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How Long Does Flexeril Stay In Your System?

Flexeril (Cyclobenzaprine) is a drug approved by the FDA as a short-term adjunct treatment for skeletal muscle spasms along with physical therapy and rest.  Although its mechanism of action isn’t fully elucidated, it is thought to act within the central nervous system, principally at the brain stem.  Within the brain stem, it is believed to activate neurons within the locus coeruleus, thereby leading to modulation of norepinephrine.

Noradrenergic modulation within the locus coeruleus facilitates alterations within gamma and alpha motor systems, which in turn reduces tonic somatic motor activity, yielding a muscle relaxant effect.  It should be noted that Flexeril is similar in structure and effect to various tricyclic antidepressants in that it exerts anticholinergic effects and is often sedating.  Though this drug is effective when utilized properly for a short-term, its therapeutic effects diminish within 2 weeks.

This means that most users will end up discontinuing Flexeril treatment in less than 14 days after their starting dose.  Some may decide to stop treatment even sooner if they experience adverse effects (e.g. dizziness, drowsiness, dry mouth, etc.) as a result of the drug.  If you’ve had to discontinue treatment, you may be wondering how long Flexeril stays in your system after your final dose.

How long does Flexeril stay in your system?

If you stop taking this drug after chronic, long-term administration, you’re likely to experience some potent Flexeril withdrawal symptoms.  If you used the drug intermittently for less than 2 weeks, discontinuation effects will be less noticeable.  In any regard, you may notice some neurophysiologic adjustments taking place or feel the effects of Flexeril after you’ve quit taking it, and may wonder how long it stays in your system.

To determine how long Flexeril stays in your system after complete cessation, it’s helpful to consider its average elimination half-life of 18 hours.  This indicates that among most Flexeril users, the drug should be cleared from systemic circulation in around 4.13 days after their final dose.  However, it is necessary to consider the fact that elimination half-life can range from 8 to 37 hours, indicating that there’s significant interindividual variability in regards to excretion.

Assuming you happen to be on the fastest end up of Flexeril’s half-life spectrum at 8 hours, you should expect the drug to be eliminated from your system in around 1.83 days (less than 48 hours).  On the other hand, if you’re on the slowest end of its half-life spectrum at 37 hours, it may take 8.48 days to fully eliminate the drug from your system.  Realize that for a majority of users, elimination will take between 4 and 5 days after discontinuation.

  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/017821s045lbl.pdf

Variables that influence how long Flexeril stays in your system

Although most users will eliminate Flexeril from their systems in just over 4 days after their final dose, reports suggest substantial interindividual variability in elimination times.  This variability in elimination half-life of Flexeril (and other drugs) is a result of a multitude of variables including: the individual taking the drug, frequency of administration, dosage, and co-administration of other drugs.  These variables may be helpful to consider if attempting to contemplate precisely how long Flexeril is likely to remain in your system.

  1. Individual factors

Two people could take the same dosage of Flexeril, three times per day, for the same duration, yet one individual would be likely to eliminate the drug in a shorter duration from his/her system than the other.  The difference in elimination speed among two users could be a result of factors such as: age, body mass, and hepatic function.

Age (+ Sex): It is understood that elderly individuals tend to excrete drugs at a slower rate than younger adults.  This is due to the fact that old age is often accompanied by poorer physiologic function.  Furthermore, elderly individuals often exhibit diminishing renal function, compromised hepatic function, and lower levels of plasma proteins.  This results in altered pharmacokinetics of Flexeril including plasma concentrations, distribution, and elimination speed.

Some research shows that steady state concentrations of Flexeril are nearly 2-fold among elderly compared to younger adults following 5 mg doses administered three times daily.  As a result of the elevation in plasma concentration by 2-fold, it should be expected that elimination half-life is likely prolonged among elderly patients (over the age of 65).  If you are a healthy young adult, expect to eliminate the drug in a normative amount of time (~4 days) compared to elderly who may take longer (over 8 days).

It should also be noted that elderly males are likely to eliminate the drug slower than elderly females (on average).  Plasma concentrations among elderly males increased to 2.4-fold that of younger adults, whereas concentrations among elderly females only increased to 1.2-fold by comparison. Therefore old age may primarily affect males, whereas females may be less affected.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11808825

Body mass: Typically the greater the size of an individual taking Flexeril (relative to the dosage they ingest), the faster they’re able to eliminate it from their system.  Contrarily, the smaller the size of an individual taking Flexeril (in respect to dosage), the slower they’re likely to eliminate it from their system after stopping.  This is due to the fact that the more massive a user, the larger the size of their system, resulting in more efficient metabolism of the drug.

Among smaller individuals, an average dose of Flexeril may be eliminated at a slower pace due to the fact that they are ingesting more of an exogenous substance relative to the size of their system.  It may also be necessary to consider a person’s body fat percentage, as this could affect the pharmacokinetics of Flexeril.  Obese individuals may excrete the drug at a faster pace than those with less body fat due to altered disposition.

