ダントロレン

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Mild, asymptomatic serum aminotransferase elevations during dantrolene therapy are relatively uncommon (1%), but clinically over liver injury is estimated to occur in 1 to 2 per thousand treated persons (0.1% to 0.2%). The liver injury can be severe; cases of acute liver failure and even death have been described (Case 1). The latency to onset of clinically apparent liver injury ranges from one week to several months, but is usually within the first 6 months of starting therapy (Case 2). More serious cases are associated with a sudden onset with jaundice, nausea and fatigue, and rapid progression. Allergic manifestations such as fever, rash and eosinophilia are rare, as are autoimmune features. The pattern of enzyme elevations is predominantly hepatocellular. Liver histology demonstrates an acute-hepatitis like picture. Recovery is usually complete within 1 to 3 months. Women, the elderly, and patients taking higher doses appear to be more susceptible to developing dantrolene hepatotoxicity.

The intravenous administration of dantrolene in healthy volunteers has resulted in skeletal muscle weakness, dyspnea, respiratory muscle weakness, and decreased inspiratory capacity. These are expected symptoms given the mechanism of action of the medication.Oral dantrolene carries a black box warning for the potential for hepatotoxicity, including overt hepatitis. Hepatic function should undergo evaluation before administering the oral capsule form and requires monitoring throughout the course of treatment. The medication should stop immediately if liver function becomes impaired.

DANTROLENE HAS SERIOUS POTENTIAL TO CAUSE HEPATOTOXICITY. FATAL HEPATITIS HAS BEEN REPORTED IN APPROX 0.1 TO 0.2% OF PATIENTS TREATED...FOR 60 DAYS OR LONGER. SYMPTOMATIC HEPATITIS MAY OCCUR IN 0.5% OF PATIENTS TREATED...FOR MORE THAN 60 DAYS, WHILE CHEMICAL ABNORMALITIES OF HEPATIC FUNCTION ARE NOTED IN UP TO 1%. ... MOST COMMON MAJOR SIDE EFFECT...IS WEAKNESS, WHICH IS PROBABLY EXTENSION OF ITS EFFECT ON SKELETAL MUSCLE. ... EUPHORIA, LIGHT-HEADEDNESS, DIZZINESS, DROWSINESS & FATIGUE OFTEN OCCUR EARLY IN TREATMENT, BUT...ARE GENERALLY TRANSIENT...

...DIARRHEA.../IS ONE OF/ MOST COMMON REACTIONS. .../IT/ MAY BE PERSISTENT & REQUIRE TREATMENT, A REDUCTION IN DOSE, OR TEMPORARY CESSATION OF THERAPY. ANOREXIA, NAUSEA, VOMITING, & AN ACNE-LIKE RASH ARE ALSO SIGNIFICANT SIDE EFFECTS. LESS FREQUENTLY...HEADACHE, NERVOUSNESS /&/ INSOMNIA...HAVE OCCURRED. PLEUROPERICARDIAL REACTIONS & VISUAL DISTURBANCES DEVELOP RARELY. /DANTROLENE SODIUM/

USE...IN ACUTE HYPERTHERMIC EMERGENCIES OR FOR PREOPERATIVE PREPN OF PATIENTS SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA IS NOT ASSOC WITH RISKS OF HEPATOTOXICITY & PLEURAL EFFUSION THAT CAN OCCUR DURING ITS PROLONGED ADMIN. HOWEVER, LARGE DOSES USED FOR PREMEDICATION MAY PRODUCE NAUSEA & DIARRHEA, BLURRED VISION, MUSCLE WEAKNESS & INCOORDINATION. /DANTROLENE SODIUM/

INTERFERENCE WITH MUSCLE FUNCTION MAY CAUSE ASTHENIA...POOR POSTURE WITH CONSEQUENT BACKACHE & MYALGIA, FEELING OF SUFFOCATION, DIFFICULTIES IN SWALLOWING... OTHER ADVERSE EFFECTS INCL CONSTIPATION...ABDOMINAL CRAMPS, GASTRIC IRRITATION, GI BLEEDING, INCR URINARY FREQUENCY, LACRIMATION, SWEATING, DISORDERS OF TASTE, HYPERTENSION, TACHYCARDIA, HYPERTRICHOSIS, PRURITIS, URTICARIA...ECZEMATOID DERMATITIS...CHILLS & FEVER. /DANTROLENE SODIUM/

For more Human Toxicity Excerpts (Complete) data for DANTROLENE (6 total), please visit the HSDB record page.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

dantrolene

Dantrium®

Muscle relaxants

8

most-DILI-concern

...UP TO 60 MG/KG/DAY /WERE GIVEN/ BY MOUTH TO PREGNANT RATS & RABBITS DURING DAYS 7 TO 17 & 6 TO 18 RESPECTIVELY. AT HIGHEST DOSE, MINOR SKELETAL VARIATIONS OCCURRED IN BOTH SPECIES & IN RAT...MATERNAL & FETAL WEIGHTS WERE REDUCED.

CHRONIC STUDIES IN RATS, DOGS & MONKEYS AT DOSAGES GREATER THAN 30 MG/KG/DAY SHOWED GROWTH OR WT DEPRESSION & SIGNS OF HEPATOPATHY & POSSIBLE OCCLUSION NEPHROPATHY, ALL OF WHICH WERE REVERSIBLE UPON CESSATION OF TREATMENT.

SPRAGUE-DAWLEY FEMALE RATS FED DANTROLENE SODIUM FOR 18 MO AT DOSAGE LEVELS OF 15, 30 & 60 MG/KG/DAY SHOWED INCR INCIDENCE OF BENIGN & MALIGNANT MAMMARY TUMORS COMPARED WITH CONCURRENT CONTROLS &, AT HIGHEST DOSAGE, INCR IN INCIDENCE OF HEPATIC LYMPHANGIOMAS & HEPATIC ANGIOSARCOMAS. THESE EFFECTS WERE NOT SEEN IN 2.5 YR-STUDIES IN SPRAGUE-DAWLEY OR FISCHER 344 RATS OR IN 2-YR STUDIES IN MICE OF HAM/ICR STRAIN.

MEDICATION

Use (kg; approx.) in Germany (2009): >100