SERTRALINE

 

• 3.13 HEMATOLOGIC
• 3.13.1 SUMMARY
• A. Anterior chamber eye hemorrhage and purpura have occurred infrequently with sertraline therapeutic use.
• 3.13.2 CLINICAL EFFECTS
• A. PURPURA
• 1. HEMORRHAGE - Anterior chamber eye hemorrhage and purpura have occurred infrequently with sertraline therapeutic use (Prod Info Zoloft(R), 1992).
• 2. A case of prolonged bleeding time associated with ecchymoses and normal prothrombin and partial thromboplastin time and normal hepatic enzymes has been reported which resolved spontaneously with drug cessation (Calhoun & Calhoun, 1996).
• B. LEUKOCYTOSIS
• 1. CASE REPORT - Leukocytosis of 24.5 x 10(9)/L was observed nine hours following an overdose in a pediatric patient. It was likely that the leukocytosis was not directly related to the overdose as a subsequent urine culture revealed greater than 100,000 lactose-fermenting Gram-negative rods (Kaminski et al, 1994).
• 3.14 DERMATOLOGIC
• 3.14.1 SUMMARY
• A. Various types of dermatitis have been reported with therapeutic use.
• B. Cutaneous vasodilation has been reported following overdose.
• 3.14.2 CLINICAL EFFECTS
• A. SUMMARY
• 1. Infrequently, rash, acne, pruritus, alopecia, hypertrichosis, dermatitis, erythema multiforme, urticaria, and skin discoloration have been reported.
• B. VASODILATATION
• 1. CASE REPORT - Vasodilation, with flushing, has been reported following a 2 gram overdose of sertraline in a 42-year-old female with concomitant alcohol ingestion (Brown & Kerr, 1994).
• 3.15 MUSCULOSKELETAL
• 3.15.1 SUMMARY
• A. Sertraline has been associated with myalgia, arthralgia, dystonia, and muscle weakness.
• B. Elevated creatine phosphokinase (CPK) levels may be seen following an acute overdose.
• 3.15.2 CLINICAL EFFECTS
• A. SUMMARY
• 1. Sertraline has been associated with myalgia, arthralgia, dystonia, and muscle weakness (Prod Info Zoloft(R), 1992).
• B. CREATINE PHOSPHOKINASE INCREASED
• 1. CASE REPORT - Elevated CPK levels were seen in a pediatric overdose of sertraline. CPK levels rose from 525 U/L on day 1 to 21,285 U/L on day 2, then gradually decreased over the following day (Kaminski et al, 1994).
• 3.16 ENDOCRINE
• 3.16.1 SUMMARY
• A. Gynecomastia, galactorrhea, breast pain, and breast enlargement have rarely been reported with sertraline use.
• 3.16.2 CLINICAL EFFECTS
• A. GYNECOMASTIA
• 1. Gynecomastia, galactorrhea, breast pain, and breast enlargement have been reported with sertraline use (Prod Info Zoloft(R), 1992; Bronzo & Stahl, 1993).
• 3.17 METABOLISM
• 3.17.1 SUMMARY
• A. Hypoglycemia, hypercholesterolemia, hypertriglyceridemia, and a small decrease in serum uric acid have been occasionally associated with therapeutic sertraline use.
• 3.17.2 CLINICAL EFFECTS
• A. SUMMARY
• 1. THERAPEUTIC ADVERSE EFFECTS - Hypoglycemia, hypercholesterolemia, hypertriglyceridemia and a small decrease in serum uric acid have been occasionally associated with therapy (Prod Info Zoloft(R), 1992).
• 3.20 REPRODUCTIVE
• 3.20.1 SUMMARY
• A. Sertraline has been classified as FDA Pregnancy Category B.
• 3.20.2 TERATOGENICITY
• A. LACK OF EFFECT
• 1. ANIMAL STUDIES - Sertraline is reported to have no teratogenic effects in rats and rabbits at maternally toxic doses. Similar to other serotonin reuptake inhibitors, decreased neonatal survival and growth was observed in these studies (Davies & Klowe, 1998).
• 3.20.3 EFFECTS IN PREGNANCY
• A. PREGNANCY CATEGORY

§             SERTRALINE          B

§             References: Prod Info Zoloft(R), 1992;  Briggs

§             et al, 1998.

• 3.20.4 EFFECTS DURING BREAST-FEEDING
• A. BREAST MILK
• 1. Sertraline and norsertraline plasma levels were measured in 3 mother-infant pairs, with maternal doses ranging from 50 to 100 mg/day. Sertraline plasma levels in the infants were low, less than 2 ng/mL of either sertraline or norsertraline. The infants showed no adverse effects (Mammen et al, 1997). Wisner et al (1998) reported sertraline and N-desmethylsertraline levels in 9 mother-infant pairs. Sertraline levels were less than 2 ng/mL in 7 of the infants, and the metabolite levels were also low, less than or equal to 6 ng/mL, in 7 of the infants.
