Muscle cramps

1st line – stretching

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1st line –

stretching

Nonpharmacologic therapy forms the cornerstone of management of acute muscle cramps.

Stretching of the affected muscle(s) will relieve cramps in most cases.[1][3][52] Both passive and active stretching are effective.

Passive stretching involves relief of the tension on the affected muscle(s) by, for example, rubbing and postural changes.[52]

Active stretching involves contraction of the antagonist muscle(s), leading to a spinal cord reflex evoking reciprocal inhibition of the cramping muscle (e.g., ankle dorsiflexion during calf muscle cramps).[1][52]

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pharmacotherapy

Approaches to preventing recurrent cramps of unknown etiology have engendered controversy for many years.

Based on available data, possible first-line choices include verapamil, diltiazem, and vitamin B complex (specifically pyridoxine).[99][104] Second-line choices include selected muscle relaxants (e.g., carisoprodol) or gabapentin.[105][106][107] However, one 2010 evidence-based review by the American Academy of Neurology (AAN) recommended only 3 possibly effective drugs: naftidrofuryl (not available in the US), vitamin B complex (specifically, pyridoxine), and diltiazem.[99] One 2020 Cochrane review concluded that it is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults with skeletal muscle cramps.[108]

Despite some evidence for the effectiveness of quinine, examination of the data has cast doubt on its efficacy and safety.[99][100][101][102][109] [ ] There are also concerns about the possibility of serious drug-drug interactions, particularly in older adults.[103] This is reflected by a warning issued by the Food and Drug Administration in the US against using quinine for leg cramps. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that quinine use should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[99]

In other countries, quinine preparations may be more readily available, but the safety concerns are such that quinine should not be considered the drug of choice for the prevention of idiopathic cramps.

Primary options

diltiazem: children: 1.5 mg/kg/day orally initially, given in 3-4 divided doses, increase according to response, maximum 3.5 mg/kg/day; adults: 30 mg orally (immediate-release) once daily at bedtime initially, increase according to response, maximum 90 mg/day

pyridoxine (vitamin B6): adults: 30 mg orally once daily

verapamil: adults: 120 mg/day orally (immediate-release) initially, given in 3-4 divided doses, increase according to response, maximum 360 mg/day; 120 mg orally (extended-release) once daily initially, increase according to response, maximum 360 mg/day

Secondary options

gabapentin: adults: 300 mg/day orally initially, given in 3 divided doses, increase according to response, maximum 1800 mg/day

carisoprodol: adults: 350 mg orally once daily initially, increase according to response, maximum 1400 mg/day given in 2-4 divided doses

exercise-associated

1st line – environmental adjustment, oral rehydration + supportive care

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1st line –

environmental adjustment, oral rehydration + supportive care

Supportive care includes rest in a comfortable environment (in terms of temperature and ventilation), along with stretching of the affected muscle(s).

Oral rehydration with balanced electrolyte solutions (or sports drinks plus foods containing sodium) is important if the urine is dark or scant during the first hours.[16][42]

Frictional icing massage of the affected muscle(s) should be considered as a form of analgesia if cramp pain is severe.[42] The patient's own medications should not be given temporarily.[42] Drug therapy specifically for cramp is not recommended.[42]

Severe exercise-associated muscle cramps are characterized by severe or generalized cramping in muscles not subjected to exercise, or localized cramping associated with altered consciousness, altered body temperature, anuria, and/or myoglobinuria. They are not defined as true exercise-associated cramps. Immediate admission to an emergency department is necessary for further assessment and management.[42]

1st line – patient education

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1st line –

patient education

Primary prevention of exercise-associated muscle cramps involves education. Athletes should be in a well-conditioned state for an event and adequately hydrated. It has been recommended that at-risk muscle groups are well stretched before activity begins, but there is inadequate evidence to support this. An appropriate diet, incorporating sufficient carbohydrates, is necessary to prevent premature muscle fatigue.[28]

hypoglycemia-associated in diabetes mellitus

1st line – glucose

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1st line –

glucose

Immediate resolution of hypoglycemia is paramount for the resolution of acute cramps, usually by ingestion of simple sugar by mouth.[64][74][75][110]

Drug therapy specifically for cramp is not recommended.

