SIBUTRAMINE (Meridia, Reductil)
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• 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. Overdoses may be expected to result in increased blood pressure and heart rate, seizures, impaired concentration and judgment, and in severe cases, serotonin syndrome.
• Refer to "SEROTONIN SYNDROME" management for further information.
• 0.2.5 CARDIOVASCULAR
• A. Increased blood pressure and heart rate may occur in overdoses.
• 0.2.6 RESPIRATORY
• A. Although not yet reported, it is possible that chronic or overdoses may result in pulmonary hypertension.
• 0.2.7 NEUROLOGIC
• A. CNS depression, headache, fatigue, dizziness, nervousness, seizures, tremors, and serotonin syndrome may occur following sibutramine toxic ingestion.
• 0.3 LABORATORY/MONITORING
• A. Sibutramine blood levels are not clinically useful.
• B. Monitor blood pressure and ECG in symptomatic patients.
• C. Echocardiogram may be indicated if valvular insufficiency or a new murmur is present on exam.
• D. No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
• 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 and seizures.
• 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. PVCS/SUMMARY - Treatment of PVCs may include lidocaine, phenytoin, or overdrive transvenous pacing. Atropine may used when severe bradycardia is present and PVCs are thought to represent an escape complex.
• F. HYPERTENSION: Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic treatment is generally not necessary. For severe hypertension nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. See main treatment section for doses.
• 0.5 RANGE OF TOXICITY
• A. Overdose experience is limited. An overdose of 400 milligrams in an adult resulted in tachycardia with no apparent sequelae. A 2-year-old child ingested up to 800 milligrams without complications.
• 1.0 SUBSTANCES INCLUDED/SYNONYMS
• 1.1 THERAPEUTIC/TOXIC CLASS
• A. Sibutramine is a nonamphetamine appetite suppressant and antidepressant, currently approved for treatment of obesity. It is a norepinephrine, serotonin and dopamine reuptake inhibitor, and does not release monoamines.
• 1.2 SPECIFIC SUBSTANCES

o              1-(p-Chlorophenyl)-alpha-isobutyl-N,N-

o                 dimethylcyclobutanemethylamine

o              BTS 54524

o              Sibutramine hydrochloride

o              Molecular Formula:  C17-H26-ClN

o              CAS 106650-56-0 (sibutramine)

o              CAS 84485-00-7 (anhydrous sibutramine hydrochloride)

o              CAS 125494-59-9 (sibutramine hydrochloride monohydrate)

