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Meg Mangin R.N.
Former Team Member
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Posted: Sat Oct 30th, 2004 02:20 |
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Benicar dosage and schedules
Initiating the Benicar blockade
Do not take a low dose of Benicar. See Why shouldn’t we ramp up the dose of Benicar?
A total of 120-160mg of Benicar in a 24hour period divided up and taken at regular intervals is needed to provide an adequate inflammatory blockade.
Hormonal adjustment symptoms may be experienced when the Benicar blockade is initiated but these are usually short-lived and tolerable.
It is usually best to have enough Benicar for Q6 hour dosing or more if required for light exposure or Immunopathology. Q8 hour dosing leaves no room for error.
Factors that affect dosage
The amount of Benicar needed to provide a satisfactory inflammatory blockade may vary slightly depending on the bacterial load, the rate at which 1,25-D is manufactured in the macrophages, the rate of Benicar metabolism by the liver or location of the inflammation.
Body weight
Benicar dosage is dependant on bacterial load, not body weight. Anyone who is ill enough to require treatment with the MP has a high bacterial load. We have seen no data confirming any direct relationship with body weight.
Other meds and Benicar
It's fine for you to take Benicar with your other meds. Most prescription meds can be taken together. Usually if a medication has restrictions, the pharmacist will tell you. Taking them together simplifies the process and increases compliance.
Food and Benicar
One thing to watch with Benicar absorption is that if taken on its own (without food) a tablet should achieve maximum concentration in 90 minutes. This increases to 4 hours if the tablet is taken with a (large) meal. The graphs showing this are in Sankyo's FDA NDA submission package.
FDA papers submitted by Sankyo in their NDA, shows that it can take 3-4 hours for Benicar to enter the bloodstream." These papers are voluminous, and are at URL
http://www.fda.gov/cder/foi/nda/2002/21-286_Benicar.htm
The graph which shows the delayed absorption is Figure 1 of the Pharmacology review at URL
http://www.fda.gov/cder/foi/nda/2002/21-286_Benicar_biopharmr_P1.pdf
They just said it was a "standard meal." Remember that all this review is contemplating once-daily dosing, so, to them, the 3-4 hours you can see for the curves to reach peak, is no big deal. When you are taking Benicar Q3h, it is a big deal indeed. Better to eat light
..Trevor..
Dosing options
40mg every six hours is ideal. It's best to start with Benicar 40mg every six hours. This usually provides a good but not too tight inflammatory blockade which is effective for most circumstances.
People taking Benicar 40mg every 6 hrs report they feel better and experience more immunopathology. Six hour dosing dampens some symptoms and helps the immune system function better. Therefore, it does two things- makes the good days/times better and the immunopathology days/times stronger.
40mg every eight hours is acceptable.
A smaller dose more frequently such as 20mg every 2 or 3 or 4 hours may keep symptoms more tolerable.
Some very symptomatic people find they feel best taking 20mg of Benicar every three hours during the day and then 40mg at bedtime with the next dose six hours later. A typical schedule would be 20mg at 6am, 9am, noon, 3pm, 6pm, 9pm and then 40mg at midnight. That would be equivalent to 40mg every six hours or 160mg in a 24 hour period.
Aussie Barb ~ I set my alarm for 6H each time I take the 40mg Benicar. and if I do need to take it before, so be it... I reset it.. if not, it is right for the 6H.
Have a dosette and reliable alarm system.
Always carry spare meds (and water) with you.
What times should I take Benicar?
Taking your Benicar at regular intervals is very important to maintain an effective inflammatory blockade. You may take your very first dose at any time that is convenient for you.
Benicar has a half-life of eight hours. Dr. Marshall has written: "8 hours is right at the extreme end of the effective period. Actually, you will note that our paper says 6-8 hours. ....the wonderful effects of the ARB dissipates after about 6 hours. There is a benefit to taking the dose every 4 hours if there has been a lapse in food intake or sun exposure."
We recommend that you take 40mg of Benicar every six hours because that is the best dosing interval for an effective blockade. It also allows you some flexibility to stretch the dosing to eight hours at night without losing the blockade. Some people feel better when they break their 40mg tablets in half and take it even more often but this isn't necessary unless you are having difficulty with intolerable symptoms.
Here's what works for me. I aim for doses at 6am, noon, 6pm and midnight. But often I take the midnight dose a little earlier at 11pm and the 6am dose a little later at 7am. This allows me a longer sleep interval if I need it and doesn't pass the eight hour interval.
