Benicar® Print E-mail

Classification

Note: Olmesartan medoxomil is known by several different names (see below). Throughout this site, for convenience, it is referred to by the brand name Benicar, the registered name used by its manufacturer Sankyo in the U.S.

Benicar® is a brand name prescription drug marketed by the Japanese pharmaceutical company Daiichi Sankyo. The patent will expire on April 25, 2016. It was approved in 2002 by the FDA to treat high blood pressure. The active ingredient in Benicar is olmesartan medoximil which is an Angiotensin Receptor Blocker (ARB). This class of drugs blocks off the receptors for angiotensin II (a hormone) which exist in inflamed tissues and elsewhere throughout the body. See this article for details about ARBs.

ARBs are commonly used to treat high blood pressure, heart failure, and kidney disease from diabetes because ARBs block the effect of angiotensin II, that can exacerbate these conditions.

Other medications in this class include:

  • Diovan (valsartan)
  • Avapro (irbesartan)
  • Micardis (telmisartan)
  • Cozaar (losartan)
  • Atacand (candesartan)
  • Teveten (eprosartan)

Basic pharmacology studies tell us that they are not the same. Although all bind the receptor for angiotensin II, and block the effect of the hormone but they vary in their fit with the receptor, how long they last in the body, how they are handled by the body and what doses should be taken. Thus, they may have differing effects in the body.

Pharmacology

"...the medoxomil-ester prodrug is rapidly and completely converted to its pharmacologically active form in the gastrointestinal mucosa, portal blood, and liver before it comes into systemic circulation."
Human Carboxymethylenebutenolidase (CMBL) as a Bioactivating Hydrolase of Olmesartan Medoxomil in Liver and Intestine

Benicar is a unique ARB

Benicar plays a key role in the recovery process. Benicar is the only ARB we have noted to effectively result in Herxheimer reactions when taken according to Inflammation Therapy guidelines. We don't recommend using any other ARB for this purpose.

Other applications for Benicar besides hypertension

Studies have found that ARBs have many applications beyond hypertension including anti-inflammatory, arthritis, liver fibrosis, neurological, oxidative stress, preventing organ damage, Raynaud's syndrome, retinopathy, migraines, kidney disease, diabetes, insulin resistance, vascular remodeling, heart failure, C-reactive protein reduction, arrhythmias, myocarditis, atherosclerosis, and antibacterial agent. A list of studies can be found in our Physicians' Reference Library.

ARBs treat inflammatory diseases

A wide variety of illnesses has been successfully treated with Inflammation Therapy.  See Diseases Believed to be Caused by Th1/Th17 Inflammation.

This study from Stanford University concluded, "Modulation of the renin-angiotensin-aldosterone system (RAAS) with inexpensive, safe pharmaceuticals used by millions worldwide is an attractive therapeutic strategy for application to human autoimmune diseases."
Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity.

FDA approval and off-label use of Benicar

Although the Food and Drug Administration (FDA) approved Benicar at the 40mg dosage once a day for hypertension. It studied 80mg/day and found it safe. Benicar has not been submitted for approval at higher doses because the prospective clinical trials that are required for FDA approval need to be funded at the cost of tens of millions of dollars. In the absence of such a current scientific clinical trial, medical journals tend not to be interested in "anecdotal" reports of therapeutic successes. Medical Practitioners, however, are free to prescribe Benicar for 'off-label' uses.

Benicar's actions are extremely complex and the five actions that have been identified as probable have two opposite effects; a temporary increase in inflammatory symptoms and the reduction of some symptoms.

We believe Benicar's primary action is to activate the vitamin D receptor (VDR) so the immune system can manufacture the proteins (antimicrobial peptides or AMPs) it needs to fight intracellular bacterial pathogens. The VDR (in the nucleus of cells) is the key to effective operation of the innate immune system; that part of the immune system which attacks intracellular organisms.
See 'Dysregulated VDR' in our article on Vitamin D.

Computer modeling (uncorroborated) by one independent researcher has shown that Benicar, at higher than anti-hypertensive doses, acts as a VDR agonist - a drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance (e.g., 1,25-dihydroxyvitamin-D). See PMID: 16403216

Theoretically, Benicar (putatively similar to 1,25-D) is also able to compete with, and dislodge, bacterial proteins from the VDR to up-regulate the VDR with these agonist effects:

  • upregulating cyp24A1 and cyp3a4, which both de-activate 1,25D, so excess 1,25D is reduced.
  • repressing transcription of cyp27b1, that hydroxylates 25D to the 1,25D form, so there is no new 1,25D made.

