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PHENACETIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Phenacetin is an aniline derivative that has analgesic and anti-pyretic properties. Phenacetin is usually considered inferior to ASA or acetaminophen, both as an antipyretic and as an analgesic.

Specific Substances

    1) Acetophenetidin
    2) Aceto-p-phenetidide
    3) Acetylphenetidin
    4) N-(4-Ethoxyphenyl)acetamide
    5) Paracetophenetidin
    6) p-ethoxyacetanilide
    7) Phenacetinum
    8) CAS 62-44-2
    9) ACETOPHENETIDINE
    10) ACETOPHENETIN
    11) ACETPHENETIDIN
    12) APC (PHENACETIN)
    13) PHENACET
    14) PHENACETINE
    15) PHENACITIN
    16) PHENIN
    17) PYRAPHEN
    18) PYRROXATE

Available Forms Sources

    A) FORMS
    1) Phenacetin is a slightly bitter, crystals or powder (Budavari, 2001). It was previously found as a constituent of many over-the-counter headache remedies such as APC, Bromo Seltzer and Empirin Compound. Usually 90 to 150 mg per tablet.
    a) Phenacetin was removed from products marketed in the United States effective August, 1983 (FDA, 1982).
    B) USES
    1) Phenacetin is included in the therapeutic category of analgesics and antipyretics (Budavari, 2001).
    2) COCAINE ADULTERANT: An HPLC-DAD method was developed and successfully used to detect the presence of phenacetin as an adulterant in 5 of 115 cocaine samples seized in Brazil between 2007 and 2012. Reportedly, phenacetin is frequently used as a cocaine adulterant in Europe, although these findings suggest that it may be developing more of a presence as a cocaine adulterant in South America as well (Floriani et al, 2014).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) NOTE - Phenacetin has not been available in the United States since August 1983.
    B) ACUTE INGESTION - The minimal acute toxic dose is not well established in the literature. Acute overdosage or chronic daily doses exceeding 1 gram may result in methemoglobinemia and hemolytic anemia.
    1) Signs and symptoms following severe intoxication may include seizures, coma, cyanosis, respiratory depression and cardiac arrest.
    C) CHRONIC INGESTION - Renal papillary necrosis may occur following long term exposure to large doses of combination analgesics containing phenacetin.
    0.2.5) CARDIOVASCULAR
    A) Chronic phenacetin abuse is associated with an increased risk of hypertension and related cardiovascular consequences, such as MI, heart failure, and stroke. Acute fatal doses may result in cardiac arrest.
    0.2.7) NEUROLOGIC
    A) Seizures and coma may be noted following massive overdose.
    0.2.9) HEPATIC
    A) Jaundice has been noted, however it does not appear that liver injury is a primary manifestation of phenacetin overdose.
    0.2.10) GENITOURINARY
    A) Chronic ingestion of analgesics containing phenacetin over a prolonged period of time (generally years), has been associated with renal papillary necrosis.
    B) Dark brown urine was noted in a number of cases. It may be an indication of phenacetin ingestion, however it is not diagnostic.
    0.2.13) HEMATOLOGIC
    A) Methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia may be noted.
    0.2.14) DERMATOLOGIC
    A) Skin rash may be noted.
    0.2.20) REPRODUCTIVE
    A) Phenacetin and its major metabolite, acetaminophen, are excreted into breast milk. It is pregnancy category B.
    0.2.21) CARCINOGENICITY
    A) Phenacetin has been classified as carcinogenic to humans (Group 1) by IARC following a systematic review and evaluation.

Laboratory Monitoring

    A) Phenacetin plasma levels are not clinically useful.
    B) Obtain a baseline CBC, monitor renal and hepatic function in symptomatic patients. Consider obtaining plasma acetaminophen (paracetamol) levels.
    C) Determine methemoglobin level in all cyanotic and dyspneic patients.

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) ACTIVATED CHARCOAL: Administer charcoal as a 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.
    C) 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 the head down 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.
    D) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    F) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    G) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.

