Dextromethorphan

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS
      1.4.2 Other numbers
   1.5 Brand names/trade names:
   1.6 Manufacturers and importers:
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Storage conditions
4. USES
   4.1 Indications
      4.1.1 Indications
      4.1.2 Description
   4.2 Therapeutic dosages
      4.2.1 Adults
      4.2.1 Children
   4.3 Contraindications
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parental
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.3 Animal data
      7.2.3 Relevant in-vitro data
   7.3 Carcinogenicity:
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND
BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological
investigations
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure.
      9.1.6 Other
   9.2 Chronic Poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin contact
      9.2.4 Eye contact
      9.2.5 Parental exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death:
   9.4 Systematic description of clinical effects:
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurologic
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatologic
      9.4.9 Eye, ear, throat: local effects
      9.4.10 Hematological
      9.4.11 Immunologic
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
    10.3 Decontamination
   10.4 Enhancd elimination
   10.5 Antidote
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case report from the literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S) DATES (INCLUDING EACH
UPDATING), COMPLETE ADDRESSES
DEXTROMETHORPHAN

International Programme on Chemical Safety

Poisons Information Monograph 179
Pharmaceutical

1. NAME

1.1 Substance

Dextromethorphan

1.2 Group

Cough and cold preparations (R05)/

Antitussives, excl. combinations with expectorants
(R05D)/ Opium alkaloids and derivatives (R05D A)

1.3 Synonyms

Dextromethorphan hydrobromide monohydrate;

dextromethorphani hydrobromidum;
demorphan hydrobromide

1.4 Identification numbers

1.4.1 CAS

125-69-9 (anhydrous)

1.4.2 Other numbers

CAS: 6700-34-1 (monohydrate)

1.5 Brand names/trade names:

 Polistirex Extended Release suspension.

1.6 Manufacturers and importers:

To be completed by each centre using the mongraph.

2. SUMMARY

2.1 Main risks and target organs

The main risks associated with dextromethorphan are

ataxia, central nervous system (CNS) stimulation, dizziness,
lethargy and psychotic behavior. Less frequently with large
doses seizures and respiratory depression can occur. Nausea,
vomiting, constipation and tachycardia may occur. The main
target organ is the central nervous system (CNS).

2.2 Summary of clinical effects

Central nervous system effects include ataxia,

drowsiness, vertigo and rarely coma. CNS stimulation may be
observed. Restlessness, increased muscle tone with body
rigidity have been reported. With extremely large ingestions
respiratory depression can occur. Gastrointestinal effects
include nausea, vomiting, constipation and dry mouth. Urinary
retention may be seen. Dextromethorphan abuse has been
described and produces euphoria, CNS stimulation, visual
and/or auditory hallucinations. There does not appear to be
any evidence of dependence of the morphine type.
The possibility of bromide poisoning should be considered in
the long term abuser.

2.3 Diagnosis

Diagnosis of dextromethorphan toxicity is primarily

based on the history of an ingestion of dextromethorphan or
dextromethorphan containing products. The presence of
dextromethorphan may be confirmed by qualitative
determination of the drug in urine.

2.4 First aid measures and management principles

Assess and support airway, respiration and

cardiovascular function if needed. Gastric decontamination is
recommended for recent ingestions of more than 10 mg/kg.
Seizures and/or CNS depression have occurred within 30
minutes of ingesting dextromethorphan.

ACTIVATED CHARCOAL/CATHARTIC.
Activated charcoal may be given alone or with a cathartic
such as sorbitol or magnesium citrate even though at this
time there is no data concerning the adsorption or clinical
efficacy of activated charcoal in the treatment of
dextromethorphan ingestions.

GASTRIC LAVAGE followed by activated charcoal may be

indicated for the treatment of recent large ingestions, or in
patients who are comatose or at risk of convulsing. NALOXONE
may be of benefit to reverse the respiratory and CNS effects
of dextromethorphan although its efficacy is yet to be
 adequately determined.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Dextromethorphan is a synthetic compound.

Dextromethorphan has been abused and is claimed to be habit
forming but has not been reported to produce physical
dependence (Ellenhorn & Barceloux 1988). It is not a
substitute for opiates in dependent individuals.

3.2 Chemical structure

Chemical name:
Dextromethorphan is 3 Methoxy-17-methylmorphinan monohydrate,
which is the d isomer of levophenol, a codeine analogue and
opioid analgesic.

Molecular formula: (Dextromethorphan Hydrobromide):

C18H25NO.HBr.H2O

Molecular weight 370.3

3.3 Physical properties

3.3.1 Colour

White

3.3.2 State/form

Solid-crystals
Solid-powder

3.3.3 Description

Odourless verging on a faint odour. Solubility

in water 1.5 g/100 mL at 25 C.
Soluble 1 in 10 of ethanol.
Practically insoluble in ether.
Freely soluble in chloroform.
pH of a 1% aqueous solution 5.2 to 6.5 (Budavari,
1996).

3.4 Other characteristics

3.4.1 Shelf-life of the substance

No information available.

