Muscle cramps

For idiopathic (ordinary) cramps and exercise-associated cramps, there are no typical time frames for return visits or follow-up tests. For cramps associated with organic diseases or pregnancy, follow-up monitoring of laboratory tests is dependent on the underlying condition. Identification of exacerbating causes is important. Specific monitoring parameters for drug efficacy and/or adverse effects of medication used for the treatment and prevention of cramps are needed for a minority of drug treatments.

• Baclofen

  • Although baclofen has several uncomfortable adverse effects (e.g., postural hypotension), no typical follow-up schedule has been recommended.

  • However, if weakness develops, this adverse effect may lead to diagnostic confusion of cramps with organic neurologic and/or muscle disease, necessitating additional follow-up, including muscle-specific diagnostic tests.

  • Additional follow-up is needed if baclofen is to be discontinued because too rapid discontinuation can lead to a dangerous constellation of signs and symptoms consistent with a drug withdrawal syndrome. These include muscle rigidity, high fever, altered mental status, and psychopathology, including auditory, visual, and tactile hallucinations, delusions, paranoia, and agitation.

• Phenytoin

  • Due to the complex saturable pharmacokinetics of phenytoin, serum concentration monitoring at steady-state after a minimum of 1 week on a given regimen is recommended, beginning after the dosage has been titrated up to 300 mg/day. If cramps have not been optimally controlled and dosage escalation is desired, further serum concentration monitoring is recommended after each dosage increment (50-100 mg/daily). This will allow the maximum safe dose of the drug to be used (total serum concentration should be maintained at ≤20 mg/L or free serum concentration at ≤2 mg/L).

  • Monitoring for loss of efficacy of other drugs (due to hepatic enzyme-stimulating effects of phenytoin, thus increasing the clearance of other drugs from the body) may necessitate further follow-up, including serum concentration monitoring of these other drugs.

  • Dental follow-up may be necessary if phenytoin results in gingival hyperplasia.

  • If the patient is planning pregnancy, or becomes pregnant, discontinuation of phenytoin therapy is strongly recommended because it is a human teratogen.

  • Recommendations to monitor liver function tests (LFTs) for hepatotoxicity and blood glucose for hyperglycemia (only in type 2 diabetes), as advocated by the manufacturer, are necessary on an annual basis.

• Carbamazepine

  • Serum concentration monitoring of carbamazepine is recommended at steady-state after a minimum of 1 week on a given regimen, beginning after the dosage has been titrated up to 600 mg/day. After each dosage increment (100-200 mg/day) for unresolved cramps, further serum concentration monitoring is recommended. This will allow the maximum safe dose of the drug to be used (maintaining the total serum concentration at ≤12 mg/L).

  • Carbamazepine is a hepatic enzyme stimulant and can increase the clearance of other drugs, thus reducing their efficacies. Further follow-up of other drugs may be necessary.

  • Other laboratory tests are necessary to monitor for adverse effects of the drug on an annual basis: LFTs (hepatotoxicity), complete blood count with differential (bone marrow suppression), serum sodium (hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone), renal function tests, and thyroid function tests.

  • If the patient is planning pregnancy, or becomes pregnant, discontinuation of carbamazepine therapy is strongly recommended because it is a known teratogen.

• Quinine

  • The Food and Drug Administration has issued a warning against the use of quinine for leg cramps. FDA: drug safety information for quinine sulfate Opens in new window In other countries, even if it is used, quinine should not be considered the drug of choice for idiopathic cramps. The American Academy of Neurology recommends that quinine use should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[99]Katzberg HD, Khan AH, So YT. Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 2010;74:691-696. http://www.neurology.org/content/74/8/691.long http://www.ncbi.nlm.nih.gov/pubmed/20177124?tool=bestpractice.com

  • Due to the ongoing controversy regarding the efficacy of quinine, a follow-up visit to assess efficacy should occur after 4 to 6 weeks. If no efficacy is demonstrated by this visit, quinine therapy should be discontinued and alternative therapy commenced.

  • Follow-up laboratory testing for quinine-associated bone marrow toxicity or hepatotoxicity is not recommended because the onset of these entities is too rapid to be discovered by infrequent screening.

  • Audiometry is not recommended for quinine-associated toxicity due to the rarity of the condition.

  • If the patient is planning pregnancy, or becomes pregnant, discontinuation of quinine therapy is strongly recommended because it is a human teratogen.

  • Follow-up serum concentration monitoring of quinine is not recommended because safe dosage augmentation beyond 648 mg daily of the sulfate salt is not possible due to the absence of any supportive clinical efficacy or safety data. However, because quinine is a cytochrome P450 isozyme 2D6 (CYP2D6) enzyme inhibitor, quinine co-therapy can interact with other drugs metabolized by CYP2D6, thus increasing their serum concentrations, predisposing to toxicity. This may necessitate follow-up serum concentration monitoring of other drugs.