Dosing and uses of Prostigmin, Bloxiverz (neostigmine)
Adult dosage forms and strengths
injectable solution (methylsulfate salt; Bloxiverz)
- 0.5mg/mL
- 1mg/mL
tablet (bromide salt; Prostigmin)
- 15mg
Myasthenia Gravis
Acute: 0.5-2.5 mg IV/IM/SC qDay
Maintenance: 15-375 mg/day PO divided q6-8hr
Use injectable with 0.6-1.2 mg atropine IV to counteract muscarinic effects
Myasthenia Gravis Diagnosis
0.022 mg/kg IM x1
Discontinue all anticholinesterase agents for >8 hr
Give atropine 0.011 mg/kg IV (if IM give 30 minutes before) with neostigmine 0.022 mg/kg Im
If cholinergic response, stop test and give 0.4-0.6 mg atropine IV
If inconclusive, retest another day with neostigmine 0.031 mg/kg IM preceded by 0.016 mg/kg atropine
Nondepolarizing Neuromuscular Blockade, Reversal
0.03-0.07 mg/kg IV will generally achieve a TOF twitch ratio of 90% within 10-20 minutes of administration
Not to exceed 0.07 mg/kg or a cumulative total of 5 mg, whichever dose is less Inject by slow IV over at least 1 minute
Dose selection should be based on the extent of spontaneous recovery that has occurred at the time of administration, the half-life of the NMBA being reversed, and whether there is a need to rapidly reverse the NMBA
Administer an IV anticholinergic (eg, atropine, glycopyrrolate) prior to, or concomitantly with neostigmine for NMB reversal; if bradycardia present, give anticholinergic before neostigmine
0.03 mg/kg
- Use for reversal of NMBAs with shorter half-lives (eg, rocuronium), OR
- When the first twitch response to the TOF stimulus is substantially >10% of baseline or when a second twitch is present
0.07 mg/kg
- Use for NMBAs with longer half-lives (eg, vecuronium, pancuronium), OR
- When the first twitch response is relatively weak (ie, not substantially >10% of baseline), OR
- There is need for more rapid recovery
Post-Op Distention or Urinary Retention
Prevention: 0.25mg IM after surgery. Repeat q4-6hr for 2-3 days
Treatment: 0.5-1 mg IM and up to q3hr PRN (for 5 doses for retention)
Colonic Pseudo-obstruction (Orphan)
Orphan designation for treatment of acute colonic pseudo-obstruction
Orphan sponsor
- Luitpold Pharmaceuticals, Inc.; One Luitpold Drive, P. O. Box 9001; Shirley, NY 11967
Administration
IV TOF monitoring for NMB reversaL
- Peripheral nerve stimulation devices capable of delivering a train-of-four (TOF) stimulus are essential to effectively and safely adjust IV dose
- There must be a twitch response to the first stimulus in the TOF of at least 10% of its baseline level (ie, the response before NMBA administration, prior to neostigmine)
Pediatric dosage forms and strengths
injectable solution (methylsulfate salt; Bloxiverz)
- 0.5mg/mL
- 1mg/mL
tablet (bromide salt; Prostigmin)
- 15mg
Myasthenia Gravis Diagnosis
Use with atropine
0.025-0.04 mg/kg IM x1
Myasthenia Gravis Treatment
Use with atropine
0.01-0.04 mg/kg IV/IM/SC q2-3hr PRn
2 mg/kg/day divided q4hr PO; no more than 375mg/day
Nondepolarizing Neuromuscular Blockade, Reversal
Adult guidelines should be followed when administered to pediatric patients, including neonates; pediatric patients require doses similar to those for adults
0.03-0.07 mg/kg IV will generally achieve a TOF twitch ratio of 90% within 10-20 minutes of administration
Not to exceed 0.07 mg/kg or a cumulative total of 5 mg, whichever dose is less Inject by slow IV over at least 1 minute
Dose selection should be based on the extent of spontaneous recovery that has occurred at the time of administration, the half-life of the NMBA being reversed, and whether there is a need to rapidly reverse the NMBA
Administer an IV anticholinergic (eg, atropine, glycopyrrolate) prior to, or concomitantly with neostigmine for NMB reversal; if bradycardia present, give anticholinergic before neostigmine
0.03 mg/kg
- Use for reversal of NMBAs with shorter half-lives (eg, rocuronium), OR
