Amlodipine + Chlorthalidone + Telmisartan

Usage

• This combination drug is prescribed for the treatment of hypertension (high blood pressure) when monotherapy or dual therapy is insufficient to control blood pressure. It may also be used to reduce the risk of cardiovascular events like heart attacks and strokes.
• Pharmacological Classification: Antihypertensive (comprising a calcium channel blocker, an angiotensin II receptor blocker, and a thiazide diuretic).
• Mechanism of Action: This combination works synergistically to lower blood pressure through multiple pathways. Amlodipine blocks calcium channels in blood vessels and the heart, leading to vasodilation and reduced cardiac workload. Telmisartan blocks the action of angiotensin II, a hormone that constricts blood vessels. Chlorthalidone is a diuretic that reduces blood volume by increasing the excretion of sodium and water.

Alternate Names

• There is no single international nonproprietary name (INN) for this specific combination. It is referred to by the names of its constituent drugs.
• Brand Names: Several brand names exist for this combination, including Telma ACT, Eritel CH 40 Trio, Tritelsar HS, Tellzy ACH 40/5/12.5, CTD T AM 12.5/40/5, Telma ACT 40/5/12.5, Stamlo Trio 40/12.5, Venpres 40 AMC, and Amlopres 3D 40/12.5. Availability of specific brands may vary by region.

How It Works

• Pharmacodynamics: Amlodipine reduces peripheral vascular resistance and myocardial oxygen demand. Telmisartan blocks angiotensin II receptors, preventing vasoconstriction and aldosterone release. Chlorthalidone inhibits sodium reabsorption in the distal convoluted tubule, promoting diuresis.
• Pharmacokinetics:
  • Absorption: All three components are orally absorbed, although bioavailability varies.
  • Metabolism: Amlodipine is extensively metabolized by the liver (CYP3A4). Telmisartan undergoes minimal metabolism. Chlorthalidone is not extensively metabolized.
  • Elimination: Amlodipine is primarily excreted in the feces, while Telmisartan and Chlorthalidone are primarily excreted in the urine.
• Mode of Action: Amlodipine blocks L-type calcium channels. Telmisartan blocks the AT1 subtype of angiotensin II receptors. Chlorthalidone inhibits the sodium-chloride symporter in the distal convoluted tubule.
• Elimination Pathways: Amlodipine undergoes hepatic metabolism (CYP3A4) and is eliminated mainly through biliary excretion. Telmisartan is excreted largely unchanged in bile and urine. Chlorthalidone is primarily excreted unchanged in the urine.

Dosage

Standard Dosage

Adults:

• Initial dose is typically Telmisartan 40 mg, Amlodipine 5 mg, and Chlorthalidone 12.5 mg once daily.
• The dosage may be titrated upwards to a maximum of Telmisartan 80 mg, Amlodipine 10 mg, and Chlorthalidone 25 mg once daily, as tolerated and based on blood pressure response.

Children:

• Use in children is not recommended as safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Initiate therapy at the lowest dose and monitor closely for hypotension and electrolyte imbalances.
• Patients with Renal Impairment: Caution is advised, and dose adjustment may be necessary. Chlorthalidone may be less effective in patients with severely impaired renal function.
• Patients with Hepatic Dysfunction: Use with caution, especially in severe hepatic impairment, as Amlodipine metabolism may be affected.
• Patients with Comorbid Conditions: Consider individual drug components and their potential interactions in patients with conditions like diabetes, heart failure, gout, and lupus.

Clinical Use Cases

• This specific triple-drug combination is not typically indicated for use in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Individual components, such as Amlodipine for perioperative hypertension, may be used in these contexts, but the combination is meant for chronic management of hypertension.

Dosage Adjustments

• Dosage should be individualized according to patient response and tolerability.
• In renal or hepatic impairment, close monitoring and dosage modifications may be necessary.
• Consider genetic polymorphisms affecting drug metabolism, especially CYP3A4 for Amlodipine, when adjusting dosages.

Side Effects

Common Side Effects:

• Dizziness, headache, fatigue, peripheral edema (swelling of ankles and feet), nausea, flushing, palpitations.

