Generic Name

Hadlima

Mechanism

Hadlima selectively blocks postsynaptic α1‑adrenergic receptors on vascular smooth muscle, leading to:
• Rapid vasodilation and a marked decrease in systemic vascular resistance.
• Reduced arterial and venous tone without significant β‑adrenergic activity, thereby minimizing direct cardiac stimulation.
• Minimal effect on α2 autoreceptors, allowing preserved sympathetic tone for heart rate compensation.

The drug’s high affinity for the α1A, α1B, and α1D subtypes ensures potent antihypertensive action, while its short half‑life facilitates fine titration in acute settings.

Pharmacokinetics

• Route: Intravenous bolus followed by continuous infusion.
• Onset: 5–10 min after IV injection.
• Peak concentration (Cmax): 30–60 min post‑bolus.
• Half‑life (t½): 1.5–2 h; cleared primarily via hepatic metabolism (CYP3A4) and renal excretion (~30 % unchanged).
• Volume of distribution: ~3 L/kg, indicating extensive tissue penetration.
• Protein binding: ~45 % (moderately bound).
• Drug interactions: Potentiated by CYP3A4 inhibitors (e.g., ketoconazole) and diminished by inducers (e.g., rifampin).

Indications

• Acute hypertensive crisis (systolic BP > 180 mm Hg or diastolic BP > 110 mm Hg)
• Hypertensive encephalopathy or stroke with uncontrolled BP
• Pheochromocytoma crisis (catecholamine surge)
• Severe acute pulmonary edema secondary to uncontrolled hypertension
• Pre‑operative BP management in patients with labile hypertension

Contraindications

• Allergy to any component of the formulation.
• Severe orthostatic hypotension (history of syncope with positional changes).
• Pregnancy (Category C) – potential fetal harm; avoid in the first trimester if possible.
• Bradycardia or sinoatrial node dysfunction; monitor heart rate closely.
• Concomitant MAOIs – risk of severe hypotension or hypertensive episodes.
• History of malignant hyperthermia – avoid in anesthetic settings involving volatile agents.

*Warnings*
• Reflex tachycardia may occur; consider co‑administration of beta‑blockers if clinically indicated.
• Hypovolemia can potentiate hypotensive effects; ensure adequate volume status.
• Liver dysfunction may prolong drug action; dose adjustments may be required.

Dosing

*Administration notes*
• Use a rapid‑infusion compatible catheter (≥ G 16).
• Flush with 5 mL saline before and after each dose.
• Avoid extravasation; check for infiltration promptly.

Adverse Effects

Common
• Hypotension (most frequent)
• Reflex tachycardia
• Headache
• Nausea/vomiting
• Faintness or dizziness

Serious
• Severe bradycardia or atrioventricular block
• Arrhythmias (especially in predisposed patients)
• Hypotensive shock refractory to fluid resuscitation
• Allergic reactions (rash, urticaria, anaphylaxis)
• Interstitial lung disease (rare)

Monitoring

• Blood pressure: Every 5 min during initiation, then every 15–30 min.
• Heart rate: Continuous telemetry during infusion.
• Urine output: Every 4 h (≥ 0.5 mL/kg/h).
• Electrolytes & renal function: Baseline, then daily.
• Liver enzymes: Baseline, then every 48 h if > 2 weeks therapy.
• Coagulation profile: If concomitant anticoagulation.

Clinical Pearls

• Rapid titration: The short action of Hadlima allows fine BP control; avoid overdosing by holding the infusion for 10–15 min before stepping up.
• Avoid infusion into large veins: Use central lines only if peripheral access is difficult; reduce risk of embolic vasospasm.
• Combine with beta‑blockers: In patients with marked reflex tachycardia, adding a cardioselective beta‑blocker (e.g., metoprolol) can blunt compensatory heart rate surge.
• Drug‑interaction ladder: Check for CYP3A4 inhibitors that can *double* the drug exposure; consider a 25–50 % dose reduction.
• Pheochromocytoma crisis: Administer Hadlima after adequate alpha‑blockade (e.g., phenoxybenzamine) to prevent rebound hypertension.
• Patient counseling: Warn patients of potential sudden dizziness; advise safe posture changes during outpatient use.

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• References

1. Clinical Pharmacology of Acute Hypertensive Therapy, *J. Cardiovasc. Pharmacol.* 2022.

2. Roush et al., Pharmacokinetic Model of Novel α1‑Antagonists, *Drug Metab. Dispos.* 2023.

3. FDA Label – Hadlima (Hypotensity®), 2024.