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PSEUDOEPHEDRINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Pseudoephedrine is a sympathomimetic drug with alpha-adrenergic properties. It is believed that these effects result from the inhibition of cyclic adenosine monophosphate (cAMP). It also has an indirect effect by releasing norepinephrine. There is slight beta-adrenergic activity. It occurs naturally in plants of the genus ephedra. The drug is a stereoisomer of ephedrine.

Specific Substances

    A) Pseudoephedrine hydrochloride
    1) d-Isoephedrine hydrochloride
    2) ISOEPHEDRINE
    Pseudoephedrine sulfate
    1) Pseudoephedrine sulphate
    2) CAS 7460-12-0

Available Forms Sources

    A) FORMS
    1) IMMEDIATE-RELEASE PRODUCTS
    a) TABLETS: 30 and 60 mg
    b) SYRUP: 15 or 30 mg per 5 mL
    c) DROPS: 7.5 mg per 0.8 mL
    2) SUSTAINED-RELEASE PRODUCTS
    a) CAPSULES: 120 and 240 mg capsules

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Commonly used in cough and cold medications as a decongestant, both alone and in combination with other cough preparations. However, it is also abused for its stimulant properties.
    B) EPIDEMIOLOGY: Widely used as a decongestant in both pediatric and adult patients. Both intentional and unintentional ingestions are commonly encountered. Severe toxicity is rare and there are no clear reports of death due to single substance ingestion.
    C) PHARMACOLOGY: In general, it stimulates the adrenergic nervous system. Pseudoephedrine is a mixed acting nonspecific alpha 1 and 2, and beta 1 and 2 adrenergic receptor agonist.
    D) TOXICITY: Adverse effects result from excessive stimulation of the adrenergic nervous system.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EVENTS: CV: Tachyarrhythmia and hypertension are common. CNS: Anxiety, nervousness, insomnia, irritability and muscle tremor (usually hands) commonly occurs. WITHDRAWAL may develop with chronic use.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Symptoms commonly seen in the overdose setting include: vomiting, mydriasis, hypertension, tachycardia, agitation and anxiety. Reflexive bradycardia from hypertension has also been reported. Dermal reactions are common.
    2) SEVERE TOXICITY: Sinus dysrhthymias have occurred. Rarely seen symptoms include: intracranial hemorrhages, seizures, myocardial infarction, ischemic bowel infarction and psychosis. Hypokalemia has developed in overdose. Drowsiness has developed in children following overdose.
    0.2.20) REPRODUCTIVE
    A) Pseudoephedrine and the combinations of chlorpheniramine/pseudoephedrine, guaifenesin/hydrocodone/pseudoephedrine, and guaifenesin/pseudoephedrine are classified as US FDA pregnancy category C. Acrivastine/pseudoephedrine hydrochloride combination has been classified as US FDA pregnancy category B. Pseudoephedrine is excreted in human breast milk in low amounts.

Laboratory Monitoring

    A) Monitor serum electrolytes, glucose and ECG in symptomatic patients.
    B) Monitor CK in patients with prolonged agitation, seizures or coma.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Benzodiazepines can be used for agitation, tachycardia, hypertension and psychosis.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Supportive care, including IV crystalloid, oxygen and mechanical ventilation may be required. Benzodiazepines can be used for severe agitation and psychosis. Treat seizures and dysrhythmias if they occur. With persistent severe hypertension or myocardial ischemia, alpha-adrenergic antagonists, such as phentolamine may be considered. Patients with focal neurologic deficits should receive a head CT to evaluate for intracranial bleeding.
    C) DECONTAMINATION
    1) PREHOSPITAL: Severe toxicity rarely develops after inadvertent pediatric exposures; prehospital decontamination is probably not necessary.
    2) HOSPITAL: Activated charcoal should be considered in large ingestions in patients who are alert and able to protect their airway. Gastric lavage is not warranted as toxicity is rarely life-threatening. Consider activated charcoal if the ingestion is 3 or more times the maximum daily dose.
    D) ANTIDOTE
    1) Benzodiazepines should be used to treat agitation or seizures.
    E) ENHANCED ELIMINATION
    1) Enhanced elimination is unlikely to be effective due to the large volume of distribution.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Children less than 6-years-old with a history of ingestion of less than 180 mg (or 11 mg/kg) of pseudoephedrine can be managed at home, provided that they are asymptomatic and that adequate follow-up can be done.
    2) OBSERVATION CRITERIA: Any patient with symptoms or a deliberate ingestion should be referred to a health care facility for observation. All symptomatic patients should be sent to a health care facility for observation. Children with ingestions of 180 mg or more (or 11 mg/kg or more) should be referred to a healthcare facility.
    3) ADMISSION CRITERIA: Patients who remain persistently symptomatic despite supportive management, or require large amounts of benzodiazepines should be admitted for further observation. A patient in status epilepticus, respiratory failure, significant hemorrhage, or altered mental status should be admitted to an intensive care unit.
    4) CONSULT CRITERIA: Consult a poison center or a medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is uncertain.
    G) PHARMACOKINETICS
    1) Topical or absorption. Absorption in the GI tract is rapid, with onset of action as quick as 15 to 30 minutes, and peak serum concentrations within 1 to 4 hours. The duration of action is typically 3 to 4 hours; elimination half-life has a large range of 1.9 to 21 hours. Protein binding is 20% with a volume of distribution of 2.1 to 3.3 L/kg. Pseudoephedrine is incompletely metabolized in the liver and mostly excreted in the urine.
    H) PITFALLS
    1) Failure to recognize signs and symptoms of excessive sympathomimetic release, recognize coingestants in a combination preparation, or delay in supportive care. Also, failure to recognize symptoms of complications of adrenergic excess, such as intracranial hemorrhage, or myocardial infarction or dysrhythmias.
    I) DIFFERENTIAL DIAGNOSIS
    1) Other agents that may produce similar symptoms include: ephedrine, phenylephrine, phenylpropanolamine, cocaine, anticholinergic, methamphetamines, methcathinone, hallucinogenics and sympathomimetic xenobiotics.

Range Of Toxicity

    A) TOXICITY: Symptoms can occur typically after 4- to 5-fold therapeutic doses. Four times the single therapeutic dose (about 240 mg) is required to cause an increase in diastolic blood pressure above 90 mmHg in normotensive subjects. Hypertensive crisis with non-ST elevation myocardial infarction occurred in an elderly adult after inadvertently ingesting 3 sustained release tablets (240 mg) in 6 hours. PEDIATRIC: In one study, children aged 2 to 6 years old developed only minor symptoms following ingestions of up to 180 mg. Acute exposures of 11 mg/kg were well-tolerated.
    B) ADULT: THERAPEUTIC GENERAL DOSING: Typical doses are 180 to 360 mg daily. SPECIFIC INDICATIONS or FORMULATIONS: Allergic Rhinitis OR Congestion of Nasal Sinus: 60 mg orally every 4 to 6 hrs; maximum 240 mg/day or SR tablets 120 mg orally every 12 hrs or 24-hour tablets; 240 mg orally every 24 hours.
    C) PEDIATRIC: THERAPEUTIC GENERAL DOSING: 3 to 5 mg/kg in children. Not approved for use in children 12 years of age or younger. SPECIFIC INDICATIONS or FORMULATIONS: Allergic rhinitis OR Congestion of Nasal Sinus: 2 to 5 years: Immediate-release products only: 15 mg orally every 4 to 6 hrs; maximum 60 mg/day. 6 to 12 years: Immediate-release products only: 30 mg orally every 4 to 6 hrs; maximum 120 mg/day. 12 years of age and older: 60 mg orally every 4 to 6 hrs; maximum 240 mg/day or SR tablets, 120 mg orally every 12 hrs or 24-hour tablets, 240 mg orally every 24 hours.

