Labegest

Approved Indications:

• Chronic Hypertension (Essential or Secondary):
  Labetalol is indicated for the treatment of mild to severe hypertension, including essential (primary) and secondary hypertension.
• Hypertensive Emergencies:
  Intravenous labetalol is used to rapidly lower severely elevated blood pressure in hypertensive crises.
• Hypertension in Pregnancy:
  Widely used for the management of gestational hypertension and preeclampsia due to its favorable safety profile in pregnancy.

Clinically Accepted Off-Label Uses:

• Acute Aortic Dissection:
  Used intravenously to reduce heart rate and blood pressure, minimizing aortic wall stress.
• Postoperative Hypertension:
  For short-term management of elevated blood pressure after surgical procedures.
• Thyrotoxic Crisis (Thyroid Storm):
  Used to control tachycardia and hypertension associated with excess thyroid hormone activity.

Adults:

• Oral (Chronic Hypertension):
  Initial dose: 100 mg twice daily
  Maintenance: 200–400 mg twice daily
  Maximum dose: 2,400 mg/day in divided doses
• Intravenous (Hypertensive Emergency):
  IV bolus: 20 mg over 2 minutes; may repeat with 40–80 mg every 10 minutes as needed (max total dose: 300 mg)
  IV infusion: Start at 1–2 mg/min; titrate based on response (max 300 mg/day)

Pregnancy-Induced Hypertension (Oral or IV):

• Oral: 100–200 mg twice daily
• IV: As per hypertensive emergency dosing, with fetal monitoring

Pediatrics (Off-Label Use):

• Oral: 1–3 mg/kg/day in divided doses
• IV: 0.25–1 mg/kg/dose every 8 hours (max: 40 mg/dose)

Elderly:

• Start at the lower end of the dosing range due to increased risk of hypotension and bradycardia

Renal Impairment:

• No dosage adjustment typically needed; monitor blood pressure and renal function

Hepatic Impairment:

• Use with caution; reduce dose as hepatic metabolism may be impaired

Administration Route:

• Oral tablets should be taken with or without food
• IV administration must be done under close hemodynamic monitoring

Duration:

• Chronic use: long-term management
• IV use: short-term until BP is stabilized

Labetalol is a combined selective α1-adrenergic receptor blocker and non-selective β-adrenergic receptor blocker. It lowers blood pressure by decreasing peripheral vascular resistance (via α1 blockade) and reducing heart rate and myocardial contractility (via β1 blockade). Its unique dual mechanism allows effective blood pressure reduction without significant reflex tachycardia. The β to α blockade ratio is approximately 3:1 orally and 7:1 intravenously.

• Absorption: Rapid and well absorbed orally; peak plasma concentrations reached in 1–2 hours
• Bioavailability: ~25% due to first-pass hepatic metabolism
• Distribution: Widely distributed; protein binding ~50%
• Metabolism: Primarily metabolized in the liver via conjugation (glucuronidation)
• Excretion: ~55% renal; remainder via bile and feces
• Half-life: 5.5 to 8 hours
• Onset of Action:
• Oral: 20 to 120 minutes
• IV: 2 to 5 minutes
• Duration:
• Oral: 6 to 12 hours
• IV: 2 to 4 hours

• Pregnancy:
  Previously classified as FDA Pregnancy Category C. Labetalol is commonly used in pregnancy-related hypertension, especially preeclampsia, and is considered a first-line agent in many clinical guidelines.
• Lactation:
  Excreted in small amounts in breast milk. Generally considered safe during breastfeeding. Monitor the infant for bradycardia or hypotension.
• Recommendation:
  Use in pregnancy and lactation when clearly indicated. Fetal and infant monitoring is advised.

• Primary Class: Antihypertensive Agent
• Subclass: Combined Alpha-1 and Non-selective Beta-Adrenergic Blocker
• Generation: Third-generation beta-blocker

• Known hypersensitivity to labetalol or any formulation component
• Bronchial asthma or other obstructive airway diseases
• Second- or third-degree AV block (without pacemaker)
• Overt or decompensated heart failure
• Cardiogenic shock
• Severe bradycardia
• Conditions associated with prolonged hypotension (e.g., aortic stenosis)

• Asthma/COPD: Risk of bronchospasm due to β2-blockade
• Heart Failure: Worsening of heart failure can occur; use with caution in compensated cases
• Bradycardia and Hypotension: Monitor closely; discontinue if HR <50 bpm
• Diabetes: May mask symptoms of hypoglycemia
• Hepatic Impairment: Risk of accumulation; monitor liver enzymes
• Abrupt Discontinuation: May cause rebound hypertension or angina; taper gradually

Common Side Effects:

• Cardiovascular: Orthostatic hypotension, bradycardia
• Central Nervous System: Dizziness, fatigue, headache, drowsiness
• Gastrointestinal: Nausea, vomiting, indigestion
• General: Weakness, nasal congestion

Serious or Rare Side Effects:

• Hepatic injury (including hepatitis and liver failure)
• Bronchospasm in susceptible individuals
• Heart block, syncope
• Exacerbation of Raynaud’s phenomenon
• Rare allergic reactions

Timing and Severity:

• Most side effects are dose-related and reversible
• Hepatic effects may take weeks to develop and require discontinuation

• Other Antihypertensives: Additive hypotensive or bradycardic effects
• Calcium Channel Blockers (e.g., verapamil, diltiazem): Risk of bradycardia or AV block
• General Anesthetics: Enhanced myocardial depression
• Insulin and Antidiabetic Agents: May mask signs of hypoglycemia
• Cimetidine: Increases labetalol plasma concentrations
• Monoamine Oxidase Inhibitors (MAOIs): Enhanced hypotensive effect

Enzyme Interactions:

• Primarily metabolized by conjugation; does not significantly interact with CYP450 enzymes

• American College of Obstetricians and Gynecologists (ACOG):
  Labetalol is a first-line therapy for the management of hypertension in pregnancy and preeclampsia.
• American Heart Association (AHA) / American College of Cardiology (ACC):
  Recommends labetalol IV as a preferred option in hypertensive emergencies and aortic dissection.
• Hepatotoxicity Warning:
  Rare but serious hepatotoxicity has been reported. Routine liver function monitoring is advised during prolonged use.

• Tablets:
  Store at 20°C to 25°C (68°F to 77°F)
  Protect from moisture and light
  Keep in tightly closed containers
• IV Solution:
  Store at 20°C to 25°C
  Do not freeze
  Inspect for particulate matter and discoloration before use
• Handling:
  Use aseptic techniques for IV administration
  Discard unused IV solution after 24 hours of opening
  No reconstitution required