Anecdotally, an activated VDR, and enhanced immune system function, is evidenced by the presence of a waxing and waning increase of inflammatory symptoms (herxing). See Herxheimer reaction.

Activating the VDR appears to occur at relatively low Benicar doses in some patients.

Benicar modulates the immune system

Second, Benicar has a modulatory effect on the immune system by slowing down cytokine production via the inflammatory pathway Nuclear Factor kappa-B which leads to fewer inflammatory symptoms.

"Olmesartan effectively suppressed the 4-hydroxy-2-nonenal protein expression and NF-kappaB..."
Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice.

Third, Benicar can also cause a shift in immune cell subsets to usually reduce inflammation overall.

"Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL)-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ)] and the protein expression of tumor necrosis factor-α..."
Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

Fourth, at higher doses, Benicar may dock into several different cellular receptors besides the VDR to provide a degree of palliation and symptom reduction.

"However, a variety of evidence has revealed that olmesartan could also be involved in other biological activities, such as anti-inflammation, anti-oxidation and anti-apoptosis independently of anti-hypertension."
Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

Fifth, Benicar reduces angiotensin II, that is significantly inflammatory in numerous disease states. 1,25-D has a similar effect by repressing renin genetic expression to down-regulate the RAS.

The effect of angiotensin receptor blockers on C-reactive protein and other circulating inflammatory indices in man

Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. 

Individualizing the dose

Benicar apears to be a somewhat unusual drug in being both immune-stimulating and immune-suppressing at the same time to varying degrees based upon individual biochemistry. There appears to be a delicate balance of VDR activation and NF-kappa-B down-regulation.

Therefore, the dose of Benicar must be individualized based upon patient response.

Treatment balance can shift, so it's important not to get lulled into exploring only one set of dosing options. Chronic Illness Recovery endeavors to determine what works best for each patient because exploring individual variations in medication response is essential for developing accurate advice based upon the experiences of previous patients.

Safety

The FDA has set no toxic level for Benicar. See Benicar Safety.

Side effects

Benicar Side Effects

Benicar has the least effect on blood pressure of all the antihypertensive drugs and only causes a very mild depression in blood pressure. This graph from the Benicar drug insert pamphlet illustrates that Benicar's direct effect on blood pressure is minimal beyond a 40mg dose. At this dose, there were no significant side effects listed beyond dizziness which occurred in 3% (the only side effect that occurred in more than 1% of the study cohort). It should be noted that reported 'side effects' were likely due to Herxheimer reactions.

When Benicar is taken per Inflammation Therapy recommendation, it appears to activate the VDR and the immune system appears to be eliminating intracellular bacteria because inflammatory symptoms worsen. These inflammatory consequences are sometimes labeled "side effects" but we believe these varied symptoms are evidence of systemic intracellular infection.

Benicar and potassium

Benicar may decrease urine potassium excretion and increase serum potassium. Other medications that may also have this effect should be avoided or used with caution (monitor potassium regularly) while taking Benicar. These include ACE inhibitors, other ARBs, NSAIDs, potassium-sparing diuretics such as spironolactone (Aldactone), triamterene (Dyrenium), and also trimethoprim-sulfamethoxazole (Bactrim).

Impact of Benicar on symptoms

Benicar lowers the level of cytokines (proteins that are released by the immune system) and this effect sometimes makes patients feel better initially.

However, some patients find that their immune system immediately recognizes and attacks the intracellular bacteria when they start taking Benicar and they experience an increase in symptoms.

Benicar does not directly cause symptoms; it merely makes Th1/Th17 inflammation evident. The cause of symptom exacerbation is the inflammatory process.

An illness that stays below the surface of clinical detection is referred to as subclinical. A subclinical disease has no recognizable clinical findings. It's distinct from a clinical disease, which has signs and symptoms that can be recognized. Many diseases can be subclinical before surfacing as clinical diseases. Symptoms that are subclinical without treatment will remain, get worse and become evident unless Th1/Th17 inflammation is resolved.

Benicar alone

Inflammation Therapy does not rely on Benicar alone. See Antibiotics-Importance During Inflammation Therapy.

Palliative effect

Palliative effect

At higher doses Benicar may have an anti-inflammatory, palliative effect due to a partial suppression of the immune system Nuclear Factor kappa-B pathway. A higher dose can provide temporary symptomatic relief but is not recommended for the long-term .This is sometimes called the Benicar 'blockade'.

There has been a tendency to believe that Benicar can "fix anything" but often palliative medications are also needed to treat certain conditions and symptoms until inflammation is resolved.

Concern has been expressed about the importance of taking enough Benicar to prevent “organ damage” during Inflammation Therapy. See Benicar Dosing to Prevent Organ Damage.