• 2. Epperson et al (1997) measured platelet 5-hydroxytryptamine levels in sertraline-treated mothers and their nursing infants. Marked declines were noted in the mothers (to 10.2 +/-2.9 percent of baseline), but little or no change in levels was reported in the infants. This is consistent with low plasma concentration of sertraline in the nursing infants.
• 3.21 CARCINOGENICITY
• 3.21.2 SUMMARY/HUMAN
• A. Animal studies have resulted in negative carcinogenicity tests.
• 3.21.3 HUMAN STUDIES
• A. ANIMAL STUDIES
• 1. Two year range finding studies in the mouse and rat, with dosing at 10, 40, and 80 mg/kg, revealed negative carcinogenicity tests in rats, while benign liver tumors, believed secondary to enzyme induction by sertraline, were reported at an increased rate in male mice (Davies & Klowe, 1998).
• 3.23 OTHER
• 3.23.2 CLINICAL EFFECTS
• A. CONTRAINDICATIONS
• 1. Do not use in combination with a monoamine oxidase inhibitor or within 14 days of discontinuing treatment or initiating treatment with a monoamine oxidase inhibitor due to the risk of serotonin syndrome.
• 2. Use with caution in patients with preexisting seizure disorders.
• 3. Caution should be used in agitated or hyperactive patients as sertraline may produce or activate mania or hypomania.
• 4. Use with caution in patients taking other psychotropic medications.
• 5. Use with caution in patients with recent myocardial infarction, unstable heart disease, hepatic or renal dysfunction.
• B. DRUG INTERACTION
• 1. SUMMARY - Sertraline is weak inhibitor of hepatic enzymes CYP1A2, CYP2C9/10, CYP2C19, CYP2D6 and CYP3A3/4. Inhibition appears to be dose-dependent, with higher doses, such as in overdoses, resulting in possible clinical relevance of drug interactions, particularly with tricyclic antidepressants (resulting in increased serum levels of TCA and toxicity).
• a. Major pharmacodynamic drug interactions concern the development of the serotonin syndrome. This is probably due to activation of 5-HT(1A) receptors in the brain. Drugs reacting with sertraline to result in serotonin syndrome include monoamine oxidase inhibitors (MAOI), tryptophan, lithium, and possibly moclobemide and rifampin (Mitchell, 1997). See DrugReax(R) for a more detailed list of drugs interacting with sertraline.
• 2. MAOI - Serotonin syndrome has been reported in patients taking sertraline and MAOI's. Hyperthermia, rigidity, myoclonus, autonomic instability, respiratory depression, syncope, incoordination, agitation, impaired memory, delirium, and coma have been reported when used in combination (Graber et al, 1994; Bhatara et al, 1993; Prod Info Zoloft(R), 1992).
• 3. TOLBUTAMIDE - Concurrent administration produced a 16% decrease in the clearance of tolbutamide (Prod Info Zoloft(R), 1992).
• 4. WARFARIN - Due to extensive protein binding, overdose with sertraline may increase the unbound amounts of warfarin in the serum (Prod Info Zoloft(R), 1992).
• 5. TRAMADOL - Coadministration of sertraline with tramadol resulted in possible serotonin syndrome in a 42-year-old female. She had been receiving sertraline therapy for about 1 yr prior to the addition of tramadol to her therapy. Within 3 weeks of tramadol dosing, symptoms of serotonin syndrome developed (Mason & Blackburn, 1997).
• 6. RIFAMPIN - Markowitz & DeVane (2000) reported rifampin-induced sertraline withdrawal syndrome in a patient 7 days after starting rifampin while already on chronic sertraline therapy. It is speculated that rifampin induced the hepatic CYP3A4 enzyme system, which is thought to metabolize sertraline.
• C. WITHDRAWAL SYNDROME
• 1. A constellation of symptoms have been reported following discontinuation of sertraline therapy. Symptoms have included: fatigue, nausea, abdominal cramps, diarrhea, shortness of breath, memory impairment, dizziness, insomnia, chills, headache, eye discomfort, tinnitus, ataxia, abnormal sensations ("electric shocks", skin tingling sensations, and involuntary movements). Symptoms typically resolve spontaneously, generally within 3 weeks, or with reinstatement of sertraline therapy (Leiter et al, 1995; Louie et al, 1994; Frost & Lal, 1995; Wolfe, 1997; Zajecka et al, 1997).
