Usage
- Azelnidipine is prescribed for the treatment of essential hypertension (high blood pressure), specifically Stage I and Stage II hypertension.
- Pharmacological classification: Dihydropyridine Calcium Channel Blocker (CCB).
- Mechanism of Action: Azelnidipine primarily blocks L-type calcium channels in vascular smooth muscle. This inhibition reduces calcium influx into cells, leading to vasodilation (widening of blood vessels). The resulting decrease in peripheral vascular resistance lowers blood pressure. It also exhibits some blocking activity on T-type calcium channels, impacting the sinoatrial (SA) node and potentially contributing to a negative chronotropic effect (reduced heart rate) and inhibition of aldosterone synthesis.
Alternate Names
- No widely used alternate names exist. It is sometimes referred to by its developmental code name CS-905.
- Brand Names: Azelikem, Calnip, Azel
How It Works
- Pharmacodynamics: Azelnidipine lowers blood pressure by inducing vasodilation through calcium channel blockade. Its selectivity for vascular tissue over cardiac tissue minimizes adverse cardiac effects. It demonstrates a slow onset and prolonged duration of action, leading to a stable antihypertensive effect. It may also exert antioxidative properties.
- Pharmacokinetics:
- Absorption: Azelnidipine is rapidly and dose-dependently absorbed after oral administration. The time to peak plasma concentration (Tmax) is approximately 2.3–3.7 hours. Food may delay the time to peak plasma concentration but doesn’t substantially alter the overall absorption.
- Metabolism: Extensively metabolized in the liver, primarily by CYP3A4 enzyme, with some metabolism also taking place in the small intestine. The dihydropyridine ring is oxidized during metabolism.
- Elimination: Approximately 26% of the drug is excreted in urine and 63% in feces within seven days of administration. The terminal elimination half-life is around 16-32.5 hours, allowing for once-daily dosing.
- Mode of Action: Azelnidipine blocks the entry of calcium ions into vascular smooth muscle and cardiac myocytes by inhibiting L-type calcium channels.
- Receptor Binding/Enzyme Inhibition: Binds to L-type calcium channels, inhibiting calcium ion influx. Primarily metabolized by CYP3A4, making it susceptible to drug interactions with CYP3A4 inhibitors and inducers.
- Elimination Pathways: Primarily hepatic metabolism via CYP3A4, followed by excretion in both urine and feces.
Dosage
Standard Dosage
Adults:
- Initial dose: 8 mg orally once daily, after breakfast.
- Maintenance dose: 8-16 mg orally once daily, adjusted based on the patient’s response.
- Maximum dose: 16 mg/day.
Children:
- Not established. Use is not recommended in children due to the lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Start with a low dose (e.g., 8 mg) and titrate cautiously while monitoring for hypotension.
- Patients with Renal Impairment: Dosage adjustments might be necessary based on kidney function and clinical response. Close monitoring of patients with severe renal impairment is advised, especially in the early stages of treatment and during dosage increases.
- Patients with Hepatic Dysfunction: Initiate with a lower dose and titrate with caution. Close monitoring is recommended for patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Dose adjustments may be needed based on existing cardiovascular disease, diabetes, and co-administered drugs.
Clinical Use Cases
Dosage recommendations for these specific medical settings have not been explicitly established. Clinical judgment and patient-specific factors should guide dosing in such situations. General dosing guidelines apply.
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
Adjustments should be based on patient-specific factors like renal/hepatic dysfunction, other medical conditions, concomitant medication, and individual patient response. Start low, go slow.
Side Effects
Common Side Effects
- Headache
- Dizziness
- Peripheral edema (swelling of ankles and feet)
- Flushing
- Palpitations
- Fatigue
Rare but Serious Side Effects
- Liver dysfunction (jaundice, elevated liver enzymes)
- Pancreatitis (severe abdominal pain, nausea, vomiting)
- Angioedema (swelling of face, lips, tongue, or throat)
- Severe hypotension
- Allergic reactions
- Myocardial Infarction
Long-Term Effects
Long-term complications are not well-documented, but monitoring of cardiovascular and metabolic parameters is advisable.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include angioedema, severe hypotension, hepatic dysfunction, and pancreatitis. Immediate intervention is required if these occur.
Contraindications
- Hypersensitivity to azelnidipine or dihydropyridine derivatives
- Pregnancy
- Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)
- Severe hypotension
- Cardiogenic shock
- Unstable angina
- Left Ventricular outflow tract obstruction
- Heart Failure after acute Myocardial Infarction
Drug Interactions
- CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors can significantly increase azelnidipine plasma levels, increasing the risk of side effects.
