Intravenous dantrolene: risk of undissolved crystals
- Medicines and Healthcare products Regulatory Agency
- 2 July 2014
- Therapeutic area:
- Anaesthesia and intensive care
Use a filter needle when drawing up reconstituted dantrolene solution.
Article date: July 2014
Intravenous dantrolene (Dantrium intravenous) is indicated for the treatment of malignant hyperthermia, a rare and potentially fatal condition induced by inhalational anaesthetics and depolarising neuromuscular blockers. Dantrium intravenous is the only product licensed in the EU for this indication.
Due to a manufacturing problem, visible crystals of undissolved dantrolene sodium have been seen in some newly issued vials following reconstitution.
Emergency measures have been put in place until a definitive solution to the manufacturing problem is found. The measures apply to newly issued stock only.
Newly issued packs of intravenous dantrolene are being supplied with one filter needle per vial of dantrolene (BD Blunt Fill Needle with 5 micron filter 18 G 40 mm). Once reconstituted, draw up the dantrolene solution with the filter needle provided to minimise the risk of administering crystals to patients. This advice applies immediately to all newly issued packs of intravenous dantrolene until further notice.
Instruction leaflets have been included in all newly issued dantrolene packs along with the filter needles. Stickers with the same information were sent in a letter to healthcare professionals in June (see further information below). When refilling emergency toolkits for malignant hyperthermia, place the dantrolene pack with the leaflet and filter needle in the toolkit and stick the sticker onto a clearly visible surface of the toolkit.
Existing stock (ie, vials supplied without a filter needle) does not require filtering.
Extension of expiry date of existing stock
In January 2014, the Department of Health and the licence-holder contacted Trust Pharmacists to extend the shelf life of some intravenous dantrolene batches (see further information below). This was to prevent a stock shortage while the manufacturing problem was being resolved.
Trusts that are currently using batches with an extended shelf life should continue to use them. The licence-holder will contact these trusts before the extended expiry date to advise on when to replace these batches and to remind trusts to use the filter needle provided when using the new stock.
Risk of skin reactions
Dantrolene is associated with injection site reactions including redness, rash, swelling, localized pain, thrombophlebitis, and tissue necrosis. This risk may be increased by the crystals from affected vials. Although using filter needles should reduce this risk, be vigilant for the development of injection site reactions.
Filtration does not reduce the amount of intravenous dantrolene in solution and will not affect efficacy. Intravenous dantrolene should be administered as currently recommended.
The product information states that the initial dantrolene dose should be 1 mg/kg. If the physiological and metabolic abnormalities persist or reappear, this dose may be repeated up to a cumulative dose of 10 mg/kg. If a relapse or recurrence occurs, dantrolene should be re-administered at the last effective dose.
Advice for healthcare professionals
- When refilling emergency toolkits for malignant hyperthermia, place the dantrolene pack with the instruction leaflet and filter needle provided into the toolkit and stick the sticker onto a clearly visible surface of the toolkit
- Use the filter needle provided when drawing up reconstituted dantrolene solution
- Use one filter needle per vial
- Administer the solution immediately once reconstituted
- Be vigilant for skin and injection site reactions
- Filtration does not reduce the amount of intravenous dantrolene in solution and will not affect efficacy
- Give an initial dose of 1mg/kg of dantrolene
- If malignant hyperthermia persists or reappears, repeat this dose up to a cumulative dose of 10 mg/kg. If a relapse or recurrence occurs, re-administer dantrolene at the last effective dose
Advice for Trusts using batches with an extended shelf life
- Trusts that are using batches with an extended shelf life should continue to use them
Article citation: Drug Safety Update volume 7 issue 12, July 2014: A2.
Published: 2 July 2014
Therapeutic area: Anaesthesia and intensive care