Genetics: Your genes may influence the hepatic metabolism of Flexeril, ultimately affecting its elimination speed.  If you have certain alleles associated with CYP3A4, CYP1A2, and/or CYP2D6, the N-demethylation (metabolism) of Flexeril may be altered – resulting in a prolonged elimination half-life (or expedited elimination half-life) depending on the specific alleles.  That said, since the majority of Flexeril is processed by the kidneys, genes regulating hepatic enzyme function may not have a clinically significant impact on this drug’s elimination.

Hepatic function: A person’s hepatic and renal function are thought to influence how long Flexeril remains in systemic circulation after cessation.  Individuals with hepatic impairment have been reported to exhibit 2-fold greater plasma concentrations of Flexeril than those with normative liver function.  As a result of these increases in plasma levels of Flexeril, the elimination is often significantly prolonged.

Those with hepatic impairment tend to experience downregulation of CYP450 (cytochrome P450) isoenzyme function, leading to a slowed metabolism of Flexeril.  In addition, renal impairment may also prolong excretion of Flexeril (and its metabolites).  Individuals with impaired renal function may experience accumulation, reabsorption, and recirculation of the drug prior to complete excretion, thereby slowing elimination.  Usually the greater degree to which a person experiences hepatic or renal impairment, the longer the drug will remain in their system.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11808825
  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/017821s045lbl.pdf

Metabolic rate: Basal metabolic rate (BMR) is thought to affect the elimination half-life of certain drugs.  Individuals with high BMRs are thought to burn more energy in a resting state, and therefore may be better equipped to metabolize and excrete exogenous substances at a fast pace.  Oppositely, individuals with low BMRs burn less energy at rest, and may not process exogenous substances such as Flexeril with as much efficiency – resulting in slower elimination.  Keep in mind that the role of metabolic rate in drug elimination is not usually clinically significant, but may have a minor impact.

  1. Frequency of administration

The greater the frequency at which you administer Flexeril, the longer you can expect it to remain in your system after cessation.  The drug is known to accumulate to a significantly greater extent within plasma when administered 3 times per day, compared to when it is administered just once per day (in a single dose).  Research shows that when administered 3 times per day, plasma levels are nearly 4-fold that of single-dose administration (once per day).

Furthermore, those taking Flexeril three times per day are known to attain steady state plasma concentrations within 4 days.  Individuals taking the drug just once per day may not reach steady state concentrations, meaning that the drug will be eliminated at a faster rate because less has “accumulated” within the plasma.  Those using Flexeril 3 times per day should take longer to eliminate it than those taking it twice per day or just a single daily dose.

In addition to the frequency of administration, it is necessary to consider the duration over which you’ve been taking Flexeril.  Someone that’s taken the drug 3 times per day for only 2 days should eliminate the drug quicker than someone taking it at an equal frequency for 5 days because the 5 day user will have reached peak concentrations of the drug (the 2 day user may not have attained peak levels).  Therefore among high frequency users, it may be necessary to account for duration of usage when contemplating elimination speed.

  1. Dosage (5 mg or 10 mg)

The greater the dosage you’re taking of Flexeril, the longer you can expect the drug to remain in your system after discontinuation.  Most individuals are instructed to take Flexeril at dosages of 5 mg, three times per day.  Among those that fail to respond to 5 mg, the dosage may be titrated upwards to 10 mg three times per day for increased potency.

If daily totals of ingested dosages are compared, the person taking 5 mg three times per day will have ingested a total of 15 mg, whereas a person taking 10 mg three times per day will have ingested a total of 30 mg.  Smaller dosages are easier for the liver to metabolize and for the kidneys to excrete because there’s less quantity of an exogenous substance to process.

Someone taking 30 mg may tax their hepatic enzymes to a greater extent, resulting in slightly impaired metabolism of the drug.  Additionally, the liver may be unable to excrete the metabolites with as much efficiency because there were a greater number formed.  With increased numbers of metabolites (and a greater amount of the drug to excrete), the efficiency of renal excretion may diminish.  Expect to eliminate the drug at a slower rate if you were taking a high dose (compared to a low one).

  1. Co-administered drugs

If you were taking any other drugs with Flexeril, it is possible that they may have affected its hepatic metabolism within your body.  Since Flexeril is metabolized chiefly by isoenzymes CYP3A4 and CYP1A2 (and to a small extent CYP2D6), any drug that decreases or enhances function of these enzymes will affect how quickly it is eliminated.  Drugs classified as “CYP3A4 inhibitors” are known to interfere with function of CYP3A4 enzymes.

These drugs may inhibit the metabolism of Flexeril, ultimately prolonging its elimination.  Examples of common CYP3A4 inhibitors include: Chloramphenicol, Ketoconazole, Nefazodone, Ritonavir, Saquinavir, Telithromycin, and Tlarithromycin.  Oppositely, agents known as CYP3A4 inducers are known to enhance function of CYP3A4 enzymes.

If you took a CYP3A4 inducer, the metabolism of Flexeril may be improved, resulting in faster elimination.  Examples of common CYP3A4 inducers include: Butalbital, Carbamazepine, Efavirenz, Modafinil, Nevirapine, Oxcarbazepine, Phenobarbital, Quercetin, Rifabutin, Rifampicin, and St. John’s wort.  Understand that CYP1A2 inducers/inhibitors (and even CYP2D6 inducers/inhibitors) may also impact the pharmacokinetics of Flexeril to a certain extent, thus influencing excretion speed.

