NEFAZODONE

• 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 EFFECTS -
• 1. Experience with overdose is extremely limited. Effects reported include nausea, vomiting, somnolence and in one mixed ingestion with ethanol and methocarbamol, seizures. In another mixed overdose, increasing lethargy, significant bradycardia, hypotension, and decreased respiratory rate were noted.
• 2. Trazodone is pharmacologically similar to nefazodone and might have similar effects in overdose. Effects commonly reported with trazodone overdose include CNS depression, nausea and vomiting. Coma is rare, but can be prolonged. Seizures and mild cardiovascular abnormalities (bradycardia and transient first degree heart block) have been described, but are rare.
• B. ADVERSE EFFECTS -
• 1. Common adverse effects at therapeutic doses include headache, dizziness, lightheadedness, somnolence, dry mouth, nausea, confusion and blurred vision. Liver failure has been reported following chronic therapy.
• 0.2.3 VITAL SIGNS
• A. Hypotension, bradycardia and respiratory depression may occur with significant ingestions.
• 0.2.5 CARDIOVASCULAR
• A. Cardiovascular effects appear to be minimal, but may include hypotension, bradycardia and ECG abnormalities. Heart block and torsades de pointes have occurred with trazodone, which is structurally similar to nefazodone.
• 0.2.6 RESPIRATORY
• A. Respiratory depression has been reported in an overdose.
• 0.2.7 NEUROLOGIC
• A. Therapeutic doses of nefazodone may produce somnolence, dizziness or asthenia. The possibility for CNS depression should be considered in overdose cases. Seizures have occurred with an overdose of nefazodone and other drugs, and in a person treated with nefazodone who had a history of seizures.
• 0.2.8 GASTROINTESTINAL
• A. Dry mouth, nausea, and constipation have been reported following therapeutic doses of nefazodone.
• 0.2.9 HEPATIC
• A. Increases in liver function tests have been reported following therapeutic doses and overdoses of nefazodone. Liver failure has been reported after 14 to 28 weeks of therapy.
• 0.2.10 GENITOURINARY
• A. Priapism might occasionally occur in overdose cases. This may be a very serious side effect requiring surgery.
• 0.2.12 FLUID-ELECTROLYTE
• A. Peripheral edema has been reported in 3% of patients receiving therapeutic doses of nefazodone compared to 2% of placebo-treated patients.
• 0.2.13 HEMATOLOGIC
• A. Rare cases of decreased hematocrit have been reported following therapeutic doses of nefazodone.
• 0.2.14 DERMATOLOGIC
• A. Diaphoresis may be seen following an overdose.
• 0.2.16 ENDOCRINE
• A. Plasma prolactin levels and cortisol may be increased following increased doses of nefazodone.
• 0.2.18 PSYCHIATRIC
• A. Activation of mania/hypomania may occur following therapeutic nefazodone doses in bipolar or unipolar patients. Panic attacks have been reported.
• 0.2.21 CARCINOGENICITY
• A. No significant increase in tumors occurred in rats or mice fed nefazodone for 2 years with daily doses approximately 3 to 6 times greater than the maximum human daily dose (Prod Info Serzone(R), 1995).
• 0.2.22 OTHER
• A. Drug interactions include drugs which are metabolized by the cytochrome P450IIIA4 enzyme and highly protein bound drugs which may displace nefazodone or the other drugs.
• 0.3 LABORATORY/MONITORING
• A. Nefazodone plasma levels are not widely available and their clinical usefulness has not been determined.
• B. Following nefazodone overdose, monitor heart rate, ECG, blood pressure, liver function tests, neurologic and respiratory status.
• 0.4 TREATMENT OVERVIEW
• 0.4.2 ORAL/PARENTERAL EXPOSURE
• A. There is no specific antidote for nefazodone overdose other than decontamination and supportive care. Nefazodone overdose alone has not been reported to produce significant cardiotoxicities and there is no evidence that therapies used in tricyclic depressant overdose (bicarbonate, phenytoin) are useful.
• 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. 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.
• E. ATROPINE: ADULT DOSE: BRADYCARDIA: 0.5 to 1 mg IV every 5 min. BRADYASYSTOLIC ARREST: 1 mg IV every 5 min. Maximum total dose 0.04 mg/kg. Minimum single dose 0.5 mg. PEDIATRIC DOSE: 0.02 mg/kg IV repeat every 5 min, minimum single dose 0.1 mg; maximum single dose 0.5 mg child, 1 mg adolescent; maximum total dose 1 mg child, 2 mg adolescent.
• F. There is only a small risk for seizures in overdose, thus prophylactic treatment with anticonvulsants is not recommended.
• 1. SEIZURES - Administer diazepam IV bolus (DOSE - ADULT - 5 to 10 mg initially which may be repeated every 15 minutes PRN up to 30 mg. CHILD - 0.25 to 0.4 mg/kg/dose up to 10 mg/dose. If seizures cannot be controlled or recur, administer phenobarbital.
• 2. Phenytoin should be avoided due to the potential effect of nefazodone on the QTc interval.
• G. PULMONARY EDEMA (NONCARDIOGENIC): Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
• H. Priapism is a medical emergency requiring immediate consult with a urologist.
• 0.5 RANGE OF TOXICITY
• A. An overdose of 16,800 mg of nefazodone along with "a handful" of verapamil resulted in lethargy, significant bradycardia, hypotension, and decreased respiratory rate.
• 1.0 SUBSTANCES INCLUDED/SYNONYMS
• 1.1 THERAPEUTIC/TOXIC CLASS
• A. Nefazodone is an antidepressant belonging to the phenylpiperazine class and is structurally related to trazodone. Nefazodone has pharmacologic actions in both the serotonergic and noradrenergic systems.
• 1.2 SPECIFIC SUBSTANCES

