Usage
- Azilsartan medoxomil + Cilnidipine is prescribed for the treatment of hypertension (high blood pressure).
- Pharmacological Classification: Antihypertensive (combination of an Angiotensin II Receptor Blocker (ARB) and a Calcium Channel Blocker (CCB)).
- Mechanism of Action: This combination therapy works by two distinct mechanisms:
- Azilsartan medoxomil: Blocks the action of angiotensin II, a hormone that causes blood vessels to narrow. This blockade leads to vasodilation (widening of blood vessels), reducing blood pressure.
- Cilnidipine: Inhibits the entry of calcium into the smooth muscle cells of blood vessels and the heart, causing vasodilation and reducing cardiac workload, thus lowering blood pressure.
Alternate Names
- No widely recognized alternate names exist for this specific combination.
- Brand Names: Myotan CN, Zilarbi CN.
How It Works
- Pharmacodynamics: Azilsartan medoxomil, after being metabolized to azilsartan, selectively blocks angiotensin II receptors (AT1 receptors) in vascular smooth muscle and the adrenal gland. Cilnidipine blocks calcium channels in vascular smooth muscle and the heart. The combined effect is a reduction in peripheral vascular resistance and cardiac workload, leading to a decrease in blood pressure.
- Pharmacokinetics:
- Azilsartan medoxomil: It is a prodrug rapidly hydrolyzed to its active metabolite, azilsartan, during absorption from the gastrointestinal tract.
- Cilnidipine: Well absorbed orally. Cilnidipine is highly lipophilic and occupies the binding site avidly.
- Mode of Action:
- Receptor Binding: Azilsartan competitively binds to and blocks AT1 receptors.
- Enzyme Inhibition/Neurotransmitter Modulation: Cilnidipine blocks calcium influx into cells by inhibiting L-type and N-type calcium channels, leading to smooth muscle relaxation.
- Elimination Pathways: Primarily hepatic metabolism for both drugs, followed by renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 40 mg azilsartan medoxomil / 5 mg cilnidipine once daily.
- Maintenance dose: May be increased to 40 mg azilsartan medoxomil / 10 mg cilnidipine after 2-4 weeks if needed.
Children:
- Not recommended for pediatric use. Safety and efficacy have not been established in children.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate cautiously based on response and tolerability.
- Patients with Renal Impairment: Dose adjustment might be needed depending upon severity.
- Patients with Hepatic Dysfunction: Dose reduction is advised in patients with moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Use cautiously in patients with diabetes, congestive heart failure, or renal artery stenosis.
Clinical Use Cases
- Not indicated for specific clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is intended for chronic hypertension management.
Dosage Adjustments
- Dose modifications should be made based on patient-specific factors, including renal function, hepatic function, and other comorbid conditions.
Side Effects
Common Side Effects
- Dizziness, headache, sleepiness, peripheral edema, flushing, nausea, taste changes, stomach upset, diarrhea.
Rare but Serious Side Effects
- Hypotension (low blood pressure), angioedema (swelling of face, lips, tongue), allergic reactions.
Long-Term Effects
- Potential for renal impairment with prolonged use, especially in patients with pre-existing kidney disease.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, acute kidney injury.
Contraindications
- Hypersensitivity to azilsartan medoxomil or cilnidipine.
- Pregnancy (especially second and third trimesters).
- Bilateral renal artery stenosis.
- Anuria (inability to produce urine).
- Concomitant use with aliskiren in patients with diabetes.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effects).
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (may reduce antihypertensive effect and increase risk of kidney impairment).
- Potassium-sparing diuretics (may increase potassium levels).
- Lithium (increased lithium levels).
- Alcohol (may enhance hypotensive effects).
- Grapefruit juice (may increase cilnidipine levels).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated during pregnancy). Can cause fetal harm.
- Breastfeeding: Information regarding use during breastfeeding is limited. Use with caution and consider the potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: ARB (azilsartan medoxomil) and CCB (cilnidipine) combination.
- Side Effects: Dizziness, headache, edema, nausea, fatigue.
- Contraindications: Pregnancy, bilateral renal artery stenosis, hypersensitivity.
- Drug Interactions: Other antihypertensives, NSAIDs, potassium-sparing diuretics.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; caution advised during breastfeeding.
- Dosage: 40/5 mg once daily, titratable to 40/10 mg.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
- Often used as a standalone therapy or in combination with other antihypertensive drugs if blood pressure goals are not achieved.
Precautions
- Monitor renal function, especially in patients with pre-existing renal disease.
- Monitor potassium levels, especially in patients taking potassium-sparing diuretics.
- Avoid alcohol and grapefruit juice.
- Advise caution while driving or operating machinery due to potential dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azilsartan medoxomil + Cilnidipine?
A: The initial recommended dose is 40 mg azilsartan medoxomil/5 mg cilnidipine once daily. This can be increased to 40 mg azilsartan medoxomil/10 mg cilnidipine after 2-4 weeks if needed.
Q2: What are the common side effects?
A: Common side effects include dizziness, headache, sleepiness, peripheral edema (swelling in the ankles or feet), flushing, nausea, and changes in taste.
Q3: Can pregnant women take Azilsartan medoxomil + Cilnidipine?
A: No, this medication is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.
Q4: How does this combination lower blood pressure?
A: Azilsartan blocks the action of angiotensin II, a hormone that narrows blood vessels, while cilnidipine blocks calcium channels in blood vessel walls and the heart, both leading to vasodilation and reduced blood pressure.
Q5: Are there any drug interactions I should be aware of?
A: Yes, potential interactions exist with other antihypertensives, NSAIDs, potassium-sparing diuretics, and lithium. Alcohol and grapefruit juice may also interact with this medication.
Q6: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and return to your regular dosing schedule. Do not double the dose to catch up.
Q7: Is Azilsartan medoxomil + Cilnidipine safe for patients with kidney disease?
A: It should be used with caution in patients with renal impairment, and dose adjustment might be necessary. Close monitoring of renal function is recommended.
Q8: What are the serious side effects to watch out for?
A: Rare but serious side effects include angioedema (swelling of face, lips, tongue, or throat), severe hypotension, and acute kidney injury. Seek immediate medical attention if these occur.
Q9: Can this medication be used in children?
A: No, Azilsartan medoxomil + Cilnidipine is not recommended for use in children as safety and efficacy have not been established in this population.