Rare but Serious Side Effects:

• Angioedema (swelling of face, lips, tongue), hypotension, syncope, hepatotoxicity, renal dysfunction, hyperkalemia.

Long-Term Effects:

• Electrolyte imbalances, worsening of heart failure (if pre-existing), renal impairment.

Adverse Drug Reactions (ADR):

• Angioedema, severe hypotension, acute renal failure, hepatitis.

Contraindications

• Hypersensitivity to any component of the drug, pregnancy (especially second and third trimesters), anuria, bilateral renal artery stenosis, hypersensitivity to dihydropyridine derivatives (in case of Amlodipine), primary aldosteronism.

Drug Interactions

• Other antihypertensives (additive hypotensive effect), potassium-sparing diuretics (risk of hyperkalemia), NSAIDs (reduced antihypertensive effect), lithium (increased lithium levels), grapefruit juice (may increase Amlodipine levels), CYP3A4 inhibitors/inducers (may affect Amlodipine metabolism).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D (contraindicated). Use during pregnancy can cause fetal harm.
• Fetal risks include fetotoxicity, growth restriction, and neonatal hypotension.
• It’s unknown whether the drugs are excreted in breast milk. Breastfeeding is not recommended during treatment.

Drug Profile Summary

• Mechanism of Action: Calcium channel blockade, angiotensin II receptor blockade, and diuresis.
• Side Effects: Dizziness, headache, edema, fatigue, nausea.
• Contraindications: Pregnancy, hypersensitivity, anuria, bilateral renal artery stenosis.
• Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; breastfeeding not recommended.
• Dosage: Start with 40/5/12.5 mg once daily, titrate as needed up to 80/10/25 mg.
• Monitoring Parameters: Blood pressure, electrolytes (potassium, sodium, magnesium), renal function, blood glucose.

Popular Combinations

• This particular combination is itself a popular and clinically used combination for hypertension management, especially when dual therapy is not sufficient.

Precautions

• General Precautions: Assess renal and hepatic function, monitor electrolytes, check for drug interactions.
• Specific Populations: Avoid use during pregnancy and breastfeeding. Use with caution in the elderly and patients with renal/hepatic impairment.
• Lifestyle Considerations: Advise patients to limit alcohol intake, avoid high-potassium foods (if on higher doses of Chlorthalidone), and caution about dizziness and potential effects on driving.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Amlodipine + Chlorthalidone + Telmisartan?

A: The starting dose is typically 40/5/12.5 mg (Telmisartan/Amlodipine/Chlorthalidone) once daily. The maximum dose is 80/10/25 mg once daily, as tolerated.

Q2: Can this combination be used in pregnancy?

A: No, it is contraindicated in pregnancy, especially during the second and third trimesters, due to the risk of fetal harm.

Q3: What are the common side effects?

A: Common side effects include dizziness, headache, peripheral edema, fatigue, nausea, and flushing.

Q4: Are there any serious drug interactions I should be aware of?

A: Yes, it can interact with other antihypertensives (causing additive hypotension), potassium-sparing diuretics (increasing the risk of hyperkalemia), NSAIDs (reducing the antihypertensive effect), and lithium (increasing lithium levels).

Q5: Can this combination be used in patients with renal impairment?

A: Use with caution in patients with renal impairment. Dose adjustment and close monitoring may be necessary.

Q6: How should I monitor patients on this medication?

A: Monitor blood pressure, electrolytes (especially potassium, sodium, and magnesium), renal function, and blood glucose levels.

Q7: What should I advise my patients about lifestyle modifications while taking this medication?

A: Advise patients to limit alcohol intake, avoid excessive potassium intake (if on higher doses of chlorthalidone), and be cautious about potential dizziness and its impact on driving.

Q8: Can patients crush or chew the combination pill?

A: No, it should be swallowed whole.

Q9: What if a patient misses a dose?

A: The patient should take the missed dose as soon as they remember, unless it is close to the time for the next dose. They should not double the dose to catch up.

Q10: Is this combination safe for breastfeeding mothers?

A: It is generally not recommended during breastfeeding, as it is unknown if the drugs are excreted in breast milk.