dantrolene sodium

dantrolene sodium

FDA Box Warning

Drug may be hepatotoxic and should be used only for recommended conditions. Daily doses of 400 mg are less likely to cause fatal and nonfatal hepatitis than daily doses above 800 mg. Overt hepatitis is most common during months 3 and 12, but may occur at any time; females, patients older than age 35, and those receiving concurrent therapy are at higher risk. Use only in conjunction with liver monitoring. Monitor liver function at baseline and regularly during therapy. Discontinue drug if values are abnormal.

Use lowest possible effective dose. If no benefit occurs after 45 days, discontinue.

Action

Relaxes skeletal muscle by affecting excitation-contraction coupling response at site beyond myoneural junction, probably by interfering with calcium release from sarcoplasmic reticulum

Availability

Capsules: 25 mg, 50 mg, 100 mg

Powder for injection: 20 mg/vial

Indications and dosages

Chronic spasticity resulting from upper motor neuron disorders, such as multiple sclerosis, cerebral palsy, or spinal cord injury

Adults: Initially, 25 mg P.O. daily, increased gradually in 25-mg increments, if needed, up to 100 mg two or three times daily, to a maximum dosage of 400 mg P.O. daily. Maintain dosage level for 4 to 7 days to gauge patient response.

Children: Initially, 0.5 mg/kg P.O. daily for 7 days, increased to 0.5 mg/kg P.O. t.i.d. for 7 days; then 1 mg/kg P.O. t.i.d. for 7 days; then 2 mg/kg t.i.d., as needed. Don't exceed 100 mg P.O. q.i.d.

Malignant hyperthermic crisis

Adults and children: Initially, 1 mg/kg by I.V. push, repeated as needed up to a cumulative dosage of 10 mg/kg/day

To prevent or minimize malignant hyperthermia in patients who require surgery

Adults and children: 4 to 8 mg/kg P.O. daily in three or four divided doses for 1 to 2 days before surgery; give last dose 3 to 4 hours before surgery. Or 2.5 mg/kg I.V. infused over 1 hour before anesthestics are given.

To prevent recurrence of malignant hyperthermic crisis

Adults: 4 to 8 mg/kg daily P.O. in four divided doses for up to 3 days after initial hyperthermic crisis

Off-label uses

• Heat stroke
• Neuroleptic malignant syndrome

Contraindications

• Active hepatic disease (oral form)
• Patients who use spasticity to maintain posture or balance (oral form)
• Breastfeeding

Precautions

Use cautiously in:
• cardiac, hepatic, or respiratory dysfunction or impairment
• women (especially pregnant women)
• adults older than age 35
• children younger than age 5.

Administration

• For I.V. use, add 60 ml of sterile water for injection to each vial; shake until solution is clear. Protect from direct light and use within 6 hours.
• Give therapeutic or emergency dose by rapid I.V. push. Administer followup dose over 2 to 3 minutes.
• Prevent extravasation when giving I.V. Drug has high pH and causes tissue irritation.

Adverse reactions

CNS: dizziness, drowsiness, fatigue, malaise, weakness, confusion, depression, insomnia, nervousness, headache, light-headedness, speech disturbances, seizures

CV: tachycardia, blood pressure fluctuations, phlebitis, heart failure

EENT: double vision, excessive tearing

GI: nausea, vomiting, diarrhea, constipation, abdominal cramps, GI reflux and irritation, hematemesis, difficulty swallowing, anorexia, GI bleeding

GU: urinary frequency, dysuria, nocturia, urinary incontinence, hematuria, crystalluria, prostatitis

Hematologic: aplastic anemia, leukopenia, thrombocytopenia, lymphocytic lymphoma

Hepatic: hepatitis

Musculoskeletal: myalgia, backache

Respiratory: suffocating sensation, respiratory depression, pleural effusion with pericarditis

Skin: rash, urticaria, pruritus, eczemalike eruptions, sweating, photosensitivity, abnormal hair growth

Other: altered taste, chills, fever, edema

Interactions

Drug-drug.CNS depressants: increased CNS depression

Estrogen: increased risk of hepatotoxicity

Verapamil (I.V.): cardiovascular collapse (when given with I.V. dantrolene)

Drug-diagnostic tests.Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen: increased values

Drug-behaviors.Alcohol use: increased CNS depression

Sun exposure: phototoxicity

Patient monitoring

• Obtain baseline liver function test results; monitor periodically during therapy.
• Monitor ECG, serum electrolytes, and urine output regularly.