o             3H-1,2,4-triazol-3-one,2-(3-(4-(3-chlorophenyl)-1-

o               piperazinyl))-propyl)-5-ethyl-2,4-dihydro-4-

o               (2-phenoxyethyl)-,monohydrochloride

o             1-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-3-

o               ethyl-4-(2-phenoxyethyl)-delta(2)-1,2,4-triazolin

o               -5-one-monohydrochloride

o             MJ 13754-1

o             Nefazodone Hydrochloride

o             Molecular Formula:  C25-H32-Cl-N5-O2.HCl

o             CAS 83366-66-9 (Nefazodone)

o             CAS 82752-99-6 (Nefazodone Hydrochloride)

• 1.6 AVAILABLE FORMS/SOURCES
• A. Nefazodone is available as 100, 150, 200, and 250 milligram oral tablets.
• 3.0 CLINICAL EFFECTS
• 3.1 SUMMARY OF EXPOSURE
• A. OVERDOSE EFFECTS -
• 1. Experience with overdose is extremely limited. Effects reported include nausea, vomiting, somnolence and in one mixed ingestion with ethanol and methocarbamol, seizures. In another mixed overdose, increasing lethargy, significant bradycardia, hypotension, and decreased respiratory rate were noted.
• 2. Trazodone is pharmacologically similar to nefazodone and might have similar effects in overdose. Effects commonly reported with trazodone overdose include CNS depression, nausea and vomiting. Coma is rare, but can be prolonged. Seizures and mild cardiovascular abnormalities (bradycardia and transient first degree heart block) have been described, but are rare.
• B. ADVERSE EFFECTS -
• 1. Common adverse effects at therapeutic doses include headache, dizziness, lightheadedness, somnolence, dry mouth, nausea, confusion and blurred vision. Liver failure has been reported following chronic therapy.
• 3.3 VITAL SIGNS
• 3.3.1 SUMMARY
• A. Hypotension, bradycardia and respiratory depression may occur with significant ingestions.
• 3.3.3 TEMPERATURE
• A. Nefazodone has been shown to cause an elevation in body temperature, which may be mediated by the metabolite, mCPP (Walsh et al, 1993).
• 3.4 HEENT
• 3.4.3 EYES
• A. Amblyopia has been reported following therapeutic doses of nefazodone (Fontaine, 1992).
• B. Blurred vision has been reported with therapeutic use (Prod Info, 1995).
• 3.5 CARDIOVASCULAR
• 3.5.1 SUMMARY
• A. Cardiovascular effects appear to be minimal, but may include hypotension, bradycardia and ECG abnormalities. Heart block and torsades de pointes have occurred with trazodone, which is structurally similar to nefazodone.
• 3.5.2 CLINICAL EFFECTS
• A. HYPOTENSION
• 1. Minimal adverse cardiovascular effects have been reported in pre-marketing studies. Postural hypotension was reported in 2.8% of cases (Prod Info Serzone (R), 1995). A few cases of decreased pulse and supine blood pressure have occurred with therapeutic doses (Fontaine, 1993). It is postulated that an acute overdose may result in significant hypotension, due to alpha-receptor blockade.
• 2. Hypotension (BP, 59/24 mm Hg) was reported 5 hours after ingestion of 16,800 mg nefazodone along with "a handful" of verapamil tablets in an adult. Following symptomatic therapy, the patient recovered (Catalano et al, 1999).
• B. BRADYCARDIA
• 1. Nefazodone does not appear to produce tachycardia, even in patients with hypotension, and may lower baseline heart rate with therapeutic doses. Pre-marketing trials have shown a small incidence of modest reduction in resting pulse following therapeutic doses of nefazodone (Fontaine, 1993). It is postulated that an acute overdose may result in bradycardia.
• a. Reports of cardiovascular/electrocardiographic toxicity of nefazodone have not always ruled out co-ingestants or underlying cardiac disease (Fontaine, 1993).
