Drugs List

Therapeutic Indications

Uses

Malignant hyperthermia

Administration

For rapid intravenous injection.

Contraindications

None known

Precautions and Warnings

Breastfeeding
Hyperkalaemia
Pregnancy

Advise patient ability to drive or operate machinery may be impaired
Contains mannitol
If extravasation occurs follow local policy & seek expert help immediately
Monitor blood oxygen concentration
Monitor for development of acidosis
Monitor serum electrolytes
Monitor urine output

All anaesthetic agents should be discontinued as soon as malignant hyperthermia is recognised.

Dantrolen therapy can cause liver damage depending on the dosage and duration of the therapy and in some cases may result in a death of the patient.

Due to the high pH of the intravenous formulation of dantrolene intravenous and potential for tissue necrosis, care must be taken to prevent extravasation of the intravenous solution into the surrounding tissue.

Hyperkalaemia and myocardial depression have also been reported rarely in malignant hyperthermia-susceptible patients receiving intravenous dantrolene sodium and concomitant calcium channel blockers. It is recommended that the combination of intravenous dantrolene sodium and calcium channel blockers, such as verapamil, is not used during the reversal of a malignant hyperthermia crisis until the relevance of these findings to humans is established.

There is a risk of undissolved crystals appearing in reconstituted solution, and a subsequent risk of exacerbation of injection site reactions or tissue necrosis. Manufacturer recommends the use of a filtration device when preparing the solution, see product literature for details.

Pregnancy and Lactation

Pregnancy

Use dantrolene with caution during pregnancy.

At the time of writing there is limited published information concerning the use of dantrolene during pregnancy and the safety of dantrolene in pregnant women has not been established. Dantrolene crosses the placenta. In a limited number of pregnancies where dantrolene was used shortly before delivery no foetal or newborn adverse effects have been observed, however there is no published experience concerning the use of dantrolene during the first and second trimesters (Briggs, 2011). The manufacturer recommends that dantrolene should only be used intravenously when the potential benefits have been weighed against the possible risk to mother and child. Schaefer (2007) states that use of myotonolytics such as dantrolene should be reserved for very special indications (e.g. malignant hyperthermia), However, exposure to dantrolene does not require either a termination of the pregnancy or invasive diagnostic procedures.

Dantrolene is embryocidal in animals and, in some species, produced minor skeletal variations at the highest dose tested (Briggs, 2011).

Lactation

Use dantrolene with caution during breastfeeding.

At the time of writing there is limited published information regarding the use of dantrolene during breastfeeding. Dantrolene has been detected in human milk at low concentrations (50 micrograms to 1.2 mg per litre) during repeat intravenous administration over 3 days. Hale (2014) states that no paediatric concerns have been reported but caution is urged. As limited information is available concerning the long-term use of dantrolene during breastfeeding, an alternate drug may be preferred. After short-term use, the drug would be expected to be eliminated from milk in 1 to 2 days. As the half life of dantrolene in milk is 9.02 hours, it is advisable to restart breastfeeding 60 hours after last dose. The infant should be observed for drowsiness, weakness, vomiting, diarrhoea and liver toxicity (which are known side effects of therapeutic doses in adults).

Side Effects

Abdominal cramps
Abdominal pain
Allergic reaction
Bradycardia
Cardiac failure
Convulsions
Crystalluria
Diarrhoea
Dizziness
Drowsiness
Erythema
Extravasation
Gastrointestinal bleeding
Headache
Hepatic impairment
Hepatitis
Hyperhidrosis
Hyperkalaemia
Injection site reactions
Jaundice
Muscle weakness
Muscular fatigue
Nausea
Pleural effusion
Pulmonary oedema
Respiratory depression
Respiratory failure
Somnolence
Speech disturbances
Tachycardia
Thrombophlebitis
Urticaria
Uterine hypotonia
Vomiting
Weakness

Presentation

Injection containing dantrolene sodium.

Drugs List

Therapeutic Indications

Uses

Malignant hyperthermia

Dosage

Adults

Children

Additional Dosage Information

Administration

For rapid intravenous injection.