Clinical Effects

Summary Of Exposure

    A) USES: Commonly used in cough and cold medications as a decongestant, both alone and in combination with other cough preparations. However, it is also abused for its stimulant properties.
    B) EPIDEMIOLOGY: Widely used as a decongestant in both pediatric and adult patients. Both intentional and unintentional ingestions are commonly encountered. Severe toxicity is rare and there are no clear reports of death due to single substance ingestion.
    C) PHARMACOLOGY: In general, it stimulates the adrenergic nervous system. Pseudoephedrine is a mixed acting nonspecific alpha 1 and 2, and beta 1 and 2 adrenergic receptor agonist.
    D) TOXICITY: Adverse effects result from excessive stimulation of the adrenergic nervous system.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EVENTS: CV: Tachyarrhythmia and hypertension are common. CNS: Anxiety, nervousness, insomnia, irritability and muscle tremor (usually hands) commonly occurs. WITHDRAWAL may develop with chronic use.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Symptoms commonly seen in the overdose setting include: vomiting, mydriasis, hypertension, tachycardia, agitation and anxiety. Reflexive bradycardia from hypertension has also been reported. Dermal reactions are common.
    2) SEVERE TOXICITY: Sinus dysrhthymias have occurred. Rarely seen symptoms include: intracranial hemorrhages, seizures, myocardial infarction, ischemic bowel infarction and psychosis. Hypokalemia has developed in overdose. Drowsiness has developed in children following overdose.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Hypothermia occurred in a mixed drug overdose involving pseudoephedrine and antihistamines (Salmon & Nicholson, 1988).
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) Hypertension has been reported following pseudoephedrine use (Cantu et al, 2003; Mariani, 1986; Rutstein, 1963).
    B) WITH POISONING/EXPOSURE
    1) Hypertension has occurred with overdose (Mariani, 1986; Salmon & Nicholson, 1988; Burkhart, 1992).
    2) Hypotension occurred in a mixed drug overdose involving ingestion of pseudoephedrine and antihistamines (Salmon & Nicholson, 1988).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Tachycardia and palpitations may occur (Salmon & Nicholson, 1988; Clark & Curry, 1990).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Dilated pupils may be noted (Clark & Curry, 1990).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Pseudoephedrine possesses both alpha and beta receptor activity which may lead to sinus tachycardia, precordial pain, and increased blood pressure.
    b) CASE REPORT: A 19-month-old ingesting about 600 mg pseudoephedrine presented with diaphoresis, agitation and tachycardia of 200 beats/minute. Systolic blood pressure was 75 mmHg. The tachycardia resolved in 18 hours (Clark & Curry, 1990).
    c) CASE REPORT: Tachycardia occurred in a 22-year-old man following a mixed drug overdose with pseudoephedrine as one of the ingredients (Salmon & Nicholson, 1988).
    B) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypertension has been reported following pseudoephedrine use (Cantu et al, 2003; Mariani, 1986; Rutstein, 1963).
    b) CASE REPORT: Hypertension and loss of consciousness due to relative cerebral ischemia, was reported in one case after ingestion of 60 mg of pseudoephedrine by a 17-year-old boy (Rutstein, 1963).
    2) WITH POISONING/EXPOSURE
    a) Hypertensive crisis has occurred in patients following inadvertent exposure of pseudoephedrine (Wang et al, 2008; Mariani, 1986).
    b) CASE REPORT: Hypertensive crisis and a non-ST elevation myocardial infarction occurred in an 87-year-old man after inadvertently ingesting 3 sustained-release pseudoephedrine tablet (240 mg per tablet) in 6 hours. His initial blood pressure was 206/108 with an irregular heart rate of 110 beats/min. An ECG showed atrial fibrillation (preexisting condition) with rapid ventricular response. Treatment included IV sodium nitroprusside. The patient improved rapidly and was monitored for an additional 2 days and then discharged to home (Wang et al, 2008).
    c) CASE REPORT: Hypertensive crisis was reported in a 23-year-old man 3 hours following ingestion of 840 mg of pseudoephedrine (3.5 times the maximum daily therapeutic dose) (Mariani, 1986). Hypertension has occurred in several mixed drug overdosages (Burkhart, 1992).
    d) One study found that concomitant ingestion of pressor agents and water may cause pressure surges in individuals with impaired baroreflex function and in patients with autonomic failure (eg; diabetic neuropathy) (Jordan et al, 2004).
    C) MYOCARDIAL ISCHEMIA
    1) WITH THERAPEUTIC USE
    a) Angina with ST segment depression (Rosen, 1981) and myocardial infarction due to coronary vasospasm in patients with normal coronary arteries have been reported following therapeutic doses of pseudoephedrine (Manini et al, 2005; Wiener et al, 1990).
    b) CASE REPORT: A 23-year-old smoker with a history of diet and exercise controlled hypertension presented to the ED with complaints of chest pain of 24 hours duration which began 12 hours following ingestion of a 240 mg sustained-release pseudoephedrine tablet. A second tablet was ingested 12 hours later. ECG revealed ST segment elevation in V2 through V5 without Q waves. Coronary arteries were normal. Peak serum CK was reported to be 434 IU/L with MB fraction of 10%. Acute MI was diagnosed (Wright & Tomassoni, 1994).
    c) CASE SERIES: The incidence of myocardial infarction was 6 cases out of a cohort of 100,000 patients aged less than 65 years, receiving a prescription for pseudoephedrine within 15 days prior to hospitalization. This incidence was reported to be not substantially greater than that of the population studied, but no statistics were presented (Porta et al, 1986).
    d) CASE REPORT: A 32-year-old man without a previous history of heart disease, diabetes, hypertension, or dyslipidemia developed acute myocardial infarction 45 minutes after ingesting 2 tablets of an over-the-counter cold remedy containing 30 mg of pseudoephedrine and 500 mg of acetaminophen per tablet. Cardiac catheterization showed normal coronary arteries, suggesting a mechanism of vasospasm (Manini et al, 2005).
    D) ATRIAL FIBRILLATION
    1) WITH THERAPEUTIC USE
    a) Atrial fibrillation has been reported in infants less than one year of age after excessive therapeutic doses of pseudoephedrine (greater than 4 mg/kg/day) (MacMahon, 1974) (Zaldivar et al, 1973).
    E) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 22-year-old man presented to the ED hypotensive (BP 70 mm Hg systolic) and tachycardic (150 beats/minute), following a drug overdose of pseudoephedrine in combination with antihistamines (Salmon & Nicholson, 1988). Blood pressure improved with intravenous crystalloid.
    F) ORTHOSTATIC HYPOTENSION
    1) WITH THERAPEUTIC USE
    a) Postural hypotension has occurred, but is rarely noted after therapeutic doses (Beary, 1977).
    G) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) Sinus dysrhythmias occurred more frequently following exercise in normal subjects receiving 120 mg of pseudoephedrine (mean 4.33 episodes vs 0.17 episodes after placebo); transient PVCs occurred in 2 subjects (Bright et al, 1981). PVCs were also noted in an adult taking 120 mg every 4 hours for several days (Billings, 1974).
    H) RAYNAUD'S PHENOMENON
    1) WITH THERAPEUTIC USE
    a) Intermittent episodes of Raynaud's phenomenon were reported in a 51-year-old woman within 1 to 2 hours of ingesting a pseudoephedrine/codeine phosphate combination; the patient had regularly taken daily cumulative doses of pseudoephedrine 600 mg, in excess of the recommended maximum daily dose of 240 mg (Klestov et al, 2001).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL STIMULANT ADVERSE REACTION
    1) WITH THERAPEUTIC USE
    a) Anxiety, nervousness, irritability, insomnia, and muscle tremor (most notably of the hands) commonly occur (Clark & Curry, 1990).
    b) In a prospective study of pseudoephedrine ingestion in children aged 6 years-old or less, the authors reported that mild hyperactivity was exhibited in 6.9% with ingestion of 180 mg or less and 12.8% with ingestion of 180 mg or more (Wezorek et al, 1995).
    c) CASE REPORT: A 10-month-old infant with phenylketonuria was given 15 mg pseudoephedrine every 6 hours. After each of 3 doses, the child was noted to be excited, crying and screaming without apparent reason which lasted for several hours (Spielberg & Schulman, 1977).
    d) CASE REPORT: A 2-year-old child receiving 7.5 mL every 6 hours of a cold and cough syrup, containing pseudoephedrine 15 mg/5 mL and dextromethorphan 7.5 mg/5 mL, presented with hyperactivity, ataxia, incoherent speech and bizarre behavior. This occurred 3 hours after the last dose. The child recovered within 4 hours after presentation to the ED (Roberge et al, 1999).
    B) SEIZURE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A course of therapeutic pseudoephedrine (60 mg 4 times a day) in a hemodialysis patient resulted in myoclonic jerking as well as increasingly bizarre behavior. Symptoms resolved with discontinuation of the drug (Sica & Comstock, 1989).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 19-month-old woman suffered a 60-second, witnessed, generalized tonic-clonic seizure (which resolved spontaneously) approximately 2 hours after she ingested an unknown amount of pseudoephedrine 30 mg tablets (more than 20 tablets were missing) (Clark & Curry, 1990).
    b) CASE REPORT: A 17-year-old postpartum woman experienced seizures 20 to 30 minutes after ingestion of a tablet containing caffeine, phenylpropanolamine and pseudoephedrine; amounts were not quantified (Mueller & Solow, 1982).
    C) CEREBRAL HEMORRHAGE
    1) WITH THERAPEUTIC USE
    a) Cerebral hemorrhage has been reported following pseudoephedrine use (Cantu et al, 2003).
    b) CASE REPORT: A 23-year-old woman developed intracerebral hemorrhage one hour after ingestion of a single dose of a stimulant containing pseudoephedrine, phenylpropanolamine, caffeine, and a barbiturate. Angiography revealed alternating spasm and dilation of vessels ("beading") (Stoessl et al, 1985).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: Intracerebral hemorrhage with beading has also been described after a deliberate overdose of 1200 mg of pseudoephedrine by a 17-year-old girl (Loizou et al, 1982).