Range Of Toxicity

    A) Insufficient data in the literature to determine the minimal acute toxic dose of phenacetin. Acute overdose or ingestion of greater than 1.0 gram daily may result in methemoglobinemia and/or hemolytic anemia.
    B) Nephropathy from chronic abuse may occur after long term accumulative ingestion of over 1 kg of the drug.

Clinical Effects

Summary Of Exposure

    A) NOTE - Phenacetin has not been available in the United States since August 1983.
    B) ACUTE INGESTION - The minimal acute toxic dose is not well established in the literature. Acute overdosage or chronic daily doses exceeding 1 gram may result in methemoglobinemia and hemolytic anemia.
    1) Signs and symptoms following severe intoxication may include seizures, coma, cyanosis, respiratory depression and cardiac arrest.
    C) CHRONIC INGESTION - Renal papillary necrosis may occur following long term exposure to large doses of combination analgesics containing phenacetin.

Heent

    3.4.3) EYES
    A) Yellow vision, lasting 2 days, was reported in an adult after ingestion of 2 grams of phenacetin (HSDB , 2002; Grant & Schuman, 1993).

Cardiovascular

    3.5.1) SUMMARY
    A) Chronic phenacetin abuse is associated with an increased risk of hypertension and related cardiovascular consequences, such as MI, heart failure, and stroke. Acute fatal doses may result in cardiac arrest.
    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) Chronic ingestion of phenacetin-containing analgesics was associated with an increased risk of hypertension (relative risk 1.6), and cardiovascular disease, such as myocardial infarction, heart failure, and stroke (relative risk 1.8) in a study of 623 women followed for 20 years.
    a) The incidence of hypertension was 29%. Evidence of abuse of phenacetin was suggested in the hypertensive subgroup, as measured by urinary metabolites (Dubach et al, 1991; Thomas, 1991).
    B) CARDIAC ARREST
    1) Fatal doses of phenacetin have resulted in cardiac arrest (HSDB , 2002).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) Fatal doses of phenacetin are associated with cyanosis, respiratory depression and cardiac arrest (HSDB , 2002).

Neurologic

    3.7.1) SUMMARY
    A) Seizures and coma may be noted following massive overdose.
    3.7.2) CLINICAL EFFECTS
    A) COMA
    1) Severe intoxication can result in seizures and coma.
    B) NEUROPATHY
    1) CNS CHANGES - Phenacetin may have a higher incidence of CNS complications associated with chronic abuse, mainly non-specific neurofibrillary changes and accelerated neuronal aging.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) PEPTIC ULCER
    1) Chronic abuse of high phenacetin doses may result in gastrointestinal disturbances, including peptic ulcer (HSDB , 2002).

Hepatic

    3.9.1) SUMMARY
    A) Jaundice has been noted, however it does not appear that liver injury is a primary manifestation of phenacetin overdose.
    3.9.2) CLINICAL EFFECTS
    A) JAUNDICE
    1) Acute onset of jaundice may occur, possibly due to a rare auto-immune antibody to phenacetin in the red blood cells.
    B) LIVER DAMAGE
    1) Phenacetin may have a direct toxic effect on the liver; however, acute lethal doses have not been associated with hepatic damage (HSDB , 2002).
    a) Although metabolized to acetaminophen, phenacetin and it congeners appear to protect the liver from injury by inhibiting toxic activation of acetaminophen, at least in the mouse (Kapetanovic & Mieyal, 1979).

