amlodipine/hydrochlorothiazide/olmesartan

Amlodipine: Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.
Hydrochlorothiazide: Increases excretion of sodium and water by inhibiting sodium reabsorption in the distal tubule.
Promotes excretion of chloride, potassium, hydrogen, magnesium, phosphate, calcium, and bicarbonate.
May produce arteriolar dilation.
Olmesartan: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II at various receptor sites, including vascular smooth muscle and the adrenal glands.

Therapeutic effects:

Lowering of BP.

Pharmacokinetics ⬆ ⬇

Absorption: Amlodipine: Well absorbed after oral administration (64–90%); Hydrochlorothiazide: Rapidly absorbed after oral administration; Olmesartan: Converted to olmesartan (the active component); 26% bioavailability of olmesartan.

Distribution: Amlodipine: Widely distributed to tissues; Hydrochlorothiazide: Distributed into extracellular space; Olmesartan: Well distributed to tissues.

Protein Binding: Amlodipine: 95–98%; Olmesartan: 99%.

Metabolism/Excretion: Amlodipine: Mostly metabolized by the liver; Hydrochlorothiazide: Excreted mainly unchanged by the kidneys; Olmesartan: No further metabolism following conversion of prodrug to active drug; 35–50% excreted unchanged in urine; remainder eliminated in feces via bile.

Half-Life: Amlodipine: 30–50 hr (↑ in older adults and patients with hepatic impairment); Hydrochlorothiazide: 6–15 hr; Olmesartan: 13 hr.

Time/Action Profile ⬆ ⬇

(antihypertensive effect)

ROUTE	ONSET	PEAK	DURATION
amlodipine PO	unknown	6–9 hr	24 hr
hydrochlorothiazide PO	3–4 days	7–14 days	24 hr
olmesartan PO	within 1 wk	2 wk	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity with other thiazides or sulfonamides may exist);
Anuria;
Concurrent use with aliskiren in patients with diabetes or moderate to severe renal impairment (CCr <60 mL/min);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Aortic stenosis;
History of HF;
Volume- or salt-depleted patients or patients receiving high doses of diuretics (correct deficits before initiating therapy or initiate at lower doses);
Renal impairment or diabetes (↑ risk of hyperkalemia);
Black patients (may not be as effective);
Renal impairment due to primary renal disease or HF (may worsen renal function);
Severe hepatic impairment (↓ dose);
Pedi: Safety and effectiveness not established in children;
Geri: Dose reduction recommended; ↑ risk of hypotension.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, angina, bradycardia, hypotension, palpitations

Derm: flushing, photosensitivity, rash

GI: anorexia, cramping, gingival hyperplasia, hepatitis, nausea, vomiting

Endo: hyperglycemia

F and E: hypokalemia, dehydration, hypercalcemia, hyperkalemia, hypochloremic alkalosis, hypomagnesemia, hyponatremia, hypophosphatemia, hypovolemia

GU: renal impairment

Hemat: blood dyscrasias

Metab: hypercholesterolemia, hyperuricemia

MS: muscle cramps

Neuro: headache, dizziness, fatigue, dizziness, drowsiness, lethargy, weakness

Misc: ANGIOEDEMA

Interactions ⬆ ⬇

Drug-drug:

Additive hypotension may occur when used concurrently with fentanyl, other antihypertensives, nitrates, acute ingestion of alcohol, or quinidine.
Antihypertensive effects may be ↓ by concurrent use of NSAIDs.
Amlodipine may ↑ risk of neurotoxicity with lithium.
Cholestyramine and colestipol may ↓ absorption of hydrochlorothiazide.
Concurrent use of corticosteroids or adrenocorticotropin hormone (ACTH) may ↑ risk of electrolyte depletion associated with hydrochlorothiazide, including hypokalemia.
Hydrochlorothiazide may ↑ levels and risk of toxicity of lithium.
↑risk of hyperkalemia with potassium supplements,potassium-containing salt substitutes, ACE inhibitors, or potassium-sparing diuretics.

Drug-Food:

Grapefruit juice↑ levels and risk of toxicity of amlodipine.

Route/Dosage ⬆ ⬇

PO (Adults ): Initiate at equivalent doses of current single agents; may be ↑ every 2 wk, ↑ one component at a time to a maximum of olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg once daily.

Availability ⬆ ⬇

Tablets: olmesartan 20 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg; olmesartan 40 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg; olmesartan 40 mg/amlodipine 5 mg/hydrochlorothiazide 25 mg; olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 12.5 mg; olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg

Assessment ⬆ ⬇

Assess orthostatic BP and HR periodically during therapy.
Assess for signs/symptoms of angioedema (dyspnea, facial swelling). If symptoms occur, discontinue amlodipine/hydrochlorothiazide/olmesartan.

Lab Test Considerations:

Monitor renal function (BUN, serum creatinine) periodically during therapy. If progressive renal impairment occurs, consider holding or discontinuing therapy.
Monitor serum electrolytes and glucose periodically during therapy. May cause hypokalemia, hyperkalemia, hypomagnesemia, hyperglycemia, metabolic acidosis, dilutional hyponatremia, ↑ urinary calcium, and hyperuricemia.
- May ↑ hepatic enzymes, cholesterol, and triglycerides.

Implementation ⬆ ⬇

Correct volume depletion, if possible, before initiation of therapy.
PO: Administer without regard to food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Emphasize the importance of continuing therapy even if feeling well. Take missed doses as soon as remembered if not almost before next dose; do not double doses. Medication controls but does not cure hypertension. Instruct patient to take medication at the same time each day. Warn patient not to discontinue therapy unless directed by health care provider.
Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care provider. See Food Sources for Specific Nutrients.
Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, stress management). Medication controls but does not cure hypertension.
Instruct patient and family on proper technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care provider.
May cause light-headedness, especially initially or with dose adjustments. Advise patient to hold and notify health care provider if light-headedness occurs. Caution patient to avoid sudden position changes to ↓ orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may ↑ symptoms.
Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products, especially NSAIDs and cough, cold, or allergy medications, without consulting health care provider.
Instruct patient to notify health care provider of medication regimen before treatment or surgery.
Instruct patient to notify health care provider if swelling of face, eyes, lips, or tongue; difficulty swallowing or breathing; dry mouth; thirst; weakness; tiredness; restlessness; confusion; seizures; muscle pain or cramps; dizziness or fainting; low or no urine output; fast heartbeat; nausea or vomiting; or visual changes occur.
Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
Olmesartan may cause fetal harm. Advise women of reproductive potential of risk and to discontinue medication as soon and pregnancy is detected. Advise patient to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. If used during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing for oligohydramnios may be used, based on the week of gestation; may not appear until after fetus has sustained irreversible injury. Monitor infants exposed to olmesartan in utero for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur, use measures to maintain adequate blood pressure and renal perfusion. May require exchange transfusions or dialysis to reversing hypotension and supporting renal function.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