lamotrigine’s half-life, elimination metabolism, drug-drug & drug-food interactions, how long until lamotrigine clears your system and more



Consumer Reviews & Comments | LamictalPagesIndex | Mechanism/Methods of Action/How it Works
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1.  In a Nutshell

Pharmacokinetics (PK)1 is what your body does to a drug, as well as what a drug does to your body in specific ways that usually don’t have much to do with most of the effects of most crazy meds. Unless you count side effects. Pharmacokinetics is a geek’s paradise. This is hardcore, detailed, technical information about a medication2 that explains things like drug-drug interactions, how long it takes to work, why you get certain side effects, and a lot more. Maybe even why some of the meds work the way they do after all. Explaining the various aspects of PK is so long and involved it requires its own page.

2.  How Long Lamictal (lamotrigine) Hangs Around

The numbers here are known as “plasma clearance,” which is how long it takes until there is no significant amount of a drug in your blood. I.e. you’re clear of it. How that is determined is very simple: the half-life times five.3

Half-life is the average time it takes for you to metabolize4 half of the drug’s active ingredient. If a drug has a half-life of around 24 hours and you take a dose of 100mg, you’ll have roughly the equivalent a 50mg dose after one day, a 25mg dose after two days, and so on.

The more-accurate complete clearance requires a hell of a lot more data, often, but not always including your weight and the dosage you’re taking. There may also be numerous passes required to fully metabolize a drug, and that applies even to medications that don’t have active metabolites! If we have the data, which we usually don’t, we’ll provide the best estimate we have for how long it really takes for a drug to clear your system. The data we need are found below in the bioavailability section and miscellaneous PK data because we rarely see them section. The formulae vary slightly depending on drug’s pharmacokinetics and how much we know about it. Dosage divided by AUC is the next step up in complexity. We can ratchet it up to Cp(t) = ((dosage * ka)/(V/F)*((ka - (CL/V)))*(e-(CL/V)*t - e-(CL/ka)*t), or even more complicated formulae. To make matters worse, practically all the data come from a small sample of professional lab rats healthy volunteers.

The stupid thing is: complete clearance usually winds up being 2–5 days after plasma clearance no matter what5, but can take weeks. Sometimes a drug will clear from your brain and other organs before it clears from your blood. Prozac is one such drug, but with a half-life measured in days, that doesn’t surprise me too much.

2.1  Plasma Half-Life

lamotrigine has a plasma half-life of: 14 to 103 hours.

2.2  Estimated Time lamotrigine is Cleared/Eliminated from your System

lamotrigine has an estimated plasma clearance of: 3 to 21 days.



3.  How lamotrigine is Metabolized, and What the Effects and Results of the Metabolism Are

For most people reading this site, elimination metabolism is what pharmacokinetics is all about. How a drug is metabolized in order to be eliminated / cleared from your body. If and how it is transformed into something else and what that is. How it affects the metabolism of other meds6 (see below). To what extent everything is involved. E.g. by the time your liver and kidneys are through with it, 97% of Paxil (paroxetine HCl) has been converted to inactive stuff that gets flushed down the toilet, whereas 70% of the Topamax (topiramate) you take is unchanged in your urine. See the section on CYP450 and UGT enzymes on the Pharmacokinetics page for more details.

3.1  Elimination Method

Lamotrigine is eliminated via glucuronidation - mainly UGT1A4, with UGT2B7 and UGT1A1 helping out.

3.2  Transformation Method

N/A

3.3  Active Metabolites

None

The pill you take is not necessarily the drug that actually does something. Trileptal, Effexor and Risperdal themselves don’t do squat, but are each transformed into active metabolites that do the real work. Predigested versions of Risperdal and Effexor are now available as Invega and Pristiq. Other meds, like Wellbutrin, do something and are transformed into one or more active metabolites that also do something.

3.4  CYP450 or UGT Enzymes lamotrigine Inhibits/Induces/Suppresses

We try to list CYP/UGT/etc in descending order of extent. The first one that does the most of the work, the last one does the least7. That’s how it is on most PI sheets these days.
Lamotrigine is a weak inducer of UGT1A4, which helps to explain its wacky pharmacokinetics. Eventually you can take enough Lamictal to the point where it will speed up its own clearance.