Metabolism and Excretion

Neither the liver nor kidneys break down Benicar. The drug will eventually go to the liver unchanged, about 50% to the liver and about the same to kidney elimination. The liver portion will be excreted via the bile into to the small intestine where some of it will no doubt be absorbed and recirculated again via the portal system.

According to the FDA Olmesartan Drug Information:
"Following the rapid and complete conversion of olmesartan medoxomil to olmesartan during absorption, there is virtually no further metabolism of olmesartan. Total plasma clearance of olmesartan is 1.3 L/h, with a renal clearance of 0.6 L/h. Approximately 35% to 50% of the absorbed dose is recovered in urine while the remainder is eliminated in feces via the bile.

Renal Function

Patients with impaired kidney function may do better with a smaller dose of Benicar. Studies show that in patients with renal insufficiency, serum concentrations of olmesartan were elevated compared with subjects with normal renal function.

According to the FDA Olmesartan Drug Information:
"In patients with renal insufficiency, serum concentrations of olmesartan were elevated compared to subjects with normal renal function." See Kidney Function.

Long-term use

Long-term use of Benicar (as used on IT) appears to be safe and may provide continued protection from inflammation even after overt symptoms have resolved. The long term effect of higher dose Benicar, in regards to partially blocking the NF kappa-B cytokine pathway which is essential for immune system function, is not known.

Therapeutic probe with Benicar

When a patient with obvious Th1/Th17 inflammatory symptoms doesn't test strongly for Th1/Th17 inflammation via the D-metabolites tests, or doesn't test at all, it's possible to determine if Inflammation Therapy will be an effective treatment by doing a therapeutic probe. This is accomplished by avoiding foods high in vitamin D, avoiding sunlight and beginning Benicar to see how the patient reacts.

Persons without Th1/Th17 inflammation usually note only a mild reduction in blood pressure. Most patients with Th1/Th17 inflammation will experience a reduction in elevated 1,25-D with an accompanying reduction in symptoms or an exacerbation of symptoms due to the Herxheimer reaction. This response would then indicate that continued treatment is warranted. Patients who do not respond to Benicar should add 25mg Minocycline every other day to continue the therapeutic probe See Therapeutic Probe.

The right kind of Benicar

It's important to take the form of Benicar that doesn't contain any other ingredients.

Benicar manufactured by Sankyo Pharmaceuticals is a white tablet with these markings:

  • 40 mg tabs have C-15 on one side and SANKYO on the other side
  • 20 mg tabs have C-14 on one side and SANKYO on the other side

BenicarAnother form of Benicar also contains Hydrochlorothiazide (HCTZ), a diuretic, and should NOT be used. HCTZ is too hard on the kidneys and liver, and these are organs in which patients with chronic illnesses may have undetected problems. These tablets are orange.

Benicar (Votum) tablets from Germany may not have the Sankyo name on them.



Sources of Benicar
(olmesartan medoxomil)

Olmesartan medoxomil) is available in both generic and brand name forms worldwide in more than 50 in countries, including:

  • Australia (Olmetec) Olmetec is on the approved PBS list of medications in Australia.
  • Austria (Olmetec, Mencord)
  • Belgium (Olmetec, Belsar)
  • Canada (Olmetec)
  • Chile (Cardioplus by Cardiopharm)
  • Cyprus (Olartan)
  • Czech Republic (Olmetec, Sarten)
  • Denmark (Olmetec, Benetor)
  • Egypt (Erastapex)
  • EU (Olmetec)
  • Germany (Votum, Olmetec, Olmes)
  • Greece (Olmetec, Olartan)
  • Finland (Olmetec, Benetor)
  • France (Olmetec, Olmes, Alteis)
  • Iceland (Olmetec, Benetor)
  • Ireland (Benetor, Omesar)
  • India (WinBP, Golme,olmesartan, olvance, olmecip, olmezest)
  • Italy (Olmetec, Plaunac, Olpress)
  • Japan (Olmetec)
  • Luxembourg (Olmetec, Belsar)
  • Malta (Omesar)
  • Mexico/Almetec
  • Netherlands (Olmetec)
  • Norway (Olmetec, Benetor)
  • Peru (Iltex)
  • Poland (Olmetec, Revival)
  • Portugal (Olmetec, Olsar)
  • Slovenia (Tensiol)
  • Spain (Olmetec, Openvas, Ixia)
  • USA (Benicar)
  • UK (Olmetec)

Olmesartan is not available in: Cambodia, New Zealand, or South Africa.

Benicar may be purchased from another country if necessary.

