MIRTAZAPINE   Also explore   Side-Effects

• 0.0 OVERVIEW
• 0.1 LIFE SUPPORT
• A. This overview assumes that basic life support measures have been instituted.
• 0.2 CLINICAL EFFECTS
• 0.2.1 SUMMARY OF EXPOSURE
• A. OVERDOSE -
• 1. Overdose experience is limited. Reported effects have included tachycardia, disorientation, drowsiness and impaired memory. Overdoses of 10 to 30 times the maximum recommended dose produced no serious adverse effects in a series of 6 patients. Overdoses of 30 and 50 times the normal daily dose produced no complications in 2 patients.
• B. ADVERSE EFFECTS AT THERAPEUTIC DOSE -
• 1. Tachycardia, hypertension and hypotension have been reported. CNS depression, including somnolence and confusion, have been reported following therapeutic dosing. Liver dysfunction is a rare effect at therapeutic doses.
• 0.2.3 VITAL SIGNS
• A. Hypotension and tachycardia have been reported following therapeutic use. Tachycardia has been reported in overdose.
• 0.2.5 CARDIOVASCULAR
• A. Tachycardia and hypotension may occur.
• 0.2.7 NEUROLOGIC
• A. CNS depression with somnolence, dizziness, and disorientation may occur following overdose.
• 0.2.8 GASTROINTESTINAL
• A. Dry mouth and constipation are common adverse effects.
• 0.2.9 HEPATIC
• A. Clinically significant elevated serum liver enzymes have been reported as adverse effects of mirtazapine.
• 0.2.13 HEMATOLOGIC
• A. Agranulocytosis and leukopenia are very rare adverse effects of mirtazapine.
• 0.2.15 MUSCULOSKELETAL
• A. Arthralgia and myalgia have been reported as adverse clinical effects.
• 0.2.17 METABOLISM
• A. Increases in serum cholesterol and triglycerides have been reported in a substantial number of patients following therapeutic doses.
• 0.3 LABORATORY/MONITORING
• A. Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposures.
• B. Monitor vital signs and institute continuous cardiac monitoring.
• 0.4 TREATMENT OVERVIEW
• 0.4.2 ORAL/PARENTERAL EXPOSURE
• A. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
• B. GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first.
• 1. CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
• C. ACTIVATED CHARCOAL: Administer charcoal as slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
• D. SEIZURES: Administer a benzodiazepine IV; DIAZEPAM (ADULT: 5 to 10 mg, repeat every 10 to 15 min as needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min as needed) or LORAZEPAM (ADULT: 4 to 8 mg; CHILD: 0.05 to 0.1 mg/kg).
• 1. Consider phenobarbital if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years).
• 2. Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia.
• E. HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid, place in Trendelenburg position. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to desired response.
• 0.5 RANGE OF TOXICITY
• A. An overdose of 30 to 45 milligrams of mirtazapine, in conjunction with amitriptyline and chlorprothixene, produced CNS depression and tachycardia. NO ECG changes, coma, or seizures were evident following overdoses of mirtazapine alone during premarketing clinical trials.
• B. Overdoses of 10 to 30 times the maximum recommended dose have produced no serious adverse effects in a series of 6 patients. Overdoses of 30 to 50 times the normal daily dose produced no complications in 2 adults.
• 1.0 SUBSTANCES INCLUDED/SYNONYMS
• 1.1 THERAPEUTIC/TOXIC CLASS
• A. Mirtazapine is a tetracyclic antidepressant belonging to the piperazinoazepine group of compounds. It is a 5-HT2 and 5-HT3 receptor antagonist, a histamine- 1 receptor antagonist, a moderate peripheral alpha-1 adrenergic antagonist, and a moderate muscarinic receptor antagonist. It is a noradrenergic and specific serotonergic antidepressant (NaSSA).
• 1.2 SPECIFIC SUBSTANCES