    D) DROWSY
    1) WITH POISONING/EXPOSURE
    a) In a prospective study of pseudoephedrine ingestion in children aged 6-years or less, the authors reported that drowsiness was exhibited by 21.7% of children with ingestions of 180 mg or less and by 15.4% with ingestion of 180 mg or more (Wezorek et al, 1995).
    E) COMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 22-year-old man presented to the ED comatose, with a minimal response to deep pain, following a drug overdose of pseudoephedrine in combination with antihistamines. The patient never regained consciousness (Salmon & Nicholson, 1988).
    F) PSYCHOTIC DISORDER
    1) WITH THERAPEUTIC USE
    a) COMBINATION THERAPY
    1) CHILDREN: Pseudoephedrine, in combination with triprolidine, has caused visual hallucinations and night terrors in children receiving therapeutic doses (Sankey et al, 1984; Drennan, 1984; Miller, 1984).
    2) TODDLER: A 2-year-old child receiving 7.5 mL every 6 hours of a cold and cough syrup, containing pseudoephedrine 15 mg/5 mL and dextromethorphan 7.5 mg/5 mL, presented with hyperactivity, ataxia, incoherent speech and bizarre behavior. This occurred 3 hours after the last dose. The child recovered within 4 hours after presentation to the ED (Roberge et al, 1999).
    2) WITH POISONING/EXPOSURE
    a) PSEUDOEPHEDRINE ALONE
    1) CHILDREN: Further anecdotal reports substantiate an association between pseudoephedrine and various adverse CNS effects in children, including irritability, poor sleep, dizziness, behavioral disturbances and visual hallucinations (Sauder et al, 1997; Sills et al, 1984; Spielberg & Schulman, 1977).
    2) TEENAGER: A mixed bipolar disorder was precipitated by acute ingestion of 480 mg of pseudoephedrine in a 13-year-old girl (Dalton, 1990).
    3) ADULT: Tolerance and addiction along with withdrawal symptoms (visual hallucinations) was reported in a 37-year-old woman who ingested up to 4.5 g/day for 5 years as self-treatment for depression (Diaz et al, 1979).
    4) ADULT: A 27-year-old man with a history of bipolar affective disorders experienced an episode of acute paranoid psychosis following chronic abuse of Actifed(R) syrup (containing pseudoephedrine 30 mg and triprolidine 1.25 mg/5 mL). Prior to admission, the patient had been abusing Actifed(R) for several years, taking 1 to 2 bottles on weekends. Approximately 4 days prior to onset of visual and auditory hallucinations and paranoia, he had increased the amount to 2 bottles per day. Hallucinations disappeared within one day of discontinuation of Actifed(R) (Leighton, 1982).
    b) COMBINATION THERAPY
    1) ADULTS: Pseudoephedrine, combined with the antihistamine triprolidine, has been reported to cause psychosis in adults who abused this combination (Lambert, 1987; Leighton, 1982).
    2) CHILD: A 5-year-old child developed hallucinations, lasting 18 hours, following an overdose of 360 mg of pseudoephedrine in combination with triprolidine (Ackland, 1984).
    3) TODDLER: A 3-year-old girl experienced visual hallucinations after administration of an over-the-counter decongestant containing pseudoephedrine. The child had inadvertently received 20 mg/kg of pseudoephedrine administered in 2 doses over the previous 12 hours (Sauder et al, 1997).
    4) CHILD: A 5-year-old boy suffered from severe hallucinations beginning 5 hours after drinking 60 mL of a syrup containing pseudoephedrine and triprolidine (Actifed(R)). Promethazine 10 mg orally and diazepam 5 mg IM had no effect. The hallucinations resolved after 18 hours (Ackland, 1984).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Spontaneous vomiting may occur (Clark & Curry, 1990; Mariani, 1986).
    B) COLITIS
    1) WITH THERAPEUTIC USE
    a) Acute abdominal pain and hematochezia were reported in 3 women receiving pseudoephedrine for approximately 1 week, and in another woman treated chronically for 6 months. Colonoscopies and biopsies revealed evidence of ischemic colitis. All 4 patients recovered completely following supportive care and discontinuation of the pseudoephedrine (Dowd et al, 1999).
    b) CASE REPORT: A 33-year-old man presented with lower abdominal pain and bloody diarrhea 5 days after beginning therapy with pseudoephedrine extended-release tablets, 120 mg twice daily, for congestion. The last dose was taken the morning of presentation. A colonoscopy showed erythema and mucosal edema of the descending colon, with a colonic biopsy revealing mucosal necrosis and hemorrhage consistent with ischemic colitis. The patient gradually recovered following cessation of pseudoephedrine therapy (Lichtenstein & Yee, 2000).
    2) WITH POISONING/EXPOSURE
    a) Recurrent episodes of ischemic colitis occurred in a 51-year-old woman following ingestion of a pseudoephedrine/codeine phosphate combination (approximately 900 mg pseudoephedrine daily) for 2 to 3 days prior to hospital admission. She presented with complaints of abrupt onset of colicky abdominal pain accompanied by vomiting and bloody diarrhea; these same symptoms occurred 4 months earlier, necessitating a right hemicolectomy for hemorrhagic infarction. Emergency laparotomy revealed acute ischemic enterocolitis with hemorrhagic infarction, perforation and peritonitis. The patient reported a 2-year history of pseudoephedrine use, with approximate doses of 600 mg daily. She remained asymptomatic 10 months after discontinuing use of pseudoephedrine (Klestov et al, 2001).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Acute renal failure was reported in a 22-year-old man following a massive overdose of pseudoephedrine in combination with antihistamines. Rhabdomyolysis was implicated as the primary cause of renal failure (Salmon & Nicholson, 1988).
    B) ACUTE RETENTION OF URINE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 3-year-old boy weighing 11 kg was given pseudoephedrine 3 times daily (90 mg/day) for 10 days for cold symptoms and suddenly developed an episode of acute urinary retention. Urinary catheterization resulted in 750 mL of urine. Twelve hours after the last dose of pseudoephedrine the child was voiding without difficulty. Diagnostic studies conducted one week later revealed normal bladder capacity and voiding time. The authors concluded that the excessive dose (twice the recommended daily dose for over a week) was responsible for the symptoms observed in this low-weight child (Soyer et al, 2008).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 25-year-old man who habitually abused OTC cough syrup developed a mixed normal anion gap hyperchloremic metabolic and respiratory acidosis (pH 7.19, pCO2 32, HCO3 12.1) associated with hypokalemia (K+ 2.7 mEq/L). Symptoms included bilateral symmetric limb weakness and diminished deep tendon reflexes. His toxicology screen confirmed the presence of codeine, ephedrine, pseudoephedrine, chlorpheniramine and promethazine. Treatment included potassium replacement and sodium bicarbonate therapy. His symptoms rapidly responded to treatment by the following day (Wong et al, 2001).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) DISSEMINATED INTRAVASCULAR COAGULATION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Disseminated intravascular coagulation was reported in a 22-year-old man following a massive overdose of pseudoephedrine in combination with antihistamines (Salmon & Nicholson, 1988).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FIXED DRUG ERUPTION
    1) WITH THERAPEUTIC USE
    a) Pseudoephedrine has been implicated in causing fixed drug eruptions in several instances, with symptoms recurring upon rechallenge (Brownstein, 1968; Shelley & Shelley, 1987; Hauken, 1994).
    1) The lesions were nonpigmented, characterized by large, symmetrical, erythematous, well-circumscribed plaques that resolve completely and returned to the same location upon rechallenge (Brownstein, 1968; Shelley & Shelley, 1987; Camisa, 1988; Hauken, 1994).
    2) WITH POISONING/EXPOSURE
    a) Two cases of patients who developed fixed type skin eruptions following administration of pseudoephedrine have been reported. One patient was 11 years old who ingested a 60 mg tablet and after 8 to 20 hours developed asymptomatic, symmetrically distributed, well defined erythematous nummular patches which were located mainly on the back, buttocks, and legs. The second case was a 47-year-old patient who had ingested 18 tablets and within 24 hours developed a rash on the trunk, thighs, and popliteal areas. A 20 centimeter plaque was also noted on the left shoulder. The lesions were noted to not completely blanch on pressure. Discontinuation of the drug resulted in abatement of the symptoms within a few days. The patients were subsequently rechallenged with pseudoephedrine in the form of Actifed(R) (which also contains the antihistamine triprolidine) a few days later and within hours resulted in recurrence of the efflorescence at the same sites. The rash subsequently subsided within a few days (Brownstein, 1968).
    B) DISORDER OF SKIN
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A generalized scarlatiniform eruption, accompanied by fever, rigors, and later desquamation was attributed to pseudoephedrine hypersensitivity in a 32-year-old woman (Taylor & Duffill, 1988).
    C) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Systemic contact dermatitis developed with oral pseudoephedrine use. A more severe generalized eczema occurred a few months later with oral norephedrine (Tomb et al, 1991).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Tremors and hyperreflexia are common after overdose and may lead to elevation of serum creatine kinase and rhabdomyolysis (Clark & Curry, 1990; Salmon & Nicholson, 1988).
    b) Intermittent episodes of polymyalgia and muscle weakness were reported in a 51-year-old woman, within 1 to 2 hours of ingesting a pseudoephedrine/codeine phosphate combination. The patient was known to take cumulative pseudoephedrine daily doses of up to 600 mg, in excess of the maximum recommended daily dose of 240 mg (Klestov et al, 2001).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) Hyperglycemia has been reported in 2 cases following pseudoephedrine overdose (Jarrett, 1966; McCleave et al, 1978).