- CYP3A4 Inducers: CYP3A4 inducers (e.g., rifampicin, phenytoin, St. John’s Wort) can decrease azelnidipine plasma concentrations, potentially reducing its effectiveness.
- Other Antihypertensives: Combining with other antihypertensives may enhance blood pressure lowering, requiring dosage adjustments.
- Grapefruit juice: Avoid concurrent consumption as it inhibits CYP3A4 and may increase azelnidipine levels.
- Other medications: Itraconazole, miconazole, HIV protease inhibitors (ritonavir, saquinavir, indinavir), phenytoin, phenobarbital, simvastatin, digoxin, rifampicin.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy. Animal studies have shown adverse effects on fetal development.
- Breastfeeding: Not recommended. Azelnidipine is excreted in rat milk. Data in humans is limited.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker, primarily blocking L-type calcium channels in vascular smooth muscle, leading to vasodilation and lowered blood pressure.
- Side Effects: Headache, dizziness, peripheral edema, flushing, palpitations, fatigue. Serious but rare: liver dysfunction, pancreatitis, angioedema, severe hypotension.
- Contraindications: Hypersensitivity, pregnancy, strong CYP3A4 inhibitors, severe hypotension.
- Drug Interactions: CYP3A4 inhibitors and inducers, other antihypertensives, grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended while breastfeeding.
- Dosage: 8-16 mg orally once daily, adjusted based on patient response and specific conditions.
- Monitoring Parameters: Blood pressure, heart rate, signs of peripheral edema, liver function tests (especially with prolonged use).
Popular Combinations
- Azelnidipine + Telmisartan: Combines a calcium channel blocker with an angiotensin receptor blocker for synergistic blood pressure control.
- Azelnidipine + Olmesartan medoxomil: Combines a calcium channel blocker with an angiotensin receptor blocker for synergistic blood pressure control.
Precautions
- General Precautions: Assess for allergies, hepatic and renal function, and concomitant medications before starting treatment. Monitor blood pressure regularly.
- Specific Populations: Avoid use during pregnancy. Caution advised for breastfeeding women, elderly patients, and those with hepatic or renal impairment.
- Lifestyle Considerations: Encourage lifestyle modifications, such as diet, exercise, and weight management, alongside medication for better blood pressure control. Limit alcohol intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azelnidipine?
A: The standard adult dosage is 8-16 mg once daily, taken orally. Dosage adjustments may be needed for elderly patients and those with hepatic or renal impairment. It is not recommended for children.
Q2: How does Azelnidipine compare to other calcium channel blockers?
A: Azelnidipine shows greater selectivity for vascular tissue compared to cardiac tissue, potentially minimizing adverse cardiac effects. Also, Azelnidipine is highly lipophilic suggesting strong tissue penetration and long duration of action, supporting its once-daily dosing.
Q3: What are the most common side effects of Azelnidipine?
A: Headache, dizziness, peripheral edema, flushing, and palpitations are common side effects.
Q4: Can Azelnidipine be used during pregnancy?
A: No, azelnidipine is contraindicated during pregnancy due to potential adverse effects on fetal development.
Q5: Are there any specific drug interactions I should be aware of with Azelnidipine?
A: Yes, azelnidipine interacts with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) and inducers (e.g., rifampicin, phenytoin), potentially affecting its plasma concentration and effectiveness. Avoid grapefruit juice as it can interact with Azelnidipine.
Q6: How should I manage a missed dose of Azelnidipine?
A: Take the missed dose as soon as remembered, unless it’s close to the time for the next dose. Do not double the dose.
Q7: What monitoring parameters are important while a patient is on Azelnidipine?
A: Regular monitoring of blood pressure and heart rate is essential. Monitor for signs of peripheral edema and periodically assess liver function, especially during long-term therapy.
Q8: Can Azelnidipine be combined with other antihypertensive medications?
A: Yes, azelnidipine can be combined with other antihypertensive drugs for synergistic blood pressure control. However, careful dosage adjustments might be required to avoid excessive blood pressure lowering. Monitor patient for potential additive hypotension. Popular combinations include Telmisartan or Olmesartan Medoxomil.
Q9: Are there any specific dietary restrictions with Azelnidipine?
A: Avoid grapefruit and grapefruit juice as they can increase azelnidipine levels in the body, leading to increased risk of side effects.
