Drug profile Cilnidipine Class Generic name Brand Formulation Dose Content Mfg date -Expire date Mechanism of action Pharmacology Pk and pd Route of administration Uses Adverse drug reaction Mild, Moderate, Severe (2 Examples in each category) Drug durg interaction Mild, Moderate, Severe (2 Examples in each category) Source-
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https://www.efda.gov.et/wp-content/uploads/2024/01/Cilnidipi…
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PMID: 38881084
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💊 DRUG PROFILE: CILNIDIPINE
CLASS
Calcium Channel Blocker (CCB) - Dihydropyridine (DHP) subclass, 3rd Generation
- Dual L-type and N-type calcium channel blocker
GENERIC NAME
Cilnidipine
BRAND NAMES
| Region | Brand Name | Manufacturer |
|---|---|---|
| India | Cilacar | Sun Pharma |
| India | Clinidine, Cilinorm | Various |
| Japan | Atelec | Forest Labs / Fuji Viscera |
| Korea | Cinalong | Boryung Pharmaceuticals |
| India | CILACAR-5, CILACAR-10, CILACAR-20 | Sun Pharma |
FORMULATION
- Oral Tablet: 5 mg, 10 mg, 20 mg (film-coated tablets)
- Appearance: White to off-white, round, biconvex, film-coated tablets
- Inactive excipients: Microcrystalline Cellulose (Avicel PH-102), Lactose USP-NF, Magnesium Stearate, Sodium Starch Glycolate, Opadry White II (film coating)
DOSE
| Indication | Dose | Frequency |
|---|---|---|
| Hypertension (adults) | 5-20 mg | Once daily (OD) |
| Starting dose | 5-10 mg | Once daily |
| Maximum dose | 20 mg/day | Once daily |
- Taken orally, preferably at the same time each day
- No dose adjustment typically needed for mild-moderate renal impairment, but caution in hepatic impairment
CONTENT (Tablet Composition - per unit)
| Ingredient | Role |
|---|---|
| Cilnidipine (active) | 5 mg / 10 mg / 20 mg |
| Microcrystalline Cellulose | Diluent/Binder |
| Lactose | Filler |
| Magnesium Stearate | Lubricant |
| Sodium Starch Glycolate | Disintegrant |
| Opadry White (film coat) | Coating agent |
MFG DATE / EXPIRE DATE
- Shelf life: 24 months from date of manufacture (typically labeled on blister/carton)
- Storage: Store below 30°C, in a dry place, away from light
- (Specific lot dates vary by manufacturer and batch - always check individual pack labeling)
MECHANISM OF ACTION
Cilnidipine is unique among CCBs in that it blocks two types of voltage-dependent calcium channels:
1. L-type (Long-lasting) Calcium Channel Blockade
- Found in vascular smooth muscle cells and cardiac muscle
- Inhibits calcium influx → reduces vascular smooth muscle tone → vasodilation → lowers systemic vascular resistance → reduces blood pressure
- This is the mechanism shared with all dihydropyridines (amlodipine, nifedipine, etc.)
2. N-type (Neuronal) Calcium Channel Blockade (Unique Feature)
- Found at presynaptic sympathetic nerve terminals at the neuroeffector junction
- N-type channels are responsible for norepinephrine (NE) release
- Cilnidipine inhibits N-type channels → reduces norepinephrine release → suppresses sympathetic outflow → additional antihypertensive effect + reduced reflex tachycardia
- Also reduces efferent renal sympathetic nerve activity → renoprotection (reduced proteinuria)
This dual L/N blockade is what distinguishes cilnidipine from conventional DHP-CCBs like amlodipine (pure L-type blockers). - Mehta et al., JAPI 2024
PHARMACOLOGY
Pharmacodynamics (PD)
- Antihypertensive: Reduces both systolic and diastolic blood pressure effectively
- No reflex tachycardia: Unlike pure L-type CCBs, N-type blockade suppresses compensatory sympathetic activation and prevents heart rate increase
- Renoprotection: Reduces intraglomerular pressure and proteinuria by dilating the efferent arteriole (via N-type blockade on renal sympathetic nerves)
- Cardioprotective: Reduces left ventricular hypertrophy (LVH), improves coronary flow
- Lipid effects: May favorably modify lipid profile - reduces total cholesterol, TG, VLDL-C while increasing HDL-C
- Morning BP surge: Effective in blunting early morning blood pressure rise due to sympatholytic N-type blockade
- Less pedal edema than amlodipine due to balanced vasodilatation (both afferent and efferent vessels)
Selectivity
- More vascular selective than cardiac - minimal negative inotropic effect
- Greater affinity for N-type channels compared to other DHP CCBs
PHARMACOKINETICS (PK)
| Parameter | Value |
|---|---|
| Route | Oral |
| Bioavailability | ~13% (first-pass metabolism) |
| Tmax | 1-3 hours |
| Half-life (t½) | 2.1-2.5 hours |
| Duration of action | ~24 hours (once-daily dosing) |
| Protein binding | High (>95%, lipophilic) |
| Distribution | High lipophilicity - extensive tissue distribution |
| Metabolism | Hepatic - primarily CYP3A4, minor CYP2C19 |
| Excretion | Fecal (biliary) and urinary |
Despite its short half-life (2.1-2.5 h), cilnidipine has a 24-hour duration of action due to its high lipophilicity, which allows it to accumulate in and slowly release from vascular smooth muscle membranes, compensating for the short plasma t½. - [CILACAR-5 package insert; EFDA 2024]
