Schedule H

Intravenous (IV) only

• IV emulsion for injection: 0.5 mg/mL (50 mg/100 mL lipid emulsion vial)

Note: Lipid-based formulation in glass vial; requires specific handling and aseptic technique

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Hypertension (Perioperative and Emergency/ICU Settings)

⚠️ Administer only in settings with continuous arterial blood pressure monitoring

Parameter Recommendation

Starting dose 1–2 mg/hour IV infusion

Titration Double the dose every 90 seconds initially until approaching target BP; then increase by smaller increments at intervals of 5–10 minutes

Usual maintenance dose 4–6 mg/hour IV infusion

Maximum dose 16 mg/hour (most patients achieve target with ≤16 mg/hour)

Key Clinical Notes:

• Onset of action: 2–4 minutes

• Ultra-short half-life (~1 minute) allows rapid titration and recovery

• Administer via dedicated IV line using infusion pump only — NOT for bolus use

• Use exclusively in ICU, operating theatre, or high-dependency settings

• Transition to oral antihypertensives before stopping infusion to prevent rebound hypertension

• Do not infuse for more than 72 hours due to lipid load considerations

Secondary Indications — Adults Only (Off-label)

Indication Aortic Dissection — Adjunctive BP Control

Dose Starting: 2 mg/hour; titrate rapidly to target SBP (usually 100–120 mmHg)

Duration Until surgical intervention or stabilisation; transition to oral agents

Status OFF-LABEL; Specialist only

Requirements Must be combined with IV β-blocker (e.g., esmolol) to control reflex tachycardia and aortic shear stress

Evidence Emergency protocols in Indian tertiary cardiac surgery centres; international guidelines for type A/B dissection management

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

• NOT routinely recommended for paediatric use in India

• No approved paediatric indications; safety and efficacy data are very limited

Secondary Indications — Paediatric Doses (Off-label)

Parameter Acute Hypertensive Emergency in PICU

Starting dose 0.5–1 mcg/kg/min IV infusion

Titration Increase by 0.5–1 mcg/kg/min every 2–5 minutes based on BP response

Usual maintenance dose 1–3 mcg/kg/min

Maximum dose Up to 5–7 mcg/kg/min in select critically ill cases

Status OFF-LABEL; Specialist only (Paediatric Intensivist/Cardiologist)

Evidence Extrapolated from limited international paediatric critical care data; not standardised in Indian paediatric guidelines

Safety Monitoring:

• Continuous invasive arterial BP and ECG monitoring mandatory

• Monitor serum triglycerides if infusion exceeds 24 hours

• Assess for lipid overload in neonates/infants

⚠️ Not recommended below 1 month of age except under specialist supervision in tertiary PICU

All stages (including dialysis) No dose adjustment required

• Known hypersensitivity to clevidipine or any component

• Allergy to soy or egg products (lipid emulsion contains soy and egg phospholipids)

• Disorders of lipid metabolism (e.g., pathological hyperlipidaemia, lipoid nephrosis, acute pancreatitis with hyperlipidaemia)

• Severe aortic stenosis — vasodilation may worsen outflow obstruction and precipitate cardiovascular collapse

• Defective lipid metabolism (e.g., familial lipoprotein lipase deficiency)

• Reflex tachycardia — use with caution in patients with coronary artery disease or acute coronary syndrome

• Rebound hypertension on abrupt discontinuation — transition to oral antihypertensives before stopping

• Prolonged infusions (>24 hours) — monitor for hypertriglyceridaemia and lipid overload

• Concurrent lipid infusions (e.g., propofol, parenteral nutrition) — cumulative lipid load; adjust total fat intake

• Strict aseptic handling required — lipid emulsion supports microbial growth

• Heart failure with reduced ejection fraction — limited data; use cautiously

• Pheochromocytoma — control catecholamine effects with β-blocker before use

Parameter Information

Risk category Safety not established; avoid unless no alternatives available

Preferred alternatives Labetalol IV, hydralazine IV for hypertensive emergencies in pregnancy (per Indian obstetric protocols)

When to use Only if potential benefit clearly justifies fetal risk; specialist supervision mandatory

Monitoring Maternal BP continuously; fetal heart rate monitoring

Parameter Information

Compatibility Not recommended — insufficient human data

Preferred alternatives Labetalol, nifedipine for postpartum BP control

Expected levels in milk Unknown

Infant monitoring If inadvertently exposed: feeding difficulties, sedation, hypotension