1st line – optimization of glycemic control

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1st line –

optimization of glycemic control

Optimization of blood sugar control to avoid recurrent hypoglycemia is mandatory to prevent further episodes.

This may involve adjustments to diet (including snacks to cover at-risk time periods and adequate carbohydrates to cover exercise periods), avoiding alcohol, and adjustment of injectable and/or oral antidiabetic therapies.

Intensive glycemic control in diabetes is associated with an increased risk for hypoglycemia compared with conventional treatment.[111][112]

pregnancy-associated

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supportive measures

Management of acute cramp is supportive with stretching of the affected muscle(s).

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pharmacotherapy

Data regarding the efficacy of therapies for the prevention of recurrent cramps in pregnancy are conflicting. It is unclear whether oral magnesium, calcium, vitamin B, or vitamin C are effective preventive treatments.[35][108] However, magnesium salts (most commonly oxide, citrate, or hydroxide) are safe, and worthy of a trial as agents of first choice.[113] Diarrhea may be a dose-limiting adverse effect.

Should this therapy prove inadequate, a trial of a combination of vitamins B1 (thiamine) and B6 (pyridoxine), is probably worthwhile.[99][114] Calcium salts and sodium chloride are of no benefit and should not be used.[37][38]

Other drug therapies have not been evaluated in pregnancy-associated cramps, and may lead to adverse fetal outcomes.[115]

Cramps significantly remit after delivery.[17]

Primary options

magnesium oxide: adults: 140-400 mg/day orally

Secondary options

thiamine (vitamin B1): adults: 250 mg orally twice daily

and

pyridoxine (vitamin B6): adults: 250 mg orally twice daily

dialysis-associated

1st line – hemodialysis procedural adjustments by specialist

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1st line –

hemodialysis procedural adjustments by specialist

Procedural adjustments to the hemodialysis regimen can be made by nephrologists if acute cramp occurs in a patient during a hemodialysis session. These measures are beyond the scope of this topic.

1st line – preemptive hemodialysis procedural measures

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1st line –

preemptive hemodialysis procedural measures

Patients undergoing hemodialysis may be able to undergo preemptive measures to avoid the development of intradialytic cramps.

These are specialist measures and are beyond the scope of this topic.

Consider – pharmacotherapy

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Consider –

pharmacotherapy

Treatment recommended for SOME patients in selected patient group

If nonpharmacologic specialist procedural measures are inadequate to prevent intradialytic cramps, a combination of vitamin E (alpha-tocopherol) plus vitamin C (ascorbic acid) is reasonable.[116]

Vitamin E at bedtime was shown to be effective in an open-label trial and in a comparative trial with quinine.[117][118]

Creatine monohydrate is thought to improve muscle metabolism by increasing the creatine phosphate stores in the muscle, which, in turn, donate high-energy phosphate groups to adenosine diphosphate to create adenosine triphosphate. This has been documented in athletes receiving creatine supplementation.[119] It may be beneficial in the reduction of cramps associated with hemodialysis.[120]

There is evidence that quinine is effective in significantly reducing cramp frequency and cramp severity in patients using hemodialysis or continuous ambulatory peritoneal dialysis.[118][121] However, in some countries, quinine therapy should only be considered if vitamin therapy has not produced the desired results. The Food and Drug Administration has issued a warning against using quinine for leg cramps. FDA: drug safety information for quinine sulfate Opens in new window 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 where side effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[99]

Primary options

alpha-tocopherol (vitamin E): adults: 400 units orally once daily

and

ascorbic acid (vitamin C): adults: 250 mg orally once daily

alpha-tocopherol (vitamin E): adults: 400 units orally once daily

Secondary options

creatine: adults: 12 g in 100 mL of water orally 5 minutes before each hemodialysis session

cirrhosis-associated

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supportive measures

Management of acute cramp is supportive with stretching of the affected muscle(s).