• 1.6 AVAILABLE FORMS/SOURCES
• A. FORMS
• 1. This drug is available as 5 mg, 10 mg and 15 mg capsules (Prod Info Meridia(R), 1997).
• B. USES
• 1. Sibutramine is used in the management of obesity and is used in conjunction with a reduced calorie diet (Prod Info Meridia(R), 1997).
• 2. Sibutramine is controlled in Schedule IV of the Controlled Substances Act (CSA) (Prod Info Meridia(R), 1997).
• 3. Clinical trials are being conducted with sibutramine for treatment of depression.
• 3.0 CLINICAL EFFECTS
• 3.1 SUMMARY OF EXPOSURE
• A. Overdoses may be expected to result in increased blood pressure and heart rate, seizures, impaired concentration and judgment, and in severe cases, serotonin syndrome.
• Refer to "SEROTONIN SYNDROME" management for further information.
• 3.3 VITAL SIGNS
• 3.3.3 TEMPERATURE
• A. Fever, accompanied by symptoms of flushed face, sweating, and shivering, may occur with sibutramine overdose. This would be due to the thermogenesis action of sibutramine (Stock, 1997).
• 3.4 HEENT
• 3.4.3 EYES
• A. Overdoses may cause mydriasis and may aggravate pre-existing narrow angle glaucoma (Prod Info Meridia(R), 1997).
• 3.5 CARDIOVASCULAR
• 3.5.1 SUMMARY
• A. Increased blood pressure and heart rate may occur in overdoses.
• 3.5.2 CLINICAL EFFECTS
• A. HYPERTENSION
• 1. Therapeutic doses have been associated with increases in blood pressure. Larger doses in clinical trials were associated with higher increases in blood pressure in a small percent of patients (Prod Info Meridia(R), 1997; Weintraub et al, 1991; King & Devaney, 1988).
• B. TACHYCARDIA
• 1. Overdoses and therapeutic doses have been associated with tachycardia (Weintraub et al, 1991; Prod Info Meridia(R), 1997; Hanotin et al, 1998; King & Devaney, 1988). Increased pulse rate that was dose responsive was noted in subjects in a clinical trial (Ryan et al, 1995).
• 2. Increased heart rate of 120 bpm was reported in a 45-year-old male following an ingestion of 400 mg (Prod Info Meridia(R), 1997).
• 3. Palpitations and tachycardia leading to drug withdrawal were reported in 0.3% and 0.4% of treated patients, respectively, in phase I trials (Lean, 1997). Significant increases in heart rate (about 4 beats/min) were reported in patients receiving 10mg or 15mg sibutramine in clinical trials (Hanotin et al, 1998).
• C. ECG ABNORMAL
• 1. Due to its mechanism of action, it may be possible in an overdose to see tachycardias, extrasystoles, increased PVC's, and ventricular fibrillation.
• 2. Weintraub et al (1991) reported 3 participants receiving 20 mg sibutramine in a clinical trial had increased numbers of premature contractions with no symptoms or cardiac signs.
• 3.6 RESPIRATORY
• 3.6.1 SUMMARY
• A. Although not yet reported, it is possible that chronic or overdoses may result in pulmonary hypertension.
• 3.6.2 CLINICAL EFFECTS
• A. HYPERTENSION PULMONARY
• 1. Primary pulmonary hypertension has not been reported with sibutramine use in clinical trials; however, due to its centrally-acting effects of causing serotonin release from nerve terminals, it is possible that an overdose or chronic dosing may result in pulmonary hypertension (Prod Info Meridia(R), 1997).
• 3.7 NEUROLOGIC
• 3.7.1 SUMMARY
• A. CNS depression, headache, fatigue, dizziness, nervousness, seizures, tremors, and serotonin syndrome may occur following sibutramine toxic ingestion.
• 3.7.2 CLINICAL EFFECTS
• A. SEIZURES
• 1. Seizures have been reported in less than 1% of patients in clinical trials. Due to its mechanism of action, seizures may occur in overdoses (Prod Info Meridia(R), 1997).
• B. SEROTONIN SYNDROME
• 1. Serotonin syndrome, which may include cognitive changes, rigidity, hyperreflexia, tachycardia, diaphoresis, tremulousness, and fever, may theoretically occur after sibutramine overdose due to its serotonin reuptake inhibiting action (Prod Info Meridia(R), 1997). Drug interactions with sibutramine and MAO inhibitors, selective serotonin reuptake inhibitors or other drugs which increase brain serotonin may result in serotonin syndrome.
• C. CNS EFFECTS
• 1. Toxic ingestions of sibutramine have the potential of impairing judgment, thinking or motor skills due to the CNS activity of the drug (Prod Info Meridia(R), 1997).
• 2. Irritability, insomnia, headache, and decreased duration of sleep have been reported in patients receiving sibutramine in clinical trials. Although CNS stimulation has occurred, euphoria has not been reported (Weintraub et al, 1991; Lean, 1997; Ryan et al, 1995).
• 3.8 GASTROINTESTINAL
• 3.8.2 CLINICAL EFFECTS
• A. CONSTIPATION
• 1. In clinical trials, constipation and dry mouth were the most common adverse events reported (Ryan et al, 1995; Bray et al, 1996).
• 3.9 HEPATIC
• 3.9.2 CLINICAL EFFECTS
• A. HEPATIC ENZYMES INCREASED
• 1. Elevations in ALT, AST, and alkaline phosphatase occurred in 17 of 60 patients (28.3%) receiving sibutramine in clinical trials (Golik et al, 1991); however, a causal relationship could not be determined.
• 3.13 HEMATOLOGIC
• 3.13.2 CLINICAL EFFECTS
• A. THROMBOCYTOPENIA
• 1. One case of reversible thrombocytopenia has been reported during a clinical trial with sibutramine (Weintraub et al, 1997). Platelet function may be affected by sibutramine due to its effect on serotonin uptake. Ecchymosis has been observed in 0.7% of treated patients in premarketing studies (Prod Info Meridia(R), 1997).
• 3.20 REPRODUCTIVE
• 3.20.3 EFFECTS IN PREGNANCY
• A. PREGNANCY CATEGORY
• 1. FDA pregnancy category C (Prod Info Meridia(R), 1997).
• 3.20.4 EFFECTS DURING BREAST-FEEDING
• A. BREAST MILK
• 1. It is unknown if sibutramine or its metabolites are excreted in human breast milk (Prod Info Meridia(R), 1997).
• 3.21 CARCINOGENICITY
• 3.21.4 ANIMAL STUDIES
• A. LACK OF EFFECT
• 1. In 2 year mice and rat studies, with a combined maximum plasma AUC of the 2 major metabolites of sibutramine equivalent to up to 21 times those following the maximum daily human dose (20 mg), no carcinogenicity was reported (Prod Info Meridia(R), 1997).
• 3.22 GENOTOXICITY