You should set an alarm if you need to. If you have a cell phone, the alarm feature comes in handy for this. If you are prepared ahead of time, with your alarm, your pills and some water all in place, you may find it easier to be on time.
Ensure an adequate supply of Benicar
Have a good supply of Benicar on hand in case you need to take it more often or have trouble sourcing the next prescription. See How much is an adequate emergency supply of Benicar and Mino to keep on hand?
To maintain the blockade
The half-life of 1,25-D in the body is about 4-6 hours. However, new Angiotensin receptors are manufactured in the inflamed tissue in about 6 hours after the blockade is released and they stay active for 3-5 days. Therefore, it is important to maintain an adequate Benicar blockade by setting a timer and taking the dose at precise intervals.
The palliative effect of the blockade may be lost quickly if a dose is delayed beyond eight hours. Dosing every six hours allows some leeway for error if a dose is forgotten for a couple hours. Never go anywhere without a small container of Benicar in case you are unavoidably detained.
What if I forget a dose?
The Benicar blockade is lost if it's been longer than eight hours since your last dose.
If you have forgotten a dose, take 40mg immediately sublingually. See How to make Benicar act faster.
Then take 40mg every four hours for a few doses and work your way back into an effective schedule that works for you, keeping in mind the minimum dosing interval of eight hours.
Staying on schedule with Benicar is important but if you fail, don't panic. The inflammatory blockade will be reestablished in a day or two.
"There is one situation where a higher dose pulse of benicar (40m)may be more effective than a steady dose. When the blockade has been lost, and other molecules have bound into the receptor socket, a higher concentration of the ARB will displace those molecules from the receptor binding sockets, whereas a lower dose background level may not.
This is a theoretical analysis. Just how one applies this to practice is difficult to judge, but, since figuring out exactly how the ARB works, I am being less dogmatic about saying that 20mg every 4 hours is the same as 40mg every 8 hours. It might not be. It all depends on the state of the receptors, and whether blockade has been (temporarily) lost (eg by exposure to sun or forgetting a tablet)."
..Trevor..
If brain fog is a problem
If you aren't sure if you took your Benicar dose, you can wait to see if you feel worse as the blockade dissipates and then take your dose.
Or you can take a half dose sublingually as an 'insurance policy' and then resume your usual schedule. It will not hurt to take extra Benicar. Putting your Benicar in a mediplanner or pillminder is a handy way of telling if you took a scheduled dose or not.
We recommend extra caution and special attention to detail if you have any level of brain fog or memory impairment. It's important to use a medication dosette and reliable alarm system. If necessary ask for support from a reliable family member when dividing, setting out and or taking meds.
We recommend to use digital timers/ watches/ pillboxes; pill reminder alarms
Modifying the six hour schedule to sleep longer at night
Many people who take Benicar "every six hours" actually do it on a modified schedule because they want to sleep more than six hours at night. A typical modification would be to take it at noon, 6pm, 11pm and 7am. As long as no one interval exceeds eight hours, the inflammatory blockade will not be lost.
When to tighten the blockade
The recommended first step when symptoms are intolerable is to take an extra 40mg Benicar immediately. Chewing the tablet and placing it under the tongue will promote faster absorptiona and quicker symptom relief. See How to make Benicar act faster
If intolerable symptom/s persist, increase oral Benicar to every three-fours hours around the clock. This schedule may be continued until symptoms are tolerable. See Benicar is safe to take at MP recommended doses
If you anticipate an increase in symptoms, you may increase dosing frequency.
Dr Marshall says, "I used to make sure that I was never more than 4 hours from my last Benicar whenever I had to go outdoors. Then, after the exposure, I needed to keep the 4 hour going for 12 hours after the final exposure. Beyond that I could slip back to normal dosing, as the 1,25-D had dissipated (6 hour half-life)."
Increasing Benicar keeps 1,25-D down to minimize symptoms caused by exposure to natural light or bright lights. See What precautions do I need to take when I am going out or when traveling away?
If you are in a 'crisis' situation
During a 'crisis' situation, an extra 20mg of Benicar may be taken sublingually with each every three-four hour oral Benicar dose.
Stopping Benicar
As recovery progresses and the innate immune system becomes more active, 1,25-D will recommence its role as VDR agonist. At some point the immunosuppressive action of Benicar (and it's ability to reduce symptoms) becomes dominant over its role in activation of the VDR (which is so critically important at the start of treatment).
