The alkaline pH of the reconstituted dantrolene causes venous irritation (pain) and thrombophlebitis with an incidence of 9%.3 Unintended extravasation can cause tissue necrosis, highlighting that dantrolene should only be given through a central vein or a large peripheral vein. There is no evidence to suggest allergic cross-reactivity with dantrolene in patients with prior phenytoin allergy.
When given to healthy persons or for MH prophylaxis or treatment, dantrolene causes skeletal muscle weakness (but not paralysis) in 15% to 22% of cases, as well as diaphragm weakness (dyspnea).3,34 In healthy volunteers, dantrolene 2.5 mg/kg does not reduce respiratory rate, vital capacity, or peak expiratory flow rate.8 However, in patients with diminished respiratory reserve (eg, end-stage pulmonary disease, preexisting neuromuscular disease), dantrolene may precipitate respiratory failure.3,17 Dantrolene may cause gastrointestinal upset, nausea, and vomiting. Other reported side effects include dizziness, somnolence, disorientation, ptosis, blurred vision, and difficulty swallowing.3,8,34 Uncommonly, compartment syndrome is observed and, even though likely secondary to MH or trauma, may be associated with dantrolene administration.3
Dantrolene and verapamil should not be used in combination because of the risk of hyperkalemia and hypotension; however, the mechanistic details of this drug interaction remain unclear.17,25,27 IV calcium salts are safe to administer with dantrolene if needed, such as for the treatment of cardiac dysrhythmias or hyperkalemia (during an episode of MH).
When dantrolene is given orally for more than 2 months to treat skeletal muscle spasticity, there is a 1.8% risk of dose- and duration-related chronic hepatitis, including elevated aminotransferase concentrations, hyperbilirubinemia, or jaundice31 that may not be fully reversible after dantrolene is discontinued.4