Primary Periodic Paralysis (PPP) Information

Primary Periodic Paralysis PPP is a complex condition

The disorder is described as a group of rare channelopathies with varying subtypes and triggers

Primary Periodic Paralysis PPP is very rare, ~4,000 to 5,000 individuals have been diagnosed with PPP in the United States.1 This condition includes a spectrum of chronic, genetic, neuromuscular disorders with autosomal dominant inheritance that cause recurrent, progressive, and debilitating episodes of extreme muscle weakness and temporary paralysis that can negatively impact patients’ daily lives.2-7

Educational segment in Primary Periodic Paralysis

Strongbridge Biopharma sponsored an educational segment about Primary Periodic Paralysis on The Balancing Act, “Behind the Mystery: Rare and Genetic Diseases.” The segment features Linda Feld, Vice President of Periodic Paralysis Association (PPA), and Steve Cannon, MD, PhD, neurologist and professor of physiology at UCLA. A broad range of topics related to Primary Periodic Paralysis are addressed within the segment, including symptoms, triggers, misdiagnosis, and genetic testing.

There are 2 more common types of Primary Periodic Paralysis PPP

Although there are related variants, the most common forms are hyperkalemic and hypokalemic periodic paralysis.8-12

Hyperkalemic Periodic Paralysis13
Hypokalemic Periodic Paralysis14
Associated with:
  • Paralytic episodes with a serum potassium increase of at least 1.5 mmol/L during an attack
Triggers may include:
  • Cold environment
  • Rest after exercise
  • Stress or fatigue
  • Alcohol and certain foods/beverages
  • Potassium in food
  • Hunger/fasting
  • Changes in activity level
  • Changes in humidity
  • Extra sleep
  • Pregnancy and menstruation
  • Illness of any type
  • Some medications
  • Potassium supplements
Associated with:
  • Paralytic episodes with concomitant hypokalemia (<2.5 mmol/L)
Triggers may include:
  • Rest after exercise
  • Carbohydrate-rich evening meals
  • Periods of inactivity, including nocturnal rest
  • Heavy meals
  • Sweets
  • Salt
  • Cold
  • Stress

Genetic inheritance is the major risk factor13,14

Primary Periodic Paralysis PPP is usually inherited from a parent to a child and may affect multiple individuals within a family7
  • In hyperkalemic periodic paralysis, SCN4A is primarily associated; if no pathogenic variant is identified, sequencing of KCNJ2 and CACNA1S may be considered13
  • In hypokalemic periodic paralysis, 3 genes have been associated; all encode subunits of ion channels that are primarily expressed in skeletal muscle cells14
    • CACNA1S (60% of patients)
    • SCN4A (20% of patients)
    • KCNJ18 (3.5% of patients)
However, while usually inherited, Primary Periodic Paralysis PPP sometimes presents as a de novo mutation, adding to the difficulty of diagnosing the disorder. For this reason, it should not necessarily be ruled out in patients who are exhibiting suggestive signs and symptoms but have no family history of the disorder.2

Signs and symptoms may vary among patients2

The clinical manifestations of Primary Periodic Paralysis PPP vary not only by the area of the body affected but also by the frequency of attacks.2 In a survey of 66 self-selected adults over the age of 40 diagnosed with Primary Periodic Paralysis PPP, episodes occured weekly in 59% of patients and daily in 28%. Attacks may not be present in as many as 11%.5

Symptoms are often nonspecific with varying clinical presentations5*

*Based on a survey of 66 self-selected patients over the age of 40 years with a clinical diagnosis of Primary Periodic Paralysis who sought support via the Internet. Symptoms of permanent muscle weakness reported in the subgroup of patients with permanent weakness (n=45).5

May be the only clinical sign present between attacks.2

Primary Periodic Paralysis PPP can greatly impact patients’ lives

Primary Periodic Paralysis PPP is a rare, physically disabling condition with unpredictable attacks that vary in severity and duration and can take a toll on a patient’s ability to confidently engage in everyday activities.2*
  • Anxiety: Patients may suffer social anxiety for fear of an attack2
  • Lingering symptoms: Symptoms of attack may linger after a paralytic episode2,13
    • May include clumsiness, extreme fatigue, weakness, and pain
    • Can cause patients to fear oncoming attacks and miss out on daily activities2
  • Persistent muscle weakness: As they age, some patients may experience permanent weakness, further impacting their quality of life2

*These symptoms need to be considered within the overall treatment plan. No treatment for Primary Periodic Paralysis PPP is indicated to address all of these symptoms.

KEVEYIS is the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of Primary Periodic Paralysis. Learn more.



KEVEYIS is indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants.

