LD₅₀=215 mg/kg, in rats.MSDS

Overdose

Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs. Serious cardiorespiratory adverse reactions have occurred, sometimes ending in death or permanent neurologic effects, after the administration of midazolam.^{FDA label}

A note on cardiac and respiratory depression

After administration of midazolam, continuous monitoring of respiratory and cardiac function is recommended until the patient is in stable condition. Serious and life-threatening cardiorespiratory adverse reactions, including hypoventilation, airway obstruction, apnea, and hypotension have been reported with the use of midazolam. Patients should be monitored in a setting with immediate access to resuscitative drugs if they are required. Resuscitation equipment and personnel trained in their use and skilled in airway management should be available when midazolam is administered.^{FDA label}

The usual recommended intramuscular pre-medicating doses of midazolam do not depress the ventilatory response to carbon dioxide stimulation to a clinically significant extent in adults. Intravenous induction doses of midazolam depress the ventilatory response to carbon dioxide stimulation for at least 15 minutes longer than the duration of ventilatory depression following administration of thiopental in adults. Impairment of ventilatory response to carbon dioxide is more severe in adult patients diagnosed with chronic obstructive pulmonary disease (COPD).^F2434

A note on dependence

When midazolam is used in long-term sedation in the ICU (intensive care unit) or other settings, physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment; this risk is also greater in patients with a medical history of substance abuse.^L5074

Special caution should be exercised when administering midazolam in the following populations

High-risk patients include adults over 60 years of age, chronically ill or debilitated patients, which may include patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function, pediatric patients (especially those with cardiovascular instability). These high-risk patients require lower dosages and should be monitored on a continuous basis for early signs of alterations of vital functions, so that appropriate management may be administered.^L5074

Mutagenesis

Midazolam was negative for genotoxicity during in vitro and in vivo assays.^{FDA label}

Impairment of Fertility

When midazolam (0, 1, 4, or 16 mg/kg) was given orally to male and female rats before and during mating and continuing in females throughout gestation and lactation, no adverse effects on male or female fertility were observed. Midazolam plasma exposures (AUC) at the highest dose tested were approximately 6 times that in humans at the recomended human dose.^{FDA label}