• b. Pre-marketing studies of nefazodone vs. placebo have shown a significant degree of ECG changes reflecting sinus bradycardia in nefazodone recipients (Prod Info Serzone(R), 1995).
• 2. In an overdose of 16,800 mg nefazodone along with "a handful" of verapamil, significant bradycardia (42 beats/minute) was reported in an adult (Catalano et al, 1999). ECG revealed normal sinus rhythm with a prolonged QT interval and occasional premature ventricular contractions.
• C. ARRHYTHMIA
• 1. TRAZODONE - Nefazodone has been compared pharmacologically to trazodone (D'Amico et al, 1990), a drug which has occasionally produced cardiovascular effects in overdose, primarily when other drugs were also taken.
• a. Sporadic reports of hypotension, nonspecific ST-T wave changes, premature ventricular beats, torsades de pointes, right bundle-branch block, T wave inversion, bradycardia and AV block have been associated with trazodone overdoses (Lippman et al, 1982; Gamble & Peterson, 1986; Henry & Ali, 1983; Himmelhoch et al, 1984; Dubot et al, 1986; Augenstein et al, 1987; Irwin & Spar, 1983).
• b. Based on structural similarities, it is conceivable that cardiovascular effects associated with trazodone may also occur with nefazodone overdose.
• 3.6 RESPIRATORY
• 3.6.1 SUMMARY
• A. Respiratory depression has been reported in an overdose.
• 3.6.2 CLINICAL EFFECTS
• A. RESPIRATORY DEPRESSION
• 1. Overdose information is limited with nefazodone. Trazodone has produced respiratory arrest in rare overdose cases (Lippmann et al, 1982; Gamble & Peterson, 1986. The possibility of respiratory depression should be considered in cases of nefazodone overdose, as these drugs are pharmacologically similar (D'Amico et al, 1990).
• 2. Respiratory depression, resulting in decreased oxygen saturation (O2, 83%), was reported in a 31-year-old female following the ingestion of 16,800 mg nefazodone and "a handful" of verapamil (Catalano et al, 1999).
• 3.7 NEUROLOGIC
• 3.7.1 SUMMARY
• A. Therapeutic doses of nefazodone may produce somnolence, dizziness or asthenia. The possibility for CNS depression should be considered in overdose cases. Seizures have occurred with an overdose of nefazodone and other drugs, and in a person treated with nefazodone who had a history of seizures.
• 3.7.2 CLINICAL EFFECTS
• A. SEIZURES
• 1. A limited review of unpublished overdoses reported to the manufacturer identified seizures in one overdose case involving 2000 to 3000 mg nefazodone, methocarbamol and alcohol (Prod Info Serzone(R), 1995).
• 2. Pre-marketing clinical studies reported petit mal seizures in a patient with a history of petit mal seizures (Prod Info Serzone(R), 1995).
• B. CNS DEPRESSION
• 1. Most common adverse effects following therapeutic doses of nefazodone have included somnolence, dizziness, and asthenia (Fontaine, 1992; D'Amico et al, 1990). These effects have tended to be dose related.
• 2. The incidence of CNS effects in cases of nefazodone overdose is limited. The possibility of CNS depression should be considered in severe overdoses. Manifestations of CNS depression, in general, can range from lethargy to coma.
• a. In an overdose of 16,800 mg nefazodone along with "a handful" of verapamil, a 31-year-old female experienced increasing lethargy and slurred speech (Catalano et al, 1999).
• C. AGITATION
• 1. Agitation, anxiety and tremor have been reported in pre-marketing studies following therapeutic doses of nefazodone, but these effects were less than reported for other 5-HT uptake inhibitors (Fontaine, 1992). There is insufficient information concerning agitation and anxiety following nefazodone overdoses.