Genitourinary

    3.10.1) SUMMARY
    A) Chronic ingestion of analgesics containing phenacetin over a prolonged period of time (generally years), has been associated with renal papillary necrosis.
    B) Dark brown urine was noted in a number of cases. It may be an indication of phenacetin ingestion, however it is not diagnostic.
    3.10.2) CLINICAL EFFECTS
    A) PAPILLARY NECROSIS
    1) Chronic exposure to large doses of phenacetin in combination with other analgesics, has been associated with nephritis, renal tubular disease, renal papillary necrosis and renal carcinoma (Baselt, 2000; NIH Consensus, 1984).
    2) Nephropathy from chronic abuse may occur after long-term cumulative ingestion of over 1 kilogram of drug (Pommer, 1989).
    a) The patient with the syndrome of analgesic nephropathy usually presents with the following symptoms: UTI 70%; sterile pyuria 47%; bacteruria 36%; renal colic or hematuria 32%; decreased GFR 90%; abnormal IVP and hypertension 36%; dyspepsia 86%; and occult GI bleeding 36%.
    b) The mechanism of renal damage remains speculative.
    3) MORTALITY - The 20-year death rate in women taking chronic high doses of phenacetin was 4.3% related to renal disease, compared to 0.2% in a control group (Dubach et al, 1991).
    B) ABNORMAL URINE
    1) DARK BROWN URINE, with unusual property of reducing silver-nitrate solution in the cold, may be a useful clue in recognizing phenacetin intoxication (Miller et al, 1970). However, it is not diagnostic since it has been reported in other cases of intoxications.

Dermatologic

    3.14.1) SUMMARY
    A) Skin rash may be noted.
    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) Skin rashes may be noted occasionally. The rash is generally erythematous or urticarial, but may be more serious and may be accompanied by drug fever and mucosal lesions (HSDB , 2002).

Reproductive

    3.20.1) SUMMARY
    A) Phenacetin and its major metabolite, acetaminophen, are excreted into breast milk. It is pregnancy category B.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    PHENACETINB
    Reference: Briggs et al, 1998.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Phenacetin and its major metabolite, acetaminophen, are excreted into breast milk. An average phenacetin milk concentration of 71 ng/mL was produced in a woman who consumed 2 tablets of Empirin Cpd with Codeine No. 3 (Briggs et al, 1998).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS62-44-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Phenacetin
    b) Carcinogen Rating: 1
    1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    3.21.2) SUMMARY/HUMAN
    A) Phenacetin has been classified as carcinogenic to humans (Group 1) by IARC following a systematic review and evaluation.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) The International Agency for Research on Cancer (IARC) has determined that phenacetin is carcinogenic to humans (Group 1) after a systematic review and evaluation of the scientific evidence by leading independent experts (International Agency for Research on Cancer, 2015).
    B) RENAL CARCINOMA
    1) RENAL PELVIS CARCINOMA: Animal and human data suggest an association between chronic abuse of phenacetin-containing mixtures and the development of transitional cell carcinoma of the renal pelvis as well as carcinomas of the ureter and bladder.
    a) This is presumably due to the 2-hydroxyphenetidine metabolite (HSDB , 2002; Gonwa et al, 1979; Bengtsson & Angervall, 1970; Nakanishi et al, 1982; Isaka et al, 1979).

Hematologic

    3.13.1) SUMMARY
    A) Methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia may be noted.
    3.13.2) CLINICAL EFFECTS
    A) METHEMOGLOBINEMIA
    1) Acute, toxic doses may result in methemoglobinemia and sulfhemoglobinemia (HSDB , 2002; Basset et al, 1981; Kneezel & Kitchens, 1976; Easley & Condon, 1974). Therapeutic doses have been reported to cause methemoglobinemia (Baselt, 2000).
    B) GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA
    1) G-6-PD - Toxicity can be potentially serious in patients with G-6-PD deficiency, renal failure or prior anemia.
    C) HEMOLYTIC ANEMIA
    1) HEINZ-BODY HEMOLYTIC ANEMIA has been reported to occur in 50% of patients abusing phenacetin (Von Marti, 1958) and has been described after single oral doses of 30 mg/kg in susceptible individuals (Shahidi, 1968). Methemoglobinemia and hemolytic anemia are reported to occur as a form of acute phenacetin toxicity or due to chronic overdosage. The hemolytic anemia associated with chronic abuse is generally mild, but may be progressive in the presence of uremia or other exacerbating factors. Hemolytic anemia occurring following an acute overdose is generally severe and may be accompanied by intravascular hemolysis, hemoglobinuria and/or acute anuria (HSDB , 2002).
    D) SIDEROBLASTIC ANEMIA
    1) Sideroblastic anemia may occur with chronic use, however it is reversible upon termination of phenacetin ingestion (Basset et al, 1981).
    E) THROMBOCYTOPENIC DISORDER
    1) Therapeutic use of phenacetin has resulted in autoimmune thrombocytopenia with resultant increased peripheral platelet destruction (HSDB , 2002).

