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How Long Does Unisom Stay In Your System?

Unisom (doxylamine succinate) is a first-generation antihistamine available as an over-the-counter medication in the United States.  It is commonly used as a sleep aid (to combat insomnia), an antiallergenic (to reduce severe allergies), and sometimes to treat symptoms of the common cold.  The pharmacological ingredient within Unisom, known as “doxylamine,” functions predominantly via antagonism of H1 histamine receptors, thereby attenuating histaminergic neurotransmission.

Doxylamine exhibits sedative properties superior to pharmaceutical-grade hypnotics such as phenobarbital, and is clearly among the most potent over-the-counter hypnotic agents on the market.  In addition to its effect as an antihistamine and sedative, Unisom has notable anticholinergic properties.  The anticholinergic properties may lead some users to experience adverse reactions such as: ataxia, brain fog, dry mouth, memory impairment, and prolonged drowsiness.

Though Unisom is clearly an effective sleep-aid, sometimes the costs (in terms of adverse effects) outweigh the benefits of sleep induction.  Furthermore, many users of Unisom may be concerned that the drug may impair their performance at work, school, increase their likelihood of a motor vehicle accident, or perhaps cause dementia.  As a result, many frequent users of this over-the-counter sleep aid will cease usage, only to wonder how long it stays in their system.

How long does Unisom stay in your system?

If you were a regular user of Unisom and stop taking it abruptly, it is possible that you may experience some Unisom withdrawal symptoms.  It is also possible that you may continue to experience side effects associated with the drug, leaving you to question whether any of the chemical is still in your system.  To determine how long Unisom is likely to remain in systemic circulation, we must analyze the half-life of its active ingredient “doxylamine succinate.”

Doxylamine succinate is reported to have an elimination half-life of approximately 10 hours in humans.  Based on this information, we know that 50% of your final Unisom dosage should be out of your system in less than half-a-day.  However, for complete 100% systemic elimination, it’ll likely take an average of 2.29 days for healthy adults.

Keep in mind that this estimation of elimination is aimed at users of Unisom in the United States.  Outside of the United States, Unisom formulations contain the active ingredient “diphenhydramine hydrochloride,” the primary ingredient in Benadryl.  To learn how long Unisom sold outside of the United States stays in your system, simply reference the article, “How long does Benadryl stay in your system?”

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/doxylamine
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/4056080

Variables that influence how long Unisom stays in your system

Though we can estimate that Unisom manufactured in the United States is likely to remain in a user’s system for approximately 2.29 days after cessation, there is often interindividual variance in elimination speed.  In other words, not everyone will eliminate the drug in precisely 2.29 days; some will be faster or slower than average in regards to excretion.  The variance in interindividual excretion speed is a byproduct of variables such as: the specific person taking Unisom, dosage, frequency of administration, and whether other drugs were simultaneously administered.

  1. Individual factors

Consider the idea that two individuals could simultaneously ingest a single identical (6.25 mg) dosage of Unisom.  Though each user may eliminate the drug in less than 3 days, one user may eliminate the drug in exactly 50 hours, yet the other person may eliminate it from his/her system in 60 hours.  Assuming equal-strength single doses were ingested simultaneously, the 10 hour difference in elimination speed can usually be explained by individual factors.

Age + Sex: One study compared the pharmacokinetics of doxylamine succinate among young adults (ages 20 to 43) to that among elderly (ages 60 to 87).  Single oral doses of 25 mg were administered to each of the participants and researchers took note of pharmacokinetic differences.  It appeared as though elderly men exhibited reduced doxylamine clearance and a prolonged half-life compared to young adults and elderly women.

The half-life of doxylamine succinate among elderly men increased by approximately 5.3 hours to 15.5 hours.  This suggests that elderly men may take 3.55 days to eliminate the drug from their system, compared to less than 2.5 days for elderly women and young adults.  Though the exact reason for which Unisom is likely to remain in the system of elderly men for a longer duration isn’t well known, it is speculatively associated with reduced efficiency of transformation via oxidation.