• 2. A clinical trial involving 90 patients reported improvement of depression-associated anxiety symptoms following nefazodone treatment (Fontaine et al, 1994). Fontaine (1993) reported a lower incidence of agitation in nefazodone treated patients (27 out of 1,022; 2.6%) as compared to placebo treated patients (30 out of 672; 4.5%).
• 3. Discontinuation of nefazodone resulted in agitation in 1.2% of patients in clinical trials (Prod Info Serzone (R), 1995).
• D. CONFUSION
• 1. Confusion was reported in 7% of 393 patients treated with nefazodone in 6 to 8 week clinical trials. Confusion was reported in 2% of 394 patients in the placebo group (Prod Info Serzone(R), 1995).
• E. HEADACHE
• 1. Headache was reported as frequently or more frequently in placebo treated patients compared to patients treated with nefazodone at 200 to 300 mg/day. The incidence of headache in nefazodone treated patients was not positively correlated with dose (D'amico et al, 1990).
• F. SEROTONIN SYNDROME
• 1. Discontinuation of drugs similar to nefazodone, followed by the use of a monoamine oxidase inhibitor (MAOI) have resulted in signs and symptoms of serotonin syndrome (mental status changes, agitation, myoclonus, hyper-reflexia, diaphoresis, shivering, tremor, diarrhea, fever or incoordination (Prod Info Serzone(R), 1995).
• a. Nefazodone should not be used with a MAOI, or within 14 days of discontinuing use of a MAOI. A period of at least 1 week should be awaited after discontinuing nefazodone before starting a MAOI (Prod Info Serzone(R), 1995).
• 3.8 GASTROINTESTINAL
• 3.8.1 SUMMARY
• A. Dry mouth, nausea, and constipation have been reported following therapeutic doses of nefazodone.
• 3.8.2 CLINICAL EFFECTS
• A. ANTICHOLINGERGIC SYNDROME
• 1. Dry mouth (25%), nausea (22%), constipation (14%), and nausea with vomiting (2%) were reported in clinical trials (Prod Info Serzone(R), 1995; Rickels et al, 1994).
• a. Other studies reported nausea in 15% of patients receiving doses of up to 300 mg daily and in 32% of those treated with up to 600 mg daily (D'Amico et al, 1990; Fontaine, 1992; Ansseau et al, 1994). Nausea has decreased with continued nefazodone use (D'Amico et al, 1990).
• 2. One study reported that nefazodone has a lower propensity to cause anti- cholinergic adverse effects, such as dry mouth and constipation, compared to imipramine (Fontaine et al, 1994).
• 3. Following an overdose of 16,800 mg nefazodone along with "a handful" of verapamil, a 31-year-old experienced constipation and abdominal distention (Catalano et al, 1999).
• 3.9 HEPATIC
• 3.9.1 SUMMARY
• A. Increases in liver function tests have been reported following therapeutic doses and overdoses of nefazodone. Liver failure has been reported after 14 to 28 weeks of therapy.
• 3.9.2 CLINICAL EFFECTS
• A. HEPATIC ENZYMES INCREASED
• 1. Increases in liver function tests, specifically, LDH, SGOT, and SGPT, were reported infrequently following therapeutic nefazodone doses. Hepatitis has been reported as a rare adverse event of nefazodone therapy (Prod Info Serzone(R), 1995) and following overdoses (Catalano et al, 1999).
• B. HEPATIC FAILURE
• 1. Subfulminant liver failure due to severe hepatocellulur injury from nefazodone, an idiosyncratic reaction, has been reported after 14 to 28 weeks of therapy in 3 separate cases (Aranda-Michel et al, 1999). Prominent centrilobular collapse and necrosis was evident in all 3 cases. A 4 to 6 week duration of jaundice preceded onset of hepatic encephalopathy.
• 3.10 GENITOURINARY
• 3.10.1 SUMMARY
• A. Priapism might occasionally occur in overdose cases. This may be a very serious side effect requiring surgery.
• 3.10.2 CLINICAL EFFECTS
• A. PRIAPISM