o             1,2,3,4,10,14B-hexahydro-2-methylpyrazino 

o               (2,1-A) pyrido (2,3-C) benzazepine 

o             6-Azamianserin 

o             Mepirzepine 

o             ORG 3770 

o             Molecular Formula:  C17-H19-N3 

o             CAS 61337-67-5 

• 1.6 AVAILABLE FORMS/SOURCES
• A. FORMS: Available as tablets containing 15 or 30 mg mirtazapine (Prod Info Remeron(R), 1996).
• B. USES: Mirtazapine is used in the short-term treatment of major depressive disorders (Prod Info Remeron(R), 1996).
• 3.0 CLINICAL EFFECTS
• 3.1 SUMMARY OF EXPOSURE
• A. OVERDOSE -
• 1. Overdose experience is limited. Reported effects have included tachycardia, disorientation, drowsiness and impaired memory. Overdoses of 10 to 30 times the maximum recommended dose produced no serious adverse effects in a series of 6 patients. Overdoses of 30 and 50 times the normal daily dose produced no complications in 2 patients.
• B. ADVERSE EFFECTS AT THERAPEUTIC DOSE -
• 1. Tachycardia, hypertension and hypotension have been reported. CNS depression, including somnolence and confusion, have been reported following therapeutic dosing. Liver dysfunction is a rare effect at therapeutic doses.
• 3.3 VITAL SIGNS
• 3.3.1 SUMMARY
• A. Hypotension and tachycardia have been reported following therapeutic use. Tachycardia has been reported in overdose.
• 3.3.4 BLOOD PRESSURE
• A. Clinically significant orthostatic hypotension has been reported in normal subjects given mirtazapine in early pharmacologic trials (Prod Info Remeron(R), 1996).
• 3.3.5 PULSE
• A. Tachycardia has been reported following overdose with mirtazapine during premarketing clinical studies (Prod Info Remeron(R), 1996).
• B. Accidental overdose of 60 mg in a 3-year-old child produced rapid heart rate. No other adverse effects were reported, and the child recovered with no adverse sequelae (Bremner et al, 1998).
• 3.5 CARDIOVASCULAR
• 3.5.1 SUMMARY
• A. Tachycardia and hypotension may occur.
• 3.5.2 CLINICAL EFFECTS
• A. TACHYCARDIA
• 1. Tachycardia was reported following overdose, either with mirtazapine alone or in combination with other drugs, during premarketing clinical studies. ECG changes were not observed following the overdose, however, approximately 3% of patients in clinical studies were reported to have ECG changes that were reportedly not significant (Prod Info Remeron(R), 1996).
• 2. Accidental overdose of 60 mg in a 3-year-old child produced tachycardia (139 beats/minute). No other adverse effects were reported, and the child recovered with no adverse sequelae (Bremner et al, 1998).
• B. HYPOTENSION
• 1. Clinically significant orthostatic hypotension was reported in normal subjects given mirtazapine in early pharmacology studies and infrequently observed in premarketing trials when given to depressed patients (Prod Info Remeron(R), 1996).
• 2. CASE REPORT - Following an overdose of mirtazapine 1200 mg and lorazepam 20 mg and laying outside for 10 hours at a temperature of 0 degrees C, a 41-year-old female was transferred to the ED with a blood pressure of 90/60 mm Hg. Her body temperature was reduced to 26 degrees C. Recovery was complete (Retz et al, 1998).
• C. ECG ABNORMAL
• 1. Retz et al (1998) report a patient with bradydysrhythmia and atrial fibrillation with a heart rate of 42 bpm on ECG following an overdose of mirtazapine 1200 mg and lorazepam 20 mg complicated by severe environmental hypothermia (core temperature 26 C). Complete right bundle branch block and a prolonged QT interval (660 ms, QTc 552 ms) was also apparent on ECG readings. Following rewarming and supportive care, the dysrhythmias resolved and the patient was discharged on day 5. The dysrhythmias were most likely secondary to the hypothermia.
• 3.7 NEUROLOGIC
• 3.7.1 SUMMARY
• A. CNS depression with somnolence, dizziness, and disorientation may occur following overdose.
• 3.7.2 CLINICAL EFFECTS
• A. CNS DEPRESSION
• 1. Drowsiness, disorientation and impaired memory have been reported after overdose (Prod Info, Remeron (R), 1996; Bremner et al, 1998; Holzbach et al, 1998; Gerritson, 1997). Following an overdose of 900 mg, an 81-year-old woman was admitted in a semi-comatose condition, with no other reported neurological symptoms. Following arousal, she was observed with transitory somnolence for 3 days (Hoes & Zeijpveld, 1996).
