Amlodipine and olmesartan

Amlodipine is a calcium channel blocker. It works by relaxing the muscles of your heart and blood vessels.

Olmesartan is an angiotensin II receptor antagonist. Olmesartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Amlodipine and olmesartan is a combination medicine used to treat high blood pressure (hypertension). Lowering blood pressure may lower your risk of a stroke or heart attack.

Amlodipine and olmesartan may also be used for purposes not listed in this medication guide.

Amlodipine and olmesartan is a combination of medicines that may be used alone or with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of strokes and heart attacks.

Amlodipine is a calcium channel blocker (CCB). It affects the movement of calcium into the cells of the heart and blood vessels. As a result, amlodipine relaxes the blood vessels and increases the supply of blood and oxygen to the heart while reducing its workload.

Olmesartan is an angiotensin II receptor blocker (ARB). It works by blocking a substance in the body that causes the blood vessels to tighten. As a result, olmesartan relaxes blood vessels. This lowers the blood pressure and increases the supply of blood and oxygen to the heart.

amlodipine and olmesartan is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For amlodipine and olmesartan, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to amlodipine and olmesartan or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amlodipine and olmesartan combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of amlodipine and olmesartan combination in the elderly. However, elderly patients may need a lower dose of amlodipine and olmesartan.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking amlodipine and olmesartan, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amlodipine and olmesartan with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Aliskiren

Using amlodipine and olmesartan with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Atazanavir
• Benazepril
• Captopril
• Ceritinib
• Clarithromycin
• Clopidogrel
• Conivaptan
• Cyclosporine
• Dantrolene
• Digoxin
• Domperidone
• Droperidol
• Eliglustat
• Enalapril
• Enalaprilat
• Fosinopril
• Idelalisib
• Lacosamide
• Lisinopril
• Moexipril
• Netupitant
• Perindopril
• Piperaquine
• Quinapril
• Ramipril
• Simvastatin
• Tacrolimus
• Tegafur
• Telaprevir
• Trandolapril
• Trimethoprim

Using amlodipine and olmesartan with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Colesevelam
• Indinavir

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of amlodipine and olmesartan. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (chest pain) or
• Electrolyte imbalances (eg, low sodium in the body) or
• Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
• Heart attack, acute or
• Heart failure or other heart problems (eg, aortic stenosis, obstructive coronary artery disease) or
• Kidney problems—Use with caution. May make these conditions worse.

• Congestive heart failure, severe—Use may lead to kidney problems.

• Diabetes patients who are also taking aliskiren (Tekturna®) or
• Patients with kidney problems who are taking aliskiren (Tekturna®)—Should not be used in these patients.

• Liver disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

In addition to the use of amlodipine and olmesartan, treatment for your high blood pressure may include weight control and a change in the types of foods you eat, especially foods high in sodium (salt). Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that amlodipine and olmesartan will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

You may take amlodipine and olmesartan with or without food.

If you are also using colesevelam (Welchol®), take it at least 4 hours after taking Azor®.

Dosing

The dose of amlodipine and olmesartan will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of amlodipine and olmesartan. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults—One tablet containing 5 milligrams (mg) of amlodipine and 20 mg of olmesartan once a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 10 mg of amlodipine and 40 mg of olmesartan per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of amlodipine and olmesartan, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• Tell all of your health care providers that you take amlodipine and olmesartan. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• It is rare, but worse chest pain and heart attack can happen after amlodipine and olmesartan is first started or after the dose is raised. The risk may be greater in people who have very bad heart blood vessel disease. Talk with the doctor.
• Talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• If you are taking a salt substitute that has potassium, potassium-sparing diuretics, or potassium, talk with your doctor.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• If you also take colesevelam, take it at least 4 hours after you take this medicine.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking amlodipine and olmesartan with your other drugs.
• Talk with your doctor before you drink alcohol.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
• If you are 65 or older, use this medicine with care. You could have more side effects.

Use amlodipine and olmesartan as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Take this medicine at the same time of day.
• Keep taking amlodipine and olmesartan as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Flushing.
• Dizziness.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Amlodipine Besylate and Olmesartan Medoxomil
• Olmesartan and Amlodipine
• Olmesartan Medoxomil and Amlodipine Besylate

Avoid salt substitutes which contain potassium.

Concerns related to adverse effects:

• Angioedema: Angioedema has been reported rarely with some angiotensin II receptor antagonists (ARBs) and may occur at any time during treatment (especially following first dose). It may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE-inhibitor therapy may be at an increased risk. Prolonged frequent monitoring may be required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. Intramuscular (IM) administration of epinephrine may be necessary. Do not readminister to patients who have had angioedema with ARBs.

• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.

• Gastrointestinal effects: Symptoms of sprue-like enteropathy (ie, severe, chronic diarrhea with significant weight loss) has been reported with olmesartan; may develop months to years after treatment initiation with villous atrophy commonly found on intestinal biopsy. Once other etiologies have been excluded, discontinue treatment and consider other antihypertensive treatment. Clinical and histologic improvement was noted after treatment was discontinued in a case series of 22 patients (Rubio-Tapia 2012).

• Hyperkalemia: May occur with olmesartan use; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.

• Hypotension: Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics); also may occur in patients with severe aortic stenosis; correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with amlodipine/olmesartan.

• Peripheral edema: The most common side effect of amlodipine is peripheral edema; occurs within 2 to 3 weeks of starting therapy.

• Renal function deterioration: Olmesartan may be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.

Disease-related concerns:

• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia; symptomatic hypotension may occur in patients with severe aortic stenosis.

• Hepatic impairment: Use with caution in patients with hepatic impairment; amlodipine and olmesartan exposure is increased. Initial therapy is not recommended; the appropriate combination dosage form is not available.

• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use amlodipine with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACCF/AHA [Gersh 2011]).

• Renal artery stenosis: Use olmesartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Initial therapy is not recommended in patients ≥75 years; the appropriate combination dosage form is not available.

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

• Surgical patients: In patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011).

Initial dose: Amlodipine 5 mg-Olmesartan 20 mg orally once a day; may increase dose after 1 to 2 weeks of therapy.

Maximum dose: Amlodipine 10 mg-Olmesartan 40 mg orally once a day

Uses:
-Substitution therapy for patients maintained on the individual components separately or for patients not adequately controlled with one of the components or a component within the same antihypertensive class.
-Initial therapy in patients who are likely to need more than 1 antihypertensive agent to control blood pressure.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes (amlodipine); Unknown (olmesartan) Excreted into animal milk: Yes (olmesartan)