Olmesafe AM5 mg+20 mg

Olmesafe AM is a fixed-dose combination of a dihydropyridine calcium channel blocker (amlodipine) and an angiotensin II receptor blocker (ARB, olmesartan medoxomil), indicated for:

• Established/FDA-approved use: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily stroke and myocardial infarction.
• Olmesafe AM is generally used in patients whose blood pressure is not adequately controlled on either amlodipine or olmesartan monotherapy alone, or as initial therapy in patients likely to need multiple drugs to reach their blood pressure goal.

Olmesafe AM is not indicated for initial therapy in patients who require blood pressure reduction of more than 20/10 mmHg without prior assessment, as recommended by treating physicians on a case-by-case basis, and is not intended as a first-line drug for hypertensive emergencies.

Each tablet of Amlodipine + Olmesartan Medoxomil contains amlodipine (as amlodipine besylate) and olmesartan medoxomil in fixed-dose combinations, commonly available as 5 mg/20 mg, 5 mg/40 mg, 10 mg/20 mg, and 10 mg/40 mg (amlodipine/olmesartan medoxomil) strengths, along with pharmaceutically acceptable excipients.

Olmesafe AM combines two complementary antihypertensive mechanisms in a single tablet. Amlodipine is a long-acting dihydropyridine calcium channel blocker that relaxes vascular smooth muscle, while olmesartan medoxomil is a prodrug that is hydrolyzed to olmesartan, an angiotensin II receptor (AT1 subtype) blocker. Combining the two provides complementary blood-pressure-lowering effects and is used when a single agent does not adequately control blood pressure.

Olmesafe AM belongs to the therapeutic class of antihypertensive combination agents, specifically a calcium channel blocker (dihydropyridine) combined with an angiotensin II receptor blocker (ARB).

Amlodipine + Olmesartan Medoxomil has a dual mechanism of action:

• Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, causing relaxation of vascular smooth muscle (vasodilation) and a resultant reduction in peripheral vascular resistance and blood pressure.
• Olmesartan medoxomil is rapidly hydrolyzed to olmesartan during absorption, which is a selective AT1 (angiotensin II type 1) receptor antagonist. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II, resulting in decreased peripheral vascular resistance without significant reflex tachycardia.

Together, the two components of Amlodipine + Olmesartan Medoxomil act on different pathways involved in blood pressure regulation, producing an additive antihypertensive effect.

Olmesafe AM should be taken by mouth once daily, at approximately the same time each day, with or without food. Tablets should be swallowed whole with a glass of water and should not be crushed or chewed unless otherwise directed by a physician.

Clinically significant drug interactions with Olmesafe AM include:

• Dual blockade of the renin-angiotensin system (e.g., ACE inhibitors, aliskiren): Combining olmesartan (a component of Olmesafe AM) with other agents that block the renin-angiotensin system increases the risk of hypotension, hyperkalemia, and changes in renal function compared to monotherapy. Coadministration of Olmesafe AM with aliskiren is contraindicated in patients with diabetes.
• NSAIDs (including selective COX-2 inhibitors): May reduce the antihypertensive effect of the olmesartan component and, in elderly, volume-depleted, or renally impaired patients, may increase the risk of acute renal failure when combined with Olmesafe AM. Renal function should be monitored.
• Potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium: May increase the risk of hyperkalemia when used with Olmesafe AM.
• Lithium: Increased serum lithium concentrations and lithium toxicity have been reported when lithium is co-administered with angiotensin II receptor antagonists such as the olmesartan component of Olmesafe AM; monitor lithium levels.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir): May increase plasma concentrations of the amlodipine component of Olmesafe AM, increasing the risk of hypotension and edema.
• Simvastatin: The amlodipine component of Olmesafe AM increases simvastatin exposure; simvastatin dose should be limited to 20 mg daily in patients on Olmesafe AM.
• Cyclosporine or tacrolimus: The amlodipine component of Olmesafe AM may increase blood levels of these agents; monitoring of drug levels is advised.
• Colesevelam: Reduces absorption and systemic exposure of the olmesartan component of Olmesafe AM; Olmesafe AM should be administered at least 4 hours before colesevelam.

The most common adverse effect reported with Olmesafe AM is:

• Edema (peripheral swelling, dose-related, more common in women) — the most frequently reported adverse reaction.
• Headache
• Dizziness
• Flushing
• Fatigue
• Upper respiratory tract infection symptoms

Less common but clinically important adverse effects include:

• Hyperkalemia and changes in renal function — see Precautions and Warnings.
• Sprue-like enteropathy: rare cases of severe, chronic diarrhea with substantial weight loss, sometimes occurring months to years after starting olmesartan-containing products; usually resolves after discontinuation of Olmesafe AM.
• Angioedema (swelling of face, lips, tongue, throat) — rare but potentially serious; discontinue Olmesafe AM immediately if this occurs.
• Elevated liver enzymes and, rarely, rhabdomyolysis, have been reported post-marketing.