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

Body Fat %: It is apparent that the doxylamine succinate within Unisom is highly lipophilic, meaning it is soluble in fat.  For this reason, it may be necessary to consider a Unisom user’s body fat percentage when estimating how long the doxylamine succinate is likely to remain in his/her system after discontinuation.  Among users with a high percentage of body fat, an increased propensity of doxylamine accumulation is likely because they have a greater number of fat stores.

Greater accumulation of the drug within fat stores means that it will be eliminated from a user’s system at a slower rate.  On the other hand, a person with a low percentage of body fat will not have as many fat stores to harbor the same quantity of doxylamine after ingestion, meaning it is likely to get eliminated at a faster rate.  Furthermore, it is necessary to also consider that individuals with a high percentage of body fat may affect disposition of Unisom, perhaps also contributing to a prolonged elimination.

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

Genetics: When contemplating how long doxylamine from Unisom is likely to stay in your system, it helps to know your genetics.  Though the specific metabolism pathways for doxylamine succinate aren’t fully elucidated, it is believed to undergo hepatic metabolism via CYP450 (cytochrome P450) enzymes.  Some have gone as far as to hypothesize that CYP2D6 isoenzymes have the highest affinity for doxylamine succinate metabolism.

Since many CYP450 genes are subject to polymorphisms that in turn affect enzymatic function, your genes may affect how quickly Unisom is metabolized and cleared from your system.  Since CYP2D6 is highly polymorphic, and likely to facilitate most of Unisom metabolism, it is possible that you (as a user) may exhibit poor metabolism based on CYP2D6 allelic expression.

Assuming you are in fact a poor metabolizer of doxylamine as a result of alleles associated with the CYP2D6 gene, the half-life of doxylamine may increase significantly.  On the other hand, if you exhibit optimal expression of CYP2D6 alleles as to facilitate peak CYP2D6 isoenzyme function, you may metabolize doxylamine much quicker and eliminate it faster from systemic circulation.  Though the differences in half-lives of Unisom aren’t fully understood based on CYP2D6 alleles, they likely affect how long it stays in your system compared to the mean elimination time.

Hepatic function: The doxylamine succinate within Unisom is known to function as an H1 receptor antagonist.  Some reports suggest that H1 receptor antagonists are eliminated at a slower rate among those with severe hepatic impairment (e.g. cirrhosis).  Therefore if you have a severe form of liver disease, expect the elimination half-life of doxylamine succinate to increase compared to those with normative hepatic function.

Prolonged elimination likely occurs among those with hepatic impairment as a result of decreased enzymatic function.  When liver function is impaired, the function of hepatic enzymes decreases, leading to higher plasma concentrations of drugs and poorer metabolism.  Users of Unisom should expect altered elimination speed reflective of the extent to which they are hepatically impaired.

Metabolic rate: A person’s BMR (basal metabolic rate) is thought to affect how long certain drugs remain in systemic circulation.  Individuals with extremely high BMRs (such as evidenced in cases of hyperthyroidism) are believed to metabolize and eliminate drugs at a faster rate than those with extremely low BMRs (as evidenced by cases of hypothyroidism).  Assuming you have neither hyper- nor hypo-thyroidism, your metabolic rate may still differ slightly from that of another Unisom user’s.

Though the effect of BMR on elimination of Unisom may not be regarded as clinically significant in most cases, it is likely to affect speed to a minor (perhaps negligible) extent.  If you have a higher BMR than average, you may also be likely to eliminate Unisom faster than average.  However, BMR in and of itself is likely not a major determinant of Unisom’s elimination rate – unless an individual is extremely high or low BMR.

Other drugs: It is necessary to consider that taking other drugs may affect how long Unisom stays in your system.  Though doxylamine succinate may not undergo extensive hepatic metabolism like many other drugs, at least 40% of an ingested dose is hepatically metabolized.  Should a co-administered drug interfere with this hepatic metabolism, plasma concentrations of the parent compound may increase, and elimination may be extended.

