The European Medicines Agency (EMA) announced that market approval should be granted for the orphan drug Agilus (Dantrolene Sodium, Hemiheptahydrate) for the treatment of malignant hyperthermia.
Malignant hyperthermia is a rare condition where the skeletal muscles are overstimulated and cannot relax. A sudden outbreak can be triggered by volatile anesthetics and the muscle relaxant succinylcholine, or occasionally by stress such as intense physical activity or heat. Malignant hyperthermia can be life-threatening as it leads to a rapid increase in body temperature and/or metabolic acidosis.
Agilus is a hybrid drug containing the muscle relaxant Dantrolene Sodium (Dantrolene IV 20 mg), which has been approved in the European Union since 1984. It works by binding to the Ryanodine receptor 1, preventing the release of calcium from the sarcoplasmic reticulum.
Agilus contains the same active ingredients as Dantrolene IV 20 mg but will be available as a 120 mg powder for preparing an injection solution. In the formulation of Agilus, mannitol and sodium hydroxide have been replaced by hydroxypropyl-beta-cyclodextrin and Macrogol 3350 to shorten preparation time and improve user-friendliness.
The Committee for Medicinal Products for Human Use (CHMP) stated that studies have shown Agilus to be of satisfactory quality and bioequivalence compared to the reference product Dantrolene IV 20 mg.
Agilus is indicated for the treatment of malignant hyperthermia in adults and children of all ages when used with appropriate supportive measures. The most common side effect is muscle weakness.
Approval of Neoatricon for Pediatric Hypotonia
During its March meeting, the CHMP also recommended pediatric market approval for Neoatricon (Dopamine hydrochloride) for the treatment of hypotonia in newborns, infants, and children under 18 years of age.
Dopamine hydrochloride stimulates the adrenergic receptors of the sympathetic nervous system, increasing systemic vascular resistance and blood pressure in a dose-dependent manner.
Neoatricon is a hybrid drug containing sterile Dopamine concentrate BP 40 mg/ml, which has been approved in the European Union since 1989. Neoatricon contains the same active ingredient as the reference product but is available in lower concentrations (1.5 mg/ml and 4.5 mg/ml).
The CHMP stated that it was satisfied with studies showing the quality of Neoatricon. Since Neoatricon is administered intravenously and is 100% bioavailable, a bioequivalence study compared to the reference product was not necessary, according to the CHMP.
The most common side effects include headaches, ectopic heartbeats, tachycardia, angina pectoris pain, palpitations, hypotonia, vasoconstriction, shortness of breath, nausea, and vomiting.
Neoatricon should be prescribed by a pediatric specialist or pediatric intensive care physician with access to suitable monitoring facilities, emphasized the Committee.
Both Agilus and Neoatricon were submitted in hybrid applications, partly based on the results of preclinical tests and clinical studies of an already approved reference product, and partly on new data.