FLUOXETINE

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).

c. FOSPHENYTOIN

(1) ADULT DOSAGE AND ADMINISTRATION: The dose, concentration in dosing solutions, and infusion rate of fosphenytoin are expressed as phenytoin sodium equivalents.
(2) ADULT LOADING DOSE FOSPHENYTOIN: 15 to 20 milligrams/kilogram of phenytoin sodium equivalents at a rate of 100 to 150 milligrams phenytoin equivalent/minute.
(3) Fosphenytoin should not be infused at rates greater than 150 milligrams phenytoin equivalent/minute because of the risk of hypotension.
(4) CAUTIONS: Perform continuous monitoring of respiratory function, cardiac rhythm, and blood pressure throughout infusion and for at least 30 minutes thereafter.
(5) ADULT MAINTENANCE DOSING: 4 to 6 milligrams phenytoin equivalents/kilogram/day. Rate of administration should not exceed 150 milligrams phenytoin equivalent/minute.
(6) SERUM LEVEL MONITORING: Monitor serum phenytoin levels over the next 12 to 24 hours; therapeutic levels 10 to 20 microgram/milliliter. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin.

B. MONITORING PARAMETERS

1. Obtain an ECG in symptomatic patients. Monitor for evidence of serotonin syndrome.

C. DYSRHYTHMIAS/QRS WIDENING

1. Intravenous sodium bicarbonate reversed QRS widening associated with fluoxetine overdose in one case report (Graudins et al, 1997).
2. A reasonable starting dose is 1 to 2 milliequivalents/kilogram repeated as needed to maintain serum pH 7.45-7.55. Monitor ECG, serum electrolytes and arterial blood gases carefully.

D. SEROTONIN SYNDROME

1. HYPERTHERMIA

a. Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans.
b. MUSCLE ACTIVITY - Benzodiazepines may be useful. Diazepam: Adult: 5 to 10 milligrams IV every 5 to 10 minutes as needed, monitor for respiratory depression and need for intubation. Child: 0.25 milligram/kilogram IV every 5 to 10 minutes; monitor for respiratory depression and need for intubation.
c. Non-depolarizing paralytics may be used in severe cases.

2. HYPERTENSION

a. Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic intervention may not be necessary. For hypertensive emergencies (emergent need to lower mean BP 30 percent within 30 minutes and achieve diastolic BP of 100 mmHg or less within one hour), nitroprusside is preferred.
b. NITROPRUSSIDE

(1) NITROPRUSSIDE/INDICATIONS

(a) Nitroprusside is preferred for hypertensive emergencies (emergent need to lower mean BP 30 percent within 30 minutes and achieve a diastolic BP of 100 mmHg or less within one hour).

(2) NITROPRUSSIDE/DOSE

(a) 0.1 to 5 microgram/kilogram/minute intravenous infusion; up to 10 micrograms/kilogram/minute may be required (AHA, 1992).

(3) NITROPRUSSIDE/SOLUTION PREPARATION

(a) Dilute a 50-milligram vial in 500 milliliters of dextrose 5 percent in water (100 micrograms/milliliter). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution.

(4) NITROPRUSSIDE/MAJOR ADVERSE REACTIONS

(a) Severe hypotension; cyanide toxicity; methemoglobinemia; lactic acidosis; chest pain or arrhthymias (high doses).

(5) NITROPRUSSIDE/MONITORING PARAMETERS

(a) Monitor blood pressure every 30 to 60 seconds at onset of drip; once stabilized, monitor every 30 minutes.

c. NITROGLYCERIN

(1) In theory, nitroglycerin may help alleviate the serotonin syndrome through nitric oxide mediated downregulation of serotonin.
(2) ADULT - Begin continuous infusion at 5 micrograms/minute and titrate to desired effect.
(3) CHILD - Begin infusion at 0.25 to 0.5 micrograms/kilogram/minute and titrate to desired effect.

3. HYPOTENSION

a. Administer 10 to 20 milliliters/kilogram 0.9% saline bolus and place patient in Trendelenburg position. Further fluid therapy should be guided by central venous pressure or right heart catheterization to avoid volume overload.
b. Control hyperthermia.
c. Pressor agents with dopaminergic effects may theoretically worsen serotonin syndrome and should be used with caution.
d. DOPAMINE

(1) PREPARATION: Add 200 or 400 milligrams to 250 milliliters of normal saline or dextrose 5% in water to produce 800 or 1600 micrograms per milliliter or add 400 milligrams to 500 milliliters of normal saline or dextrose 5% in water to produce 800 micrograms per milliliter.
(2) DOSE: Begin at 2 to 5 micrograms per kilogram per minute progressing in 5 to 10 micrograms per kilogram per minute increments as needed.
(3) CAUTION: If VENTRICULAR ARRHYTHMIAS occur, decrease rate of administration.

e. NOREPINEPHRINE

(1) PREPARATION: Add 4 milliliters of 0.1 percent solution to 1000 milliliters of dextrose 5% in water to produce 4 micrograms/milliliter.
(2) INITIAL DOSE

(a) ADULTS: 2 to 3 milliliters (8 to 12 micrograms)/minute
(b) ADULT AND CHILD: 0.1 to 0.2 microgram/kilogram/minute. Titrate to maintain adequate blood pressure.