Though we cannot pinpoint the specific enzymes responsible for the majority of Unisom’s metabolism, some speculate that CYP2D6 plays a prominent role.  If CYP2D6 isoenzymes are the major determinant of Unisom metabolism, any co-administered agent (drug or supplement) that interferes with CYP2D6 function would likely prolong elimination of Unisom, whereas co-administered agents that bolster CYP2D6 function may reduce elimination time.

Renal function: Most orally ingested drugs undergo hepatic metabolism are distributed, and are then eliminated via the urine by way of the kidneys.  Since the kidneys play a role in the elimination of Unisom, the degree to which they are functioning properly or improperly may influence how long the drug stays in a person’s system after discontinuation.  Individuals with renal impairment may accumulate more of the Unisom in their kidneys and excrete it with reduced efficiency than someone with normative renal function.

The extent to which renal impairment will affect Unisom’s elimination half-life is likely reflective upon the severity of the actual impairment.  Severe forms of impairment likely reduce clearance speed and efficiency, perhaps allowing greater amounts of Unisom to be reabsorbed prior to complete elimination.

  1. Dosage (6.25 mg to 25 mg)

The amount of Unisom (doxylamine succinate) an individual ingests is likely to dictate how long it stays in their system (to a certain extent).  When considering the drug’s half-life of approximately 10 hours, it is apparent that a person taking a single dose of 20 mg would have less of the drug in his/her system than a user taking just 10 mg.  After 20 hours post-ingestion, the 20 mg user would still have 10 mg lingering in his/her system, whereas the 10 mg user would only have 5 mg.

Though both would be likely to eliminate the drug in under 3 days, dosage may slightly affect how long the drug stays in systemic circulation.  Among high dose users, a greater quantity of the drug is ingested, and as a result, it forces hepatic CYP450 enzymes in the liver to work harder for its metabolism.  Up to a certain threshold, these enzymes can tolerate the extra quantity, but once that threshold is exceeded, their efficiency plummets; meaning poorer metabolism of Unisom.

It is this reason that we’d expect the half-life of Unisom to be much longer among someone who had taken a supratherapeutic dose (or deliberately overdosed) than someone taking the drug within normal dosage guidelines.  Furthermore, we could expect a greater quantity of Unisom to accumulate in fat stores throughout the body, and an increasing number of metabolites to form.  This also means that elimination efficiency will be prolonged because there’s a greater amount of the drug that necessitates elimination, taxing the kidneys to a greater extent than they would under normative circumstances (e.g. taking a standard dose).

Among a low dose user, the liver isn’t taxed to as great of an extent, allowing it to efficiently metabolize doxylamine succinate.  The body isn’t overloaded with distribution of large quantities of a highly lipophilic compound, and as a result, less accumulation is likely.  Finally, low dose users have less of the drug to eliminate (because they ingested less), so the body will clear it from the system with greater efficiency.

  1. Frequency of administration

How often a person administers Unisom could also affect the duration it stays in their system after discontinuation.  Research shows that multi-dose users of Unisom are likely to retain the drug for a longer duration after discontinuation than single-dose users.  There are a number of reasons as to why multi-dose users retain the drug for a longer duration after cessation including: greater doses ingested per day, heightened accumulation of doxylamine succinate (and metabolites), and attainment of steady state concentrations.

Though multi-dose users may take “less” Unisom on a per dose basis than a single-dose user, the multi-dose users tend to ingest a greater amount of the drug per 24 hours than a single-dose user.  A single dose user may take 20 mg once before bed, while a multi-dose user may take 15 mg twice throughout the day for a total of 30 mg ingested; 10 mg more than the single-dose user.  As was already mentioned, increased doses, especially over a short-term such as 1 day, are likely to extend elimination half-life.

