Danlene

Approved Indications:

• Malignant Hyperthermia (MH):
• Treatment and prophylaxis of malignant hyperthermia episodes triggered by volatile anesthetics and/or succinylcholine during surgery.
• Spasticity:
• Management of severe spasticity associated with upper motor neuron disorders such as multiple sclerosis, cerebral palsy, spinal cord injury, and stroke.

Clinically Accepted Off-label Uses:

• Neuroleptic malignant syndrome (NMS) adjunct therapy.
• Muscle spasms in certain neurologic conditions.

Adults:

• Malignant Hyperthermia Treatment:
• Initial dose: 2.5 mg/kg IV as a single dose; repeat as needed every 5–10 minutes up to a cumulative dose of 10 mg/kg.
• Maintenance: 1 mg/kg IV every 4–6 hours or continuous infusion.
• Malignant Hyperthermia Prophylaxis:
• 1 mg/kg orally 1 to 2 hours prior to anesthesia, repeated every 6 hours for 24 to 48 hours.
• Spasticity:
• Start with 25 mg orally once daily; increase gradually to a usual maintenance dose of 100 mg 3–4 times daily (max 400 mg/day).
• Dose adjustments based on therapeutic response and tolerability.

Pediatrics:

• Malignant Hyperthermia: Same dosing as adults for treatment.
• Spasticity: Safety not well established; use with caution.

Elderly:

• Use lower starting doses with cautious titration; monitor closely for adverse effects.

Renal and Hepatic Impairment:

• Use with caution in hepatic impairment; lower doses or extended intervals may be required.
• Renal impairment: No specific dose adjustment but monitor.

Route: Intravenous for MH treatment; oral for spasticity and prophylaxis.

Dantrolene sodium acts directly on skeletal muscle by inhibiting the ryanodine receptor (RyR1) on the sarcoplasmic reticulum, blocking abnormal calcium release into the cytoplasm. This reduces intracellular calcium concentrations, thereby decreasing excitation-contraction coupling and muscle contraction strength. In malignant hyperthermia, dantrolene interrupts the hypermetabolic state caused by uncontrolled calcium release triggered by anesthetics, restoring normal muscle function and reducing heat production. In spasticity, it decreases muscle tone by diminishing excessive muscle fiber contraction.

Absorption:

• Oral bioavailability is low and variable (~35%). Peak plasma concentrations occur 3–6 hours after oral dose.

Distribution:

• Widely distributed in body tissues; crosses blood-brain barrier poorly.

Metabolism:

• Extensively metabolized in the liver, primarily by hydroxylation.

Elimination:

• Excreted mainly in urine as metabolites.
• Plasma half-life approximately 8.7 hours.

• Pregnancy:
• Category C (FDA): Animal studies show adverse effects at high doses; use only if benefits justify risks.
• Lactation:
• Unknown if excreted in human milk; caution advised. Breastfeeding not recommended during therapy.

• Primary Class: Muscle relaxant
• Subclass: Direct-acting skeletal muscle relaxant

• Known hypersensitivity to dantrolene.
• Active hepatic disease or impaired liver function (relative contraindication).
• Patients with spasticity related to rheumatic disorders where muscle weakness may worsen.

• Hepatotoxicity: Significant risk especially in long-term use; monitor liver function tests regularly.
• Respiratory Depression: Caution in patients with compromised respiratory function.
• Muscle Weakness: May worsen functional mobility; monitor strength.
• Intravenous Administration: Must be prepared and administered carefully; reconstitute promptly.
• Renal Impairment: Monitor function due to metabolite excretion.
• Use in Elderly: Increased risk of adverse effects; dose cautiously.

Common:

• Muscle weakness
• Drowsiness, dizziness
• Fatigue
• Gastrointestinal symptoms: nausea, diarrhea

Serious/Rare:

• Hepatotoxicity including fatal liver failure
• Respiratory insufficiency
• Hypersensitivity reactions
• Photosensitivity

• Calcium Channel Blockers: Increased risk of hyperkalemia and cardiac effects; avoid combination if possible.
• CNS Depressants: Additive sedative effects.
• Alcohol: May increase CNS depression and hepatotoxicity risk.
• Other muscle relaxants: Enhanced muscle weakness.

• Recent anesthesia guidelines reinforce immediate availability of dantrolene for malignant hyperthermia management in surgical centers.
• Updated safety monitoring recommendations emphasize early detection of hepatotoxicity during prolonged spasticity treatment.
• Ongoing research into formulations with improved solubility and reduced adverse effect profile.

• Store dry powder at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Reconstituted solution stable for up to 6 hours at room temperature or 24 hours refrigerated (2°C to 8°C).
• Do not freeze.
• Keep vial and reconstitution materials ready in operating rooms or anesthesia areas.