(3) MAINTENANCE DOSE

(a) 0.5 to 1 milliliter (2 to 4 micrograms)/minute

4. SEIZURES

a. DIAZEPAM

(1) MAXIMUM RATE: Administer diazepam intravenously over 2 to 3 minutes (maximum rate = 5 milligrams/minute).
(2) 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.
(3) 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.
(4) RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (not FDA approved), or lorazepam may be given intramuscularly.

b. LORAZEPAM

(1) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 milligrams/minute (Prod Info Ativan(R), 1991).
(2) ADULT LORAZEPAM DOSE: 4 to 8 milligrams intravenously. Initial doses may be repeated in 10 to 15 minutes if seizures persist (AMA, 1991).
(3) PEDIATRIC LORAZEPAM DOSE: 0.05 to 0.1 milligram/kilogram intravenously, repeated twice at intervals of 15 to 20 minutes (Benitz & Tatro, 1988; Giang & McBride, 1988).

c. RECURRING SEIZURES: If seizures cannot be controlled with diazepam or recur, give phenobarbital.
d. PHENOBARBITAL

(1) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (15 to 25 micrograms per milliliter).
(2) 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.
(3) ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 milligrams may be given every 20 minutes.
(4) 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 or a total dose of 10 milligrams/kilogram.
(5) PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 milligrams per kilogram of phenobarbital intravenously at a rate of 25 to 50 milligrams per minute.
(6) PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 milligrams per kilogram may be given every 20 minutes.
(7) 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.
(8) INDICATIONS FOR INTUBATION: Intubation should be considered after total doses of greater than 20 milligrams/kilogram.
(9) 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.
(10) 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.
(11) 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.
(12) CAUTIONS: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.

5. CYPROHEPTADINE

a. Cyproheptadine is a non-specific 5-HT antagonist that has been shown to block development of serotonin syndrome in animals (Sternbach, 1991). Cyproheptadine has been used in the treatment of serotonin syndrome (Mills, 1997; Goldberg & Huk, 1992). There are no controlled human trials substantiating its efficacy.
b. ADULT - 4 to 8 milligrams orally repeated every 1 to 4 hours until therapeutic response is observed or maximum of 32 milligrams administered (Mills, 1997).
c. CHILD - 0.25 milligram/kilogram/day divided every 6 hours, maximum dose 12 milligrams/day (Mills, 1997).

6. NITROGLYCERIN

a. In theory nitroglycerin may help alleviate the serotonin syndrome through nitric oxide mediated downregulation of serotonin. It has been used in human cases with apparent benefit (Brown et al, 1996). There are no human trials substantiating its efficacy
b. ADULT - Begin continuous infusion at 5 micrograms/minute and titrate to desired effect.
c. CHILD - Begin infusion at 0.25 to 0.5 microgram/kilogram/minute and titrate to desired effect.

7. PROPRANOLOL

a. Propranolol is a 5-HT1A receptor antagonist (Sternbach, 1991). Propranolol has been used in human cases of serotonin syndrome with apparent benefit (Guze & Baxter, 1986; Dursun et al, 1997). There are no controlled human trials substantiating its efficacy.
b. PROPRANOLOL/ADULT DOSE

(1) 1 milligram/dose intravenously, administered no faster than 1 milligram/minute repeated every 2 to 5 minutes until desired response is seen or a maximum of 5 milligrams has been given.

c. PROPRANOLOL/PEDIATRIC DOSE

(1) 0.01 to 0.1 milligram/kilogram/dose over 10 minutes. Maximum 1 milligram/dose (Benitz & Tatro, 1988).

8. CHLORPROMAZINE -

a. Chlorpromazine is a 5-HT2 receptor antagonist that has been used to treat cases of serotonin syndrome (Graham, 1997; Gillman, 1996). Controlled human trial documenting its efficacy are lacking.
b. ADULT - 25 to 100 milligrams intramuscularly repeated in one hour if necessary.
c. CHILD - 0.5 to 1 milligram/kilogram repeated as needed every 6 to 12 hours not to exceed 2 milligrams/kilogram/day.

9. OTHER

a. Other agents which have been used to treat serotonin syndrome include methysergide and mirtazapine (Mills, 1997; Hoes, 1996).

