The AAN has published a new guideline on symptomatic treatment for muscle cramps. The guideline recommends that the drug quinine, although effective, be avoided for treatment of routine muscle cramps due to uncommon but serious side effects. Lead guideline author Hans D. Katzberg, MD, spoke with Neil A. Busis, MD, FAAN, AAN.com Practice & Technology Website Associate Editor.
AAN.com: Please tell us about the 2006 Food and Drug Administration advisory that warned against the off-label use of quinine sulfate and its derivatives in the treatment of muscle cramps.
Katzberg: In December 2006, the FDA issued a statement ordering unapproved quinine drugs to be pulled off the market and warning consumers against the use of these drugs for the treatment of muscle cramps. The reason for the statement was 663 reports of serious adverse events (the main ones being hematologic events such as idiopathic thrombocytopenic purpura (ITP), or thrombotic thrombocytopenic purpura (TTP)), as well as 93 deaths attributed to quinine drugs reported since 1969. The FDA stated that these harms outweighed any potential benefit from the medication for use in treatment of muscle cramps. This statement has now made it onto a boxed warning for quinine sulfate, which is still manufactured in limited amounts and indicated only for the treatment of plasmodium falciparum malaria in the United States.
AAN.com: What is the purpose of this AAN clinical practice guideline?
Katzberg: To educate physicians and the public on the role of quinine for treatment of muscle cramp symptoms and to increase knowledge of alternative symptomatic treatments for muscle cramps. By highlighting the lack of available evidence, we also hope to encourage research on alternative treatments for muscle cramps.
AAN.com: Who is the target audience?
Katzberg: Health care providers who treat patients with muscle cramps as well as patients with muscle cramps and their families and caregivers.
AAN.com: What are the main conclusions of these new guidelines?
Katzberg: First, there are several drugs available to treat muscle cramp symptoms, but more research is needed on their safety and effectiveness. Also, we found evidence that quinine drugs effectively treat muscle cramp symptoms, but should be generally avoided due to uncommon but serious side effects.
AAN.com: How should these guidelines be used in clinical practice?
Katzberg: Physicians should be aware that disabling muscle cramps may be due to a number of medical or neurologic conditions, which should be ruled out before diagnosing someone with idiopathic cramps. When symptomatic treatment is required, a number of drugs included in our review may be used, including calcium channel blockers and vitamin B complex. Quinine drugs should be considered only in special cases: when cramp symptoms are very disabling, when other drugs don’t help, and when side effects are carefully watched.
AAN.com: Class I studies showed the efficacy of quinine derivatives for treatment of muscle cramps. However, their benefit was modest. Please explain.
Katzberg: In the two Class I studies identified, there was a reduction of approximately 25 to 40 percent in number of muscle cramps, which translated into a reduction of two to five cramps per three-week treatment phase: this is significant, but it does not eliminate or even nearly eliminate muscle cramps.
AAN.com: There were significant adverse effects from quinine derivatives in published prospective trials as well as case reports. What were they?
Katzberg: The significant major side effects from quinine drugs were hematological abnormalities such as hemolytic uremic syndrome-thrombotic thrombocytopenia purpura (HUS-TTP), disseminated intravascular coagulation (DIC), and bleeding diathesis. Less common side effects included hypoglycemia, retinal toxicity, hepatotoxicity, cardiac arrhythmias, pulmonary edema, and hypersensitivity reactions.
AAN.com: The guidelines recommended against routine use of quinine derivatives for the management of cramps, but in select patients it can be considered for an individual therapeutic trial. How do you recommend clinicians work through this decision process?
Katzberg: We recommend that clinicians use any of the alternate medications listed in the practice parameter that have some evidence for efficacy in the management of muscle cramps. If a patient is experiencing significant disability from cramps and is still refractory to these treatments, a trial of quinine drugs may be warranted if the patient is aware of all the potential side effects, including death, associated with their use.
AAN.com: What are the roles of vitamin B complex, naftidrofuryl, and calcium channel blockers such as diltiazem in the management of cramps?
Katzberg: Diltiazem and vitamin B complex each have Level C evidence and are acceptable medications as first and second line treatment of symptomatic muscle cramps. Naftidrofuryl also has Level C evidence for treatment of muscle cramps; however, it is not available for use in the United States.
Within the past 24 months, Dr. Busis received personal compensation for his work as AAN.com Practice and Technology Editor, as well as for speaking at AAN and AANEM courses. In the same period, he served as Editorial Advisor for Neurology Coding Alert. He has also given expert testimony on coding issues.