Contraindications

None known

Precautions and Warnings

Breastfeeding
Hyperkalaemia
Pregnancy

Advise patient ability to drive or operate machinery may be impaired
Contains mannitol
If extravasation occurs follow local policy & seek expert help immediately
Monitor blood oxygen concentration
Monitor for development of acidosis
Monitor serum electrolytes
Monitor urine output

All anaesthetic agents should be discontinued as soon as malignant hyperthermia is recognised.

Dantrolen therapy can cause liver damage depending on the dosage and duration of the therapy and in some cases may result in a death of the patient.

Due to the high pH of the intravenous formulation of dantrolene intravenous and potential for tissue necrosis, care must be taken to prevent extravasation of the intravenous solution into the surrounding tissue.

Hyperkalaemia and myocardial depression have also been reported rarely in malignant hyperthermia-susceptible patients receiving intravenous dantrolene sodium and concomitant calcium channel blockers. It is recommended that the combination of intravenous dantrolene sodium and calcium channel blockers, such as verapamil, is not used during the reversal of a malignant hyperthermia crisis until the relevance of these findings to humans is established.

There is a risk of undissolved crystals appearing in reconstituted solution, and a subsequent risk of exacerbation of injection site reactions or tissue necrosis. Manufacturer recommends the use of a filtration device when preparing the solution, see product literature for details.

Pregnancy and Lactation

Pregnancy

Use dantrolene with caution during pregnancy.

At the time of writing there is limited published information concerning the use of dantrolene during pregnancy and the safety of dantrolene in pregnant women has not been established. Dantrolene crosses the placenta. In a limited number of pregnancies where dantrolene was used shortly before delivery no foetal or newborn adverse effects have been observed, however there is no published experience concerning the use of dantrolene during the first and second trimesters (Briggs, 2011). The manufacturer recommends that dantrolene should only be used intravenously when the potential benefits have been weighed against the possible risk to mother and child. Schaefer (2007) states that use of myotonolytics such as dantrolene should be reserved for very special indications (e.g. malignant hyperthermia), However, exposure to dantrolene does not require either a termination of the pregnancy or invasive diagnostic procedures.

Dantrolene is embryocidal in animals and, in some species, produced minor skeletal variations at the highest dose tested (Briggs, 2011).

Lactation

Use dantrolene with caution during breastfeeding.

At the time of writing there is limited published information regarding the use of dantrolene during breastfeeding. Dantrolene has been detected in human milk at low concentrations (50 micrograms to 1.2 mg per litre) during repeat intravenous administration over 3 days. Hale (2014) states that no paediatric concerns have been reported but caution is urged. As limited information is available concerning the long-term use of dantrolene during breastfeeding, an alternate drug may be preferred. After short-term use, the drug would be expected to be eliminated from milk in 1 to 2 days. As the half life of dantrolene in milk is 9.02 hours, it is advisable to restart breastfeeding 60 hours after last dose. The infant should be observed for drowsiness, weakness, vomiting, diarrhoea and liver toxicity (which are known side effects of therapeutic doses in adults).

Side Effects

Abdominal cramps
Abdominal pain
Allergic reaction
Bradycardia
Cardiac failure
Convulsions
Crystalluria
Diarrhoea
Dizziness
Drowsiness
Erythema
Extravasation
Gastrointestinal bleeding
Headache
Hepatic impairment
Hepatitis
Hyperhidrosis
Hyperkalaemia
Injection site reactions
Jaundice
Muscle weakness
Muscular fatigue
Nausea
Pleural effusion
Pulmonary oedema
Respiratory depression
Respiratory failure
Somnolence
Speech disturbances
Tachycardia
Thrombophlebitis
Urticaria
Uterine hypotonia
Vomiting
Weakness

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ). .

Further Information

Last Full Review Date: June 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Dantrium IV 20 mg powder for solution for injection. Norgine Limited. Revised November 2022.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 02 August 2017.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Dantrolene. Last revised: 7 September 2013.
Last accessed: 3 June 2016.