10. NOT RECOMMENDED

a. BROMOCRIPTINE - Is used in the treatment of neuroleptic malignant syndrome but is NOT RECOMMENDED in the treatment of serotonin syndrome as it has serotonergic effects (Gillman, 1997). In one case the use of bromocriptine was associated with a fatal outcome (Kline et al, 1989).

6.11 ENHANCED ELIMINATION

A. HEMODIALYSIS

1. Hemodialysis did not significantly change the plasma concentration of either fluoxetine or norfluoxetine and would not be expected to have a beneficial effect during overdose (Aronoff et al, 1984).

7.0 RANGE OF TOXICITY

7.1 SUMMARY

A. Ingestions of 40 to 800 milligrams have generally produced minimal toxicity in adults.
B. Seizures have been reported in adults after ingestions of 900 milligrams or more.

7.2 THERAPEUTIC DOSE

7.2.1 ADULT

A. GENERAL

1. The therapeutic dose differs significantly from patient to patient, but would be expected to be in the range of 20 to 60 milligrams/day (Prod Info Prozac(R), 1999).

7.3 MINIMUM LETHAL EXPOSURE

A. ACUTE

1. Two deaths have been reported following fluoxetine overdose, however, both patients had other contributory causes (Tech Info, 1987).

a. A 42-year-old woman reported to ingest 1600 milligrams of fluoxetine along with maprotiline was found dead; postmortem fluoxetine concentrations were 4570 nanograms/milliliter and maprotiline 4180 nanograms/milliliter (Tech Info, 1987).
b. In the second case, a 24-year-old woman was found dead with a piece of plastic wrap on her face and a partially empty bottle of fluoxetine. The estimated amount ingested was 1580 milligrams. A preliminary autopsy report showed some signs of asphyxia and a fluoxetine level of 1934 nanograms/milliliter (Tech Info, 1987).

2. The estimated human lethal dose of fluoxetine is 1200 to 2000 milligrams (60 to 100 20-milligram capsules) (Kincaid et al, 1990).

B. ANIMAL DATA

1. Lethal seizures were seen in 50 percent of various animals given 200 to 700 milligrams/kilogram. The exact dose needed is species dependent (Wernicke, 1985).

7.4 MAXIMUM TOLERATED EXPOSURE

A. ADULT

1. Acute ingestions in adults of 300 to 440 milligrams, with no co-ingestants, resulted in no reported signs or symptoms in 2 patients. Coma was reported in one patient with a questionable history of ingestion of 340 milligrams. Ingestion of 900 to 1200 milligrams resulted in minor EKG changes (Tech Info, 1987).
2. A woman with a history of epilepsy experienced generalized seizures, ECG changes and tachycardia, dizziness, and blurred vision after ingesting approximately 3 grams of fluoxetine (Perse et al, 1991).
3. A 33-year-old male coingested 120 20-mg (2400 milligrams) fluoxetine capsules and 100 500-mg acetaminophen tablets and developed QRS prolongation that was responsive to intravenous sodium bicarbonate (Graudins et al, 1997).

B. PEDIATRIC

1. A 12-year-old boy who ingested 1,880 milligrams (26 milligrams/kilogram) had a single seizure, depressed ST segments on EKG, nausea, dizziness, blurred vision, and headache (Riddle et al, 1989).
2. No information is currently available regarding accidental ingestion in children.

7.5 SERUM/PLASMA/BLOOD CONCENTRATIONS

7.5.2 TOXIC CONCENTRATIONS

A. CASE REPORTS

1. HUMAN - Normal therapeutic values are approximately 400 nanograms/milliliter (Wernicke, 1985). A daily dosing of 60 mg would be expected to result in a steady state plasma range of 103 to 282 mcg of fluoxetine and 47 to 181 mcg of norfluoxetine/liter.
2. FATALITIES -

a. Plasma concentrations in 2 fatal cases were 1.93 and 4.57 milligrams/liter (Rohrig & Prouty, 1989). The heart blood concentration in a case of fatal combined ethanol/fluoxetine toxicity was 0.8 milligram/liter (Rohrig & Prouty, 1989).
b. Fluoxetine and norfluoxetine concentrations found in blood were 6000 and 5000 nanograms/milliliters, respectively, in a 58-year-old found dead of a suspected fluoxetine overdose (Kincaid et al, 1990).
c. Serum fluoxetine and norfluoxetine levels were 1956 mcg/L and 416 mcg/L respectively, 11 hours after ingestion in a 15 year old woman who developed seizures after fluoxetine overdose (Braitberg & Curry, 1994).
d. In a series of 168 coroner's cases in whom SSRIs were detected, fluoxetine was considered a primary contributing factor in 4 deaths, with blood levels typically greater than 1 milligram/liter. Fluoxetine and norfluoxetine levels were 3.67 and 0.38 milligrams/liter, respectively, in the one case certified as a fluoxetine overdose (Goeringer et al, 2000).