4.  Drug-Drug, Drug-Supplement, Drug-Food Interactions

Most drug-whatever interactions involve elimination metabolism. With crazy meds the best known example is Lamictal and Depakote or whichever flavor of carbamazepine you’re taking. If you’re taking Depakote you need to take less Lamictal less often. With Tegretol or Equetro you need to take more Lamictal more often. That’s not always the case. Interactions can affect transformation, which is why Paxil + tamoxifen = that breast cancer isn’t going anywhere, because tamoxifen itself doesn’t do shit, your liver turns it into endoxifen (and perhaps others), which does all the dirty work. Interactions can also be potentiations, where one drug enhances the effect of another without slowing its clearance. All patient information leaflets and drug-drug interaction checkers have boilerplate potentiation interactions along the lines of, “two or more antidepressants meds can make you extra drowsy/spacey/ready to go on a tri-state multicide spree.” Alcohol potentiates the sedative effects of TCAs, while alcohol and benzodiazepines potentiate each other8. There can be interactions that are beneficial, and those rarely show up in PI sheets or drug-drug interaction checkers.

4.1  Noted Drug-Whatever Interactions

  • Rooibos (Aspalathus linearis)/ red tea may be a potent inducer of UGTs. As such you should probably avoid Rooibos/red tea/whatever it’s called where you live if you’re taking Lamictal.
  • Like many crazy meds, especially AEDs, you may need to take more Lamictal and/or take it more often if you smoke.
  • I cannot stress often enough the interaction between Lamictal and anything containing ethinyl estradiol, which is practically every form of pharmacological birth control except the Depo-Provera (medroxyprogesterone) injection.
  • Lamictal’s bioavailability may be affected by food. That’s the only study I’ve found showing any affect food has had on Lamictal, but this med is so screwy it wouldn’t surprise me if it can make enough of a difference for some people.
  • Like most AEDs, Lamictal messes with how your body deals with folate. So you’ll probably need to take a folic acid supplement.
  • Your doctor and pharmacist should have at least mentioned Lamictal’s interactions with Tegretol/Equetro (carbamazepine) and the valproates: Depakote, valproic acid, Stavzor, and commie Depakote sodium valproate / valproate sodium. There are even more interactions involved. So, if you have multiple brain cooties or your doctor hasn’t quite pinned down what the hell is wrong with you:
    • Lamictal + carbamazapine could be a bad idea.
    • Lamictal + Trileptal (oxcarbazepine) could be an even worse idea.
    • While Lamictal + Depakote can be a really good idea if either med by itself isn’t working well enough to control your seizures.
    • And Lamictal + Topamax can be a good idea, but only if you take around the same amount of each and you aren’t taking high dosages of either.
  • What’s the deal with the above? It’s in how the meds work, specifically with sodium channels. Too much and you don’t just get stupid, you may as well not be taking an AED. But if the drugs compliment each other, then your brain will be a lot happier.
  • Lamictal is notorious for causing multiday hangovers if you drink the least amount of alcohol.
    • Drinking while taking AEDs isn’t that great an idea, but unless you enjoy waking up with an epic hangover, don’t even drink half a lite beer if you’re taking Lamictal.

4.2  Check for Drug-Drug-Drug Interactions

Drugs.com’s drug-drug and drug-food interaction checker

It’s always a good idea to check for drug-drug interactions yourself. Just because most people in the crazy meds business know about really important interactions (e.g. MAOIs and a lot of stuff, warfarin and everything on the planet) doesn’t mean the person who prescribed your meds told you about them, or the pharmacist has all the meds you take at their fingertips like they’re supposed to. Or they have the time to do their jobs properly when not dealing with complete idiots or playing Angry Farmers on the Faecesbooks.

5.  lamotrigine Bioavailability and Bioequivalence Data

Bioavailability is what PK is really all about. How well a drug is distributed through your body after you take it is important to understand for two critical aspects of pharmacology: these are the numbers a generic manufacturer has to meet for a drug to be considered as bioequivalent; and they help to explain why the raw numbers you see on the SSRI/SNRI equivalence page don’t seem to add up.
If these data aren’t entered, look them up in the pharmacokinetics section of the PI sheet. These data are usually in the US PI sheets - almost always for newer meds, less often in older ones. You’ll also find a wealth of information at Japan’s Pharmaceuticals and Medical Devices Agency site. These data are now appearing in more and more PI sheets / specifications of product characteristics (SPCs) from other countries.