Flexeril: Absorption, Metabolism, Excretion (Details)

Following oral administration of Flexeril, its chemical ingredient “cyclobenzaprine” is absorbed slowly by the gastrointestinal (GI) tract with a bioavailability between 33% and 55%.  It is highly bound to plasma proteins and is extensively distributed throughout various bodily tissues including the small intestine, lungs, kidneys, and liver.  When administered consistently three times per day (t.i.d.), Flexeril accumulates to reach steady state concentrations within 72 to 96 hours (3 to 4 days).

Among adults that have attained steady state concentrations from 10 mg Flexeril three times per day, peak plasma levels average 25.9 ng/ml.  After absorption, the drug is metabolized by various isoenzymes within the liver including: CYP3A4, CYP1A2, and to a minor extent, CYP2D6.  CYP3A4 and CYP1A2 chiefly facilitate N-demethylation of cyclobenzaprine.  A majority of the drug is subject to glucuronidation via the kidneys prior to excretion.

Prominent metabolites formed from cyclobenzaprine metabolism include: cyclobenzaprine glucuronide and 10,11-dihydroxynortriptyline.  As a result of its long half-life of 18 hours (on average), it takes over 4 days to completely eliminate the drug from systemic circulation after discontinuation.  A bulk of the drug is excreted as metabolites in the urine, mostly as cyclobenzaprine glucuronides, while a small percentage is excreted via feces.

  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/017821s045lbl.pdf
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/33029
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8818577

Tips to clear Flexeril from your system

Most individuals won’t need to worry about getting Flexeril out of their system as soon as possible.  If there’s any sort of emergency associated with Flexeril treatment, you should contact a medical professional.  Below are some tips that may facilitate the elimination of Flexeril from your body after your final dose, resulting in faster detoxification.  Prior to implementing any of these suggestions, it is recommended to consult a medical professional to verify their safety and hypothesized efficacy.

  1. Discontinuation: Working with a medical professional to discontinue Flexeril is recommended. It may be difficult to stop taking this drug, especially if you’ve used it regularly for longer than the clinically recommended 2 week period. That said, if you want to ensure that the drug fully leaves your system, it is necessary to completely cease treatment; the sooner you stop – the quicker it’ll be out of your body.
  2. Activated charcoal: Since this drug is slowly absorbed, activated charcoal may be administered in the event that a person regrets taking Flexeril and/or needs it out of their system. The charcoal binds to the drug via adsorption and prevents it from circulating throughout your body. Even if you’ve fully metabolized your final dose, charcoal may help clear up any remnants of the drug and/or other endotoxins stemming from medication usage.
  3. Calcium-D-Glucarate: A gem-of-a-supplement to consider taking for detox purposes is that of calcium-d-glucarate. This supplement helps your kidneys by eliminating any toxins that have built up or accumulated in detoxification pathways. It acts as a beta-glucuronidase inhibitor, thereby allowing the kidneys to excrete waste material that may have been accumulating.  Think of this supplement as something that supports kidney function.
  4. Hydration: Maintaining adequate hydration may be helpful for elimination of certain drugs. Since Flexeril is excreted via the kidneys, and hydration may expedite renal excretion, staying hydrated could facilitate optimal or faster-than-average excretion of Flexeril metabolites. Understand that overhydration is never recommended, but adequate hydration may aid renal excretion.
  5. CYP450 inducers: Taking an inducer of CYP3A4 and/or CYP1A2 may promote a faster metabolism of the parent cyclobenzaprine to form metabolites. This faster metabolism may mean that the drug will get excreted at a quicker pace. Various CYP450 inhibitors are thought to prolong elimination half-life, while CYP450 inducers may have the opposite effect.

How long has Flexeril stayed in your system after stopping?

If you’ve stopped taking Flexeril, share a comment regarding how long you believe it stayed in your system after your final dose.  Do you think that the drug may have cleared from your system quicker than usual in under 4.13 days?  Or do you think it took considerably longer than usual to detoxify from Flexeril (e.g. over 8 days)?

Understand that while most research indicates that systemic elimination of Flexeril is likely to take around 4.13 days, other studies suggest that average elimination may take more like 6 to 8 days.  Realize that if you experience any lingering side effects after you’ve been off of Flexeril, these effects do not necessarily mean that the drug is still in your system.  In some cases these effects may stem from lasting neurophysiological changes induced by the drug, some of which may linger for awhile even though the drug is out of your body.

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  • Abby September 23, 2016, 12:44 pm

    My neurologist has had me on Flexeril for 5 years. My Rx ran out and then there has been a problem at the pharmacy causing me to be without for 5 days now. I was taking 10mg once a day (at night). The first day and a half I didn’t notice any adverse effects, and then the symptoms began. I have had nausea, headaches, muscle weakness, shortness of breath and difficulty sleeping. I have also experienced bouts of disorientation on and off, along with slight dizziness. I really want to be off this medication, but it’s been 5 days and I still feel awful.

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