• 1. Trazodone may cause priapism in overdose and might occur with nefazodone overdose. However, priapism is not expected to occur as frequently with nefazodone, due to a lesser degree of alpha-adrenergic blocking activity. If priapism does occur, it may be a serious adverse consequence requiring surgery (Ware et al, 1994). Patients with prolonged or inappropriate erections should be referred to a physician.
• 3.12 FLUID-ELECTROLYTE
• 3.12.1 SUMMARY
• A. Peripheral edema has been reported in 3% of patients receiving therapeutic doses of nefazodone compared to 2% of placebo-treated patients.
• 3.12.2 CLINICAL EFFECTS
• A. EDEMA PERIPHERAL
• 1. Peripheral edema was described during therapeutic use in 3% of patients receiving doses of 300 to 600 mg/day. Dose reduction or discontinuation resulted in prompt resolution. Two percent of patients treated with a placebo also had peripheral edema (Prod Info Serzone(R), 1995).
• 3.13 HEMATOLOGIC
• 3.13.1 SUMMARY
• A. Rare cases of decreased hematocrit have been reported following therapeutic doses of nefazodone.
• 3.13.2 CLINICAL EFFECTS
• A. ANEMIA
• 1. Pre-marketing clinical trials of nefazodone have shown rare cases of decreased hematocrit following therapeutic doses (Prod Info Serzone(R), 1995).
• 3.14 DERMATOLOGIC
• 3.14.1 SUMMARY
• A. Diaphoresis may be seen following an overdose.
• 3.14.2 CLINICAL EFFECTS
• A. SWEATING INCREASED
• 1. Sweating occurred in 2.6% (27 out of 1.022; placebo group 2.4%) of patients following therapeutic doses of nefazodone (Fontaine, 1993).
• B. RASH
• 1. Rash and pruritus occurred in a small number of patients (2% -vs- 1% in the placebo group) following therapeutic nefazodone doses (Prod Info Serzone(R), 1995).
• 3.16 ENDOCRINE
• 3.16.1 SUMMARY
• A. Plasma prolactin levels and cortisol may be increased following increased doses of nefazodone.
• 3.16.2 CLINICAL EFFECTS
• A. HYPERPROLACTINEMIA
• 1. Oral nefazodone (50 to 200 mg) was associated with dose-related increases in plasma prolactin levels in one study involving healthy male volunteers. The drug did not significantly alter levels of corticotropin (ACTH), although a trend toward elevation of cortisol levels was reported (Walsh et al, 1993).
• 3.18 PSYCHIATRIC
• 3.18.1 SUMMARY
• A. Activation of mania/hypomania may occur following therapeutic nefazodone doses in bipolar or unipolar patients. Panic attacks have been reported.
• 3.18.2 CLINICAL EFFECTS
• A. MANIC REACTION
• 1. In pre-marketing clinical trials nefazodone was shown to activate hypomania or mania in a small number of unipolar and bipolar patients following therapeutic doses (Prod Info Serzone(R), 1995).
• B. AGITATION
• 1. Panic attacks were reported in 1 out of 20 patients treated with 0.25 mg/kg and 3 out of 20 patients treated with 0.5 mg/kg of m-chlorophenylpiperazine (mCPP), a nefazodone metabolite and direct 5HT receptor agonist (Kahn et al, 1990).
• 3.20 REPRODUCTIVE
• 3.20.3 EFFECTS IN PREGNANCY
• A. PREGNANCY CATEGORY
• 1. Nefazodone is classified as Pregnancy Category C by the FDA. No malformations were observed in rat or rabbit fetuses in reproductive studies, however, increased early pup mortality was reported at doses approximately 5 times the maximum human dose (Prod Info Serzone(R), 1995).
• 3.20.4 EFFECTS DURING BREAST-FEEDING
• A. BREAST MILK
• 1. It is not known if nefazodone or its metabolites are excreted in human milk (Prod Info Serzone(R), 1995).
• 3.20.5 FERTILITY
• A. FERTILITY DECREASED FEMALE
• 1. A slight decrease in fertility occurred in rats at doses of 200 mg/kg/day, which is approximately 3 times the maximum human daily dose. Lower doses did not decrease fertility (Prod Info Serzone(R), 1995).
• 3.21 CARCINOGENICITY
• 3.21.2 SUMMARY/HUMAN