Genotoxicity

    A) Phenacetin tests negative for inducing DNA breaks in cultured human or rat hepatocytes (Robbiano et al, 1994).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Phenacetin plasma levels are not clinically useful.
    B) Obtain a baseline CBC, monitor renal and hepatic function in symptomatic patients. Consider obtaining plasma acetaminophen (paracetamol) levels.
    C) Determine methemoglobin level in all cyanotic and dyspneic patients.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Baseline renal and hepatic function tests should be obtained. Consider obtaining plasma acetaminophen (paracetamol) levels.

Methods

    A) CHROMATOGRAPHY
    1) Phenacetin can be analyzed by high pressure liquid chromatography (Gotelli et al, 1977) and gas chromatography-mass spectrometry (Garland et al, 1977).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Phenacetin plasma levels are not clinically useful.
    B) Obtain a baseline CBC, monitor renal and hepatic function in symptomatic patients. Consider obtaining plasma acetaminophen (paracetamol) levels.
    C) Determine methemoglobin level in all cyanotic and dyspneic patients.

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. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    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 (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    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 (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). 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 (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    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 (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    B) 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: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat 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 (Caravati et al, 2001).
    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) SUPPORT
    1) Treatment is symptomatic and supportive. Phenacetin is normally present in only very low concentrations in combination products, so acute toxicity is usually more likely from other ingredients in the product.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, 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).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) MONITORING OF PATIENT
    1) A METHEMOGLOBIN LEVEL should be determined in all cyanotic or dyspneic patients following acute phenacetin overdosage.
    2) Obtain a baseline CBC, monitor renal and hepatic function.
    D) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

Range Of Toxicity

Summary

    A) Insufficient data in the literature to determine the minimal acute toxic dose of phenacetin. Acute overdose or ingestion of greater than 1.0 gram daily may result in methemoglobinemia and/or hemolytic anemia.
    B) Nephropathy from chronic abuse may occur after long term accumulative ingestion of over 1 kg of the drug.

Maximum Tolerated Exposure

    A) ACUTE
    1) INGESTION - There are few studies on the acute toxicity of pure phenacetin.
    2) A single oral dose of 30 milligrams/kilogram in a 17-year-old increased methemoglobin from 0.2 percent to 11.4 percent within 6 hours; Heinz bodies were present in peripheral blood. Evaluation of 7 controls revealed methemoglobin levels of less than 2.8 percent.
    a) This patient exhibited altered phenacetin metabolism, excreting only 30 percent of the total dose as acetaminophen, compared to 62 percent in controls; a greater proportion of 2-hydroxy derivatives were excreted (Shahidi, 1968).
    B) CHRONIC
    1) Chronic ingestion of 1 to 2 grams/day (Hutchison & Jackson, 1962), 2 to 3 grams/day (Easley & Condon, 1974), 3 to 4 grams/day (Basset et al, 1981), and 2 to 5 grams (Shahidi, 1968) resulted in methemoglobinemia and hemolytic anemia.

Workplace Standards

    A) ACGIH TLV Values for CAS62-44-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS62-44-2 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS62-44-2 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 1 ; Listed as: Phenacetin
    a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS62-44-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INHALATION)MOUSE:
    a) 34 g/m(3) (RTECS, 2002)
    2) LD50- (INTRAPERITONEAL)MOUSE:
    a) 540 mg/kg (RTECS, 2002)
    3) LD50- (ORAL)MOUSE:
    a) 866 mg/kg (RTECS, 2002)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 634 mg/kg (RTECS, 2002)
    5) LD50- (ORAL)RAT:
    a) 1650 mg/kg (RTECS, 2002)

Pharmacology Toxicology

Toxicologic Mechanism

    A) METHEMOGLOBINEMIA - 0.1% of phenacetin is deacetylated to para-phenetidin which can be metabolized to N- or 2-OH phenetidin and these compounds in turn are responsible for the formation of methemoglobin.
    B) HEMOLYTIC ANEMIA - Para-chloroacetanilide and para-phenetidine were shown to be responsible for the Heinz body hemolytic anemia in rats (Schnitzer, 1971).
    C) CARCINOGENICITY - 2-Hydroxyphenetidine is believed to be responsible for the carcinogenicity of phenacetin (Bengtsson & Angervall, 1970).

