DANTRIUM

What it is

Dantrium is dantrolene sodium hemiheptahydrate, available as 25 mg and 50 mg capsules. Dantrium produces relaxation of the contractile state of skeletal muscle by an effect beyond the myoneural junction and directly on the muscle itself, uncoupling the excitation and contraction of skeletal muscle, probably by interfering with the release of calcium ions from the sarcoplasmic reticulum.

Approved indications

— Controlling the manifestations of clinical spasticity resulting from serious chronic disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis.

Dosing overview

For adults, therapy begins with 25 mg once daily, increasing to 25 mg two, three, or four times daily and then by increments of 25 mg up to as high as 50 mg two, three or four times daily if necessary, with a maximum recommended dose of 200 mg per day. Each dosage level should be maintained for four to seven days to determine the patient's response. For children, a similar approach is used starting with 0.5 mg per kilogram of body weight twice daily, increased to 0.5 mg/kg three or four times daily and then by increments to a maximum of 2 mg/kg three times daily, with doses higher than 50 mg four times daily not recommended. Therapy should be stopped if benefits are not evident within 45 days due to the potential for liver damage in long-term use.

Key safety warnings

Dantrium should be used with caution in patients with a history of previous liver disease or dysfunction and has potential for hepatotoxicity; symptomatic hepatitis (fatal and non-fatal) has been reported at various dose levels, with hepatotoxicity appearing to be dose-related above 200 mg per day, which is the maximum recommended dose. At the start of Dantrium therapy, it is essential to perform liver function studies (SGOT, SGPT, alkaline phosphatase, total bilirubin) for baseline assessment or to establish whether there is pre-existing liver disease. Dantrium should be used with particular caution in females and in patients over 35 years of age in view of the apparently greater likelihood of drug-induced, potentially fatal, hepatocellular disease in these groups. The most frequently occurring adverse effects are drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhoea, experienced by approximately 20 per cent of patients; these effects are generally transient, occurring early in treatment, and can often be obviated by beginning with a low dose and increasing dosage gradually. Diarrhoea may be severe and may necessitate temporary withdrawal of therapy; if diarrhoea recurs upon readministration, therapy should probably be withdrawn permanently. Dantrium should be used with caution in patients with impaired pulmonary function, particularly those with obstructive pulmonary disease, and in patients with severely impaired cardiac function due to myocardial disease. There are very rare reports of cardiovascular collapse in patients treated simultaneously with verapamil and dantrolene sodium hemiheptahydrate, and until the relevance of these findings to humans is established, the combination of dantrolene sodium hemiheptahydrate and calcium channel blockers such as verapamil is not recommended.

Contraindications

Active hepatic disease, such as acute hepatitis and active cirrhosis, is a contraindication for use of Dantrium. Dantrium is contraindicated where spasticity is utilised to sustain upright posture and balance in locomotion, or whenever spasticity is utilised to obtain or maintain increased function.

Regulatory history

Dantrium 25 mg capsules were first listed on the Australian Register of Therapeutic Goods on 3 February 1993, as was the 50 mg capsule formulation.