• A. No significant increase in tumors occurred in rats or mice fed nefazodone for 2 years with daily doses approximately 3 to 6 times greater than the maximum human daily dose (Prod Info Serzone(R), 1995).
• 3.23 OTHER
• 3.23.1 SUMMARY
• A. Drug interactions include drugs which are metabolized by the cytochrome P450IIIA4 enzyme and highly protein bound drugs which may displace nefazodone or the other drugs.
• 3.23.2 CLINICAL EFFECTS
• A. DRUG INTERACTION
• 1. Nefazodone may cause increased serum levels of drugs which are metabolized by cytochrome P450IIIA4 enzyme. Some of these drugs include terfenadine, astemizole, alprazolam, and triazolam. A dosage reduction of these drugs is recommended when nefazodone is to be taken concurrently (Prod Info Serzone(R), 1995).
• 2. Since nefazodone is highly bound to plasma protein, it may cause increased free concentrations of other drugs which are also highly protein bound or conversely, increased free concentrations of nefazodone may result (Prod Info Serzone(R), 1995).
• 3. Co-administration with monoamine oxidase inhibitors (MAOI), or the use of nefazodone within a short time of discontinuing or starting a MAOI may result in a serotonin syndrome reaction (Prod Info Serzone(R), 1995), which can be fatal in some cases.
• a. A serotonin syndrome may consist of mental status changes (e.g. confusion, hypomania, agitation, myoclonus, hyper-reflexia, diaphoresis, shivering, tremor, diarrhea, fever or incoordination).
• 4. Concomitant of ethanol and nefazodone is discouraged (Prod Info Serzone(R), 1995).
• 4.0 LABORATORY/MONITORING
• 4.1 MONITORING PARAMETERS/LEVELS
• 4.1.1 SUMMARY
• A. Nefazodone plasma levels are not widely available and their clinical usefulness has not been determined.
• B. Following nefazodone overdose, monitor heart rate, ECG, blood pressure, liver function tests, neurologic and respiratory status.
• 4.1.2 SERUM/BLOOD
• A. BLOOD/SERUM CHEMISTRY
• 1. Quantitative determination of nefazodone plasma levels is not widely available and its clinical utility has not been determined.
• 2. Following oral doses of 150 mg BID, plasma levels of approximately 1200 ng/mL were determined after 30 minutes in one female patient. Peak levels of the metabolites hydroxynefazodone and m-chlorophenylpiperazine (mCPP) were approximately 400 and 25 ng/mL, respectively, each occurring 2 hours following nefazodone administration (Franc et al, 1991).
• 4.1.4 OTHER
• A. ECG
• 1. Although cardiovascular toxicity has been minimal in reports of overdose, ECG monitoring is recommended. There are insufficient data to determine the duration of monitoring required.
• B. MONITORING
• 1. Monitor the chest x-ray for patients with significant exposure.
• 2. Monitor blood gases and pulmonary function if respiratory or CNS depression is suspected.
• 4.3 METHODS
• A. CHROMATOGRAPHY
• 1. Franc et al (1991), describe a quantitative method utilizing high- performance liquid chromatography and ultraviolet detection for the determination of nefazodone and its metabolites, m-chlorophenylpiperazine (mCPP), p-hydroxynefazodone (PHN), and hydroxynefazodone (HO-NEF), in human plasma. However, the clinical utility of quantitative determination of nefazodone plasma levels has not yet been determined.
• 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. All patients with suspected nefazodone poisoning should be monitored in view of a small possibility of cardiovascular and neurological disturbances.
• B. Although cardiovascular toxicity has been minimal in reports of overdose, ECG monitoring is recommended since reports of cardiotoxicity have occurred. There are insufficient data to determine the duration of monitoring required.