Usage
- Amlodipine + Telmisartan is prescribed for the treatment of essential hypertension (high blood pressure) in adults. It is used when monotherapy with either amlodipine or telmisartan alone does not adequately control blood pressure, or as initial therapy when it is anticipated that a single agent would be insufficient. It may also be used with other antihypertensive agents.
- Pharmacological classification: This combination drug belongs to two classes: Angiotensin II Receptor Blockers (ARBs) and Calcium Channel Blockers (CCBs).
- Mechanism of Action: Telmisartan, an ARB, blocks the action of angiotensin II, a hormone that narrows blood vessels. This action leads to vasodilation (widening of blood vessels) and a reduction in blood pressure. Amlodipine, a CCB, also promotes vasodilation by inhibiting the influx of calcium ions into vascular smooth muscle cells. The combination of these two mechanisms provides a synergistic antihypertensive effect.
Alternate Names
- This combination is commonly referred to as telmisartan/amlodipine.
- Brand names: Twynsta (though this brand name has been discontinued in some regions), other brand names may be marketed internationally and regionally.
How It Works
- Pharmacodynamics: Telmisartan blocks angiotensin II receptors (AT1 subtype), inhibiting the vasoconstricting and aldosterone-secreting effects of angiotensin II. Amlodipine inhibits calcium influx across cell membranes in vascular smooth muscle and cardiac muscle. This leads to vasodilation and a decrease in peripheral vascular resistance, lowering blood pressure. Neither drug affects heart rate significantly.
- Pharmacokinetics: Both drugs are orally administered and well-absorbed. Telmisartan is primarily eliminated through biliary excretion (feces), while amlodipine is extensively metabolized by the liver and excreted in the urine and feces. Food does not significantly affect the absorption of either drug.
- Mode of Action: At the molecular level, telmisartan competitively binds to the AT1 receptor, preventing angiotensin II from binding and exerting its effects. Amlodipine blocks L-type calcium channels, reducing calcium influx into cells and inhibiting smooth muscle contraction.
- Elimination pathways: Telmisartan is primarily eliminated via biliary/fecal excretion with minimal renal excretion. Amlodipine is extensively metabolized by CYP3A4 and other CYP isoenzymes in the liver before excretion in urine and feces.
Dosage
Standard Dosage
Adults:
- Initial dose: 40 mg telmisartan/5 mg amlodipine once daily.
- May be increased after 2 weeks to a maximum of 80 mg telmisartan/10 mg amlodipine once daily as needed to achieve blood pressure control. Dosage should be individualized based on patient response.
Children:
- The safety and efficacy of this combination have not been established in children under 18 years of age.
Special Cases:
- Elderly Patients (≥65 years): Start with a lower dose of amlodipine and titrate cautiously due to potential age-related decreases in renal and hepatic function. Initiation of therapy with this drug is not recommended in patients 75 years or older.
- Patients with Renal Impairment: No initial dose adjustment is necessary for mild to moderate impairment. Caution is advised in severe renal impairment, as both drugs are minimally dialyzable.
- Patients with Hepatic Dysfunction: Initiate with a lower dose, especially of amlodipine. The combination is contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustment may be required in patients with heart failure, diabetes, or other conditions.
Clinical Use Cases
- This combination is not typically used in the context of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is chronic hypertension management.
Dosage Adjustments
- Dose adjustments should be based on blood pressure response and tolerability.
- Consider lower initial doses and cautious titration in elderly patients, those with renal or hepatic impairment, and patients with certain comorbid conditions.
Side Effects
Common Side Effects
- Peripheral edema (swelling in hands or feet)
- Dizziness
- Flushing
- Headache
- Fatigue
- Nausea, diarrhea, abdominal pain
Rare but Serious Side Effects
- Hypotension (low blood pressure)
- Angioedema (swelling of face, lips, tongue, or throat)
- Hyperkalemia (high potassium levels)
- Rhabdomyolysis (muscle breakdown)
Long-Term Effects
- Long-term use can potentially worsen existing kidney disease, particularly in patients with renal artery stenosis. Periodic monitoring of renal function is essential.
Adverse Drug Reactions (ADR)
- Angioedema requiring emergency treatment
- Severe hypotension
- Hyperkalemia requiring medical intervention
Contraindications
- Hypersensitivity to telmisartan, amlodipine, or dihydropyridine derivatives.
- Second and third trimesters of pregnancy.
- Biliary obstructive disorders.
- Severe hepatic impairment.
- Severe hypotension or shock.
- Obstruction of the left ventricular outflow tract (e.g., severe aortic stenosis).
- Hemodynamically unstable heart failure after acute myocardial infarction.
- Concomitant use of aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2).