• 2. Somnolence is the most common adverse effect of mirtazapine (Claghorn et al, 1987; Mattila et al, 1989; Fink & Irwin, 1982; Prod Info Remeron(R), 1996; Claghorn & Lesem, 1995; Bremner, 1995). Other common effects include dizziness, disorientation, and impaired memory.
• b. INCIDENCE - In a premarketing clinical trial, up to 54% of patients experienced somnolence and 7% experienced dizziness (Prod Info Remeron(R), 1996; Mattila et al, 1989).
• c. Similar degrees of somnolence were reported with amitriptyline in two studies, with an incidence greater than 60% (Mattila et al, 1989; Smith et al, 1990).
• d. Decreased alertness, drowsiness, weakness and difficulty with vision occurred following single doses of mirtazapine in depressed patients in a dose-ranging, crossover clinical trial (Fink & Irwin, 1982).
• e. Four patients (n=6) experienced CNS depressant effects following overdoses of 10 to 30 times the maximum recommended doses. These effects may be attributable to co-ingestion of other depressant medications. All patients fully recovered (Bremner et al, 1998).
• B. SEIZURES
• 1. Seizure has only been reported in one patient out of 2,796 in premarketing clinical trials, and in none of the 8 overdose cases reported in premarketing clinical trials (Prod Info Remeron(R), 1996).
• C. OTHER NON-SPECIFIC
• 1. In premarketing clinical studies, tremor, confusion, abnormal thinking, and abnormal dreams were reported in 1% or more of the patients, and were more frequent than in the placebo group (Prod Info Remeron(R), 1996).
• 3.8 GASTROINTESTINAL
• 3.8.1 SUMMARY
• A. Dry mouth and constipation are common adverse effects.
• 3.8.2 CLINICAL EFFECTS
• A. MOUTH DRY
• 1. Dry mouth has occurred in 25% to 54% of patients being studied and constipation in up to 13% of patients during premarketing clinical studies following therapeutic doses (Prod Info Remeron (R), 1996 & Bremner, 1995).
• 2. Dry lips and mouth have been reported following single doses of mirtazapine (Fink & Irwin, 1982; Bremner et al, 1998).
• B. VOMITING
• 1. Infrequently (1%), vomiting and/or diarrhea have been reported (Prod Info Remeron (R), 1996).
• C. CONSTIPATION
• 1. A 13% incidence of constipation was reported by Smith et al (1990) in a double-blind comparative study.
• 3.9 HEPATIC
• 3.9.1 SUMMARY
• A. Clinically significant elevated serum liver enzymes have been reported as adverse effects of mirtazapine.
• 3.9.2 CLINICAL EFFECTS
• A. HEPATIC ENZYMES INCREASED
• 1. Transient and clinically significant elevation of plasma ALT (SGPT) (greater than 3 times the upper limit), without clinical signs/symptoms, has been reported following therapeutic use of mirtazapine during premarketing clinical trials in approximately 2% of the patients (Prod Info Remeron(R), 1996).
• 3.13 HEMATOLOGIC
• 3.13.1 SUMMARY
• A. Agranulocytosis and leukopenia are very rare adverse effects of mirtazapine.
• 3.13.2 CLINICAL EFFECTS
• A. AGRANULOCYTOSIS
• 1. In premarketing clinical trials symptomatic agranulocytosis was reported in 2 out of 2796 patients and one patient developed severe neutropenia. All 3 patients recovered following discontinuation of mirtazapine (Prod Info Remeron(R), 1996). Although the incidence of agranulocytosis and neutropenia is low, the possibility exists following overdose.
• B. OTHER NON-SPECIFIC
• 1. Rarely reported adverse effects during premarketing clinical trials of mirtazapine have included pancytopenia, anemia, thrombocytopenia, leukopenia, lymphocytosis, lymphadenopathy, and petechiae (Prod Info Remeron(R), 1996).
• 3.15 MUSCULOSKELETAL
• 3.15.1 SUMMARY
• A. Arthralgia and myalgia have been reported as adverse clinical effects.
• 3.15.2 CLINICAL EFFECTS
• A. ARTHRALGIA
• 1. Mirtazapine therapy has been associated with the development of joint symptoms, including arthralgias and myasthenia, during its use in premarketing clinical trials (Prod Info Remeron(R), 1996). One patient developed some muscle rigidity for 45 minutes following a dose of mirtazapine, which subsided over the next several hours (Ruigt et al, 1990).
• 3.17 METABOLISM
• 3.17.1 SUMMARY
• A. Increases in serum cholesterol and triglycerides have been reported in a substantial number of patients following therapeutic doses.
