Labetalol





See Beta blockers (Class) for general information on the drug class

PD

MOA

Combined alpha and beta blocker

  • Selective alpha1 blockade
  • Non selective beta blockade

Two chiral centres:

  • 4 isomers
  • SR is probably responsible for alpha1 blockade
  • RR is probably responsible for beta blockade

Ratio of alpha1 : beta blockade

  • Depends on route of administration
    • Greater beta blockade with IV formulation
  • IV = 1 : 7
  • Oral = 1 : 3

NB:

  • No intrinsic sympathomimetic activity
  • Some membrane stabilising activity
    • Less than propranolol

Actions

  • Selective alpha1 blockade → Peripheral vasodilation

  • Beta blockade → Prevents reflex tachycardia

Overall effect = Reduction of BP without cardiac stimulation (HR doesn't change too much)

IV labetalol will reduce HR more

PK

A

  • Oral bioavailability = 35 to 40% [PI]
    • Increases with age and with food
  • Extensive first-pass metabolism

NB:

  • ?WPH says 20% oral bioavailability

D

  • 50% protein bound

M

  • Hepatic metabolism with inactive metabolites

AP

Oral route:

  • Peak plasma at 1 to 2 hours
  • T1/2 = 6 to 8 hours
  • Duration of action up to 11 hours

IV route:

  • Maximal effect ≤ 5 minutes
  • Elimination T1/2 = 5.5 hr

PC

Oral

  • 100mg or 200mg tablets

IV

Availiability:

  • Not available in Australia
  • Available in UK

In vials of

  • 100 mg in 20 mL
  • 200 mg in 40 mL

i.e. 5 mg/mL

Other contents in the IV forumlation:

  • Dextrose 45 mg
  • Edetate disodium 0.10 mg
  • Methylparaben 0.80 mg (preservatives)
  • Propylparaben 0.10 mg (preservatives)
  • Citric acid, anhydrous hydroxide, sodium hydroxide (for pH adjustments)

NB:

  • pH = 3.0 to 4.5

Clinical

Dosage

IV

IV bolus dose = 5 to 20 mg

  • Slow IV
  • Repeat dose every 10 min
    • Titrated to effect
  • Maximum dose = 200 mg

As an infusion = 1 to 2 mg/min

  • Dilute to 1 mg/mL before use
  • Maximum dose = 200 mg
  • Discontinue infusion when satisfactory response

Oral

Oral dosage = 100 to 200 mg BD

Range 200 mg to 2400 mg in 24 hours

Caution

  • Risk of excessive bradycardia if used IV
  • NOT recommended for untreated phaeochromocytoma

Hepatic injury

  • Periodic LFT recommended
  • Rare cases of severe hepatocellular injury

In hepatic impairment

  • Higher bioavailability
    • Due to lower first-pass metabolism
  • Elimination T1/2 not altered