• 2. CASE REPORT/PEDIATRIC - Withdrawal symptoms in a neonate after maternal sertraline therapy has been reported. Symptoms included: agitation, restlessness, poor feeding, constant crying, insomnia and an enhanced startle reaction. The child had been well until one day postpartum and symptoms resolved gradually over the course of a week. The mother remained asymptomatic (Kent & Laidlaw, 1995).
• 4.0 LABORATORY/MONITORING
• 4.1 MONITORING PARAMETERS/LEVELS
• 4.1.1 SUMMARY
• A. Asymptomatic elevations in serum transaminases have been reported within the first 9 weeks of sertraline treatment and have disappeared promptly upon discontinuation of sertraline.
• B. Sertraline produces a mean 7% decrease in serum uric acid concentrations.
• C. A decreased white count has been seen therapeutically. It has not been reported in overdoses.
• D. The syndrome of inappropriate secretion of antidiuretic hormone with significant hyponatremia, elevated urinary sodium, and decreased serum osmolarity has been reported with sertraline therapy.
• E. Monitor for signs/symptoms of serotonin syndrome and possible seizures.
• 4.1.2 SERUM/BLOOD
• A. BLOOD/SERUM CHEMISTRY
• 1. LIVER FUNCTION TESTS - Asymptomatic elevations in serum transaminases have been reported within the first 9 weeks of sertraline treatment and have disappeared promptly upon discontinuation of the drug (Cohn et al, 1990; Prod Info Zoloft(R), 1992).
• 2. URIC ACID - Sertraline produces a mean 7% decrease in serum uric acid concentrations (Prod Info Zoloft(R), 1992).
• 3. HYPONATREMIA associated with SIADH has been reported with sertraline therapy.
• B. HEMATOLOGIC
• 1. WHITE CELL COUNT - A decreased white blood cell count has been seen therapeutically. It has not been reported in overdoses.
• 4.1.3 URINE
• A. URINALYSIS
• 1. Increased urinary sodium excretion associated with SIADH has been reported with sertraline therapy. Urinalysis may be recommended.
• 4.3 METHODS
• A. CHROMATOGRAPHY
• 1. Sertraline can be analyzed by gas chromatographic-mass spectrometric analysis (Fouda et al, 1987).
• 5.0 ABSTRACTS
• 5.1 CASE REPORTS
• A. ADULT
• 1. A 23-year-old female with depression took an overdose of 750 to 1000 milligrams. She was lavaged, observed, and treated symptomatically. She recovered without sequelae (Prod Info Zoloft(R), 1992).
• 2. A 43-year-old female took 1400 milligrams with unknown amounts of alcohol, temazepam, and mefenamic acid. She was observed overnight and discharged without sequelae the next day (Prod Info Zoloft(R), 1992).
• B. PEDIATRIC
• 1. A 9-year-old ingested an unknown quantity of sertraline and presented to the emergency department with tachycardia, hypertension, hallucinations, hyperthermia, vasodilation, and tremors in all extremities. The patient was extremely agitated and delirious. His pupils became fixed and dilated and tonic shaking activity became more intense over the next several hours (Kaminski et al, 1994).
• a. Laboratory tests revealed increased levels of liver enzymes, CPK, and leukocytes.
• b. Activated charcoal with sorbitol was administered in the ED. Since the child was exhibiting an anticholinergic reaction, physostigmine was administered by slow intravenous infusion in a dose of 0.5 mg every 10 minutes for a total of 2 mg. An appropriate reduction in heart rate and temperature resulted. By the fourth hospital day, a mild tremor was still present, and the child was subsequently discharged to home.
• 2. Meier & Lam (1998) report a sertraline overdose of 4000 mg and naproxen 7700 mg in a 14-year-old girl. Decontamination with activated charcoal was given 3 hours post-ingestion. Mild sedation was noted. Treatment included prochlorperazine for mild nausea and vomiting, lactated ringer's solution and repeated activated charcoal.
• a. The girl sustained a grand mal seizure at 4.5 hours post-ingestion followed by sinus tachycardia (102-108 bpm). Approximately 5.5 hours post-ingestion she experienced a second seizure. No anticonvulsants were given. No anion gap was noted on laboratory reports. Serum sertraline level was reported to be >1000 ng/mL. Urine toxicology was negative for other drugs. The patient was discharged to psychiatric care 2 days later.
• 6.0 TREATMENT
• 6.1 LIFE SUPPORT
• A. Support respiratory and cardiovascular function.
• 6.3 PATIENT DISPOSITION
• 6.3.1 DISPOSITION/ORAL EXPOSURE
• 6.3.1.5 OBSERVATION CRITERIA/ORAL
• A. A minimum observation period of 6 hours is recommended in cases of massive sertraline overdoses in order to prevent complications associated with sertraline-induced seizures. When serotonin syndrome is suspected, longer observation periods may be necessary.