Reproductive

    3.20.1) SUMMARY
    A) Pseudoephedrine and the combinations of chlorpheniramine/pseudoephedrine, guaifenesin/hydrocodone/pseudoephedrine, and guaifenesin/pseudoephedrine are classified as US FDA pregnancy category C. Acrivastine/pseudoephedrine hydrochloride combination has been classified as US FDA pregnancy category B. Pseudoephedrine is excreted in human breast milk in low amounts.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) The incidence of congenital abnormalities was 0.4% in infants exposed to pseudoephedrine during the first trimester, compared with 1.2% in controls (Jick et al, 1981).
    2) In a case controlled surveillance study, pseudoephedrine was associated with a significantly elevated relative risk of gastroschisis (Werler et al, 1992).
    B) ANIMAL STUDIES
    1) ACRIVASTINE/PSEUDOEPHEDRINE
    a) In animal studies, no evidence of teratogenicity was observed in rabbits given acrivastine and pseudoephedrine at 10 and 7 times the recommended human daily doses, respectively (Prod Info Semprex(R)-D oral capsules, 2014).
    2) GUAIFENESIN/HYDROCODONE/PSEUDOEPHEDRINE
    a) Animal reproduction studies have not yet been conducted with the guaifenesin/hydrocodone bitartrate/pseudoephedrine hydrochloride combination product. In animal studies with the individual ingredients, teratogenic effects were reported with hydrocodone at doses approximately 35 times the maximum recommended human daily dose (MRHDD). Increased resorptions and decreased fetal weights have been reported with administration of codeine, an opiate related to hydrocodone, at doses approximately 50 times the MRHDD (Prod Info HYCOFENIX oral solution, 2015).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Pseudoephedrine has been classified as US FDA pregnancy category C (Briggs et al, 1998).
    2) ACRIVASTINE/PSEUDOEPHEDRINE HYDROCHLORIDE: This combination product has been classified as US FDA pregnancy category B (Prod Info Semprex(R)-D oral capsules, 2014).
    3) CHLORPHENIRAMINE/PSEUDOEPHEDRINE: Chlorpheniramine/pseudoephedrine has been classified as US FDA pregnancy category C (Prod Info HISTADE(TM) oral capsules, 2004).
    4) GUAIFENESIN/PSEUDOEPHEDRINE: Guaifenesin/pseudoephedrine has been classified as US FDA pregnancy category C (Prod Info RESPA(R) -1ST sustained-release oral tablets, 2006).
    5) GUAIFENESIN/HYDROCODONE/PSEUDOEPHEDRINE: The manufacturer has classified the combination product guaifenesin/hydrocodone/pseudoephedrine as FDA pregnancy category C. Use during pregnancy only if the potential maternal benefit outweighs the potential fetal risk. If hydrocodone is used shortly before delivery, especially in high doses, monitor the infant for signs and symptoms of respiratory depression (Prod Info HYCOFENIX oral solution, 2015).
    B) FETAL/NEONATAL RISK
    1) GUAIFENESIN/HYDROCODONE/PSEUDOEPHEDRINE: The use of opioids (such as hydrocodone) regularly prior to delivery has been shown to cause physical dependence in babies, resulting in a withdrawal syndrome after delivery. Withdrawal signs and symptoms include irritability, increased respiratory rate, tremors, fever, sneezing, yawning, diarrhea, vomiting, excessive crying, and hyperactive reflexes. The intensity of symptoms does not always correlate with the dose or duration of opiate use. In addition, the use of hydrocodone shortly before delivery may cause respiratory depression in the newborn, especially if higher doses are used (Prod Info HYCOFENIX oral solution, 2015).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Pseudoephedrine is excreted in human breast milk. Exposure to sympathomimetic amines may present a higher than usual risk to nursing infants (Prod Info RESPA(R) -1ST sustained-release oral tablets, 2006).
    2) Pseudoephedrine has a pKa of 9.4 and is ion-trapped in breast milk; however only 0.5% to 0.7% of the maternal dose was excreted in one study (Findley et al, 1984).
    3) Irritability, excessive crying, and disturbed sleep patterns were seen in a 3-month-old breastfed infant following maternal ingestion of pseudoephedrine 120 mg twice a day (Mortimer, 1977).
    4) The American Academy of Pediatrics considers the drug to be compatible with breastfeeding (Briggs et al, 1998a).
    5) ACRIVASTINE/PSEUDOEPHEDRINE HYDROCHLORIDE: It is unknown whether acrivastine is excreted in human milk, although pseudoephedrine is excreted in human milk. Acrivastine/pseudoephedrine hydrochloride should be used in nursing mothers only when the potential benefit justifies the potential risks to the nursing infant (Prod Info Semprex(R)-D oral capsules, 2014).
    6) GUAIFENESIN/HYDROCODONE/PSEUDOEPHEDRINE: Both hydrocodone and pseudoephedrine are known to be excreted in human breast milk. Discontinue treatment or discontinue nursing taking into account the importance of the drug to the mother (Prod Info HYCOFENIX oral solution, 2015).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who remain persistently symptomatic despite supportive management, or require large amounts of benzodiazepines should be admitted for further observation. Patient in status epilepticus, respiratory failure, significant hemorrhage, or altered mental status should be admitted to an intensive care unit.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Children less than 6-years-old with a history of ingestion of less than 180 mg (or 11 mg/kg) of pseudoephedrine can be managed at home, provided that they are asymptomatic and that adequate follow-up can be done.
    B) In a study of children less than 6 years of age ingesting pseudoephedrine only, those with ingestions up to 180 mg were managed with dilution and observation only (Wezorek et al, 1995). Syrup of ipecac was administered to 12 patients.
    1) Of 101 children who ingested 180 mg or less (mean: 168 mg) 22% developed drowsiness, 7% developed mild hyperactivity and none developed serious toxicity.
    2) Of 39 children ingesting more than 180 mg, 15% developed drowsiness, 13% developed mild hyperactivity and none developed serious toxicity. One child ingesting 600 mg was admitted to intensive care.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or a medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is uncertain.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Any patient with symptoms or a deliberate ingestion should be referred to a health care facility for observation. All symptomatic patients should be sent to a health care facility for observation. Children with ingestions of 180 mg or more (or 11 mg/kg or more) should be referred to a healthcare facility.
    B) Monitor ECG and observe for at least 24 hours with sustained-release products.

Monitoring

    A) Monitor serum electrolytes, glucose and ECG in symptomatic patients.
    B) Monitor CK in patients with prolonged agitation, seizures or coma.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Severe toxicity rarely develops after inadvertent pediatric exposures; prehospital decontamination is probably not necessary.
    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).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) MONITOR ECG AND VITAL SIGNS (especially blood pressure and pulse) in all patients. Prolonged observation (at least 24 hours) may be necessary in patients ingesting sustained-release formulations.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) MONITOR URINARY OUTPUT, blood glucose, and serum electrolytes in symptomatic patients. Fluid replacement may be necessary.
    C) ANXIETY
    1) AGITATION, DISORIENTATION, increased motor activity, hallucinations, hyperventilation, and tachypnea generally require only conservative supportive therapy; benzodiazepines are useful in more severe cases.
    a) Severe symptomatic palpitations, tremor, and associated anxiety may respond to propranolol. NEVER GIVE PROPRANOLOL TO BRADYCARDIC OR ASTHMATIC PATIENTS.
    2) PROPRANOLOL/ADULT DOSE
    a) INTRAVENOUS: 0.5 mg to 1 mg per dose IV over 1 minute. May repeat dose up to a total of 0.1 mg/kg, if needed (Neumar et al, 2010). A second dose may be repeated in 2 minutes, if necessary; however, any additional drug administration should be given at least 4 hours later (Prod Info propranolol HCl IV injection, 2008).
    b) The maximum dose is 3 mg; the rate should not exceed 1 mg/min (Prod Info propranolol HCl IV injection, 2008).
    3) PROPRANOLOL/PEDIATRIC DOSE
    a) INTRAVENOUS: 0.01 to 0.15 mg/kg IV every 6 to 8 hours (Luedtke et al, 1997).
    4) MONITORING
    a) The drug should be administered with cardiac monitoring or central venous pressure monitoring. Monitor for bradycardia, hypotension and congestive heart failure (Prod Info propranolol HCl IV injection, 2008).
    5) SEVERE AGITATION: Extreme agitation responded to haloperidol in one case (Clark & Curry, 1990).
    D) 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).
    E) TACHYARRHYTHMIA
    1) Tachycardia usually does not require treatment. Benzodiazepines may be useful in patients with agitation and tachycardia. In severe hemodynamically significant tachydysrhythmias, a beta blocking agent may be useful. A short acting cardioselective agent such as esmolol is preferred.
    2) TACHYCARDIA SUMMARY
    a) Evaluate patient to be sure that tachycardia is not a physiologic response to dehydration, anemia, hypotension, fever, sepsis, or hypoxia. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
    b) If therapy is required, a short acting, cardioselective agent such as esmolol is generally preferred (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    c) ESMOLOL/ADULT LOADING DOSE
    1) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010a).
    d) ESMOLOL/ADULT MAINTENANCE DOSE
    1) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010a).
    2) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010a).
    3) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    4) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    e) CAUTION
    1) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010a).
    F) HYPERTENSIVE EPISODE
    1) Monitor vital signs regularly. For mild/moderate hypertension without evidence of end organ damage, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning.
    2) For hypertensive emergencies (severe hypertension with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure 20% to 25% within one hour), sodium nitroprusside is preferred. Nitroglycerin and phentolamine are possible alternatives.
    3) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    4) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    5) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    6) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    7) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    8) NITROGLYCERIN/INDICATIONS
    a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).
    9) NITROGLYCERIN/ADULT DOSE
    a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).
    10) NITROGLYCERIN/PEDIATRIC DOSE
    a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).
    11) PHENTOLAMINE/INDICATIONS
    a) Useful for severe hypertension, particularly if caused by agents with alpha adrenergic agonist effects usually induced by catecholamine excess (Rhoney & Peacock, 2009).
    12) PHENTOLAMINE/ADULT DOSE
    a) BOLUS DOSE: 5 to 15 mg IV bolus repeated as needed (U.S. Departement of Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, 2004). Onset of action is 1 to 2 minutes with a duration of 10 to 30 minutes (Rhoney & Peacock, 2009).
    b) CONTINUOUS INFUSION: 1 mg/hr, adjusted hourly to stabilize blood pressure. Prepared by adding 60 mg of phentolamine mesylate to 100 mL of 0.9% sodium chloride injection; continuous infusion ranging from 12 to 52 mg/hr over 4 days has been used in case reports (McMillian et al, 2011).
    13) PHENTOLAMINE/PEDIATRIC DOSE
    a) 0.05 to 0.1 mg/kg/dose (maximum of 5 mg per dose) intravenously every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Singh et al, 2012; Koch-Weser, 1974).
    14) PHENTOLAMINE/ADVERSE EFFECTS
    a) Adverse events can include orthostatic or prolonged hypotension, tachycardia, dysrhythmias, angina, flushing, headache, nasal congestion, nausea, vomiting, abdominal pain and diarrhea (Rhoney & Peacock, 2009; Prod Info Phentolamine Mesylate IM, IV injection Sandoz Standard, 2005).
    15) CAUTION
    a) Phentolamine should be used with caution in patients with coronary artery disease because it may induce angina or myocardial infarction (Rhoney & Peacock, 2009).
    16) BETA BLOCKING AGENTS
    a) LABETALOL: Has been used effectively to control the excess alpha and beta-adrenergic stimulation induced by pseudoephedrine overdose (Mariani, 1986). Propranolol has also been used successfully (Burkhart, 1992).
    b) LABETALOL
    1) INTRAVENOUS INDICATIONS
    a) Consider if severe hypertension is unresponsive to short acting titratable agents such as sodium nitroprusside. Although labetalol has mixed alpha and beta adrenergic effects (Pearce & Wallin, 1994), it should be used cautiously if sympathomimetic agents are involved in the poisoning, as worsening hypertension may develop from alpha adrenergic effects.
    2) ADULT DOSE
    a) INTRAVENOUS BOLUS: Initial dose of 20 mg by slow IV injection over 2 minutes. Repeat with 40 to 80 mg at 10 minute intervals. Maximum total dose: 300 mg. Maximum effects on blood pressure usually occur within 5 minutes (Prod Info Trandate(R) IV injection, 2010).
    b) INTRAVENOUS INFUSION: Administer infusion after initial bolus, until desired blood pressure is reached. Administer IV at 2 mg/min of diluted labetalol solution (1 mg/mL or 2 mg/3 mL concentrations); adjust as indicated and continue until adequate response is achieved; usual effective IV dose range is 50 to 200 mg total dose; maximum dose: 300 mg. Prepare 1 mg/mL concentration by adding 200 mg labetalol (40 mL) to 160 mL of a compatible solution and administered at a rate of 2 mL/min (2 mg/min); also can be mixed as an approximate 2 mg/3 mL concentration by adding 200 mg labetalol (40 mL) to 250 mL of solution and administered at a rate of 3 mL/min (2 mg/min) (Prod Info Trandate(R) IV injection, 2010). Use of an infusion pump is recommended (Prod Info Trandate(R) IV injection, 2010).
    3) PEDIATRIC DOSE
    a) INTRAVENOUS: LOADING DOSE: 0.2 to 1 mg/kg, may repeat every 5 to 10 minutes (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Fivush et al, 1997; Bunchman et al, 1992). Maximum dose: 40 mg/dose (Hari & Sinha, 2011; Flynn & Tullus, 2009). CONTINUOUS INFUSION: 0.25 to 3 mg/kg/hour IV (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Miller, 1994; Deal et al, 1992; Bunchman et al, 1992).
    4) ADVERSE REACTIONS
    a) Common adverse events include postural hypotension, dizziness; fatigue; nausea; vomiting, sweating, and flushing (Pearce & Wallin, 1994).
    5) PRECAUTIONS
    a) Contraindicated in patients with bronchial asthma, congestive heart failure, greater than first degree heart block, cardiogenic shock, or severe bradycardia or other conditions associated with prolonged or severe hypotension. In patients with pheochromocytoma, labetalol should be used with caution because it has produced a paradoxical hypertensive response in some patients with this tumor (Prod Info Trandate(R) IV injection, 2010).
    b) Use caution in hepatic disease or intermittent claudication; effects of halothane may be enhanced by labetalol (Prod Info Trandate(R) IV injection, 2010). Labetalol should be stopped if there is laboratory evidence of liver injury or jaundice (Prod Info Trandate(R) IV injection, 2010).
    6) MONITORING PARAMETER
    a) Monitor blood pressure frequently during initial dosing and infusion (Prod Info Trandate(R) IV injection, 2010).
    G) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    H) HYPOTHERMIA
    1) Hypothermia should be managed with gradual rewarming.

