What is the initial treatment for primary periodic paralysis?

Treatment of Primary Periodic Paralysis

The initial treatment for primary periodic paralysis is dichlorphenamide (Keveyis) at a starting dose of 50 mg once or twice daily, with dosage adjustments based on individual response. 1

Understanding Primary Periodic Paralysis

Primary periodic paralysis (PPP) is a group of rare inherited muscle disorders characterized by episodes of flaccid weakness affecting one or more limbs, lasting several hours to several days. These conditions are caused by mutations in skeletal muscle ion channel genes, primarily affecting sodium, calcium, or potassium channels 2. The two main types are:

• Hypokalemic periodic paralysis (HypoPP) - associated with low serum potassium
• Hyperkalemic periodic paralysis (HyperPP) - associated with high serum potassium

First-Line Treatment

Dichlorphenamide (Keveyis)

Dichlorphenamide is an oral carbonic anhydrase inhibitor that has demonstrated significant efficacy in both hypokalemic and hyperkalemic periodic paralysis:

• Initial dosing: 50 mg orally once or twice daily 1
• Titration: Dose may be increased or decreased based on individual response at weekly intervals 1
• Dosage range: Minimum recommended total daily dosage is 50 mg, maximum is 200 mg 1
• Efficacy assessment: Evaluate response after 2 months of treatment to determine whether to continue therapy 1

Evidence supporting dichlorphenamide shows:

• Significantly reduced attack frequency in both HypoPP and HyperPP patients 3, 4
• In clinical trials, dichlorphenamide demonstrated an eightfold lower paralytic attack rate in HypoPP and approximately fivefold lower attack rate in HyperPP compared to placebo 4
• Efficacy in both adolescents and adults 5

Monitoring and Safety Considerations

• Baseline and periodic measurements of serum potassium and sodium bicarbonate are recommended during treatment 1
• Monitor for adverse effects:
  • Most common: paresthesias, cognitive disorders, and dysgeusia 1, 4
  • In adolescents: skin rash is more common (33%) 5
  • In adults: numbness is more common (48%) 5

Alternative Treatment Options

If dichlorphenamide is not tolerated or ineffective, consider:

Acetazolamide

• Another carbonic anhydrase inhibitor that has shown efficacy in improving muscle strength in some patients with HypoPP 3
• Important caveat: Some patients with HypoPP may experience worsening of attacks with acetazolamide 6, so careful monitoring is essential

Triamterene

• May be effective in patients who worsen with acetazolamide 6
• Works by increasing potassium levels

Treatment Algorithm

1. Initial therapy: Start dichlorphenamide 50 mg once or twice daily
2. Assess response after 2 months
3. If effective: Continue treatment with periodic monitoring of serum potassium and bicarbonate
4. If inadequate response: Titrate dose up to maximum of 200 mg daily
5. If ineffective or not tolerated: Consider acetazolamide (with careful monitoring) or triamterene

Special Considerations

• Contraindications for dichlorphenamide 1:

  • Hepatic insufficiency
  • Severe pulmonary disease
  • Hypersensitivity to sulfonamides
  • Concomitant use with high-dose aspirin

• Hypokalemia risk: Dichlorphenamide increases potassium excretion and can cause hypokalemia, requiring careful monitoring 1

• Metabolic acidosis: As a carbonic anhydrase inhibitor, dichlorphenamide can cause metabolic acidosis 1

By following this treatment approach and monitoring protocol, patients with primary periodic paralysis can experience significant reduction in attack frequency and severity, leading to improved quality of life.