Usage
- Medical Conditions: Amlodipine + Ramipril is prescribed for the treatment of hypertension (high blood pressure) in patients whose blood pressure is adequately controlled with amlodipine and ramipril given concurrently, but as separate medications. It is also used to reduce the risk of heart attack, stroke and cardiovascular death in patients over 55 with high risk.
- Pharmacological Classification: Antihypertensive (a combination of a calcium channel blocker and an ACE inhibitor).
- Mechanism of Action: This combination therapy works by two distinct mechanisms: Amlodipine, a calcium channel blocker, relaxes and widens blood vessels by preventing calcium from entering the cells of the heart and blood vessel walls. Ramipril, an ACE inhibitor, blocks the action of the angiotensin-converting enzyme (ACE), which produces angiotensin II, a substance that narrows blood vessels. The combined effect leads to vasodilation, lowering blood pressure and improving blood flow.
Alternate Names
- No widely recognized alternate names for the combination exist.
- Brand Names: Examples of Brand Names: Cardace® am, Ramipril/Amlodipine Adamed, Ramipril/Amlodipine Sandoz. It is important to consult local or regional pharmaceutical resources for specific brand names available in India.
How It Works
- Pharmacodynamics: Amlodipine reduces blood pressure by causing vasodilation. Ramipril inhibits the formation of angiotensin II, a potent vasoconstrictor, and reduces aldosterone secretion. This combined action lowers peripheral resistance, thereby decreasing blood pressure.
- Pharmacokinetics: Both drugs are orally administered. Amlodipine is well absorbed, with peak plasma concentrations reached in 6 to 12 hours. Ramipril is a prodrug converted to its active metabolite, ramiprilat, in the liver. Ramiprilat has a longer half-life, allowing for once-daily dosing.
- Mode of Action: Amlodipine blocks calcium influx into vascular smooth muscle and cardiac muscle, leading to vasodilation. Ramipril, through its active metabolite ramiprilat, inhibits ACE, thereby reducing angiotensin II formation and aldosterone secretion.
- Receptor Binding/Enzyme Inhibition: Amlodipine binds to L-type calcium channels. Ramipril inhibits ACE.
- Elimination Pathways: Amlodipine is primarily metabolized by the liver and excreted in the urine and feces. Ramiprilat is mainly excreted by the kidneys.
Dosage
Standard Dosage
Adults:
- Initial dose: Amlodipine 2.5 mg + Ramipril 2.5 mg once daily.
- Maintenance dose: Titrated up to a maximum of Amlodipine 10 mg + Ramipril 10 mg per day as a single dose or in two divided doses, as directed by the physician, based on blood pressure response and tolerability.
Children:
- Not recommended for use in children under 18 years of age due to lack of sufficient data on safety and efficacy.
Special Cases:
- Elderly Patients: Initial dose reduction and slower titration may be necessary.
- Patients with Renal Impairment: Lower initial dose and careful monitoring are advised, especially for those with creatinine clearance <60 ml/min.
- Patients with Hepatic Dysfunction: Dose adjustments may be required due to altered pharmacokinetics. Start at the lower end of the dosing range.
- Patients with Comorbid Conditions: Careful monitoring is required for patients with diabetes, heart failure, or other cardiovascular diseases.
Clinical Use Cases
- Intubation: No specific dosage adjustments for intubation.
- Surgical Procedures: No specific dosage adjustments for surgical procedures.
- Mechanical Ventilation: No specific dosage adjustments for mechanical ventilation.
- Intensive Care Unit (ICU) Use: Dose adjustments are based on patient specific factors such as hemodynamic stability and renal function.
- Emergency Situations: Not typically indicated for emergency situations requiring immediate blood pressure lowering. other agents are generally preferred.
Dosage Adjustments
- Dose adjustments based on patient response, renal function, hepatic function, and concomitant medications.
Side Effects
Common Side Effects
- Dizziness, headache, fatigue, peripheral edema (swelling of ankles and feet), cough, nausea, flushing.