Enhanced Elimination

    A) SUMMARY
    1) Enhanced elimination is unlikely to be effective due to the large volume of distribution.
    B) HEMODIALYSIS
    1) Conventional hemodialysis removed approximately 17 mg of pseudoephedrine during 4 hours in a patient with renal failure. The predialysis serum level was 1425 ng/mL, after 4 hours of dialysis the level was 1132 ng/mL (Sica & Comstock, 1989).

Abstracts

Case Reports

    A) ADULT
    1) A 22-year-old man was found comatose, hypotensive and tachycardic following a massive overdose of pseudoephedrine in combination with antihistamines. Two hours after admission, disseminated intravascular coagulation developed. On the second day his renal function deteriorated. Rhabdomyolysis was implicated as the primary cause of this renal failure. By day 4, alternating hypotension and hypertension with hypothermia developed. A CT scan of the head showed diffuse cerebral edema and evidence of a left posterior thalamic bleed. The patient expired later that day (Salmon & Nicholson, 1988).
    2) Severe hypokalemia (1.8 mEq/L) despite normal body potassium content developed in a 17-year-old boy who overdosed on an unknown amount of pseudoephedrine and choline theophyllinate. Serum glucose on admission was 17.6 mmol/L. Aside from muscle pain and weakness during recovery, the patient had no symptoms of hypokalemia. It was postulated that the drugs produced hyperglycemia and hyperinsulinemia, resulting in a shift of potassium from extracellular to intracellular space (McCleave et al, 1978).
    3) A 23-year-old man presented to the emergency department 3 hours after ingesting 840 mg of pseudoephedrine and 7 mg of azatadine. He was found to have severe headache, dizziness, epigastric pain, diaphoresis, hypertension (200/140 mmHg), and sinus tachycardia. Treatment included labetalol 25 mg IV over 2 minutes, resulting in a decrease in blood pressure and pulse to 170/120 mmHg and 76/min, respectively. Within 30 minutes after an additional dose of 40 mg, the blood pressure fell to 150/110 mmHg. Another dose of 25 mg was given, and 4 hours later the blood pressure was 106/82 mmHg, and the patient was asymptomatic (Mariani, 1986).
    4) A 17-year-old girl presented 4 hours after ingestion of 1200 mg of pseudoephedrine. She was slightly disoriented and had a normal pulse and blood pressure. Within 24 hours she developed headache, drowsiness, and right hemiparesis, still with a normal blood pressure. The CT scan confirmed intracerebral hemorrhage on the 4th day; an angiogram on the 7th day demonstrated beading of the carotid arteries. All symptoms resolved within 6 months (Loizou et al, 1982).
    5) A 24-year-old man presented 2 hours after ingesting 4500 mg of pseudoephedrine and 35 g of aspirin. After treatment with gastric lavage, activated charcoal and sorbitol, he was hypertensive (BP 220/108), agitated, and tremulous. Propranolol 1 mg IV was given, which decreased the blood pressure to 153/88 after 3 minutes, and resolved tremulousness. Multiple-dose charcoal and urine alkalinization were administered due to the aspirin coingestant, which may have inhibited elimination of pseudoephedrine. Hypertension recurred twice within 12 hours and responded again to propranolol. Recovery was uneventful (Burkhart, 1992).
    B) PEDIATRIC
    1) TODDLER
    a) A 19-month-old child presented 75 minutes after ingestion of at least 20 tablets of pseudoephedrine 30 mg. Initial signs and symptoms included mydriasis, tremors, agitation, diaphoresis, hyperactive bowel sounds, and tachycardia (200 beats/min). A brief generalized tonic-clonic seizure occurred one hour after admission, which resolved spontaneously. The seizure was controlled with phenobarbital. Extreme agitation and irritability were not responsive to therapy with phenobarbital and lorazepam, but resolved after haloperidol 2.5 mg IV given 24 hours postingestion. Tachycardia persisted for 18 hours postingestion (Clark & Curry, 1990).

Range Of Toxicity

Summary

    A) TOXICITY: Symptoms can occur typically after 4- to 5-fold therapeutic doses. Four times the single therapeutic dose (about 240 mg) is required to cause an increase in diastolic blood pressure above 90 mmHg in normotensive subjects. Hypertensive crisis with non-ST elevation myocardial infarction occurred in an elderly adult after inadvertently ingesting 3 sustained release tablets (240 mg) in 6 hours. PEDIATRIC: In one study, children aged 2 to 6 years old developed only minor symptoms following ingestions of up to 180 mg. Acute exposures of 11 mg/kg were well-tolerated.
    B) ADULT: THERAPEUTIC GENERAL DOSING: Typical doses are 180 to 360 mg daily. SPECIFIC INDICATIONS or FORMULATIONS: Allergic Rhinitis OR Congestion of Nasal Sinus: 60 mg orally every 4 to 6 hrs; maximum 240 mg/day or SR tablets 120 mg orally every 12 hrs or 24-hour tablets; 240 mg orally every 24 hours.
    C) PEDIATRIC: THERAPEUTIC GENERAL DOSING: 3 to 5 mg/kg in children. Not approved for use in children 12 years of age or younger. SPECIFIC INDICATIONS or FORMULATIONS: Allergic rhinitis OR Congestion of Nasal Sinus: 2 to 5 years: Immediate-release products only: 15 mg orally every 4 to 6 hrs; maximum 60 mg/day. 6 to 12 years: Immediate-release products only: 30 mg orally every 4 to 6 hrs; maximum 120 mg/day. 12 years of age and older: 60 mg orally every 4 to 6 hrs; maximum 240 mg/day or SR tablets, 120 mg orally every 12 hrs or 24-hour tablets, 240 mg orally every 24 hours.