If stopping the Benicar means less activation of VDR, symptoms could be lessened; if stopping the Benicar means less immunosurpression, symptoms could increase. See Do I have to wean off Benicar?
What if I took too much Benicar?
High-dose exposure to valsartan with suicidal intention (This report demonstrates the effect/side effect profile of valsartan (ARB similar to olmesartan) when taken at a high dose, not achievable in a clinical trial.)
One member's experience with an inadvertant higher dose:
Just thought you would like to hear of my latest escapade. One morning last week at 6 a.m. dumped the whole days worth of Benicar into my mouth and they were down before I could stop them. Had forgotten I hadn't just put the one 6 a.m. dose in the container. Anyway apart from feeling a little whoozy around 2-3 hrs later no adverse effects. Just letting you know so you can reassure someone who might do the same stupid thing. Carrying boldly on, despite the lack of intelligence at times  ~Linda
Absorption rate, concentration and potency
Drug clearance tests (clearance pathways) do not determine medication concentration. The key issue is absorption.
Some have found that Benicar does seem to be absorbed more quickly by breaking the tablet in two to disrupt the microcoating and/or take it with a hot drink (eg weak tea).
Crushing Benicar and placing it in a capsule might increase the speed and efficiency of intestinal absorption, particularly in folks who have gastrointestinal malabsorption problems. For those folks, crushing might result in a higher tissue concentration and a more consistent Benicar blockade.
Crushing would not increase the potency of Benicar because it would still be subject to the same gastric and intestinal enzymes and it would still be metabolized by the liver. Crushed Benicar would also present the same stimulus as a noncrushed tablet to the intestinal tract of someone with food allergies. The assumption that crushing Benicar changes its properties to cause it to be more effective is speculation, something we discourage. We don't believe there is any pharmaceutical evidence that routine crushing of Benicar is necessary.
Sublingual Benicar can provide rapid absorption and quick relief when an intolerable immune system reaction strikes. See How to make Benicar act faster. Do not take Benicar sublingually on a routine basis. Since it doesn't pass through the liver, the metabolic action will not be the same.
Timed release Benicar (available in Canada only)
Timed release (TR) Benicar has been trialed and reported to be effective by many Canadian members. If everything is stable and there are no GI absorption problems, the time release formulations, like that from Canada, will do a good job for 12+ hours, but you may require bolus peaks if you are having trouble maintaining the blockade.
Pulsed Benicar dosing will be superior to timed-released Benicar for most folks.
The advantage of TR Benicar is that you can take the capsules less frequently, which may be convenient, especially when you want to sleep for longer periods. the minimum dose per day is 120mg per day. (ie equal to 40mg every 8 hours)
I don't think it will be a problem but I am a little concerned about whether the absorption profile of folks with sick GI tracts is the same as healthy folks. That could make this slow-release formula Benicar dissolve at a different rate than regular Benicar, over (say) 10 or 16 hours rather than the designed 12 hours. I can't guarantee TR Benicar will work exactly the same as regular Benicar.
Pharmacodynamics
I used to think that a steady baseline concentration of Benicar (olmesartan) would be the best way to provide an effective inflammatory blockade. But while I was computing the molecular genomics, it occurred to me that the pulses of concentration which result from taking discrete, rather than time-release tablets, also have a function. It is the pulses that will dislodge any other ligands docked into the receptors, and put the Benicar in place to do its job.
The pharmacodynamic half life of Benicar is not the same as the pharmacokinetic half-life because there is a disassociation constant involved. That means Benicar loses its affinity for the A-II receptor more quickly than it decays from the bloodstream. So the effective useful lifetime is 6-8 hours rather than the approx. 13 hours of the plasma half-life.
The affinity for the VDR of Benicar is low. That's why we need to use a higher concentration. Although Benicar closes off the Angiotensin II Receptor (AT2R) at below 20mg/day, we need a much higher dose to properly activate the VDR. Thus the displacement of ligands from the VDR is easier to control by dosage than its blockade of the AT2R.
Additionally, if you take Benicar with a big meal, the data presented to the FDA by Sankyo show it can take 3-4 hours for Benicar to enter the bloodstream.
The total effect is not 24 hours. That is a marketing fallacy. Sankyo's own studies show a dis-assocation constant in the 4 hour region, and we find that the drug has to be dosed every 4-8 hours for a proper blockade.