3.4.2 Storage conditions

Powder should be preserved in air-tight

containers and solutions stored in light-resistant
containers (USP National Formulary).

Lozenges: store between 15 and 30 degrees C in well

closed containers.
 Syrup USP: Store between 15 and 30 degrees C in light,
resistant container, protected from freezing.

4. USES

4.1 Indications

4.1.1 Indications

Cough/cold preparation
Antitussive (not with expectorant);
cough/cold
Opioid;
antitussive

4.1.2 Description

Antitussive.

4.2 Therapeutic dosages

4.2.1 Adults

Oral doses of 10 to 20 mg every four hours or

30 mg every 6 to 8 hours not to exceed 120 mg
daily.

Long-acting preparations: 60 mg twice a day.

4.2.1 Children

Children aged 6 to 12 years may be given 5 to

10 mg every 4 hours or 15 mg every six to eight hours,
not to exceed 60 mg daily.

Children aged 2 to 6 years 2.5 to 5.0 mg every 4 hours

or 7.5 mg every 6 to 8 hours not to exceed 30 mg
daily.
The recommended dose in a child is 1 mg/kg/day to 2
mg/kg/day given in three to four divided doses (Benitz
& Tatro, 1988).
Dextromethorphan is not generally recommended in
children less than two years of age unless under
medical supervision (USPC, 1991).

Long-acting preparations: children aged 6 to 12 years

30 mg twice a day and children aged 2 to 6 years 15 mg
twice a day (AHFS, 1992).

4.3 Contraindications

Dextromethorphan should not be administered in patients

taking selective serotonin reuptake inhibitors (eg
fluoxetine, paroxetine) (Skop et al., 1994) and monoamine

oxidase inhibitors (Rivers & Horner, 1970). This may produce

a life threatening serotonergic syndrome which consists of:
restlessness, sweating, hypertension, hyperthermia, tremor,
myoclonus and seizures.
 Dextromethorphan may be associated with histamine release and
should not be used in atopic children. Dextromethorphan
should not be taken for persistent or chronic cough (e.g.
with smoking, emphysema, asthma) or when coughing is
accompanied by excessive secretions, unless directed by a
physician (AHFS, 1992).
Alcohol and CNS depressants should be avoided with
dextromethorphan.

5. ROUTES OF EXPOSURE

5.1 Oral

Dextromethorphan is usually taken orally.

It has been abused orally.

5.2 Inhalation

Dextromethorphan has been sniffed in the abuse setting.

5.3 Dermal

No data available

5.4 Eye

No data available

5.5 Parental

No data available

5.6 Others

No data available

6. KINETICS

6.1 Absorption by route of exposure

Dextromethorphan is well absorbed from the

gastrointestinal tract with maximum serum level occurring at
2.5 hours (Barnhart et al., 1979). Peak concentration of the
major metabolite dextrorphan) was 1.6 to 1.7 hours (Silvasti
et al., 1987). Onset of effect is rapid, often beginning 15
to 30 minutes after oral ingestion (Pender & Parks, 1991).

Peak levels for sustained release products generally occur

about 6 hours after ingestion (Amsel, 1981) although
absorption may be erratic.

6.2 Distribution by route of exposure

There is no information about the volume of distribution

in humans. In dogs, the volume of distribution is reported to
range from 5.0 to 6.4 L/Kg (Baselt & Cravey, 1989).

6.3 Biological half-life by route of exposure

The half life of the parent compound is approximately 2

 to 4 hours in people with normal metabolism.

6.4 Metabolism

There is a clear first pass metabolism and it is

generally assumed that the therapeutic activity is primarily
due to its active metabolite, dextrophan (Silvasti et al.,
1987; Baselt & Cravey, 1982).
Genetic polymorphism has profound effects on its metabolism
(Hildebrand et al 1989). Dextromethorphan undergoes
polymorphic metabolism depending on variation in cytochrome
P-450 enzyme phenotype. The specific cytochrome P-450 enzyme
is P450 2D6(CYP2D6) (Schadel et al., 1995).
Fast metabolizers constitute about 84% of the population.
After a 30 mg dose plasma levels are less than 5 ng/mL four
hours postingestion (Woodworth et al., 1987). Intermediate
metabolizers constitute about 6.8% of the population. After
an oral dose of 30 mg plasma levels are 10 to 20 ng/mL at 4
hours and less than 5 ng/mL at 24 hours postingestion
(Woodworth et al., 1987). Poor metabolizers constitute 5% to
10% of the Caucasian population. The ratio of metabolite to
parent drug in 8 hour urine sample is less than 10 to 1 after
a 15 mg dose (Hildebrand et al., 1989). After an oral dose
of 30 mg plasma levels are greater than 10 ng/mL at 4 hours
and greater than 5 ng/mL at 24 hours (Woodworth et al.,
1987).
It is metabolized in the liver by extensive metabolizers to
dextrorphan. Dextrorphan is itself an active antitussive
compound (Baselt & Cravey, 1982). Only small amounts are
formed in poor metabolizers (Kupfer, 1986). Less than 15% of
the dose form minor metabolites including D-methoxymorphinane
and D-hydroxmorphinane (Kupfer, 1986).