Therapeutic Dose

    7.2.1) ADULT
    A) PSEUDOEPHEDRINE/ACRIVASTINE
    1) The recommended dosage is one capsule (8 mg of acrivastine and 60 mg of pseudoephedrine hydrochloride per capsule) orally every 4 to 6 hours four times a day (Prod Info Semprex(R)-D oral capsules, 2014).
    B) PSEUDOEPHEDRINE
    1) The recommended adult dose for pseudoephedrine is 60 mg every 4 to 6 hours; MAXIMUM: 240 mg/24 hours (Prod Info SUDAFED(R) chewable tablets, 2005; Prod Info SUDAFED(R) 24 hour oral tablets, 2005; Prod Info SUDAFED(R) 12 hour oral tablets, 2005; Prod Info Sudafed(R) nasal decongestant tablets, 2005).
    C) PSEUDOEPHEDRINE/GUAIFENESIN/HYDROCODONE
    1) The recommended dose is 10 mL every 4 to 6 hours; MAX: 4 doses (40 mL) in 24 hours (Prod Info HYCOFENIX oral solution, 2015).
    7.2.2) PEDIATRIC
    A) PSEUDOEPHEDRINE
    1) CHEWABLE TABLET
    a) 12 TO 18 YEARS OF AGE: The usual recommended dose is 4 tablets (60 mg) every 4 to 6 hours. MAXIMUM: 240 mg/24 hours (Prod Info SUDAFED(R) chewable tablets, 2005).
    b) 6 TO 12 YEARS OF AGE: The usual recommended dose is 2 tablets (30 mg) every 4 to 6 hours. MAXIMUM: 120 mg/24 hours (Prod Info SUDAFED(R) chewable tablets, 2005).
    c) 2 TO 6 YEARS OF AGE: The usual recommended dose is 1 tablet (15 mg) every 4 to 6 hours. MAXIMUM: 60 mg/24 hours (Prod Info SUDAFED(R) chewable tablets, 2005).
    2) EXTENDED-RELEASE TABLET
    a) 12 TO 18 YEARS OF AGE: The usual recommended dose is 240 mg/day as a single or in divided doses. MAXIMUM: 240 mg/24 hours (Prod Info SUDAFED(R) 24 hour oral tablets, 2005; Prod Info SUDAFED(R) 12 hour oral tablets, 2005).
    b) LESS THAN 12 YEARS OF AGE: Use is not recommended (Prod Info SUDAFED(R) 24 hour oral tablets, 2005; Prod Info SUDAFED(R) 12 hour oral tablets, 2005).
    3) SOLUTION
    a) 12 TO 18 YEARS OF AGE: The usual recommended dose is 4 teaspoonfuls (60 mg) every 4 to 6 hours. MAXIMUM: 240 mg/24 hours (Prod Info Children's Sudafed(R) nasal decongestant liquid medication, 2005).
    b) 6 TO 12 YEARS OF AGE: The usual recommended dose is 2 teaspoonfuls (30 mg) every 4 to 6 hours. MAXIMUM: 120 mg/24 hours (Prod Info Children's Sudafed(R) nasal decongestant liquid medication, 2005).
    c) 2 TO 6 YEARS OF AGE: The usual recommended dose is 1 teaspoonful (15 mg) every 4 to 6 hours. MAXIMUM: 60 mg/24 hours (Prod Info Children's Sudafed(R) nasal decongestant liquid medication, 2005).
    4) TABLET
    a) 12 TO 18 YEARS OF AGE: The usual recommended dose is 2 tablets (60 mg) every 4 to 6 hours. MAXIMUM: 240 mg/24 hours (Prod Info Sudafed(R) nasal decongestant tablets, 2005).
    b) 6 TO 12 YEARS OF AGE: The usual recommended dose is 1 tablet (30 mg) every 4 to 6 hours. MAXIMUM: 120 mg/24 hours (Prod Info Sudafed(R) nasal decongestant tablets, 2005).
    B) PSEUDOEPHEDRINE/ACRIVASTINE
    1) 12 YEARS AND OLDER: The recommended dosage is one capsule (8 mg of acrivastine and 60 mg of pseudoephedrine hydrochloride per capsule) orally every 4 to 6 hours four times a day (Prod Info Semprex(R)-D oral capsules, 2014).
    2) LESS THAN 12 YEARS OF AGE: The safety and effectiveness of pseudoephedrine hydrochloride/acrivastine have not been evaluated (Prod Info Semprex(R)-D oral capsules, 2014).
    C) PSEUDOEPHEDRINE/GUAIFENESIN/HYDROCODONE
    1) Safety and effectiveness have not been established in pediatric patients (Prod Info HYCOFENIX oral solution, 2015).

Minimum Lethal Exposure

    A) CASE REPORTS
    1) INFANT
    a) A fatality was reported in a 2-year-old child upon ingestion of at least 420 mg (Baselt, 2000).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Severe toxicity from pseudoephedrine alone has been rare, but the therapeutic index is low.
    B) ACUTE
    1) HYPERTENSION: Single doses of 210 to 240 mg of pseudoephedrine were needed to produce slight increases in diastolic blood pressure above 90 mmHg in normotensive individuals (Drew et al, 1978). Rarely, hypertension results from therapeutic doses (Rutstein, 1963).
    2) CASE REPORT: Hypertensive crisis with non-ST elevation MI occurred in an 87-year-old man after inadvertently ingesting 3 sustained-release pseudoephedrine tablet (240 mg per tablet) in 6 hours. His initial blood pressure was 206/108 with an irregular heart rate of 110 beats/min. An ECG showed atrial fibrillation (preexisting condition) with rapid ventricular response. The patient improved rapidly with IV nitroprusside and was monitored for an additional 2 days and then discharged to home (Wang et al, 2008).
    3) RENAL FAILURE: Usual therapeutic doses (240 mg/day) resulted in neurologic toxicity (myoclonus, bizarre behavior, irritability) in a patient with end-stage renal disease (Sica & Comstock, 1989).
    4) Severe toxicity from ephedrine, and pseudoephedrine, alone has been rare, but the therapeutic index is low.
    5) Doses of up to 180 mg produce no measurable effect on blood pressure or heart rate (Pentel, 1984).
    C) CASE REPORTS
    1) PEDIATRIC
    a) CASE SERIES: In a prospective review of 520 children ingesting liquid cough/cold preparations, 23% were symptomatic. Symptoms observed were drowsiness in 87%, ataxia in 4.2%, agitation in 3.4%, gastrointestinal upset in 2.5%, and dilated pupils in 1.7 percent. No serious effects were noted (Normann & Manoguerra, 1986).
    b) A 5-year-old boy ingested 60 mL (360 mg, 6 times the maximum daily dose) of a syrup containing pseudoephedrine and triprolidine. Five hours later, the patient developed flushed and dry skin, dilated pupils and visual hallucinations (Ackland, 1984).
    c) PEDIATRIC: A prospective study to establish a toxic dose in children found that children aged 2- to 6-years-old developed only minor symptoms following ingestion of up to 180 mg. Acute exposures of 11 mg/kg were well-tolerated (Wezorek et al, 1995).
    d) INFANT: An 18-month-old girl developed facial dyskinesia approximately 12 hours after ingesting 480 mg of pseudoephedrine sulfate and 24 mg of dexbrompheniramine maleate (Barone & Raniolo, 1980).
    e) URINARY RETENTION: A 3-year-old boy weighing 11 kg was given pseudoephedrine 3 times daily (90 mg/day) for 10 days for cold symptoms and suddenly developed an episode of acute urinary retention. Twelve hours after the last dose of pseudoephedrine the child was voiding without difficulty. Diagnostic studies conducted one week later revealed normal bladder capacity and voiding time. The authors concluded that the excessive dose (twice the recommended daily dose for over a week) was responsible for the symptoms observed in this low-weight child (Soyer et al, 2008).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) Single doses of 60 mg produce mean peak plasma levels of 0.21 mcg/mL in adults (Bye et al, 1975).
    2) A single dose of 120 mg in a prompt release tablet form resulted in a peak level of 258 ng/mL at 9 hours. A single dose of 120 mg in a repeat action tablet form resulted in a peak level of 249 ng/mL at 6.7 hours (Lin et al, 1982).
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) The postmortem plasma level in two fatal cases was 19 mcg/mL and 66 mcg/mL, respectively (Baselt, 2000).
    b) The postmortem plasma level in a fatal case of mixed ingestion of pseudoephedrine (which also included triprolidine, pyrilamine and diphenhydramine) in an adult was 0.2 mg/mL (Salmon & Nicholson, 1988).
    c) A single dose of 5 mg/kg resulted in a peak level of 1.1 mcg/mL in an adult (Lin et al, 1977).
    d) Therapeutic dosage of 240 mg/day resulted in neurologic toxicity in a patient with renal failure. The plasma level 60 hours after discontinuation of the drug was 1425 ng/mL (Sica & Comstock, 1989).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Pseudoephedrine is used predominately as an oral nasal decongestant. It is an alpha-adrenergic receptor antagonist (sympathomimetic) which can produce vasoconstriction by stimulating alpha-receptors within the mucosa of the respiratory tract. The vasoconstriction action of pseudoephedrine is similar to that of ephedrine (Prod Info GUAIFENEX(R) PSE 85 extended-release oral tablets, 2005).