• 3.17.2 CLINICAL EFFECTS
• A. HYPERCHOLESTEREMIA
• 1. Nonfasting serum cholesterol levels were reported to increase greater than 20% above upper normal levels in 15% of patients following therapeutic use in premarketing clinical trials. In the same trials, nonfasting triglyceride increases of greater than 500 mg/dL were reported in 6% of subjects (Prod Info Remeron(R), 1996).
• 3.18 PSYCHIATRIC
• 3.18.2 CLINICAL EFFECTS
• A. DELIRIUM
• 1. Bailer et al (2000) reported mirtazapine-induced delirium in 3 patients with organic brain disorder following therapeutic dosing. After initiation of mirtazapine, the patients exhibited hallucinations, psychomotor agitation and cognitive changes, which improved following drug discontinuation. The authors speculated that the delirium may have been a result of a central increase of norepinephrine after acute dosing of mirtazapine.
• 3.20 REPRODUCTIVE
• 3.20.2 TERATOGENICITY
• A. LACK OF EFFECT
• 1. There are currently no human reports of teratogenicity. Reproductive studies in rats and rabbits at doses of 20 and 17 times the maximum recommended human dose, respectively, have shown no evidence of teratogenicity. Post-implantation losses were increased in rat dams and there was a decrease in pup birth weights (Prod Info Remeron(R), 1996).
• 3.20.3 EFFECTS IN PREGNANCY
• A. PREGNANCY CATEGORY
• 1. Pregnancy Category C (Prod Info Remeron(R), 1996).
• 3.20.4 EFFECTS DURING BREAST-FEEDING
• A. BREAST MILK
• 1. It is not known if mirtazapine is excreted in human milk (Prod Info Remeron(R), 1996).
• 3.21 CARCINOGENICITY
• 3.21.4 ANIMAL STUDIES
• A. HEPATIC CARCINOMA
• 1. An increased incidence of hepatocellular adenomas and carcinomas was reported in male mice receiving higher doses (200 mg/kg/day) of mirtazapine. Female rats receiving 20 to 60 mg/kg/day experienced a higher incidence of hepatocellular adenomas while male rats experienced a higher incidence of hepatocellular tumors and thyroid carcinomas at the higher doses (Prod Info Remeron(R), 1996).
• 3.22 GENOTOXICITY
• A. Mirtazapine was not mutagenic or clastogenic and did not induce general DNA damage during in vitro tests in hamsters, rabbits and rats (Prod Info Remeron(R), 1996).
• 3.23 OTHER
• 3.23.2 CLINICAL EFFECTS
• A. DRUG INTERACTION
• 1. ALCOHOL - In combination with mirtazapine may result in potentiation of impairment of cognitive and motor skills (Prod Info Remeron(R), 1996).
• 2. DIAZEPAM - In combination with mirtazapine may result in potentiation of impairment of motor skills (Mattila et al, 1989; Prod Info Remeron(R), 1996).
• 3. MAOI - At least 14 days should be allowed between therapy with a monoamine oxidase inhibitor (MAOI) and mirtazapine (Prod Info Remeron(R), 1996).
• 4. LEVODOPA - Psychosis was reported after the addition of mirtazapine to a chronic levodopa treatment regimen. The interaction was probably a result of postsynaptic serotonin receptor supersensitization caused by low central serotonin levels in treated Parkinson's disease (Normann et al, 1997).
• 4.0 LABORATORY/MONITORING
• 4.1 MONITORING PARAMETERS/LEVELS
• 4.1.1 SUMMARY
• A. Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposures.
• B. Monitor vital signs and institute continuous cardiac monitoring.
• 4.1.2 SERUM/BLOOD
• A. HEMATOLOGIC
• 1. Monitor CBC.
• B. BLOOD/SERUM CHEMISTRY
• 1. Monitor liver and kidney function tests in patients with significant exposures.
• 2. Although not commonly available, mirtazapine and metabolites plasma levels may be helpful in determining the extent of toxicity.
• 4.1.3 URINE
• A. URINALYSIS
• 1. Monitor urinalysis in patients with significant exposure.
• 4.1.4 OTHER
• A. MONITORING
• 1. Monitor vital signs and institute continuous cardiac monitoring.
• 4.3 METHODS
• A. CHROMATOGRAPHY
• 1. A capillary gas chromatographic assay method with nitrogen-sensitive detection for the determination of mirtazapine in human plasma is described by Paanakker & van Hal (1987).
• 6.0 TREATMENT
• 6.1 LIFE SUPPORT
• A. Support respiratory and cardiovascular function.
• 6.4 MONITORING
• A. Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposures.
• B. Monitor vital signs and institute continuous cardiac monitoring.
• 6.5 ORAL EXPOSURE
• 6.5.1 PREVENTION OF ABSORPTION/PREHOSPITAL
• A. EMESIS/NOT RECOMMENDED -
