Amlodipine Besilate + Olmesartan Medoxomil
Indications
Indicated for the treatment of hypertension
alone or with other antihypertensive agents, to lower blood pressure.
This combination drug is indicated as initial therapy in patients likely
to need multiple antihypertensive agents to achieve their blood
pressure goals. The decision to use a combination as initial therapy
should be individualized and shaped by considerations such as baseline
blood pressure, the target goal, and the incremental likelihood of
achieving goal with a combination compared to monotherapy. Individual
blood pressure goals may vary based upon the patient’s risk.
Pharmacology
Amlodipine is a dihydropyridine calcium
channel blocker that inhibits the transmembrane influx of calcium ions
into vascular smooth muscle and cardiac muscle. Amlodipine has a greater
effect on vascular smooth muscle cells than on cardiac muscle cells.
Amlodipine is a peripheral arterial vasodilator that acts directly on
vascular smooth muscle to cause a reduction in peripheral vascular
resistance and reduction in blood pressure.
Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the Renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex.
Olmesartan Medoxomil blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that Olmesartan Medoxomil is a reversible, competitive inhibitor of the AT1 receptor. Olmesartan Medoxomil does not inhibit ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin).
Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the Renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex.
Olmesartan Medoxomil blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that Olmesartan Medoxomil is a reversible, competitive inhibitor of the AT1 receptor. Olmesartan Medoxomil does not inhibit ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin).
Dosage & Administration
Substitute individually titrated components
for patients on Amlodipine and Olmesartan Medoxomil. This combination
may also be given with increased amounts of Amlodipine, Olmesartan
Medoxomil, or both, as needed.
Initial therapy: Initiate with 5/20 mg once daily for 1 to 2 weeks and titrate as needed up to a maximum of 10/40 mg once daily. Due to decreased clearance of Amlodipine among elderly patients the recommended starting dose of Amlodipine is 2.5 mg in patients 75 years. The lowest dose of the combination is 5/20 mg; therefore, initial therapy with this combination drug is not recommended in patients >75 years old.
Initial therapy: Initiate with 5/20 mg once daily for 1 to 2 weeks and titrate as needed up to a maximum of 10/40 mg once daily. Due to decreased clearance of Amlodipine among elderly patients the recommended starting dose of Amlodipine is 2.5 mg in patients 75 years. The lowest dose of the combination is 5/20 mg; therefore, initial therapy with this combination drug is not recommended in patients >75 years old.
Interaction
The antihypertensive effect of angiotensin
II receptor antagonists, including Olmesartan Medoxomil may be
attenuated by NSAIDs including selective COX-2 inhibitors. Blood
pressure, renal function and electrolytes should be closely monitored in
patients on combination therapy and other agents that affect the RAS.
Contraindications
Cannot be co-administered with Aliskiren in patients with diabetes.
Side Effects
The most common side effects include
peripheral edema, headache, flushing, and dizziness. It can also cause
Intestinal problems known a sprue-like enteropathy.
Pregnancy & Lactation
Pregnancy Category D. Amlodipine and Olmesartan Medoxomil combination should not be used in 2nd and 3rd
trimester because it can cause fetal death. When pregnancy is detected
this combination should be discontinued as soon as possible. It is not
known whether Olmesartan and Amlodipine are excreted in human milk.
Because of the potential for adverse effects on the nursing infant, a
decision should be made whether to discontinue nursing or discontinue
the drug, taking into account the importance of the drug to the mother.
Precautions & Warnings
Amlodipine and Olmesartan Medoxomil combination should be used with caution because there is a risk for-
- Hypotension in volume- or salt depleted patients.
- Vasodilation in patients with severe aortic stenosis.
- Increased frequency, duration or severity of angina or acute Ml in patients with severe obstructive coronary artery disease.
Use in Special Populations
Pediatric use: The safety and effectiveness have not been established in pediatric patients.
Geriatric use:
No overall differences in safety or effectiveness were observed between
subjects 65 years of age or older and younger subjects.
Renal impairment: There are no studies in patients with renal impairment.
Hepatic impairment: Initial therapy is not recommended in hepatically impaired patients.
Overdose Effects
There is no information on over dosage in humans.
Therapeutic Class
Combined antihypertensive preparations
Storage Conditions
Do not store above 30°C. Keep away from light and out of the reach of children.