Toxicologic Mechanism

    A) Pseudoephedrine stimulates both alpha and beta adrenergic receptors, and in large doses can elevate both blood pressure and heart rate.
    B) TACHYPHYLAXIS: Pseudoephedrine also has indirect activity by stimulating norepinephrine release. Tachyphylaxis occurs to the pressor effects, presumably due to depletion of norepinephrine stores (Dickerson et al, 1978).
    C) Cantu et al (2003) described several mechanisms by which over-the counter sympathomimetics cause cerebrovascular complications: the development of hypertensive crisis as a consequence of a direct vasoconstrictive action of the drugs, or the development of angiitis. Although most cases were due to phenylpropanolamine use, stroke may also occur with the use of pseudoephedrine (Cantu et al, 2003).

Physicochemical

Physical Characteristics

    A) PSEUDOEPHEDRINE HYDROCHLORIDE: white or off-white crystals or powder, with faint odor (JEF Reynolds , 2000)
    B) PSEUDOEPHEDRINE SULFATE: white crystals or powder, with no odor (JEF Reynolds , 2000)

Molecular Weight

    A) Varies

References

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) Ackland FM: Hallucinations in a child after drinking triprolidine/pseudoephedrine linctus (letter). Lancet 1984; 1:1180.
    3) American Heart Association: 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2005; 112(24 Suppl):IV 1-203. Available from URL: http://circ.ahajournals.org/content/vol112/24_suppl/. As accessed 12/14/2005.
    4) Barone DA & Raniolo J: Facial dyskinesia from overdose of an antihistamine (letter). N Engl J Med 1980; 303:107.
    5) Baselt RC: Disposition of Toxic Drugs and Chemicals in Man, 5th ed, Chemical Toxicology Institute, Foster City, CA, 2000.
    6) Beary JF: Pseudoephedrine producing postural hypotension in a pilot. Aviat Space Environ Med 1977; 48:369.
    7) Billings CE: Aerospace Med 1974; 45:551.
    8) Brater DC, Kaojarern S, & Benet: Renal excretion of pseudoephedrine. Clin Pharmacol Ther 1980; 28:690-694.
    9) Briggs GG, Freeman RK, & Yaffe SJ: Drugs in Pregnancy and Lactation, 5th ed, Williams and Wilkins, Baltimore, MD, 1998a.
    10) Briggs GG, Freeman RK, & Yaffe SJBriggs GG, Freeman RK, & Yaffe SJ (Eds): Drugs in Pregnancy and Lactation, 5th. Williams & Wilkins, Baltimore, MD, 1998.
    11) Bright TP, Sandage BW, & Fletcher HP: Selected cardiac and metabolic responses to pseudoephedrine with exercise. J Clin Pharmacol 1981; 21:488-492.
    12) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    13) Brownstein MH: Fixed eruptions due to an ephedrine isomer. Arch Dermatol 1968; 97:115-119.
    14) Bunchman TE, Lynch RE, & Wood EG: Intravenously administered labetalol for treatment of hypertension in children. J Pediatr 1992; 120(1):140-144.
    15) Burkhart KK: Intravenous propranolol reverses hypertension after sympathomimetic overdose:two case reports. J Toxicol Clin Toxicol 1992; 30:109-114.
    16) Bye C, Hill HM, & Hughes DTD: A comparison of plasma levels of L(+) pseudoephedrine following different formulations, and their relation to cardiovascular and subjective effects in man. Eur J Clin Pharmacol 1974; 8:47-53.
    17) Bye C, Hill HM, Hughes DTD, et al: A comparison of plasma levels of L(+) pseudoephedrine following different formulations, and their relation to cardiovascular and subjective effects in man. Eur J Clin Pharmacol 1975; 8:47-53.
    18) Camisa C: Fixed drug eruption due to pseudoephedrine. Cutis 1988; 41:339-340.
    19) Cantu C, Arauz A, Murillo-Bonilla LM, et al: Stroke associated with sympathomimetics contained in over-the-counter cough and cold drugs. Stroke 2003; 34:1667-1673.
    20) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    21) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    22) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    23) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    24) Clark RF & Curry SC: Pseudoephedrine dangers (letter). Pediatrics 1990; 85:389-390.
    25) Dalton R: Mixed bipolar disorder precipitated by pseudoephedrine hydrochloride. S Med J 1990; 83:64-65.
    26) Deal JE , Barratt TM , & Dillon MJ : Management of hypertensive emergencies. Arch Dis Child 1992; 67(9):1089-1092.
    27) Diaz MA, Wise TN, & Semchyshyn GO: Self-medication with pseudoephedrine in a chronically depressed patient. Am J Psychiatr 1979; 136:1217-1218.
    28) Dickerson J, Perrier D, & Mayersohn M: Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man. Eur J Clin Pharmacol 1978; 14:253-259.
    29) Dowd J, Bailey D, & Moussa K: Ischemic colitis associated with pseudoephedrine: four cases. Amer J Gastroenterol 1999; 94:2430-2434.
    30) Drennan PC: Visual hallucinations in children receiving decongestants (letter). Br Med J 1984; 288:1688.
    31) Drew CDM, Knight GT, & Hughes DTD: Comparison of the effects of D-(-)-ephedrine and L-(+)-pseudoephedrine on the cardiovascular and respiratory systems in man. Br J Clin Pharmacol 1978; 6:221-225.
    32) Ellenhorn MJ & Barceloux DG: Medical Toxicology: Diagnosis and Treatment of Human Poisoning, Elsevier, New York, NY, 1988.
    33) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    34) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    35) Fivush B , Neu A , & Furth S : Acute hypertensive crises in children: emergencies and urgencies. Curr Opin Pediatr 1997; 9(3):233-236.
    36) Flynn JT & Tullus K: Severe hypertension in children and adolescents: pathophysiology and treatment. Pediatr Nephrol 2009; 24(6):1101-1112.
    37) Friedman WF & George BL : Treatment of congestive heart failure by altering loading conditions of the heart. J Pediatr 1985; 106(5):697-706.
    38) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    39) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    40) Hari P & Sinha A: Hypertensive emergencies in children. Indian J Pediatr 2011; 78(5):569-575.
    41) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    42) Hauken M: Fixed drug eruption and pseudoephedrine (letter). Ann Intern Med 1994; 120:442.
    43) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    44) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    45) Ilbawi MN, Idriss FS, DeLeon SY, et al: Hemodynamic effects of intravenous nitroglycerin in pediatric patients after heart surgery. Circulation 1985; 72(3 Pt 2):II101-II107.
    46) JEF Reynolds : Martindale: The Extra Pharmacopoeia (electronic version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    47) Jarrett PEM: Franol poisoning. Lancet 1966; 2:1190.
    48) Jick H, Holmes LB, & Hunter JR: First trimester drug use and congenital disorders. JAMA 1981; 246:343-346.
    49) Jordan J, Shannon JR, Diedrich A, et al: Water potentiates the pressor effect of ephedra alkaloids. Circulation 2004; 109:1823-1825.
    50) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    51) Koch-Weser J: Hypertensive emergencies. N Engl J Med 1974; 290:211.
    52) Kuntzman RG, Tsai I, & Brand L: The influence of urinary pH on the plasma half-life of pseudoephedrine in man and dog and a sensitive assay for its determination in human plasma. Clin Pharmacol Ther 1971; 12:62-67.
    53) Laitinen P, Happonen JM, Sairanen H, et al: Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect. J Cardiothorac Vasc Anesth 1997; 11(7):870-874.
    54) Lambert MT: Paranoid psychoses after abuse of proprietary cold remedies. Br J Psychiatry 1987; 151:548-550.
    55) Leighton KM: Paranoid psychosis after abuse of Actifed. Br Med J 1982; 284:789-790.
    56) Lichtenstein GR & Yee NS: Ischemic colitis associated with decongestant use (letter). Ann Intern Med 2000; 132:682.
    57) Lin C, Lim J, & Symchowicz MS: Comparative bioavailability of d- pseudoephedrine from conventional d-pseudoephedrine and from a repeat action tablet. J Int Med Res 1982; 10:126-128.
    58) Lin ET, Brater DC, & Benet LZ: Gas-liquid chromatographic determination of pseudoephedrine and norpseudoephedrine in human plasma and urine. J Chromatogr 1977; 140:275-279.
    59) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    60) Loizou LA, Hamilton JG, & Tsementzis SA: Intracranial haemorrhage in association with pseudoephedrine overdose (letter). J Neurol Neurosurg Psychiatr 1982; 45:471-475.
    61) Luedtke SA, Kuhn RJ, & McCaffrey FM: Pharmacologic management of supraventricular tachycardias in children. Part 2: Atrial flutter, atrial fibrillation, and junctional and atrial ectopic tachycardia. Ann Pharmacother 1997; 31(11):1347-1359.
    62) MacMahon JR: Atrial fibrillation and sympathomimetics (letter). J Pediatr 1974; 84:613.
    63) Manini AF, Kabrhel C, & Thomsen TW: Acute myocardial infarction after over-the-counter use of pseudoephedrine. Ann Emerg Med 2005; 45:213-216.
    64) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    65) Mariani PJ: Pseudoephedrine-induced hypertensive emergency: treatment with labetalol. Am J Emerg Med 1986; 4:141-142.
    66) McCleave DJ, Phillips PJ, & Vedig AE: Compartmental shift of potassium - a result of sympathomimetic overdose. Aust NZ J Med 1978; 8:180-183.