With long-term oral therapy, monitor patient for signs and symptoms of hepatotoxicity. Be prepared to discontinue drug if these occur.
• Assess for muscle weakness, poor coordination, and reduced reflexes before and during therapy. Drug may weaken muscles and impair ambulation.

Patient teaching

Instruct patient receiving prolonged oral therapy to immediately report weakness, malaise, fatigue, nausea, rash, itching, severe diarrhea, bloody or black tarry stools, or yellowing of skin or eyes.
• Inform patient that drug may cause drowsiness, dizziness, or light-headedness.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

dantrolene sodium

[dan′trəlēn]
a skeletal muscle relaxant that acts directly on the skeletal muscle to prevent the release of calcium from the sarcoplasmic reticulum that is needed for muscle contraction.
indications It is prescribed in the treatment of muscle spasticity resulting from injury to the spinal cord or cerebrum when the person is immobile and flaccid limbs are preferable to spastic limbs. It is not indicated in treatment of spasm from rheumatic disorders. It is used intravenously for the management of malignant hyperthermia.
contraindications Dantrolene should not be used when spastic muscles are needed to maintain posture or balance. Liver dysfunction or known hypersensitivity to this drug also prohibits its use.
adverse effects The most serious adverse reaction is potentially fatal hepatotoxicity. Common reactions include confusion, drowsiness, diarrhea, dizziness, fatigue, and muscular weakness. Side effects may continue for several days.

dantrolene sodium

(dăn′trō-lēn)
A muscle relaxant used to relieve spasticity.

dantrolene sodium

(dantrōlēn),
n brand name: Dantrium;
drug class: skeletal muscle relaxant, direct acting;
action: interferes with intracellular release of calcium necessary to initiate contraction;
uses: spasticity in multiple sclerosis, stroke, spinal cord injury, cerebral palsy, malignant hyperthermia.
References in periodicals archive ?
Other products in US WorldMeds' product portfolio include Revonto(TM), a fast-reconstituting form of Dantrolene Sodium for Injection for the treatment of malignant hyperthermia, and Lofexidine, a non-narcotic treatment in late-stage development for acute opiate withdrawal symptoms.
Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with dantrolene sodium therapy.
2001), In vitro antioxidant properties of dantrolene sodium, Pharmacol.
Dantrolene sodium (Dantrium) was ordered as a direct-action muscle relaxant.
A week before we were scheduled to leave, we realized that none of the hospital pharmacies would be able to donate dantrolene sodium, a costly drug used to treat malignant hyperthermia.
It further acquired in 2008 the full rights for Europe and other territories worldwide to dantrolene sodium (Dantrium([R])/Dantrolen([R])/Dantamacrin([R])) from Procter & Gamble Pharmaceuticals, and in 2010 the worldwide (with the exception of North and South America) rights to Savene[R] from TopoTarget A/S.
The time to reconstitute dantrolene sodium for injection has been dramatically reduced to approximately 20 seconds or until the solution is clear.
Ketel and Kolb (1984) conducted a study of dantrolene sodium (Dantrium) in 18 adults, 48-78 years old, who experienced stroke.
SpePharm completed two pan-European license/distribution agreements in 2007 and 2008 for respectively MuGard([R]) and Xerotin([R]) and also acquired in 2008 the full rights for Europe and other territories worldwide to dantrolene sodium (Dantrium([R])/Dantrolen([R])/Dantamacrin([R])) from Procter & Gamble Pharmaceuticals.
SpePharm has completed two pan-European license/distribution agreements in 2007 & 2008 for respectively MuGard([R]) and Xerotin([R])and, acquired last year the full rights for Europe and other territories of dantrolene sodium (Dantrium([R]) / Dantrolen([R]) / Dantamacrin([R])) from Procter and Gamble Pharmaceuticals.
US WorldMeds, a Kentucky-based specialty pharmaceutical company, today announced that it has completed development of and filed a provisional patent for Dantrolene Sodium for Injection that will dramatically enhance the medication's reconstitution time to 20 seconds or less.