Important Safety Information

  • Hypersensitivity to dichlorphenamide or other sulfonamides
  • Concomitant use of KEVEYIS and high-dose aspirin
  • Severe pulmonary disease, limiting compensation to metabolic acidosis caused by KEVEYIS
  • Hepatic insufficiency: KEVEYIS may aggravate hepatic encephalopathy
Warnings and Precautions

Hypersensitivity and Other Life-Threatening Reactions

  • Fatalities associated with the administration of sulfonamides have occurred because of adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
  • Pulmonary involvement can occur in isolation or as part of a systemic reaction.
  • Discontinue KEVEYIS at the first appearance of skin rash or any sign of immune-mediated or other life-threatening adverse reaction.

Concomitant Use of Aspirin or Other Salicylates

  • Carbonic anhydrous inhibitors, including KEVEYIS, can cause metabolic acidosis, which can increase the risk of salicylate toxicity.
  • Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin.
  • Concomitant use of KEVEYIS and high-dose aspirin is contraindicated. Use with caution and carefully monitor in patients receiving low-dose aspirin.


  • KEVEYIS increases potassium excretion and can cause hypokalemia.
  • The risk of hypokalemia is greater when KEVEYIS is used in patients with conditions associated with hypokalemia (e.g., adrenocortical excess, renal tubular acidosis type 1 and 2), and in patients receiving other drugs that may cause hypokalemia (e.g., loop diuretics, thiazide diuretics, laxatives, antifungals, penicillin, and theophylline).
  • Baseline and periodic measurements of serum potassium are recommended.
  • If hypokalemia develops or persists, consider reducing the dose or discontinuing KEVEYIS and correction of potassium levels.

Metabolic Acidosis

  • KEVEYIS can cause hyperchloremic non-anion gap metabolic acidosis.
  • Concomitant use of KEVEYIS with other drugs that cause metabolic acidosis may increase the severity of acidosis.
  • Concomitant use of KEVEYIS in compensated patients with respiratory acidosis, such as in advanced lung diseases, may lead to respiratory decompensation.
  • Baseline and periodic measurements of serum bicarbonate during KEVEYIS treatment are recommended.
  • If metabolic acidosis develops or persists, consider reducing the dose or discontinuing KEVEYIS.


  • KEVEYIS increases the risk of falls; risk is greater in the elderly and with higher doses.
  • Consider dose reduction or discontinuation of KEVEYIS in patients who experience falls while treated with KEVEYIS.
Pregnancy and Lactation

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known in humans whether dichlorphenamide is excreted in human milk; exercise caution when administered to a nursing woman.

Adverse Reactions

The most common adverse reactions seen in clinical trials (incidence ≥ 10% and greater than placebo) include paresthesias, cognitive disorder, dysgeusia, and confusional state.


  1. Data on file. Feasterville-Trevose, PA: Strongbridge Biopharma; 2017.
  2. Charles G, Zheng C, Lehmann-Horn F, Jurkat-Rott K, Levitt J. Characterization of hyperkalemic periodic paralysis: a survey of genetically diagnosed individuals. J Neurol. 2013;260:2606-2613.
  3. Arya SN. Periodic paralysis. Journal, Indian Academy of Clinical Medicine. 2002;3:374-382.
  4. Cannon SC. Channelopathies of skeletal muscle excitability. Compr Physiol. 2015;5:761–790.
  5. Cavel-Greant D, Lehmann-Horn F, Jurkat-Rott K. The impact of permanent muscle weakness on quality of life in periodic paralysis: a survey of 66 patients. Acta Myol. 2012;31:126–133.
  6. Grieg SL. Dichlorphenamide: a review in primary periodic paralyses. Drugs. 2016;76:501-507.
  7. Fontaine B, Phillips LH. A newly approved drug for a rare group of diseases: dichlorphenamide for periodic paralysis. Neurology. 2016;86:1366-1367.
  8. National Institutes of Health. Hyperkalemic periodic paralysis. Available at: Accessed December 5, 2016.
  9. National Institutes of Health. Hypokalemic periodic paralysis. Available at: Accessed December 5, 2016.
  10. National Institutes of Health. Anderson-Tawil syndrome. Available at: Accessed December 5, 2016.
  11. National Institutes of Health. Potassium-aggravated myotonia. Available at: Accessed December 5, 2016.
  12. National Institutes of Health. Paramyotonia congenita. Available at: Accessed December 5, 2016.
  13. Weber F, Jurkat-Rott, Karin, Lehmann-Horn F. Hyperkalemic Periodic Paralysis. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. 2016.
  14. Vicart S, Sternberg D, Arzel-Hezode M, et al. Hypokalemic Periodic Paralysis. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. 2014.