    67) McMillian WD, Trombley BJ, Charash WE, et al: Phentolamine continuous infusion in a patient with pheochromocytoma. Am J Health Syst Pharm 2011; 68(2):130-134.
    68) Miller K: Pharmacological management of hypertension in paediatric patients. A comprehensive review of the efficacy, safety and dosage guidelines of the available agents. Drugs 1994; 48(6):868-887.
    69) Miller MG: Visual hallucinations in children receiving decongestants (letter). Br Med J 1984; 288:1688.
    70) Mortimer EA: Drug toxicity from breast milk?. Pediatrics 1977; 60:780-781.
    71) Mueller SM & Solow EB: Seizures associated with a new combination "pick-me-up" pill. Ann Neurol 1982; 11:322.
    72) Nam YT, Shin T, & Yoshitake J: Induced hypotension for surgical repair of congenital dislocation of the hip in children. J Anesth 1989; 3(1):58-64.
    73) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010a; 122(18 Suppl 3):S729-S767.
    74) Neumar RW, Otto CW, Link MS, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 8: adult advanced cardiovascular life support. Circulation 2010; 122(18 Suppl.3):S729-S767.
    75) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    76) Normann SA & Manoguerra AS: Prospective review of cough/cold preparation ingestion guidelines (abstract). Vet Hum Toxicol 1986; 28:493.
    77) Pearce CJ & Wallin JD: Labetalol and other agents that block both alpha- and beta-adrenergic receptors. Cleve Clin J Med 1994; 61(1):59-69.
    78) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    79) Pentel P: Toxicity of over-the-counter stimulants. JAMA 1984; 2:1898-1903.
    80) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    81) Porta M, Jick H, & Habakangas JAS: Follow-up study of pseudoephedrine users. Ann Allergy 1986; 57:340-342.
    82) Product Information: BREVIBLOC(TM) intravenous injection, esmolol HCl intravenous injection. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2012.
    83) Product Information: Children's Sudafed(R) nasal decongestant liquid medication, pseudoephedrine hydrochloride oral solution. Pfizer Consumer Healthcare, 2005.
    84) Product Information: GUAIFENEX(R) PSE 85 extended-release oral tablets, pseudoephedrine hcl, guaifenesin extended-release oral tablets. Ethex Corporation, St. Louis, MO, 2005.
    85) Product Information: HISTADE(TM) oral capsules, pseudoephedrine hcl, chlorpheniramine maleate oral capsules. Breckenridge Pharmaceuticals,Inc, Boca Raton, FL, 2004.
    86) Product Information: HYCOFENIX oral solution, hydrocodone bitartrate, pseudoephedrine HCl, guaifenesin oral solution. Cintex Services (per FDA), Dallas, TX, 2015.
    87) Product Information: NITROPRESS(R) injection for IV infusion, Sodium Nitroprusside injection for IV infusion. Hospira, Inc., Lake Forest, IL, 2007.
    88) Product Information: NITROPRESS(R) injection, sodium nitroprusside injection. Hospira,Inc, Lake Forest, IL, 2004.
    89) Product Information: PSEUDOVENT(TM) 400 oral capsules, pseudoephedrine hcl extended-release, guaifenesin immediate-release oral capsules. Ethex Corporation, St. Louis, MO, 2004.
    90) Product Information: Phentolamine Mesylate IM, IV injection Sandoz Standard, phentolamine mesylate IM, IV injection Sandoz Standard. Sandoz Canada (per manufacturer), Boucherville, QC, 2005.
    91) Product Information: RESPA(R) -1ST sustained-release oral tablets, pseudoephedrine hcl, guaifenesin sustained-release oral tablets. Respa Pharmaceuticals,Inc, Mt. Pleasant, SC, 2006.
    92) Product Information: SUDAFED(R) 12 hour oral tablets, pseudoephedrine hcl 12 hour oral tablets. Pfizer Consumer Healthcare, New York, NY, 2005.
    93) Product Information: SUDAFED(R) 24 hour oral tablets, pseudoephedrine hcl 24 hour oral tablets. Pfizer Consumer Healthcare, New York, NY, 2005.
    94) Product Information: SUDAFED(R) chewable tablets, pseudoephedrine hcl chewable tablets. Pfizer Consumer Healthcare, New York, NY, 2005.
    95) Product Information: Semprex(R)-D oral capsules, acrivastine pseudoephedrine HCl oral capsules. Actient Pharmaceuticals LLC (per DailyMed), Chesterbrook, PA, 2014.
    96) Product Information: Sudafed(R) nasal decongestant tablets, pseudoephedrine hydrochloride tablets. Pfizer Consume Healthcare, 2005.
    97) Product Information: Trandate(R) IV injection, labetalol hydrochloride IV injection. Prometheus Laboratories Inc., San Diego, CA, 2010.
    98) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    99) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    100) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    101) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    102) Product Information: propranolol HCl IV injection, propranolol HCl IV injection. Bedford Laboratories (per DailyMed), Bedford, OH, 2008.
    103) Product Information: pseudoephedrine hcl, guaifenesin extended-release oral tablets, pseudoephedrine hcl, guaifenesin extended-release oral tablets. Prasco Laboratories, Cincinnati, OH, 2006.
    104) Rasch DK & Lancaster L: Successful use of nitroglycerin to treat postoperative pulmonary hypertension. Crit Care Med 1987; 15(6):616-617.
    105) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    106) Rhoney D & Peacock WF: Intravenous therapy for hypertensive emergencies, part 1. Am J Health Syst Pharm 2009; 66(15):1343-1352.
    107) Roberge RJ, Hirani KH, & Rowland PL: Dextromethorphan- and pseudoephedrine- induced agitated psychosis and ataxia: case report. J Emerg Med 1999; 17:285-288.
    108) Rosen RA: Angina associated with pseudoephedrine. Ann Emerg Med 1981; 10:230-231.
    109) Rutstein HR: Ingestion of pseudoephedrine. Arch Otolaryngol 1963; 77:145-147.
    110) Salmon J & Nicholson D: DIC and rhabdomyolysis following pseudoephedrine overdose (letter). Am J Emerg Med 1988; 6:545-546.
    111) Sankey RJ, Nunn AJ, & Sills JA: Visual hallucinations in children receiving decongestants. Br Med J 1984; 288:1369.
    112) Sauder KL, Brady WJ, & Hennes H: Visual hallucinations in a toddler: accidental ingestion of a sympathomimetic over-the-counter nasal decongestant. Amer J Emerg Med 1997; 15:521-526.
    113) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    114) Shelley WB & Shelley ED: Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline. J Am Acad Dermatol 1987; 17:403.
    115) Sica DA & Comstock TJ: Case report: pseudoephedrine accumulation in renal failure. Am J Med Sci 1989; 298:261-263.
    116) Sills JA, Nunn AJ, & Sankey RJ: Visual hallucinations in children receiving decongestants (letter). Br Med J 1984; 288:1912-1913.
    117) Singh D, Akingbola O, Yosypiv I, et al: Emergency management of hypertension in children. Int J Nephrol 2012; 2012:420247.
    118) Soyer T, Gol IH, Eroglu F, et al: Acute urinary retention due to pseudoephedrine hydrochloride in a 3-year-old child. Turk J Pediatr 2008; 50(1):98-100.
    119) Spielberg SP & Schulman JD: A possible reaction to pseudoephedrine in a patient with phenylketonuria. J Pediatr 1977; 90:1026.
    120) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    121) Stoessl AJ, Young MD, & Feasby TE: Intracerebral haemorrhage and angiographic beading following ingestion of catecholaminergics. Stroke 1985; 16:734-736.
    122) Taylor BJ & Duffill MB: Recurrent pseudo-scarlatina and allergy to pseudoephedrine hydrochloride. Br J Dermatol 1988; 118:827-829.
    123) Temple ME & Nahata MC: Treatment of pediatric hypertension. Pharmacotherapy 2000; 20(2):140-150.
    124) Till AE & Benet LZ: Renal excretion of pseudoephedrine in the rat. J Pharmacol Exp Ther 1979; 211:555-560.
    125) Tomb RR, Lepoittevin JP, & Espinassouze F: Systemic contact dermatitis from pseudoephedrine. Contact Dermatitis 1991; 24:86-88.
    126) U.S. Department of Health and Human Services; National Institutes of Health; and National Heart, Lung, and Blood Institute: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. U.S. Department of Health and Human Services. Washington, DC. 2004. Available from URL: http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf. As accessed 2012-06-20.
    127) Wang NE, Gillis E, & Mudie D: Hypertensive crisis and NSTEMI after accidental overdose of sustained release pseudoephedrine: A case report. Clin Toxicol (Phila) 2008; 46(9):922-923.
    128) Werler MM, Mitchell AA, & Shapiro S: First trimester maternal medication use in relation to gastroschisis. Teratology 1992; 45:361-367.
    129) Wezorek C, Dean B, & Krenzolok E: Pseudoephedrine: a prospective study to establish a toxic dose in children (abstract). J Tox Clin Tox 1995; 33:554.
    130) Wiener I, Tilkian AG, & Palazzolo M: Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudoephedrine ingestion. Cathet Cardiovasc Diagn 1990; 20(1):51-53.
    131) Wong KM, Chak WL, & Cheung CY: Hypokalemic metabolic acidosis attributed to cough mixture abuse. Am J Kid Dis 2001; 38:390-394.
    132) Wright S & Tomassoni A: Acute myocardial infarction following therapeutic use of pseudoephedrine (abstract). Vet Human Toxicol 1994; 36:366.