoephedrine is subject to significant variation based on a user’s urinary pH.  Some sources suggest that average elimination half-life ranges between 9 and 16 hours, whereas other sources cite a broader range between 1.9 and 21 hours.  In any regard, someone with a highly alkaline urinary pH may retain pseudoephedrine in systemic circulation for up to 4.8 days after their final NyQuil dose.

Most users, assuming their urinary pH isn’t too high (or overly alkaline), will eliminate pseudoephedrine from the plasma within 33 hours (1.38 days) after administration.  Less than 1% of pseudoephedrine is metabolized via N-demethylation within the liver (to form a metabolite), and as a result, a majority of pseudoephedrine (up to 96%) is excreted unchanged within the urine.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/pseudoephedrine

Tips to clear NyQuil from your system

If you’ve recently stopped using NyQuil and want to ensure that it is eliminated from your plasma and systemic circulation as soon as possible, you may want to consider some of the tips listed below.  Keep in mind that prior to implementing any of the suggestions listed below, you should confirm their safety and alleged efficacy with a medical professional.  Also realize that in most cases, NyQuil should be out of your system quickly – meaning you don’t need to necessarily take additional steps to detoxify.

  1. Activated charcoal: If you’ve taken a large dosage of NyQuil and/or were a frequent user before discontinuing, you may want to take some activated charcoal. Even if the NyQuil ingredients were already absorbed and/or are circulating throughout your system, activated charcoal will bind to unmetabolized ingredients and any lingering metabolites. The charcoal may also be helpful in that it binds to endotoxins in your gut that may have been generated from ingestion of NyQuil ingredients.
  2. Calcium-D-Glucarate: Most of the ingredients within NyQuil are metabolized in the liver, then excreted via the kidneys. If you’ve been taking NyQuil for a long-term and/or along with other drugs, there’s a chance that toxins may have accumulated within your kidneys. Calcium-d-glucarate is a supplement you can take that acts as a beta-glucuronidase inhibitor.  This mechanism clears molecular remnants from detoxification pathways, some of which may have been from NyQuil.
  3. Glutathione: If you’ve been using NyQuil formulations containing acetaminophen, there’s a chance that your glutathione levels are lower than usual. Though it takes a large dose of acetaminophen to yield NAPQI (toxic metabolites), your endogenous glutathione levels may have taken a beating from the acetaminophen ingestion. You may want to consider replenishing them with exogenous glutathione supplementation.  This will ensure that all NAPQI gets mopped up.
  4. Acidify urinary pH: Acidification of urinary pH can be helpful for reducing the half-lives of certain chemicals. If you’ve taken NyQuil formulations containing pseudoephedrine, lowering your urinary pH will significantly reduce its half-life. If you have a high urinary pH, certain ingredients may be subject to reabsorption and recirculation, ultimately prolonging elimination time (sometimes to a significant extent).  Acidification can be accomplished via eating acidic foods, however, be sure not to go overboard (as to avoid acidosis).
  5. Exercise & hydration: If you have a high percentage of body fat and/or don’t drink enough water, you may want to take steps to burn some of your excess fat and increase your hydration. Body fat can sometimes store lipophilic substances that may be found within NyQuil (e.g. DXM and its metabolites). Burning fat with exercise will force these metabolites to be purged from fat stores to expedite their elimination.  Hydration may ramp up urinary flow rate, ultimately increasing efficiency of renal excretion.

How long has NyQuil stayed in your system after discontinuation?

If you were a regular NyQuil user and/or were administering NyQuil heavily as a result of a sickness, but have since discontinued treatment, share a comment mentioning how long it took before you felt like your pre-NyQuil self.  How long do you believe the NyQuil ingredients remained in your system after your final dose?  To help others understand your situation, mention the specific type of NyQuil you were using, the dosage you were taking, as well as the frequency at which you were administering it.

Understand that most NyQuil users should have eliminated all of the ingredients from systemic circulation within 3 days of their final dose.  In some cases, elimination could take longer, but no user should expect to retain any ingredient for longer than 7 days.  If you used NyQuil as medically instructed, there’s no reason to believe that it’ll stay in your system for longer than a full week.

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