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Doses/dosage affect on PK: Number of Doses9
Plasma elimination half-life (T1/2): 14 to 103 hours.
Estimated plasma clearance (CL/F): 3 to 21 days.
Time to reach steady state & conc. (Css) in ng/ml: 14–28 days
Time of maximum plasma concentration (Tmax): IR: 1.5–2 hours, XR: 6–10 hours
Peak plasma concentration (Cmax) in ng/ml: IR: ~8 XR: ~6–7
Area under the curve (AUC0–24), as ng.hr/ml: 142
Overall bioavailability (F)%: 98
Protein binding%: 55

6.  Comments and Miscellaneous PK Data:

AKA whatever additional help with your homework we can provide.
When it comes to lamotrigine’s half-life, get out a dartboard or some percentile dice, because a random number is going to be just as good as anything. The folks at GSK really tried to pin down a number for immediate-release lamotrigine. It’s too bad they didn’t do much work for the extended-release version. Fortunately someone did, and they did a real pharmacokinetic study, with a lot of people with epilepsy. The results: once you reach a steady state (in two to four weeks), the half-life for the extended-release version is pretty much the same as the immediate-release version.

Either way, it so depends on what other medications you’re taking, if you take it once a day or twice a day, how much you’re taking, how old you are, your gender, and, for some women, where she is in her monthly cycle.
Taking Lamictal (lamotrigine) once a day with no other medications produced a range of half-lives from 14 to 103 hours with an average of 32.8 hours. Taking it twice a day produced a range 12 to 62 hours with an average of 25.4 hours, so lamotrigine’s aggregate half-life is 26 hours and it’s aggregate plasma clearance is 5 to six days.

If you’re taking a valproate medication (Depakene/Stavzor (valproic acid), Depakote (divalproex sodium), Depacon (valproate sodium))/whatever they call sodium valproate where you live) the half-life shoots up to 70 hours.

If you’re taking an enzyme-inducing AED like Dilantin (phenytoin), Tegretol (carbamazepine USP), or good old phenobarbital the half-life is cut to about 13 hours. Estrogen-based birth control pills do the same thing. Trileptal (oxcarbazepine) doesn’t have much of an effect. There are conflicting data regarding high dosages (400mg a day or higher) of Topamax.

Unless otherwise noted, all of the above pharmacokinetic data are for the immediate-release version (there’s so little difference with Lamictal-XR they reproduced the IR data in the XR PI sheet), and based upon people, both healthy volunteers and epileptics, not taking any other meds. The most recent PI sheet has a lot of data for people taking other meds, including the crazy-making (from a pharmacokinetic perspective) cocktail of Lamictal, Tegretol and Depakote. So look there for the PK parameters of Lamictal taken with other meds.

Additional data:

Apparent plasma clearance: 0.044 (L/h/kg)
Apparent volume of distribution: (Vd) 1.08
Cmin: (μg/ml) 4.57
Fluctuation index: 0.545

All sorts of PK info at: GlobalRPh’s PK Tools

One more thing - because you usually piss away 70–100% of the remnants of anything you take10, and almost all crazy meds (and all medications in general, including OTC drugs) affect and/or are affected by your liver, if you have a problem with either or both of your liver and kidneys, most, if not all of this information is going to be very different as far as you’re concerned. We can’t cover everything. The PI sheets usually have as much generic information as possible, but there is still a lot of individual math involved. E.g. the Topamax PI sheet gives lots of hard data about how its rate of clearance changes if you have kidney problems based upon creatine clearance and what sort of dialysis treatment you’re undergoing, written in the language of nephrologists. You could bring the PI sheet to your kidney specialist, point to that section, and the doctor would probably be able to tell you how much you’d need to adjust your dosage by. But in the very next paragraph:

Hepatic Impairment
In hepatically impaired subjects, the clearance of topiramate may be decreased; the mechanism underlying the decrease is not well understood [see Dosage and Administration (2.7)].--Topamax Full US Prescribing Information

And that’s it. So if you have liver and/or kidney problems, you’ll need to talk to your pharmacist, your doctors, and, if possible, try to get your doctors to talk to each other about it.