Drug Interactions
- Aliskiren: Concomitant use is contraindicated in patients with diabetes mellitus or renal impairment. Increases risk of hypotension, hyperkalemia, and renal dysfunction.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin): May increase amlodipine concentrations.
- CYP3A4 inducers (e.g., rifampin, St. John’s wort): May decrease amlodipine concentrations.
- Other antihypertensive medications: Additive hypotensive effects.
- Potassium-sparing diuretics or potassium supplements: Increased risk of hyperkalemia.
- Lithium: Telmisartan may increase lithium concentrations.
- NSAIDs (nonsteroidal anti-inflammatory drugs): May reduce the antihypertensive effects of telmisartan and increase the risk of renal impairment.
- Grapefruit or grapefruit juice: May increase amlodipine concentrations.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (telmisartan) and C (amlodipine). Contraindicated during the second and third trimesters. Discontinue as soon as pregnancy is detected.
- Fetal risks: Exposure to ARBs during the second and third trimesters of pregnancy can cause fetal and neonatal morbidity and mortality (e.g., hypotension, renal failure, skull hypoplasia, oligohydramnios).
- Breastfeeding: Amlodipine is excreted in breast milk, while excretion of telmisartan is unknown. Use is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker (telmisartan) and calcium channel blocker (amlodipine) combination.
- Side Effects: Peripheral edema, dizziness, flushing, headache, fatigue, nausea, hypotension, angioedema, hyperkalemia, rhabdomyolysis.
- Contraindications: Hypersensitivity, pregnancy (2nd/3rd trimesters), biliary obstruction, severe hepatic impairment, severe hypotension, LVOT obstruction, unstable heart failure post-MI, concomitant aliskiren use in patients with diabetes or renal impairment.
- Drug Interactions: Aliskiren, CYP3A4 inhibitors/inducers, other antihypertensives, potassium-sparing diuretics, lithium, NSAIDs, grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated in 2nd/3rd trimester pregnancy; not recommended during breastfeeding.
- Dosage: Adults: 40/5 mg once daily, up to 80/10 mg; elderly: initiate cautiously; hepatic/renal impairment: dose adjustment may be required.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, BUN, potassium), signs of edema, liver function tests.
Popular Combinations
- Amlodipine + telmisartan is itself a popular combination. It may be used in conjunction with hydrochlorothiazide, a thiazide diuretic, in triple therapy for more resistant hypertension.
Precautions
- General Precautions: Monitor blood pressure, renal function, potassium levels, and signs of angioedema. Correct volume or salt depletion before initiation.
- Specific Populations: As outlined in the dosage section.
- Lifestyle Considerations: Encourage patients to adopt a healthy lifestyle including a low-sodium diet, regular exercise, and moderation of alcohol intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Telmisartan?
A: The usual initial dose is 40 mg telmisartan/5 mg amlodipine once daily in adults. It can be increased to a maximum of 80 mg/10 mg once daily after at least 2 weeks, based on blood pressure response.
Q2: Can this combination be used in patients with diabetes?
A: Yes, but with caution. Monitor blood glucose closely, as telmisartan may mask hypoglycemia. Concomitant use of aliskiren is contraindicated in patients with diabetes.
Q3: What are the most serious side effects to watch out for?
A: Angioedema, severe hypotension, hyperkalemia, and rhabdomyolysis are rare but serious side effects requiring urgent medical attention.
Q4: Are there any specific contraindications to the use of this combination?
A: Yes. Contraindications include hypersensitivity, pregnancy (2nd/3rd trimesters), biliary obstruction, severe hepatic impairment, severe hypotension, left ventricular outflow tract obstruction, unstable heart failure post-MI, and concomitant aliskiren use in those with diabetes or renal impairment.
Q5: Can this medication be used in pregnant or breastfeeding women?
A: It’s contraindicated in the second and third trimesters of pregnancy and should be discontinued as soon as pregnancy is detected. It is not recommended during breastfeeding.
Q6: How does this combination affect potassium levels?
A: Telmisartan can potentially cause hyperkalemia, especially in patients with renal impairment or those using potassium-sparing diuretics. Monitor potassium levels closely.
Q7: What are the key drug interactions to be aware of?
A: Significant interactions occur with aliskiren, CYP3A4 inhibitors/inducers, other antihypertensives, potassium-sparing diuretics, lithium, and NSAIDs.
Q8: Can this drug combination be used as initial therapy for hypertension?
A: Yes, it can be initiated as first-line therapy in patients deemed unlikely to achieve blood pressure control with a single agent.
Q9: What should be monitored in patients taking this drug combination?
A: Closely monitor blood pressure, renal function (serum creatinine, BUN, potassium), signs of angioedema or peripheral edema, and potentially liver function tests, especially in patients with pre-existing liver conditions.
