Cilma

• Essential Hypertension:
  Cilnidipine is indicated for the management of high blood pressure to reduce the risk of cardiovascular events such as stroke and myocardial infarction.
• Hypertension with Comorbid Conditions:
  Often used in patients with hypertensive renal disease or diabetic nephropathy to provide blood pressure control and renal protective effects.
• Off-label Uses:
• Management of stable angina pectoris in certain populations
• Prevention of hypertensive organ damage such as left ventricular hypertrophy

• Adults:
• Initial dose: 5 mg orally once daily
• Maintenance dose: 5–10 mg once daily, depending on blood pressure response
• Maximum dose: 10 mg/day
• Elderly:
• Start at the lower dose (5 mg once daily), titrate cautiously
• Pediatrics:
• Safety and efficacy not established; not routinely recommended
• Special Populations:
• Renal Impairment: No dose adjustment necessary in mild to moderate impairment; use caution in severe renal impairment
• Hepatic Impairment: Use with caution; no specific dose recommendations
• Administration Route:
• Oral, with or without food
• Tablets should be swallowed whole with water
• Duration:
• Long-term therapy as prescribed; do not discontinue abruptly

Cilnidipine is a dual L-type and N-type calcium channel blocker. By blocking L-type calcium channels on vascular smooth muscle, it induces arterial vasodilation, reducing systemic vascular resistance and lowering blood pressure. Additionally, blockade of N-type calcium channels on sympathetic nerve terminals inhibits norepinephrine release, reducing sympathetic nervous system activity. This dual action not only lowers peripheral resistance but also decreases heart rate and suppresses sympathetic overactivity, contributing to improved cardiovascular and renal protective effects.

• Absorption:
  Rapidly absorbed after oral administration with peak plasma concentrations reached within 2–4 hours.
• Bioavailability:
  Approximately 10–20% due to first-pass metabolism.
• Distribution:
  Highly protein-bound (>99%), primarily to albumin.
• Metabolism:
  Extensively metabolized in the liver via CYP3A4 enzyme system to inactive metabolites.
• Elimination:
  Mainly excreted via urine (60–70%) and feces (30–40%) as metabolites.
• Half-life:
  Approximately 7–9 hours, supporting once-daily dosing.

• Pregnancy:
• Classified as Category C (FDA)
• Animal studies have shown adverse effects on fetus; no adequate well-controlled human studies
• Use only if potential benefit justifies the potential risk to the fetus
• Lactation:
• Unknown whether cilnidipine is excreted in human milk
• Caution advised; breastfeeding should be discontinued if drug is essential

• Primary Class: Calcium Channel Blocker
• Subclass: Dihydropyridine (dual L- and N-type calcium channel blocker)

• Known hypersensitivity to cilnidipine or other dihydropyridine calcium channel blockers
• Severe hypotension (systolic BP <90 mmHg)
• Cardiogenic shock
• Unstable angina or acute myocardial infarction in the acute phase
• Severe aortic stenosis
• Severe hepatic impairment

• Hypotension: Monitor blood pressure regularly; risk of symptomatic hypotension especially in volume-depleted patients
• Heart Failure: Use cautiously as vasodilation can precipitate symptoms
• Hepatic Impairment: Use cautiously due to extensive hepatic metabolism
• Elderly Patients: Increased sensitivity may necessitate lower doses
• Avoid Abrupt Discontinuation: Risk of rebound hypertension
• Monitor Renal Function: Especially in patients with preexisting renal disease

Common Adverse Effects:

• Dizziness
• Headache
• Flushing
• Peripheral edema
• Palpitations
• Fatigue

Less Common / Rare:

• Hypotension
• Bradycardia (due to N-type calcium channel blockade)
• Gastrointestinal disturbances (nausea, abdominal discomfort)
• Rash or pruritus
• Gingival hyperplasia (rare)

Severity: Generally mild to moderate; onset typically within first weeks of therapy; dose-dependent.

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase cilnidipine plasma levels, enhancing effects and toxicity
• CYP3A4 Inducers (e.g., rifampin, phenytoin): May reduce efficacy by lowering plasma concentrations
• Other Antihypertensives: Additive hypotensive effect
• Beta-blockers: Potential additive bradycardia
• Grapefruit Juice: May increase bioavailability and blood levels; avoid or limit intake
• NSAIDs: May reduce antihypertensive effect

• 2024 Hypertension Management Guidelines (ESH/ESC):
• Recognize cilnidipine as an effective antihypertensive agent with renal protective properties
• Recommended especially in patients with sympathetic overactivity or proteinuric kidney disease
• 2023 Clinical Trials:
• Demonstrated cilnidipine’s superiority over traditional L-type blockers in reducing microalbuminuria
• Improved tolerability profile with less reflex tachycardia

• Store tablets at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep in original packaging until use
• Keep out of reach of children
• Do not freeze