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7.  References

  1. Poore, Jerod. “Lamictal (lamotrigine): a review of the literature and consumer experience. Highlighting its use, adverse events, and pharmacology from the educated consumers’ perspective.” Crazymeds www.crazymeds.us (2014).
  2. Ma, Margaret K., Michael H. Woo, and Howard L. Mcleod. “Genetic basis of drug metabolism.” American Journal of Health System Pharmacy 59.21 (2002): 2061-2069.
  3. Julien, Robert M. Ph.D, Claire D. Advokat, and Joseph Comaty Primer of Drug Action: A comprehensive guide to the actions, uses, and side effects of psychoactive drugs 12th edition Worth Publishers 2011. ISBN:978–1429233439
  4. McHugh, Josh “Drug Test Cowboys: The Secret World of Pharmaceutical Trial Subjects” Wired Magazine 15.05 (24 April 2007) Revised 10 May 2007
  5. Lamictal (lamotrigine) Full US Prescribing Information
  6. Lynch, Tom, PharmD, and Amy Price, MD “The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects” Am Fam Physician. 2007 Aug 1;76(3):391-396.
  7. Le, Jennifer, PharmD, MAS, BCPS-ID “Pharmacokinetics” Merck Manual for Healthcare Professionals Last revised May 2014
  8. Pharmacorama’s Pharmacokinetics section
  9. Tompson, Debra J., Imran Ali, Ruth Oliver‐Willwong, Sarah Job, Li Zhu, Francesca Lemme, Anne E. Hammer, Alain Vuong, and John A. Messenheimer. “Steady‐state Pharmacokinetics of Lamotrigine when Converting from a Twice‐daily Immediate‐release to a Once‐daily Extended‐release Formulation in Subjects with Epilepsy (The COMPASS Study).” Epilepsia 49.3 (2008): 410-417.
  10. Theis, Jochen GW, Jagdev Sidhu, Joanne Palmer, Sarah Job, Jonathan Bullman, and John Ascher. “Lack of pharmacokinetic interaction between oxcarbazepine and lamotrigine.” Neuropsychopharmacology 30, no. 12 (2005): 2269-2274.
  11. Morris, Raymond G., Andrew B. Black, Anne L. Harris, Andrew B. Batty, and Benedetta C. Sallustio. “Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service.” British journal of clinical pharmacology 46, no. 6 (1998): 547-551.
  12. Almeida, A. M., A. C. Falcao, F. Sales, I. Baldeiras, M. J. Rocha, and M. M. Caramona. “Lamotrigine pharmacokinetic evaluation in epileptic patients submitted to VEEG monitoring.” European journal of clinical pharmacology 62.9 (2006): 737-742.
  13. Louis, Erik K. St. “Truly “rational” polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects.” Current neuropharmacology 7.2 (2009): 96.
  14. Johannessen Landmark, Cecilie, and Philip N. Patsalos. “Drug interactions involving the new second-and third-generation antiepileptic drugs.” Expert review of neurotherapeutics 10.1 (2010): 119-140.
  15. Lasoń, Władysław, Monika Dudra-Jastrzębska, Konrad Rejdak, and Stanisław J. Czuczwar. “Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update.” Pharmacological Reports 63.2 (2011): 271-292.
  16. Landmark, Cecilie Johannessen. “Targets for antiepileptic drugs in the synapse.” Medical science monitor: international medical journal of experimental and clinical research 13.1 (2007): RA1-7.
  17. Stahl, Stephen M. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (Essential Psychopharmacology Series) Third edition Cambridge University Press 2008. ISBN:978–0521673761
  18. Virani, Adil S., K. Bezchlibnyk-Butler, and J. Jeffries Clinical Handbook of Psychotropic Drugs 18th edition Hogrefe & Huber Publishers 2009. ISBN:978–0889373693

Consumer Reviews & Comments | Lamictal Index | Mechanism/Methods of Action/How it Works


1 Pharmacokinetics literally means how a drug moves through your body, (from the Greek pharmakon - medicine, and kinetikos - to set in motion) and that is exactly what it's about. From the time you swallow (or however it's delivered) a med until you piss it out (which is how most of the remnants of most meds finally leave).

2 However, the FDA requires only a single, frequently sub-therapeutic dose taken by healthy volunteers - who are mostly, sometimes entirely white males between the ages of 20 and 50 willing to take recently developed drugs because they need the money - to determine pharmacokinetic data, including bioavailability and bioequivalence factors.

3 Based on Julien's calculations from A Primer of Drug Action, the half-life multiplied by five is the generally accepted estimate of how long it takes a med to be eliminated from the blood stream/plasma of someone with a normal metabolism.