Research also shows that multi-dose administration of Unisom results in heightened accumulation of the drug.  In other words, plasma concentrations are elevated and fat stores retain a greater amount of Unisom in multi-dose users, leading to an increased elimination half-life.  As a general rule of thumb, realize that the greater the frequency at which you ingest Unisom, the more likely it’ll stay in your system for a longer duration after cessation.

  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021876s002lbl.pdf
  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/021876Orig1s000SumR.pdf

Unisom: Absorption, Metabolism, Excretion (Details)

Following oral administration of Unisom, its active ingredient “doxylamine succinate” is readily absorbed by the gastrointestinal (GI) tract, primarily within the jejunum. After a single 25 mg dose is administered to healthy adults, peak plasma concentrations (of approximately 100 ng/ml) are attained in an estimated 2.4 hours post-ingestion (usually between 2 and 3 hours).  The distribution volume of doxylamine succinate is reportedly 2.5 L/kg.

The drug acts as an antihistamine with hypnotic, anticholinergic, and antimuscarinic properties.  The effect of doxylamine succinate is believed to last between 6 and 8 hours, with plasma concentrations declining to 28 ng/ml after 24 hours.  By 36 hours post-ingestion, plasma concentrations will have declined to just 10 ng/ml.

It is believed that doxylamine succinate is subject to hepatic metabolism via various CYP450 enzymes.  These CYP450 enzymes facilitate N-demethylation, N-oxidation, hydroxylation, N-acetylation, and ether cleavage.  In the process, the two most notable metabolites formed include: nordoxylamine and dinordoxylamine.

The elimination half-life of doxylamine succinate is approximately 10.1 hours, indicating that it’ll be cleared from systemic circulation (likely along with its metabolites) in approximately 2.29 days after discontinuation.  The metabolites are then processed by the kidneys and eliminated via urine.  Urinary excretion consists of: 60% unchanged doxylamine succinate with the remaining 40% as nordoxylamine and dinordoxylamine metabolites.

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

Tips to clear Unisom from your system

If you are concerned that Unisom is still in your body after discontinuation, there are some steps you can actively take to ensure that it gets fully eliminated in a timely manner.  Keep in mind that the safety and alleged efficacy of these tips should be discussed with a medical professional prior to implementation.  That said, below are some strategies that could be implemented for a rapid detox.

  1. Burn fat: We all know that exercise can be a great way to detoxify from drug usage. Unisom is a lipophilic drug and may accumulate in adipose tissue or fat stores throughout the body. Burning some of this excess fat via exercise may force Unisom to be get cleared from the system faster than it usually would – especially among those with an already-high percentage of body fat.
  2. Calcium-D-Glucarate: It is known that Unisom is primarily eliminated via urine in unchanged form. The kidneys coordinate urinary excretion of drugs, but may be taxed with other toxins and potentially from large doses of Unisom (if you were a heavy user). Calcium-d-glucarate is a supplement that acts as a beta-glucuronidase inhibitor, essentially clearing detox pathways and allowing for improved elimination of toxins (and possibly drugs like Unisom).
  3. Activated charcoal: An effective way to detoxify the gastrointestinal tract and liver is via supplementation with activated charcoal. If any unmetabolized Unisom is still in your body, activated charcoal will bind to it through “adsorption,” and essentially chauffer it to be excreted as rapidly as possible. Furthermore, activated charcoal binds to endotoxins within the gut that may have been generated as a result of Unisom ingestion.
  4. Urinary pH: Although the acid lability of Unisom isn’t understood, it is possible that the drug is acid labile. If it is acid labile, increasing the acidity of your urine via modification of dietary intake may be an effective method for expediting Unisom’s excretion. Highly acidic urine may destroy some of the metabolites and/or ensure that they are eliminated with efficiency, whereas alkaline urine may promote reabsorption and redistribution, thereby prolonging elimination.

How long has Unisom stayed in your system after stopping?