3. POSTMORTEM -

a. FORENSIC - Roettger (1990) recommends that femoral blood and liver should be analyzed for fluoxetine levels in the postmortem analysis.

7.7 LD50/LC50

A. References: Stark et al, 1985

§               LD50 - (ORAL) MOUSE: 248 mg/kg

§               LD50 - (ORAL) RAT: 452 mg/kg

§               LD0 - (ORAL) CAT: > 50 mg/kg

§               LD0 - (ORAL) DOG: > 100 mg/kg

§               LD0 - (ORAL) MONKEY: > 50 mg/kg

8.0 KINETICS

8.1 ABSORPTION

A. ORAL

1. Fluoxetine is rapidly absorbed after oral dosing (Nash et al, 1982). Peak levels occurred in 4 to 6 hours after oral administration (Saletu & Grunberger, 1985).
2. Studies by Lemberger et al (1985) would indicate fluoxetine to have a bioavailability of nearly 100%. Food does not appear to alter absorption (Aronoff et al, 1984).

8.2 DISTRIBUTION

8.2.1 DISTRIBUTION SITES

A. PROTEIN BINDING

1. Fluoxetine binds to plasma proteins to the extent of 94% (Lemberger et al, 1985).

B. TISSUE/FLUID SITES

1. The half life would indicate that there is tissue storage with this agent. Animal studies indicate that such is the case with the lung being the primary sequestering organ (Lemberger et al, 1985).

C. PEAK PLASMA LEVEL

1. Peak levels occurred in 4 to 6 hours after oral administration. Peak levels for 30 mg, 60 mg, and 75 mg doses were 30.1 ng/mL, 93.0 ng/mL, and 134.6 ng/mL respectively (Saletu & Grunberger, 1985).

8.2.2 DISTRIBUTION KINETICS

A. VOLUME OF DISTRIBUTION

1. The Vd measured in 25 subjects showed great variability ranging from 11 to 88.4 L/kg (Aronoff et al, 1984).

8.3 METABOLISM

8.3.2 METABOLITES

A. GENERAL

1. Fluoxetine is metabolized to a desmethyl metabolite, norfluoxetine, which has activity similar to fluoxetine (Nash et al, 1982). Most of both of these compounds are further conjugated prior to excretion, but the percent has yet to be determined (Lemberger, 1985).
2. Peak plasma concentrations of the active metabolite, norfluoxetine, occur around 76 hours after ingestion of fluoxetine (Benfield et al, 1986).

8.4 EXCRETION

8.4.1 KIDNEY

A. 65% of radio-labeled fluoxetine C14 appeared in the urine over 35 days. Only 2.5% of the radioactivity could be attributed to the parent compound and 10% as free norfluoxetine. The remainder was conjugated metabolites (Lemberger et al, 1985).

8.4.2 FECES

A. 15% of a radio-labeled dose was found in the feces (Lemberger et al, 1985).

8.5 ELIMINATION HALF-LIFE

8.5.1 PARENT COMPOUND

A. GENERAL

1. There is a wide individual variety in the half-life with the range being from 1 to 4 days after a single dose, and averaging near 70 hours (Nash et al, 1982; Aronoff et al, 1984; Lemberger et al, 1985).
2. Patients who receive higher doses over long periods of time may exhibit prolonged elimination half-lives (Pato et al, 1991).

8.5.2 METABOLITE

A. GENERAL

1. Seven days to 330 hours (Nash et al, 1982; Benfield et al, 1986). The half-life did not change appreciably with either the elderly or those in renal failure (Lemberger et al, 1985).

9.0 PHARMACOLOGY/TOXICOLOGY

9.1 PHARMACOLOGIC MECHANISM

A. Fluoxetine is a specific inhibitor of serotonin uptake, and is virtually free of catecholamine effects. The flu-like symptoms seen with another serotonin uptake inhibitor, zimelidine, have NOT been seen with fluoxetine (Wernicke, 1985).

10.0 PHYSICOCHEMICAL

10.3 MOLECULAR WEIGHT

A. 309.33

11.0 ANIMAL TOXICOLOGY

11.1 CLINICAL EFFECTS

11.1.3 CANINE/DOG

A. Five of six dogs purposely overdosed with oral fluoxetine experienced grand mal seizures which were alleviated by administration of intravenous diazepam (Prod Info, 1990).

11.2 TREATMENT

11.2.1 SUMMARY

A. GENERAL TREATMENT

1. Begin treatment immediately.
2. Keep animal warm and do not handle unnecessarily.
3. Sample vomitus, blood, urine, and feces for analysis.
4. Remove the patient and other animals from the source of contamination.
5. Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.