Rare but Serious Side Effects
- Angioedema (swelling of face, lips, tongue, throat), hypotension, hyperkalemia, acute renal failure, liver dysfunction, neutropenia, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Long-Term Effects
- Potential for chronic complications like renal impairment or worsening of heart failure in susceptible individuals.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, hepatotoxicity.
Contraindications
- Hypersensitivity to ramipril, amlodipine, other ACE inhibitors, or dihydropyridine derivatives.
- History of angioedema related to ACE inhibitor therapy.
- Pregnancy (especially second and third trimesters).
- Breastfeeding.
- Significant bilateral renal artery stenosis.
- Hemodynamically unstable hypotension.
- Aortic stenosis, obstructive hypertrophic cardiomyopathy.
- Concomitant use of sacubitril/valsartan.
- Concomitant use of aliskiren in patients with diabetes or renal impairment (GFR <60 ml/min/1.73 m2).
Drug Interactions
- Synergistic Effects: Other antihypertensive medications (additive hypotensive effect).
- Antagonistic Effects: NSAIDs (may reduce antihypertensive efficacy).
- CYP450 Interactions: Amlodipine is metabolized by CYP3A4; inhibitors and inducers of this enzyme can alter amlodipine concentrations.
- Commonly Prescribed Medications: Diuretics, beta-blockers, other antihypertensives.
- OTC Drugs/Supplements: Potassium supplements, St. John’s wort.
- Food/Lifestyle Factors: Alcohol (additive hypotensive effect), grapefruit juice (increases amlodipine levels), high potassium foods.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated during pregnancy (especially second and third trimesters).
- Fetal Risks: Fetal renal dysfunction, growth retardation, oligohydramnios.
- Breastfeeding: Not recommended due to potential exposure to the infant.
- Alternative Safer Options: Other antihypertensives with established safety profiles for pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Calcium channel blockade (amlodipine) and ACE inhibition (ramipril).
- Side Effects: Dizziness, headache, edema, cough.
- Contraindications: Hypersensitivity, pregnancy, breastfeeding.
- Drug Interactions: Other antihypertensives, NSAIDs, potassium supplements.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Titrated to a maximum of Amlodipine 10mg + Ramipril 10mg per day.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
- Frequently used as a standalone combination therapy. May be combined with a thiazide diuretic if additional blood pressure control is needed.
Precautions
- Monitor renal function, electrolyte levels, and blood pressure regularly.
- Caution in patients with hepatic impairment.
- Avoid alcohol and grapefruit juice.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Ramipril?
A: The initial dose is typically 2.5mg/2.5mg once daily. Maximum dose 10mg/10mg once daily or in divided doses. It depends on individual patient response, age and comorbidities.
Q2: What are the common side effects?
A: Dizziness, headache, peripheral edema, cough, fatigue.
Q3: Can this combination be used in pregnancy?
A: No, it is contraindicated in pregnancy, especially during the second and third trimesters.
Q4: What are the contraindications?
A: Hypersensitivity, history of angioedema related to ACE inhibitors, pregnancy, breastfeeding, bilateral renal artery stenosis.
Q5: What are the potential drug interactions?
A: Other antihypertensives (additive effects), NSAIDs, potassium supplements, grapefruit juice.
Q6: How should the dose be adjusted in elderly patients?
A: Start with a lower dose and titrate slowly, monitoring renal function.
Q7: How should the dose be adjusted in patients with renal impairment?
A: Start with a lower dose and titrate cautiously based on renal function.
Q8: What monitoring parameters are important?
A: Blood pressure, renal function (serum creatinine, eGFR), potassium levels.
Q9: Can this drug combination be used in children?
A: No, it is not recommended for children under 18 years due to a lack of data.
Q10: What should be done in case of a missed dose?
A: Take the missed dose as soon as possible unless it is almost time for the next dose. Don’t double up on doses.
