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A marketing authorization should be given for orphan medicine Agilus (dantrolene sodium, hemiheptahydrate) for the treatment of malignant hyperthermia, the European Medicines Agency (EMA) has said.

Malignant hyperthermia is a rare disorder in which skeletal muscles are overstimulated and unable to relax. Sudden onset can be triggered by volatile anesthetics and the muscle relaxant succinylcholine, or occasionally by stresses such as vigorous exercise or heat. Malignant hyperthermia can be life-threatening because it causes a rapid rise in body temperature and/or metabolic acidosis.

Agilus is a hybrid medicine of muscle relaxant dantrolene sodium (Dantrolen IV 20 mg), which has been authorized in the European Union since 1984. It works by binding to the ryanodine receptor 1, preventing release of calcium from the sarcoplasmic reticulum.

Agilus contains the same active substances as Dantrolen IV 20 mg but will be available in a 120-mg powder for solution for injection. In the formulation of Agilus, the mannitol and sodium hydroxide have been replaced with hydroxypropyl-beta-cyclodextrin and Macrogol 3350 to shorten the preparation time and improve ease of use.

The Committee for Medicinal Products for Human Use (CHMP) said studies had demonstrated that Agilus is of satisfactory quality and bioequivalence compared with the reference product Dantrolen IV 20 mg.

Agilus is indicated for the treatment of malignant hyperthermia in adults and children of all ages in combination with adequate support measures. The most common side effect is muscle weakness.

Approval of Neoatricon for Pediatric Hypotension

Also at its March meeting, the CHMP recommended a pediatric-use marketing authorization for Neoatricon (dopamine hydrochloride) for the treatment of hypotension in neonates, infants, and children younger than 18 years.

Dopamine hydrochloride works by stimulating adrenergic receptors of the sympathetic nervous system, increasing systemic vascular resistance and blood pressure in a dose ‑ dependent manner.

Neoatricon is a hybrid medicine of sterile dopamine concentrate BP 40 mg/mL, which has been authorized in the European Union since 1989. Neoatricon contains the same active substance as the reference product but is available in lower concentrations (1.5 mg/mL and 4.5 mg/mL).

The CHMP said it was satisfied by studies demonstrating that Neoatricon is of satisfactory quality. Because Neoatricon is administered intravenously and is 100% bioavailable, a bioequivalence study versus the reference product was not required, the CHMP stated.

The most common side effects are headache, ectopic heart beats, tachycardia, anginal pain, palpitation, hypotension, vasoconstriction, dyspnea, nausea, and vomiting.

Neoatricon should be prescribed by a pediatric specialist or pediatric intensive care specialists with access to appropriate monitoring facilities, the committee stressed.

Both Agilus and Neoatricon were submitted in hybrid applications. These rely in part on the results of preclinical tests and clinical trials of an already authorized reference product and in part on new data.