• 1. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
• B. ACTIVATED CHARCOAL -
• 1. PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
• a. Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion.
• (1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should be administered by medical or paramedical personnel capable of airway management to prevent aspiration in the event of spontaneous emesis.
• 2. CHARCOAL DOSE
• a. Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years; and 1 gram/kilogram in infants up to 1 year old (USP DI, 2000; Chyka & Seger, 1997).
• (1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (Barceloux et al, 1997).
• b. ADVERSE EFFECTS/CONTRAINDICATIONS
• (1) Complications: emesis, aspiration (Chyka & Seger, 1997). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
• (2) Contraindications: unprotected airway, gastrointestinal tract not anatomically intact, therapy may increase the risk or severity of aspiration; ingestion of most hydrocarbons (Chyka & Seger, 1997).
• 6.5.2 PREVENTION OF ABSORPTION
• A. GASTRIC LAVAGE
• 1. INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
• a. Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
• 2. PRECAUTIONS:
• a. SEIZURE CONTROL: Is mandatory prior to gastric lavage.
• b. AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation.
• 3. LAVAGE FLUID:
• a. Use small aliquots of liquid. Lavage with 150 to 200 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in children over 5 or adults) and 10 milliliters/kilogram body weight of normal saline in young children. Continue until lavage return is clear.
• b. The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
• c. CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
• 4. COMPLICATIONS:
• a. Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications.
• b. Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
• 5. CONTRAINDICATIONS:
• a. Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
• B. ACTIVATED CHARCOAL
• 1. CHARCOAL ADMINISTRATION
• a. Consider administration of activated charcoal after a potentially toxic ingestion (Chyka & Seger, 1997). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
• 2. CHARCOAL DOSE
• a. Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years; and 1 gram/kilogram in infants up to 1 year old (USP DI, 2000; Chyka & Seger, 1997).
• (1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (Barceloux et al, 1997).
• b. ADVERSE EFFECTS/CONTRAINDICATIONS
• (1) Complications: emesis, aspiration (Chyka & Seger, 1997). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
• (2) Contraindications: unprotected airway, gastrointestinal tract not anatomically intact, therapy may increase the risk or severity of aspiration; ingestion of most hydrocarbons (Chyka & Seger, 1997).
• 6.5.3 TREATMENT
• A. SYMPTOMATIC/SUPPORTIVE CARE
• 1. Treatment is symptomatic and supportive. Cardiac monitoring is recommended.
• B. SEIZURES
• 1. SUMMARY
• a. Attempt initial control with a benzodiazepine (diazepam or lorazepam). If seizures persist or recur administer phenobarbital. Benzodiazepines and barbiturates are generally preferred over phenytoin for the control of overdose or withdrawal related seizures.
• b. Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
• c. Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or treat with intravenous dextrose ADULT: 50 milliliters IV, CHILD: 2 milliliters/kilogram 25% dextrose).
• 2. DIAZEPAM
• a. MAXIMUM RATE: Administer diazepam intravenously over 2 to 3 minutes (maximum rate = 5 milligrams/minute).
• b. ADULT DIAZEPAM DOSE: 5 to 10 milligrams initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
• c. PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 milligram per kilogram repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
• d. RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (generally use twice the usual initial dose because of decreased absorption), or lorazepam may be given intramuscularly.
• e. MIDAZOLAM: has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. PEDIATRIC MIDAZOLAM DOSE: INTRAMUSCULAR: 0.2 milligram/kilogram (maximum 7 milligrams) (Chamberlain et al, 1997); INTRANASAL: 0.2 milligram/kilogram (Lahat et al, 2000). Buccal midazolam, 10 milligrams, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).