Therefore, you need both timed release and some standard tablets. You will want a few standard tablets to use as a 20-40mg bolus. Use them when you feel a drop in their effect occasionally and need a bit more blockade to tide you over to the next 40-80mg TR dose.
The affinity for the VDR of Benicar is low. That's why we need to use a higher concentration.
Although Benicar closes off the Angiotensin II Receptor (AT2R) at below 20mg/day, we need a much higher dose to properly activate the VDR. Thus the displacement of ligands from the VDR is easier to control by dosage than its blockade of the AT2R.
A really high affinity VDR ligand, like the ANTAGONIST Telmisartan (which you don't want to take under any circumstances) only requires a fraction of a tablet to block the action of multiple Benicar tablets for 24 hours or so...
The FDA has a mantra "It's all a matter of Dose." The agonist effect of Olmesartan occurs at higher doses, and the degree of effect can be adjusted by adjusting the dose.
Whereas with a drug which is too high an affinity, like Telmisartan as an antagonist, you cannot adjust the dose to modulate the degree of the effect.
So Olmesartan is able to displace 1,25-D, or capnine, from the VDR LBP in a controlled manner, dependent on Olmesartan dose (and the concentration of capnine or 1,25-D).
This is called "homologous displacement" in most pharmacology texts. It follows a characteristic S-shaped curve.
..Trevor..
See also:
How does Benicar work?
Where to purchase Benicar for self pay members
Benicar-Basic Information
Last edited on Fri Aug 22nd, 2008 04:56 by Meg Mangin R.N.
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Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Aussie Barb
Research Team
| Joined: | Thu Jul 22nd, 2004 |
| Location: | Australia |
| Posts: | 19523 |
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Posted: Fri Jul 21st, 2006 15:11 |
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How to make Benicar act faster
When you have forgotten to take Benicar or if you have serious or intolerable symptom/s you may chew the tablet and place it under your tongue for faster absorption and quicker relief of symptoms. This is especially important if GI inflammation delays absorption of oral Benicar.
Sublingual is extremely helpful, as the time taken to absorb Benicar from the GI tract varies from 90 minutes on an empty stomach to 300 minutes (or so) on a full stomach.
Make sure your mouth is moist before you put the tablet in your mouth, chew it a bit to break up the microcoating and place it anywhere under your tongue. Sucking on a small square of chocolate (or hard candy) can diminish the taste of Benicar and promote absorption by stimulating the salivary glands.
Since Benicar was not manufactored for SL use, it may take longer to dissolve. You may keep it under your tongue for a long time or you may swallow any remaining Benicar after 10-15 minutes.
You may take a dose of 20mg sublingual Benicar each time you take your oral dose of Benicar, even if you are taking it every three or four hours.
Do not take an extended release form of Benicar in this way. Benicar tablets are not extended release.
Do not take all your Benicar sublingually....since it doesn't pass through the liver, the metabolic action will not be the same.
The sublingual (SL) route of medication administration uses the thin epithelium and rich network of capillaries on the underside of the tongue to gain rapid absorption and drug action. Drugs absorbed from the sublingual route have a rapid effect since they enter the bloodstream directly without being metabolized by the liver or being affected by gastric and intestinal enzymes. A good example of this is nitroglycerin.
Medications meant to be taken sublingually are usually specially prepared to make that administration method pleasant, convenient and effective. Benicar has a microcoating which inhibits sublingual absorption unless the tablet is crushed. Many folks find the taste of crushed Benicar unpleasant but it is safe to crush the tablet and place it under the tongue for a 'bolus' of medication.
The FDA has not approved sublingual use of Benicar and we do not know what effect its routine use would have on local soft tissues and tooth enamel.
Many meds can be placed under the tongue and taken sub-lingually (SL). It does not need to be formulated for this purpose. The limiting factor is usually the bad taste.
For people who get an upset stomach with pills, this seems to happen at times even if given SL because the drug can still affect the digestive tract via the blood stream independently of any direct contact with the stomach as in swallowing a pill.
-I have occasionally taken my Benicar by chewing it and leaving it under my tongue if I am late with the dose. I am not unhappy with its peculiar taste; but some might not like it enough to tolerate." ~P.Bear, RN
See also How does Benicar work?
Last edited on Mon Mar 3rd, 2008 17:04 by
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Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| Depression| 24+ years not Dx| MP Aug04| ABC of MP| MP Search|
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