Pregnancy: Olmesafe AM is contraindicated in pregnancy. Drugs that act on the renin-angiotensin system, such as the olmesartan component of Olmesafe AM, can cause injury and death to the developing fetus when used in the second and third trimesters, including fetal renal failure, oligohydramnios, hypoplasia of fetal lungs, skeletal deformations, and other abnormalities. When pregnancy is detected, Olmesafe AM should be discontinued as soon as possible, and the patient should consult her physician promptly to switch to an alternative antihypertensive agent considered safer in pregnancy.

Lactation: It is not known whether the components of Olmesafe AM are excreted in human breast milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during treatment with Olmesafe AM; a decision should be made in consultation with a physician to either discontinue nursing or discontinue Olmesafe AM, taking into account the importance of the drug to the mother.

• Fetal toxicity: See Pregnancy and Lactation — Olmesafe AM is contraindicated in pregnancy.
• Hypotension: Symptomatic hypotension may occur, particularly after the first dose or dose increase, in patients who are volume- or salt-depleted (e.g., from diuretic therapy, dietary salt restriction, or vomiting/diarrhea). Correct volume depletion before starting Olmesafe AM, or begin under close medical supervision.
• Myocardial ischemia: Rarely, patients (particularly those with severe obstructive coronary artery disease) may develop increased frequency, duration, or severity of angina, or acute myocardial infarction, on starting calcium channel blocker therapy or at the time of dose increase of Olmesafe AM.
• Renal function changes: As with other drugs that affect the renin-angiotensin system, changes in renal function, including acute renal failure, can occur in susceptible individuals (e.g., those with renal artery stenosis, severe heart failure, or volume depletion) taking Olmesafe AM. Monitor renal function periodically.
• Hyperkalemia: Monitor serum potassium periodically, especially in patients with renal impairment, diabetes, or those taking potassium supplements, potassium-sparing diuretics, or salt substitutes containing potassium, while on Olmesafe AM.
• Sprue-like enteropathy: If severe, chronic diarrhea with substantial weight loss develops during treatment with Olmesafe AM and no other cause is identified, discontinue Olmesafe AM and consider alternative antihypertensive therapy.
• Patients with hepatic impairment: Use Olmesafe AM with caution; amlodipine clearance is reduced, and dose titration should be slow.

Overdosage with Olmesafe AM may be expected to cause excessive peripheral vasodilation with marked hypotension, and possibly reflex tachycardia. Significant hypotension, dizziness, and shock have been reported with amlodipine overdose.

If overdose of Olmesafe AM is suspected, seek immediate medical attention or contact emergency services / a poison control center. Management is supportive: hemodynamic monitoring, cardiac and respiratory support, elevation of the extremities, and careful monitoring of fluid status and cardiac/renal function. Intravenous calcium gluconate may help reverse the effects of calcium channel blockade. Because amlodipine is highly protein bound, dialysis is not expected to be beneficial for the amlodipine component. Do not attempt to manage an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Pregnancy: Contraindicated — see Pregnancy and Lactation.
• Lactation: Not recommended during breastfeeding — see Pregnancy and Lactation.
• Pediatric patients: Safety and efficacy of Olmesafe AM have not been established in children; not recommended for use in this population.
• Geriatric patients (≥75 years): Greater sensitivity to the amlodipine component may be seen; Olmesafe AM as a starting fixed-dose combination is generally not recommended in this age group — dose titration with individual components is preferred.
• Renal impairment: No initial dose adjustment required for moderate to marked impairment, but monitor renal function and potassium closely while on Olmesafe AM.
• Hepatic impairment: Use Olmesafe AM cautiously with slower titration, as amlodipine clearance is reduced.

Olmesafe AM is typically used long-term for chronic management of hypertension. Duration of treatment should be determined by the prescribing physician based on blood pressure control, tolerability, and cardiovascular risk, and is usually continued indefinitely as part of ongoing hypertension management unless discontinued due to adverse effects or a change in therapy.

Calcium channel blocker (dihydropyridine) + Angiotensin II receptor blocker (ARB) — antihypertensive combination

The amlodipine component of Amlodipine + Olmesartan Medoxomil blocks calcium ion influx into vascular smooth muscle, causing vasodilation and reduced peripheral resistance. The olmesartan component blocks the AT1 receptor, preventing angiotensin II from causing vasoconstriction and aldosterone release. The combined effect in Amlodipine + Olmesartan Medoxomil produces greater blood pressure lowering than either agent alone.

D

Safety and effectiveness of Olmesafe AM in pediatric patients have not been established. Olmesafe AM is therefore not recommended for use in children and adolescents.