Generic Benicar

Generic BenicarGeneric olmesartan medoxomil is available by mail order and is reported to work as well as the brand name Benicar. It's called Olmezest or Olmecip and is made by a pharmaceutical company in India.

Some patients have reported that the Olmecip tablets don't smell like the Sankyo formulation which is an issue for some patients. Olmecip has a different binder formulation from Sankyo's Benicar, has a thinner coating and dissolves more quickly.

Ordering tips

Use care to order the correct tablets with no extra ingredients.

Plan ahead because shipping usually takes 3 weeks or longer.

It’s best not to order too many tablets at once, as there is always the chance that Customs will seize or delay the shipment.

Online mail-order sources

http://www.planetdrugsdirect.com      90/$55.00  $0.61/per tablet  (free shipping)
Call Planet Drugs Direct for a price quote on quanities of 120 and 180 tablets.

http://www.canadageneric.com            84/$143.00   $1.70/per tablet  (plus shipping)

http://www.northwestpharmacy.com   30/$29.99  $1.00/per tablet  (free shipping)

Prices were checked 2/11/14.

You can find reputable online pharmacies and compare costs of medications at Pharmacy Checker.

Australia

In Australia, Olmesartan is an unrestricted benefit on the PBS (i.e., its cost is subsidized by the Australian Government) and its use is not restricted to a particular condition. The price of PBS scripts is capped at around $30, or around $4.95 for concession card holders. Unrestricted benefit means that patients do not have to have hypertension to qualify for the PBS subsidy.

Ask your doctor to call for an Authority script. The Authority Approvals process can provide one months supply of a drug, for the PBS cost of one pack (i.e., an Authority script will provide 120 tabs for the minimum cost). If you are taking 5 x 40mg tabs/day, your doctor can prescribe 150 tabs per month (or more if needed).

Olmesartan medoxomil is also available in capsules in Australia at:
Compoundia: Australian Compounding Pharmacy
16 St Mangos Lane Melbourne Docklands VIC 3008
email: bertfrigoatcompoundia.com
Website
Phone 03 9670 2882
Fax (03) 9670-9615

Germany

Fax or mail a copy of the prescription to:
Pharmacy International Global Wholesale
Dr. Frank Stepke GmbH Adenauerallee 1
20097 Hamburg, GERMANY
or:
Marc Beisswenger Export Manager (English speaking)
Pharmacy International GMBH Adenauerallee 1
20097 Hamburg, Germany
Tel: +49 40 41 45 59 61
Fax: +49 40 280 25 18
Website
e-mail: medicineatpharmacy-international.com

India

According to the Active Pharmaceutical Index from India (available online), olmesartan medoxomil is available there. There is an email address at the bottom of that list.

Canada

Olmesartan was approved for use in Canada on Oct. 28, 2008. It is called Olmetec and the drug identification numbers are 40mg (DIN = 02318679) and 20mg (DIN = 02318660).

Olmetic is now covered by the Ontario Drug Benefit Program and a claim can be made to the Ministry of Health.

This pharmacy is in Quebec but can fill prescriptions for all Canadians. Fax the prescription (indicate timed-release or regular), credit card number and mailing address to:
La Pharmacie Obonsoins
Yetvart Paylan
8897 Boul. Lajeunesse
Montréal, Québec H2M 1R8 CANADA
tel:514-382-5921
fax: 514-382-5415
Website
E-mail: yetvartathyperidrosis.com
This pharmacy can compound olmesartan without the usual lactose filler.

The Glebe Pharmasave Apothecary Pharmacy
778 Bank Street Ottawa
Ontario, Canada K1S 3V6
Tel: (613) 234-8587
Fax: (613) 236-0393
Toll Free 1-800-461-4697
Fax Toll Free 1-877-504-5995
Website
This pharmacy cannot compound olmesartan but will compound antibiotics if the doctor writes 'compound' on the script.

Also:

New Zealand

If more than three months’ supply is ordered @ 40 mg per day, customs will return the package to sender without informing the recipient. There are three options to get around this:

  • Doctors can import the medication for their patients without restrictions
  • Order only 98 tablets per time
  • Get approval from Medsafe as an importer

Financial help to purchase Benicar

Insurance coverage

Many insurers will pay for Benicar 40mg two times a day. If a prescription's coverage is denied through an administrative decision, insurers have an appeals process. Check benefits coverage information to find out the appeals process for the plan to obtain your rightful insurance benefit. During the appeal process, emphasis should be on the fact that the doctor is in charge and s/he has determined this patient should take Benicar at this dosage.

If the lower level of coverage is all the insurer will provide, obtain a second prescription and pay out-of-pocket for the additional tablets needed. See Insurance Coverage for Inflammation Therapy.

Updated February 11, 2014