Medications That Can Cause Muscle Twitching
The most common medications causing muscle twitching include aminoglycoside antibiotics (particularly kanamycin), CNS stimulants (methylphenidate, phenytoin), lidocaine, lithium, selective serotonin reuptake inhibitors (SSRIs/SNRIs), and chemotherapy agents like irinotecan.
High-Risk Antibiotics
Kanamycin is specifically documented to cause neurotoxicity including muscle twitching and seizures, particularly when toxic levels are reached or in patients with renal impairment. 1 This aminoglycoside requires dose adjustment in renal dysfunction and periodic monitoring of renal function and hearing during prolonged therapy. 1 The mechanism involves neuromuscular effects that can progress to neuromuscular blockade if infused too rapidly. 1
CNS Stimulants and Anticonvulsants
Phenytoin causes motor twitchings as a dose-related central nervous system manifestation, along with other neurological symptoms like nystagmus, ataxia, and mental confusion. 2 The FDA label specifically lists "motor twitchings" among common adverse reactions. 2 Phenytoin-induced dyskinesias including tremor have also been reported, similar to those caused by phenothiazines. 2
Methylphenidate is documented to cause muscle twitching as part of its musculoskeletal adverse effects. 3 The FDA label explicitly lists "muscle twitching" alongside myalgia and muscle cramps. 3 This occurs more commonly with higher doses or in patients taking multiple medications metabolized by CYP3A4. 3
Cardiac Medications
Lidocaine toxicity produces muscle twitching and seizures, especially in patients with poor cardiac output or hepatic/renal failure. 1 This occurs as part of a spectrum of CNS toxicity that includes drowsiness, disorientation, and myocardial depression. 1 The American Heart Association guidelines specifically warn about this dose-related effect. 1
Digoxin can cause muscle-related symptoms when levels become toxic, though twitching is less prominent than other manifestations. 1, 4 Cardiac glycoside toxicity typically presents with gastrointestinal symptoms (anorexia, nausea, vomiting) and cardiac arrhythmias before neuromuscular effects. 1, 4
Psychiatric Medications
SSRIs and SNRIs are among the most common drugs associated with tremor and muscle twitching, particularly at higher doses or when combined with other serotonergic agents. 5 The mechanism involves increased serotonergic transmission. 6 Risk factors include polypharmacy, male gender, older age, and high doses. 5
Lithium commonly causes tremor and can induce myoclonus, with level II evidence supporting this association. 6 Lithium-induced movement disorders typically resolve after drug withdrawal but may require specific treatment in some cases. 6
Tricyclic antidepressants like amitriptyline can precipitate seizures and muscle-related symptoms in susceptible patients. 2 Cyclobenzaprine, which is structurally identical to amitriptyline, carries similar risks. 1
Chemotherapy Agents
Irinotecan can cause visible muscle twitching, particularly when competitive metabolism occurs with concomitant medications using CYP3A4 or UGT1A1 pathways. 7 This reaction may persist throughout treatment cycles despite typical supportive measures like atropine or slowing infusion rates. 7
Other Notable Medications
Amiodarone is associated with tremor, though the exact mechanism remains unclear. 5 This antiarrhythmic should be used cautiously in patients with pre-existing movement disorders. 5
Beta-adrenergic agonists and dopamine receptor antagonists can cause tremor and myoclonic movements. 5 These medications affect neurotransmitter systems involved in motor control. 5
Valproate causes tremor as a common adverse effect, with level II evidence supporting this association. 6 The mechanism may involve GABAergic effects on motor pathways. 6
Clinical Management Approach
When muscle twitching occurs, immediately assess for toxic drug levels, particularly with aminoglycosides, phenytoin, lidocaine, and lithium. 1, 2 Check renal and hepatic function as impairment increases toxicity risk. 1
Review all medications for potential drug interactions, especially those metabolized by CYP3A4 or affecting serotonergic transmission. 2, 3, 7 Polypharmacy significantly increases the risk of drug-induced movement disorders. 5
Drug-induced muscle twitching typically resolves after withdrawal of the offending medication, though some cases may require specific treatment or result in persistent symptoms (tardive phenomena). 6 Do not rechallenge with the suspected medication due to risk of serious relapse. 8
Monitor for progression to more serious neuromuscular complications including seizures, neuromuscular blockade, or myasthenic syndromes. 1, 9 Certain medications like aminoglycosides, beta-blockers, and penicillamine can aggravate or induce myasthenia gravis. 9