If you’ve recently stopped taking Unisom, share a comment regarding how long you believe it stayed in your system after your final dose.  Discuss whether you believe the Unisom stayed in your system for longer than average (2.29 days) or for a shorter duration than average.  To help support your hypothesis, mention factors such as whether you were a single-dose or multi-dose user, the dosage you were taking, as well as whether you were taking other drugs that may have interfered with its metabolism or elimination.

Realize that the majority of healthy Unisom users should eliminate the drug from their systems within 3 days of discontinuation.  Keep in mind that many people mistakenly believe that the drug is still in their “system” for longer than several days after stopping because they still experience side effects.  In most cases, these side effects are not from a lingering circulation of Unisom, rather they are from lingering neurophysiologic changes that occurred whilst Unisom was still in the system.

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4 thoughts on “How Long Does Unisom Stay In Your System?”

  1. Would appreciate any comments you might have on the following. I do not like taking sleeping aids, because of all of the actual & potential side effects, but do not have much choice if I want to get enough sleep.

    I am 75 yrs old, & when I am not using a sleeping aid, I wake up 4 – 5 times during the night, with the result that over an 8 hr period only get about 2.5 – 3.5 hrs of actual sleep. I recently started to take, for 5 nights per week, half of a 5 mg tablet (i.e. 2.5 mg) of Donormyl (also Doxylamine Succinate) plus 250 mg Panadol, about 1 hour before I go to sleep.

    I usually wake up 2 – 3 times after that, & each time I take 250mg Panadol. This increases my actual sleep time from between 2.5-3.5 hrs (without the pills) to between 5 – 6 hrs, which is a significant improvement. I drink 2 strong cups of coffee (2 heaping teaspoons Nescafe Classic) to wake me up in the morning.

    I am deliberately using a low dosage of the Donormyl, in the hope that I can take it for 5 nights of every week, together with the Panadol. For the other 2 nights of every week, I substitute the Donormyl with 1/2 of a Uniflu tablet, which I also use with the Panadol. The Uniflu/Panadol combination is not quite as effective as the Donormyl/Panadol combination, but it does not make me feel as groggy when I get up.

    The 1/2 tablet Uniflu contains 7.5 mg Diphenhydramine hydrochloride, 5 mg codeine phosphate, 5 mg Phenylephrine Hydrochloride, 250 mg Paracetamol( same as Panadol), a combination which should be very effective as a sleeping aid, but it also contains 15 mg Caffeine, which would presumably have an antagonistic effect.

    • Correction & further comment to add to my post of 6 April 2018, 7:53 AM. The Uniflu tablet that I take does NOT contain Codeine Phosphate. So the 1/2 tablet of Uniflu contains:
      -7.5 mg Diphenhydramine hydrochloride,
      -5 mg Phenylephrine Hydrochloride,
      -250 mg Paracetamol (same as Panadol),
      -15 mg Caffeine.

      I will try switch from the Uniflu tablets to Benadryl Tablets (or equivalent), which contains only the Diphenhydramine hydrochloride, which in fact is used as a sleeping aid. So the new weekly schedule would be 5 nights of Donormyl (5mg) plus 3 x 250 mg Panadol, followed by 2 nights of Benadryl (10 mg) plus 3 x 250 mg Panadol. I think the Panadol helps by reducing “discomforts” of old age.

  2. After about two to three weeks of continuous usage of Doxylamine Succinate from between 50mg to 75mg per day, I stopped taking it. The first day after was fine, but three days later there is still fairly high anxiety and mild nausea and headaches. I am very prone to anxiety and am on 40mg fluoxetine per day.

  3. Very interesting article. It certainly is not innocuous! I was wondering if you had written about use of the Z-drugs and how to get off them? I was hooked on Zopiclone for years and have recently tapered down to a very low dose. I want to be done with them. I had not realized the effects of the inter-dose withdrawal EVERY day! Zopiclone has a half life of 5-6 hours. Thanks for all your interesting articles.


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