Physicochemical

Physical Characteristics

    A) White or off-white glistening crystalline scales or fine white crystalline powder with a slightly bitter taste (Budavari, 2001).

Ph

    A) The saturated solution is neutral.

Molecular Weight

    A) 179.22 (Budavari, 2001)

Animal Toxicology

Clinical Effects

    11.1.6) FELINE/CAT
    A) Cats are very susceptible to acetaminophen toxicity. Signs may occur within a few hours of ingestion and include depression, anorexia, vomiting, cyanosis, methemoglobinemia, dyspnea, and death.

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) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    5) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) CAT
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Do not use an emetic if the animal is hypoxic.
    a) In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    b) ACTIVATED CHARCOAL -
    1) Due to controversy over adsorption of N-acetylcysteine, do not give activated charcoal and NAC within 2 hours of each other. Activated charcoal dose is 2 grams/kilogram per os or via stomach tube.
    c) CATHARTIC -
    1) If the animal is not experiencing life-threatening symptoms, administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram).
    a) If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) DOG
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os or one tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    a) Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    b) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    b) ACTIVATED CHARCOAL -
    1) Due to controversy over adsorption of N-acetylcysteine, do not give activated charcoal and NAC within 2 hours of each other. Activated charcoal dose is 2 grams/kilogram per os or via stomach tube.
    c) CATHARTIC -
    1) If the animal is not experiencing life-threatening symptoms, administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram).
    a) If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    11.2.5) TREATMENT
    A) NOTE -
    1) Oral formulations of N-acetylcysteine are used intravenously in the clinical treatment of animals, although not tested or approved for this use.
    B) CAT
    1) Treatment of phenacetin poisoning (use this protocol if within 24 hours of exposure) (Plumb, 1989; Beasley et al, 1989):
    2) DECONTAMINATION -
    a) Decontaminate as specified below.
    3) N-ACETYLCYSTEINE -
    a) For severely poisoned animals, load with 140 to 280 milligrams/kilogram per os or intravenously. Dilute in D5W to 5% solution and give either via stomach tube or intravenously slowly over a period of 15 to 20 minutes.
    1) Thereafter, give 70 milligrams/kilogram per os every 4 hours for up to 17 doses; if clinical picture is good can instead dose with 70 milligrams/kilogram per os four times daily for three days.
    2) Sodium sulfate or methylene blue can be given instead of NAC.
    4) SODIUM SULFATE -
    a) Sodium sulfate has been used as an alternative to NAC. Dose: 50 milligrams/kilogram of a 1.6% solution in water given intravenously every 4 hours for a total of 3 to 6 treatments.
    b) This treatment was found to be as effective as oral or intravenous NAC at reducing methemoglobinemia (Savides et al, 1985).
    5) METHYLENE BLUE -
    a) Prepare a solution of 10 percent methylene blue in sterile saline (1 gram methylene blue in 10 milliliters saline). Administer the solution intravenously to provide a dose of 1.5 milligrams/kilogram methylene blue.
    1) For an average 4.5 kg (10 pounds) cat, the dosage volume of 10 percent solution would be 0.07 milliliter. This agent effectively reverses methemoglobinemia. The dosage may be repeated two or three times without causing anemia (Personal Communication, 1991).
    2) This use of methylene blue is still considered experimental since it can cause a Heinz body anemia in dogs and cats. Blood smears and complete blood counts should be monitored for one week after treatment.
    6) ASCORBIC ACID -
    a) Converts methemoglobin to oxyhemoglobin. Dose at 30 milligrams/kilogram subcutaneously every 6 hours for 7 treatments. This is an adjunct therapy.
    7) CORTICOSTEROIDS/ANTIHISTAMINES -
    a) Corticosteroids and antihistamines are CONTRAINDICATED. Limit physical activity to reduce anoxia hazard. Drinking water should always be available, and food may be offered 24 hours after beginning treatment.
    8) SEIZURES -
    a) SEIZURES may be controlled with diazepam or barbiturate anticonvulsants. Dose of diazepam: 0.5 milligram/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes. Phenobarbital may be used as adjunct treatment at 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously.
    b) If the patient is presented 24 hours or more post-ingestion, treat for massive methemoglobinemia, including ascorbic acid, methylene blue, supportive care, and whole-blood transfusions. Limit physical activity.
    C) DOG
    1) Treatment of phenacetin poisoning (use this protocol if within 24 hours of exposure) (Plumb, 1989; Beasley et al, 1989):
    a) VITAL FUNCTIONS -
    1) Maintain vital functions: Secure airway, supply oxygen if cyanotic, and begin supportive fluid therapy.
    b) DECONTAMINATION -
    1) Decontaminate as specified above.
    c) N-ACETYLCYSTEINE -
    1) For severely poisoned animals, load with 280 milligrams/kilogram per os or intravenously. (Use cat dosages for dogs weighing 10 kilograms and less).
    a) Dilute in D5W to 5% solution and give either via stomach tube or intravenously slowly over a period of 15 to 20 minutes.
    b) Thereafter, give 140 milligrams/kilogram per os every 4 hours for up to 17 doses; if clinical picture is good can instead dose with 140 milligrams/kilogram per os four times daily for three days.
    d) ASCORBIC ACID -
    1) Converts methemoglobin to oxyhemoglobin. If methemoglobinemia is present, dose at 30 milligrams/kilogram subcutaneously every 6 hours for 7 treatments.
    e) CORTICOSTEROIDS/ANTIHISTAMINES -
    1) Corticosteroids and antihistamines are CONTRAINDICATED. Limit physical activity to reduce anoxia hazard. Drinking water should always be available, and food may be offered 24 hours after beginning treatment.
    f) SEIZURES -
    1) SEIZURES may be controlled with diazepam or barbiturate anticonvulsants. Dose of diazepam: 0.5 milligram/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes.
    a) Phenobarbital may be used as adjunct treatment at 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously.
    b) If the patient is presented 24 hours or more post-ingestion, treat for massive methemoglobinemia, including ascorbic acid, methylene blue, supportive care, and whole-blood transfusions. Limit physical activity.