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pharmacotherapy

Oral zinc sulfate, at least in patients with low serum zinc concentrations at baseline, is a reasonable first-line agent.[123]

Vitamin E (alpha-tocopherol), particularly for patients with low serum vitamin E concentrations at baseline, is another reasonable first-line agent.[124]

One small, randomized, double-blind, placebo-controlled trial reported that quinidine was effective in reducing the occurrence of muscle cramps in patients with cirrhosis.[125] However, there are safety concerns about quinidine or quinine therapy. In the US, there is a warning against using quinine or quinidine at all for this indication. FDA: drug safety information for quinine sulfate Opens in new window 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 where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[99]

Primary options

zinc sulfate: adults: 220 mg orally twice daily

alpha-tocopherol (vitamin E): adults: 200 units orally three times daily

multiple sclerosis- or lower motor neuron disease-associated

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supportive measures

Management of acute cramp is supportive with stretching of the affected muscle(s).

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pharmacotherapy

All evidence supporting the use of a variety of drugs for the prevention of cramps associated with multiple sclerosis and motor neuron diseases is from case reports and case series.

Drug therapy includes gabapentin for severe leg cramps in people with multiple sclerosis; levetiracetam for people with slowly progressive motor neuron disease and amyotrophic lateral sclerosis (ALS), and mexiletine for people with Machado-Joseph disease.[127][128][129] Carbamazepine may also be effective.[130] One 2009 American Academy of Neurology (AAN) guideline update and one 2012 Cochrane review concluded that there is a lack of evidence to either support, or refute, any specific intervention for the treatment of muscle cramps in patients with ALS.[131][132]

In a survey of 6 ALS treatment centers in the US, neurologists rated their top 4 drugs used for cramp relief as quinine (35%), baclofen (19%), phenytoin (10%), and gabapentin (7%).[133]

The Food and Drug Administration have issued a warning against using quinine at all for this indication. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that quinine use for muscle cramps should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effect before consenting to treatment.[99]

Specific monitoring of drug levels and adverse effects of medication are needed for phenytoin and carbamazepine.

Primary options

levetiracetam: children: 5-10 mg/kg/day orally initially, given in 1-3 divided doses, increase according to response, maximum 60 mg/kg/day; adults: 500 mg orally twice daily initially, increase according to response, maximum 3000 mg/day

mexiletine: children and adults: consult specialist for guidance on dose

baclofen: children 2-7 years of age: 10-15 mg/kg/day orally initially, given in 3 divided doses, increase according to response, maximum 40 mg/day; children ≥8 years of age: 10-15 mg/kg/day orally initially, given in 3 divided doses, increase according to response, maximum 60 mg/day; adults: 15 mg/day orally initially, given in 3 divided doses, increase according to response, maximum 80 mg/day

phenytoin: children 6 months to 3 years of age: 5-10 mg/kg/day orally given in 2-3 divided doses; children 4-6 years of age: 5-9 mg/kg/day orally given in 2-3 divided doses; children 7-9 years of age: 5-8 mg/kg/day orally given in 2-3 divided doses; children 10-16 years of age: 5-7 mg/kg/day orally given in 2-3 divided doses; adults: 100 mg/day orally initially given in 1-2 divided doses, increase according to response, maximum 300 mg/day

carbamazepine: children <6 years of age: 10-20 mg/kg/day orally given in 2-4 divided doses, increase according to response, maximum 35 mg/kg/day; children 6-12 years of age: 200 mg/day orally initially given in 2-4 divided doses, increase according to response, maximum 1000 mg/day; children >12 years of age and adults: 400 mg/day orally initially given in 2-4 divided doses, increase according to response, maximum 1200 mg/day

gabapentin: children 3-12 years of age: 10-15 mg/kg/day orally initially, given in 3 divided doses, increase according to response, maximum 50 mg/kg/day; children ≥12 years of age and adults: 300 mg/day orally given in 3 divided doses, increase according to response, maximum 1800 mg/day

familial syndrome-associated

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supportive measures

Management of acute cramp is supportive with stretching of the affected muscle(s).