Parameter Recommendation

Starting dose 0.5–1 mg/hour (lower than standard adult dose)

Titration Slower titration at longer intervals; assess BP response before each increment

Extra risks Increased sensitivity to hypotension; higher risk of falls, syncope, cerebral hypoperfusion; may have reduced hepatic reserve

Monitoring Continuous BP; frequent neurological assessment

Interacting Drug/Class Mechanism Clinical Effect Recommendation

β-blockers (metoprolol, esmolol, propranolol) Additive negative chronotropic and hypotensive effects Severe hypotension, bradycardia Monitor closely; may be intentionally combined in aortic dissection but requires careful titration

Propofol (IV anaesthetic) Both are lipid emulsions Cumulative lipid load; hypertriglyceridaemia; fat overload syndrome Adjust total lipid intake; monitor triglycerides

Other IV lipid preparations (parenteral nutrition, intralipid) Cumulative lipid load Fat overload syndrome Account for total daily lipid administration

Interacting Drug/Class Effect Recommendation

ACE inhibitors, ARBs Additive hypotension Monitor BP; adjust doses accordingly

Other antihypertensives (diuretics, alpha-blockers) Enhanced BP-lowering effect Close BP monitoring during co-administration

General anaesthetics (volatile agents) Potentiation of hypotensive effect Reduce clevidipine infusion rate as needed

Cyclosporine Theoretical competition in lipid carrier medium Monitor cyclosporine levels if prolonged infusion

Statins Additive effect on lipid metabolism Monitor triglycerides, especially with prolonged infusion

• Hypotension

• Reflex tachycardia

• Headache

• Nausea

• Vomiting

• Atrial fibrillation

Adverse Effect Action Required

Severe hypotension Reduce infusion rate or discontinue; IV fluids; vasopressors if needed

Rebound hypertension (on abrupt discontinuation) Transition to oral antihypertensives before stopping; gradual taper

Hypertriglyceridaemia (with prolonged use >24 hours) Monitor triglycerides; consider alternative if levels markedly elevated

Lipid emulsion contamination/sepsis Strict aseptic technique; discard vial 12 hours after opening

Acute pancreatitis (rare, with severe hypertriglyceridaemia) Discontinue; supportive care

Phase Parameters

Baseline BP, HR, ECG; allergy history (egg/soy); serum triglycerides if prolonged use anticipated

During infusion Continuous invasive arterial BP monitoring; continuous ECG; hourly HR assessment

If infusion >24 hours Serum triglycerides every 12–24 hours; LFTs

After discontinuation BP monitoring for rebound hypertension; ensure oral antihypertensive transition

• Cleviprex (The Medicines Company — imported)

Note: Limited availability; primarily stocked in premium tertiary care institutions for ICU/operating theatre use. Specialist/institutional procurement only.

Note: Not listed in NLEM India; high-cost imported product; usually procured through institutional channels

1. Ideal for tight perioperative BP control — Ultra-short half-life (~1 minute) allows minute-to-minute titration; particularly useful in cardiac surgery, neurosurgery, and vascular surgery settings

1. Always confirm absence of soy/egg allergy before administration — lipid emulsion contains both; anaphylaxis risk if overlooked

1. Never administer as bolus — Use only via controlled infusion pump; bolus can cause precipitous hypotension

1. Plan oral transition early — Start oral antihypertensive 1–2 hours before anticipated clevidipine discontinuation to prevent rebound hypertension

1. Discard opened vials within 12 hours — Lipid emulsion is an excellent culture medium for bacteria; strict aseptic technique mandatory

1. Account for total lipid load — When co-administering with propofol or parenteral nutrition, calculate cumulative lipid intake to avoid fat overload syndrome

Clevidipine; IV antihypertensive; calcium channel blocker; dihydropyridine; perioperative hypertension; ICU drug; hypertensive emergency; lipid emulsion; short-acting; egg-soy allergy caution

RxIndia v1.0 — 08 May 2025

• CDSCO product listings

• Manufacturer product insert (India-approved formulation)

• AIIMS Drug Formularies — ICU protocols

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• International RCTs and meta-analyses (for off-label paediatric usage and aortic dissection — clearly marked)