Range Of Toxicity

    11.3.1) THERAPEUTIC DOSE
    A) CAT
    1) PRODUCTS CONTAINING ACETAMINOPHEN or PHENACETIN SHOULD NEVER BE ADMINISTERED TO CATS. No dose is safe. Cats do not have the ability to metabolize these substances.
    11.3.2) MINIMAL TOXIC DOSE
    A) CAT
    1) Any dose of phenacetin should be considered toxic.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    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) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    5) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) CAT
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Do not use an emetic if the animal is hypoxic.
    a) In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    b) ACTIVATED CHARCOAL -
    1) Due to controversy over adsorption of N-acetylcysteine, do not give activated charcoal and NAC within 2 hours of each other. Activated charcoal dose is 2 grams/kilogram per os or via stomach tube.
    c) CATHARTIC -
    1) If the animal is not experiencing life-threatening symptoms, administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram).
    a) If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    2) DOG
    a) EMESIS AND LAVAGE -
    1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os or one tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    a) Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    b) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    b) ACTIVATED CHARCOAL -
    1) Due to controversy over adsorption of N-acetylcysteine, do not give activated charcoal and NAC within 2 hours of each other. Activated charcoal dose is 2 grams/kilogram per os or via stomach tube.
    c) CATHARTIC -
    1) If the animal is not experiencing life-threatening symptoms, administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram).
    a) If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

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