ROUTE OF ADMINISTRATION
- Oral (PO) only
- Tablets are swallowed whole with water
- Can be taken with or without food (food may slightly increase absorption)
- NOT available in parenteral (IV/IM) formulations
USES / THERAPEUTIC INDICATIONS
| Indication | Notes |
|---|---|
| Essential Hypertension (primary indication) | Mild to moderate hypertension, monotherapy or combination |
| Hypertension with CKD | Preferred due to antiproteinuric and renoprotective properties |
| Hypertension with Tachycardia | N-type blockade prevents reflex tachycardia |
| Hypertension with Diabetes | Minimal metabolic effects; renal benefits in diabetic nephropathy |
| Morning hypertension | Effective in blunting early morning BP surge |
| Hypertension with LVH | Reduces LVH regression |
| Isolated systolic hypertension (elderly) | Well tolerated in elderly patients |
ADVERSE DRUG REACTIONS (ADRs)
MILD ADRs (Common, usually transient)
| # | ADR | Mechanism |
|---|---|---|
| 1 | Headache (3.7% incidence) | Vasodilation → increased intracranial blood flow |
| 2 | Flushing / Hot flushes (4.5% incidence) | Peripheral vasodilation → skin flushing |
(Other mild: dizziness, fatigue, nausea, somnolence)
MODERATE ADRs (Clinically significant, require monitoring)
| # | ADR | Mechanism |
|---|---|---|
| 1 | Peripheral edema (less frequent than amlodipine) | Preferential precapillary arteriolar dilation → increased capillary pressure; less pronounced due to N-type blockade effect on venous capacitance |
| 2 | Gingival hyperplasia | Fibroblast proliferation triggered by CCB class effect; overgrowth of gum tissue |
(Other moderate: palpitations, orthostatic hypotension, rash)
SEVERE ADRs (Rare but serious)
| # | ADR | Mechanism / Notes |
|---|---|---|
| 1 | Severe hypotension / Syncope | Excessive vasodilation, especially in volume-depleted patients or on combination antihypertensives; requires immediate management |
| 2 | Bradycardia | N-type calcium channel blockade reduces sympathetic drive to the SA node; risk increases when combined with beta-blockers or digoxin |
(Other severe: hepatotoxicity [rare], anaphylaxis/hypersensitivity in sensitized individuals)
DRUG-DRUG INTERACTIONS (DDIs)
MILD Interactions
| # | Drug | Interaction | Management |
|---|---|---|---|
| 1 | Antacids (Mg/Al hydroxide) | May slightly alter cilnidipine absorption | Separate dosing by 2 hours |
| 2 | Alcohol | Mild additive vasodilation and BP lowering; increased dizziness | Advise to limit alcohol intake |
MODERATE Interactions
| # | Drug | Interaction | Management |
|---|---|---|---|
| 1 | Diuretics (furosemide, hydrochlorothiazide) | Additive blood pressure-lowering; risk of excessive hypotension | Monitor BP, adjust doses; useful as therapeutic combination but titrate carefully |
| 2 | Other Antihypertensives (ARBs like valsartan, ACE inhibitors, beta-blockers) | Additive antihypertensive effect; combined use is common in practice but requires BP monitoring | Beneficial combination, but titrate to avoid hypotension; cilnidipine + valsartan shown safe with additive BP reduction [PMC4199974] |
SEVERE Interactions
| # | Drug | Interaction | Mechanism | Management |
|---|---|---|---|---|
| 1 | CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Erythromycin, Clarithromycin, Ritonavir) | Significantly increase cilnidipine plasma levels → risk of severe hypotension, reflex tachycardia | CYP3A4 is the primary metabolic pathway; inhibition leads to reduced clearance and drug accumulation | Avoid concurrent use or reduce cilnidipine dose; monitor BP closely |
| 2 | CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Significantly decrease cilnidipine levels → loss of antihypertensive efficacy | Enzyme induction accelerates cilnidipine metabolism | Avoid combination; if unavoidable, monitor BP and consider dose increase |
Note: Grapefruit juice acts as a CYP3A4 inhibitor at intestinal level and can increase cilnidipine bioavailability - patients should be advised to avoid grapefruit consumption.
CONTRAINDICATIONS
- Advanced aortic stenosis
- Hypersensitivity to cilnidipine or other DHP-CCBs
- Pregnancy (no safety data; avoid)
- Lactation (insufficient data)
SPECIAL PRECAUTIONS
- Hepatic impairment: use with caution (reduced metabolism)
- Congestive heart failure: caution (vasodilation may worsen)
- Renal insufficiency: monitor; generally beneficial but watch for hypotension
- Elderly: start low (5 mg), titrate cautiously
SOURCES
- Mehta KK, Tiwaskar M, Kasture P. Cilnidipine, a Dual L/N-type Ca2+ Channel Blocker in Hypertension Management: A Review. J Assoc Physicians India. 2024 PMID: 38881084
- CILACAR-5 Package Insert - Unique Pharmaceutical Laboratories / EFDA 2024
- Kumari K et al. Blood Pressure Reducing Potential and Renoprotective Action of Cilnidipine in CKD. Cureus. 2023 PMID: 37213948
- PMC4199974 - PK/PD Interaction Study: Cilnidipine + Valsartan in healthy volunteers. Dove Medical Press 2014.
- Brenner and Rector's The Kidney, 2-Volume Set - N-type CCB antiproteinuric effect reference
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