• 6.4 MONITORING
• A. Asymptomatic elevations in serum transaminases have been reported within the first 9 weeks of sertraline treatment and have disappeared promptly upon discontinuation of sertraline.
• B. Sertraline produces a mean 7% decrease in serum uric acid concentrations.
• C. A decreased white count has been seen therapeutically. It has not been reported in overdoses.
• D. The syndrome of inappropriate secretion of antidiuretic hormone with significant hyponatremia, elevated urinary sodium, and decreased serum osmolarity has been reported with sertraline therapy.
• E. Monitor for signs/symptoms of serotonin syndrome and possible seizures.
• 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 and seizures.
• 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. Good supportive care should be available for these cases. The patient's airway should be maintained and oxygen administered as required. Monitor cardiac and other vital signs. There is no specific antidote.
• B. PHYSOSTIGMINE
• 1. In a case of a pure sertraline overdose (no mixed ingestion) physostigmine was given to counteract anticholinergic signs. A diagnosis of serotonin syndrome was made and the patient responded favorably to the physostigmine intravenous injection (Kaminski et al, 1994). It is NOT recommended to administer physostigmine in any mixed or unknown ingestions.
• 2. PHYSOSTIGMINE/INDICATIONS
• a. Physostigmine is primarily used as a diagnostic agent to distinguish anticholinergic delirium from other causes of altered mental status. Long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (20 to 60 minutes).
• b. Physostigmine has also been used to treat seizures, severe agitation, coma with hypoventilation, and hypotension with dysrhythmias in the setting of severe anticholinergic overdose. Safety and efficacy for these indications has not been established.
• c. Coma may be reversed dramatically in some cases, but physostigmine should not be used just to keep a patient awake.
• d. Physostigmine should not be used in patients with suspected tricyclic antidepressant overdose, or an ECG suggestive of tricyclic antidepressant overdose (QRS widening, R wave in aVR). In the setting of tricyclic antidepressant overdose, use of physostigmine has precipitated seizures and intractable cardiac arrest (Stewart, 1979; Newton, 1975; Pentel, 1980).
• 3. DOSE
• a. ADMINISTRATION: Dilute dose of physostigmine in 10 milliliters of dextrose 5% in water or normal saline. Give over 5 minutes.
• b. PEDIATRIC THERAPEUTIC TRIAL: 0.02 milligram/kilogram, up to 0.5 milligram of physostigmine intravenously over several minutes to reverse acute anticholinergic crisis. If the toxic effects persist and no cholinergic effects are produced, the drug should be readministered at five-minute intervals until a maximum dose of 2 milligrams is given.
• c. PEDIATRIC THERAPEUTIC DOSE: The lowest total effective trial dose of physostigmine should be repeated if life-threatening symptoms recur. Physostigmine is metabolized in 30 to 60 minutes. DO NOT USE AS A CONTINUOUS DRIP.
• d. ADOLESCENT AND ADULT DOSE TRIAL: 1 to 2 milligrams of physostigmine intravenously slowly, over 5 minutes. A second dose of 1 to 2 milligrams may be attempted in 20 minutes if no reversal has occurred.
• e. ADOLESCENT AND ADULT THERAPEUTIC DOSE: 1 to 4 milligrams intravenously slowly, over 5 to 10 minutes, should be repeated if life-threatening symptoms recur. It is metabolized within 30 to 60 minutes. DO NOT USE AS A CONTINUOUS DRIP.
• 4. CAUTIONS
• a. Relative contraindications to the use of physostigmine are asthma, gangrene, peripheral vascular disease, obstruction of the gastrointestinal tract or urogenital tract, cardiac conduction defects, and atrioventricular block.
• b. Too rapid IV administration of physostigmine has resulted in seizures and asystole.
• 5. ATROPINE FOR PHYSOSTIGMINE TOXICITY
• a. Atropine at a dose of one-half milligram per 1 milligram of physostigmine (of the last dose administered) should be available to reverse life-threatening physostigmine induced, toxic cholinergic effects such as bronchoconstriction.
• C. 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).
• 3. LORAZEPAM
• a. MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 milligrams/minute (Prod Info Ativan(R), 1999).
• b. ADULT LORAZEPAM DOSE: 2 to 8 milligrams intravenously. Initial doses may be repeated in 10 to 15 minutes if seizures persist (Prod Info, Ativan(R), 1999; AMA, 1991).
• c. PEDIATRIC LORAZEPAM DOSE: 0.05 to 0.1 milligram/kilogram intravenously, (maximum 4 milligrams/dose) repeated twice at intervals of 10 to 15 minutes (Benitz & Tatro, 1995).