- When the first twitch response to the TOF stimulus is substantially >10% of baseline or when a second twitch is present
0.07 mg/kg
- Use for NMBAs with longer half-lives (eg, vecuronium, pancuronium), OR
- When the first twitch response is relatively weak (ie, not substantially >10% of baseline), OR
- There is need for more rapid recovery
Administration
IV TOF monitoring for NMB reversaL
- Peripheral nerve stimulation devices capable of delivering a train-of-four (TOF) stimulus are essential to effectively and safely adjust IV dose
- There must be a twitch response to the first stimulus in the TOF of at least 10% of its baseline level (ie, the response before NMBA administration, prior to neostigmine)
Prostigmin, Bloxiverz (neostigmine) adverse (side) effects
Frequency not defined
Allergic: Allergic reactions and anaphylaxis
Neurologic: Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes
Cardiovascular: Cardiac arrhythmias (including bradycardia, tachycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported, as well as cardiac arrest, syncope and hypotension (predominantly with parenteral dosage form)
Respiratory: Increased oral, pharyngeal and bronchial secretions, and dyspnea; respiratory depression, respiratory arrest and bronchospasm have been reported following the use of the injectable form
Dermatologic: Rash and urticaria
Gastrointestinal: Nausea, emesis, flatulence, and increased peristalsis and salivation
Genitourinary: Urinary frequency
Musculoskeletal: Muscle cramps and spasms, arthralgia
Miscellaneous: Diaphoresis, flushing and weakness
Warnings
Contraindications
Hypersensitivity, previous history of reaction to bromides
Peritonitis or mechanical GI or urinary tract obstruction
Cautions
Caution in epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias, peptic ulcer
Neonates; because of self-limiting nature of myasthenia gravis, reduce daily dosage gradually released until drug can be withdrawn
Avoid large doses in situations where there might be an increased absorption rate from the intestinal tract; caution when coadministered with anticholinergic drugs because of decreased GI motility
Differentiate between myasthenic crisis and cholinergic crisis caused by overdosage of neostigmine; both conditions result in extreme muscle weakness but require radically different treatment
Anticholinesterase insensitivity can develop
If excess cholinergic symptoms develop, discontinue therapy
Atropine and epinephrine must be available to treat a hypersensitivity reaction
Not recomended for use in patients with vagotonia
May prolong the phase 1 block of depolarizing muscle relaxants
Pregnancy and lactation
Pregnancy: There are no adequate or well-controlled studies in pregnant women; not known whether neostigmine can cause fetal harm or affect reproductive capacity; should administer only if clearly needed
Lactation: Unknown if distributed in human breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Prostigmin, Bloxiverz (neostigmine)
Mechanism of action
Competitive inhibitor of cholinesterase resulting in decreased hydrolysis of acetylcholine by cholinesterase; by reducing the breakdown of acetylcholine, neostigmine increases acetylcholine in the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular blocking agents, and reverses the neuromuscular blockade
Absorption
Bioavailability: 1-2% (PO); general PO:IV equivalence ~15 mg neostigmine bromide PO is equivalent to 0.5 mg neostigmine methylsulfate parenteraL
Onset: 1-20 min (IV); 20-30 min (IM)
Duration: 2.5-4 hr (IM); 1-2 hr (IV)
Peak plasma time: 30 min (IM); 1-2 hr (PO)
Distribution
Protein bound: 15-25% to albumin (PO)
Metabolism
Liver microsomal enzymes and hydrolysis by cholinesterase enzymes
Elimination
Half-Life: 47-60 min (IV); 51-90 min (IM); 42-60 min (PO)
Excretion: 50% urine
Administration
IV Incompatibilities: none specified
IV Administration: slow IV injection
