PRYDOSTRIN 60 mg

Indications

• Myasthenia gravis
• Reversal of neuromuscular block
• Congenital myasthenic syndromes

Dosage

Children: Refer to BNF for Children for specific dosing guidance based on the condition being treated.

Adults: Refer to BNF for specific dosing guidance based on the condition being treated.

Mechanism of action

Pyridostigmine enhances synaptic transmission by inhibiting acetylcholinesterase, leading to increased levels of acetylcholine in the synaptic cleft. This action is particularly beneficial in myasthenia gravis, where autoantibodies impair acetylcholine receptor function. By preventing the degradation of acetylcholine, pyridostigmine effectively increases the stimulation of postsynaptic receptors, thereby improving muscle strength and reducing symptoms of weakness and fatigue.

Pharmacodynamics

Pyridostigmine is a cholinesterase inhibitor with a longer duration of action and a milder side effect profile compared to other agents like neostigmine. While it enhances cholinergic transmission, excessive doses can lead to a cholinergic crisis, characterized by symptoms such as muscle weakness, bradycardia, and excessive secretions. In such cases, atropine may be administered to counteract these effects.

Pharmacokinetics

Pyridostigmine is administered orally and is well absorbed from the gastrointestinal tract. It undergoes hepatic metabolism and is eliminated primarily through the kidneys. The onset of action is typically within 30 minutes to 1 hour after oral administration, with effects lasting for several hours, making it suitable for multiple daily dosing to maintain therapeutic levels.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Increased salivation
• Sweating
• Bradycardia
• Muscle cramps
• Cholinergic crisis

Interactions

• Aminoglycosides: Unknown (decreases effects)

Precautions

• Use with caution in patients with asthma or other obstructive pulmonary conditions.
• Caution in patients with cardiac arrhythmias.
• Monitor for signs of cholinergic crisis, especially with excessive doses.

Pregnancy

Pyridostigmine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with an obstetrician for individual assessment.

Breast-feeding

Pyridostigmine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Sustained-release tablets
• Oral solution

Indications

• Myasthenia gravis
• Reversal of non-depolarizing neuromuscular blockade
• Symptomatic treatment of Lambert-Eaton myasthenic syndrome (specialist use only)

Dosage

Children: Child 1 month to 7 years: Initially 300 micrograms/kg daily in 4 divided doses, increased

Adults: Initially, 15 mg daily in 3 divided doses, then increased in steps of 5 mg every 4 to 5 days, up to a maximum of 60 mg daily in 3 to 4 divided doses (max. per dose 20 mg).

Mechanism of action

Pyridostigmine bromide functions by inhibiting acetylcholinesterase, thereby prolonging the action of acetylcholine at cholinergic receptors. This leads to enhanced neuromuscular transmission, which is crucial for muscle contraction. The inhibition of this enzyme allows for increased acetylcholine availability, particularly at the neuromuscular junction, improving muscle strength in conditions like myasthenia gravis.

Pharmacodynamics

The pharmacodynamic effects of pyridostigmine bromide include increased muscle strength and improved neuromuscular transmission. The duration of action is typically 3 to 6 hours, with clinical effects manifesting as improved muscle function in patients with myasthenia gravis. Side effects may include gastrointestinal hypermotility and muscle cramps due to increased cholinergic activity.

Pharmacokinetics

Pyridostigmine is well absorbed when administered orally, with peak plasma concentrations attained within 1 to 2 hours post-dose. It is partially metabolized in the liver and has a bioavailability of approximately 75%. The drug is eliminated primarily through the kidneys, and its half-life is around 3 to 4 hours. Dose adjustments may be necessary in patients with renal impairment to prevent accumulation.

Contra-indications

• Congenital QT syndromes
• Epilepsy
• Uncontrolled asthma

Adverse effects

• Dizziness
• Gastrointestinal hypermotility
• Muscle cramps
• Rash
• Increased bronchial secretion
• Cough
• Sleep disorder
• Blurred vision

Interactions

• Amifampridine
• Neostigmine

Precautions

• Risk factors for schwannomas
• Caution in hepatic impairment (risk of increased exposure)
• Caution in renal impairment (consider dose reduction)

Pregnancy

Manufacturer advises to avoid.

Breast-feeding

Manufacturer advises to avoid-no information available.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablet: 15 mg
• Solution for injection: 2.5 mg/1 ml

Mechanism of action

Myasthenia gravis is an autoimmune disease involving dysfunction at the neuromuscular junction most commonly due to autoantibodies directed against the acetylcholine receptor (AChR), but also against other targets such as the muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin. In the case of AChR antibodies, AChRs are directly bound and cross-linked, impairing acetylcholine binding and contributing through various mechanisms to receptor degradation. The lack of acetylcholine signalling leads to muscle tone loss, muscle weakness, and fatigue. Pyridostigmine is a reversible acetylcholinesterase inhibitor that increases extracellular acetylcholine levels in the neuromuscular junction by impairing its breakdown by acetylcholinesterase. The increased acetylcholine leads to increased neural transmission across the junction, which drastically improves myasthenia gravis symptoms. In addition to its use in myasthenia gravis and in reversing neuromuscular blocks, pyridostigmine is also a common first-line treatment in congenital myasthenic syndromes (CMS), of which there are multiple subtypes caused by mutations in more than 30 distinct genes. CMS present similarly to myasthenia gravis, albeit due to distinct underlying causes, and often benefit from pyridostigmine. However, in some subgroups, treatment with pyridostigmine is detrimental; detailed genetic testing is required before starting therapy.

Pharmacodynamics

Pyridostigmine bromide, designated as 3-hydroxy-1-methyl-pyridinium bromide dimethyl-carbamate, is an orally active reversible cholinesterase inhibitor similar to [neostigmine] but with a milder adverse effect profile and a longer duration of action. Pyridostigmine may, specifically in the case of excessive administration, result in a cholinergic crisis, with symptoms mimicking a myasthenic crisis. Administration of atropine is recommended in the case of a true cholinergic crisis or to counteract muscarinic/nicotinic effects such as bradycardia and excessive bronchial secretions.