• A. Sibutramine showed no mutagenicity in various in vitro mouse assays. However, both active metabolites were found to have equivocal bacterial mutagenic activity in the Ames test (Prod Info Meridia(R), 1997).
• 3.23 OTHER
• 3.23.2 CLINICAL EFFECTS
• A. DRUG INTERACTION
• 1. MAO inhibitors given in conjunction with sibutramine may result in serotonin syndrome (Prod Info Meridia(R), 1997). Serotonin syndrome may also occur if sibutramine is used in conjunction with other drugs which increase brain serotonin (selective serotonin reuptake inhibitors, tricyclic antidepressants, etc.).
• 2. CNS active drugs, particularly serotonergic agents, may interact with sibutramine (Prod Info Meridia(R), 1997).
• 3. Drugs that inhibit cytochrome P450 metabolism, such as ketoconazole, erythromycin and cimetidine, may interact with sibutramine causing increased plasma concentrations of sibutramine and its metabolites (Prod Info Meridia(R), 1997).
• 4.0 LABORATORY/MONITORING
• 4.1 MONITORING PARAMETERS/LEVELS
• 4.1.1 SUMMARY
• A. Sibutramine blood levels are not clinically useful.
• B. Monitor blood pressure and ECG in symptomatic patients.
• C. Echocardiogram may be indicated if valvular insufficiency or a new murmur is present on exam.
• D. No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
• 4.1.4 OTHER
• A. MONITORING
• 1. Monitor blood pressure for possible hypertension.
• 2. Monitor temperature for possible hyperthermia.
• 3. Monitor fluid status and electrolytes as indicated in patients with profuse sweating.
• 4. ECG should be monitored for possible tachycardia.
• B. ECHOCARDIOGRAM
• 1. Echocardiogram may be indicated with symptoms of valvular insufficiency or a new murmur is present on exam.
• 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. Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
• 6.4 MONITORING
• A. Sibutramine blood levels are not clinically useful.
• B. Monitor blood pressure and ECG in symptomatic patients.
• C. Echocardiogram may be indicated if valvular insufficiency or a new murmur is present on exam.
• D. No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
• 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. EMESIS/NOT RECOMMENDED
• 1. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
• 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).
• C. 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.
• 6.5.3 TREATMENT
• A. SUMMARY
• 1. Treatment is symptomatic and supportive. Seizures may occur and should be treated aggressively. Cardiac monitoring is recommended. Cautious use of beta-blockers may be indicated for control of severe hypertension or tachycardia.
• 2. Physostigmine may INDUCE SEIZURES in the sibutramine poisoned patient and should NOT be used.
• 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).
• 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).
• 4. PHENOBARBITAL
• a. ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 milligrams of phenobarbital intravenously initially (10 to 20 milligrams per kilogram) diluted in 60 milliliters of 0.9 percent saline given at 25 to 50 milligrams per minute.
• b. ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 milligrams may be given every 20 minutes.
• c. MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 milligrams/minute until seizure control was achieved.
• d. PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 milligrams per kilogram of phenobarbital intravenously at a rate of 25 to 50 milligrams per minute.
• e. PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 milligrams per kilogram may be given every 20 minutes.
• f. MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 milligrams/kilogram within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
• g. MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation.
• h. NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 milligrams/kilogram intravenously at a rate of no more than 1 milligram/kilogram per minute in patients with no preexisting phenobarbital serum levels.
• i. NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 milligrams/kilogram every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 micrograms/milliliter.
• j. MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 milligrams/kilogram/minute up to a total of 30 milligrams/kilogram have been tolerated in neonates.
• k. CAUTIONS: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.
• l. SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (20 to 40 micrograms per milliliter).
• 5. PHENYTOIN/FOSPHENYTOIN
• a. Benzodiazepines and/or barbiturates are generally preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures.
• b. PHENYTOIN
• (1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION: Manufacturer does not recommend intravenous infusions due to lack of solubility and resultant precipitation, however infusions are commonly used.
• (a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 milligrams per milliliter solution in 50 to 100 milliliters of 0.9 percent saline.
• (2) PHENYTOIN ADMINISTRATION RATE: Rate of administration by either method should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
• (3) ADULT PHENYTOIN LOADING DOSE: 15 to 18 milligrams per kilogram of phenytoin initially. Rate of administration by very slow intravenous push or diluted to 50 milligrams per milliliter should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
• (4) ADULT PHENYTOIN MAINTENANCE DOSE: Manufacturers recommend a maintenance dose of 100 milligrams orally or intravenously every 6 to 8 hours. The goal is to maintain a serum concentration between 10 to 20 micrograms/milliliter.
• (5) PEDIATRIC PHENYTOIN LOADING DOSE: 15 to 20 milligrams per kilogram or 250 milligrams/square meter of phenytoin. Rate of intravenous administration should not exceed 0.5 to 1.5 milligrams per kilogram per minute.
• (6) PEDIATRIC PHENYTOIN MAINTENANCE DOSE: Repeat doses of 1.5 milligrams per kilogram may be given every 30 minutes to a maximum daily dose of 20 milligrams per kilogram.
• (7) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if arrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle.
• (8) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (10 to 20 micrograms per milliliter).