4 Or whatever. Metabolization, usually via the liver is just one part of process of how a drug is eliminated from your body. Not all drugs are metabolized, but as it's the best-known way many crazy meds are broken down to make it a lot easier for you to piss or push them out, I'm sticking with the less-than-accurate terminology that I've been ignorantly using for nine of the last 10 years.

5 For crazy meds. I have no idea what the average complete clearance is for other types of medications. For all I know there are drugs that utterly vanish from your system in under five passes, and others that won't let go of your squishy bits for years after you stop taking them.

6 AKA 90% of drug-drug interactions.

7 The last ones listed may not do anything at all, as the data about such things are often conflicting.

8 Or: Alcohol + TCAs = Die like a 1960s trophy wife. Alcohol + Benzos = Die like a rock star.

9 The PK of some meds is affected by the dosage (how much you take, e.g. Cymbalta), or the number of doses (how often you take it, e.g. Lamictal). If it's blank then we don't know. Otherwise:
* No: Dosage / Number of doses doesn't matter
* Dosage Proportional: How much you take affects the PK at a steady rate.
* Dosage Non-liner: The dosage affects the PK, but how it does is complicated, or makes no sense at all.
* Number of Doses: How often you take the med affects the PK.
* Other: There's an effect that isn't like any of the above.
* Unknown: We know that they don't know if there's an effect or not.

10 There are always exceptions. With Geodon you crap out 66% of the inactive stuff it's converted to for elimination, and with Latuda (lurasidone) you crap 80% of its leftovers. So anyone who calls Geodon or Latuda "a shitty drug" is a lot closer to the truth than they may realize.


If you have any questions not answered here, please see the Crazymeds Lamictal discussion board. We welcome criticisms of the articles, notifications of bad links, site problems, consumer experiences with medications, etc. I’m not always able to write back. Hence I never answer questions about meds via e-mail that are answered by this or other articles. Especially if they have been repeatedly asked on the forum. That’s why we write these damn things. Questions about which meds are best for your condition should also be asked on the forum; because this is a free site, so the price of admission is making things easier for somebody else searching for the same answer. We don’t deal with children on the forum or in private because after doing this for ten years I don’t have the emotional stamina to deal with kids who have brain cooties. How to contact Crazymeds. — Jerod Poore, CME, Publisher Crazymeds (crazymeds.us)


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Lamictal, and all other drug names on this page and used throughout the site, are a trademark of someone else. Lamictal’s PI Sheet will probably have the name of the manufacturer and trademark owner (they’re not always the same company) at or near the very bottom. Or ask Google who the owner is. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of the trademark may have changed without my noticing. It may of changed hands by the time you finished reading this article.




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Almost all of the material on this site is by Jerod Poore and is copyright © 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, 2015, and 2016 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and something along the lines of following disclaimer, I’m usually cool with it.



All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else. Plus we are big pottymouths and talk about S-E-X a lot.
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Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained from the medications’ product information / summary of product characteristic (PI/SPC) sheets and/or medication guides - which is all you get from sites like WebMD, RxList, NAMBLA NAMI, etc., the sources that are referenced throughout the site, our personal experience and the experiences family, friends, and what people have reported on various reputable sites all over teh intergoogles. As such the information presented here is not intended as a substitute for real medical advice from your real doctor, just a compliment to it. You should never, ever, replace what a real doctor tells you with something from a website on the Internet. The farthest you should ever take it is getting a second opinion from another real doctor. Educate yourself - always read the PI/SPC sheet or medication guide/patient information leaflet (PIL) that comes with your medications and never ever throw them away. OK, you can throw away duplicate copies, but keep at least one, as that’s your proof of purchase of having taken a med in case a doctor doubts your medical history. Plus they take up less space than a bottle, although keeping one inside of a pill bottle is even better.
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Very little information about visitors to this site is collected or saved. From time to time I look at search terms used and which pages they bring up in an effort to make the information I present more relevant. And the country of origin, just because I’m geeky like that. That’s about it. Depending on how you feel about Schrodinger, our privacy policy should either assuage or exacerbate your paranoia.
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1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.

3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?* I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion as anonymity on teh Intergoogles. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.

* Yes, I know I’m using open source browsers. I also test the site using the now-defunct IE and Safari browsers. Their popularity - and superiority - killed IE and Safari, so that’s why I rely on the open source browsers. It’s like brand vs. generic meds. Sometimes the generic is better than the brand.

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