6.5 Elimination by route of exposure

Dextromethorphan and its metabolites are excreted via

the kidney. Depending on the metabolism phenotype up to 11%
may be excreted unchanged or up to 100% as demethylated

conjugated morphinan compounds (Hildebrand, 1989). In the

first 24 hours after dosing, less than 0.1% is eliminated in
the faeces (Baselt & Cravey, 1989).

7. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

The toxicodynamic actions of dextromethorphan

are not completely defined. Dextromethorphan enhances
serotonin activity by inhibiting the reuptake of
serotonin (Kramei et al., 1992; Bem & Peck, 1992)
Specific non-opioid dextromethorphan binding sites are
present in the central nervous system (CNS) which
mediate the antitussive effects, separate from codeine
and other opioids (Hardman et al., 1996).
Dextromethorphan and dextrorphan both affect the NMDA
receptor (Carpenter et al., 1988; Reynolds, 1993).

7.1.2 Pharmacodynamics
 The antitussive effects of dextromethorphan and
the metabolite dextrorphan are secondary to binding in
the CNS at non-opioid receptors. Dextromethorphan does
not have analgesic or addictive properties, although
abuse and dependence have been described(Hardman et
al, 1996). One of the major metabolites, dextrorphan
has cough suppressant activity.

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

Coma was reported in an adult who

ingested 720 mg over 36 hours (Schneider,
1991). Rated as lethal at oral doses of 50
to 500 mg/kg (Gosselin, 1981).
Death has been reported after overdose in two
cases but quantity was uncertain (Rammer et
al., 1988).
Long-acting products: adults have tolerated
up to 960 mg/day with minor adverse effects
(Walker and Hunt, 1989).
Abuse: Has been used for abuse. Orally in
doses of 300 mg to 1800 mg in adults it can
cause intoxication with hyperexcitability,
visual and/or auditory hallucinations (Dodds
& Revai, 1967; Orrell & Campbell, 1986). It

has been reported that sniffing 0.25 g two to

three times a day over 2 to 3 months produced
euphoria and restlessness for up to 2 hours
followed by dizziness, nausea, depression and
fatigue (Fleming, 1986).
Chronic effects: It should be noted that
dextromethorphan is marketed as the
hydrobromide and can produce bromide toxicity
with chronic use.
Dextromethorphan has been abused at doses of
2160 to 2880 mg daily for up to five years
producing hallucinations, euphoria,
disorientation, insomnia and nausea.
Withdrawal produced dysphoria and craving for
the drug (Wolf and Caravati 1995).

7.2.1.2 Children

Toxicity may be variable in

children. Ingestion of as little as 17 mg/Kg
has resulted in signs and symptoms of
toxicity. At this dosage range some children
have shown no symptoms whilst others have
shown ataxia, stupor, transient fever,
lethargy or nystagmus (Versie et al., 1962;
Katona & Wason, 1986). Seizures have been
reported.
Long-acting products may be more toxic in
children, producing prolonged CNS depression
at 10 mg/kg (Devlin, 1985).
 7.2.3 Animal data

LD 50 in mice 165 mg/kg

LD 50 in rats 350 mg/kg (Gosselin, 1981)
LD 50 in mice 39 mg/Kg (Benson, 1953)

7.2.3 Relevant in-vitro data

No data available

7.3 Carcinogenicity:

No data available

7.4 Teratogenicity

There was no association between dextromethorphan and

malformations (Heinonen et al., 1977). Dextromethorphan is
generally considered safe to use during pregnancy (Berkowitz
et al., 1981).

7.5 Mutagenicity

No data available

7.6 Interactions

Concomitant use of monoamine oxidase inhibitors has

caused toxicity leading to death (Rivers & Horner, 1970;
Hansten, 1989).
Not to be taken with serotonin re-uptake inhibitors
(Skop et al., 1994)
Alcohol and drugs causing CNS depression should be avoided
when taking dextromethorphan.

7.7 Main adverse effects

Adverse effects are very uncommon with therapeutic doses.

Infrequent adverse effects include dizziness, drowsiness,
nausea, vomiting and stomach ache (USPC, 1989).

8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

 8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

"Basic analyses"
"Dedicated analyses"
"Optional analyses"

8.3.1.2 Urine

"Basic analyses"
"Dedicated analyses"
 "Optional analyses"

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

"Basic analyses"
"Dedicated analyses"
"Optional analyses"

8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their

interpretation

8.5 Overall interpretation of all toxicological analyses and

toxicological investigations

Monitoring dextromethorphan serum levels is not useful

clinically in the overdose situation because a correlation
between levels and clinical effects has yet to be determined
(Walker & Hunt, 1989). However plasma levels may be measured
to determine metabolizer phenotype. The presence of
dextromethorphan may be confirmed by qualitative
determination of the drug in urine or serum.

Plasma dextromethorphan concentrations have not been

correlated with clinical toxicity. Monitoring concentrations
of dextromethorphan, therefore, would not be useful
(Ellenhorn & Barceloux, 1983; Walker & Hunt, 1989) Plasma
dextromethorphan concentrations are used to determine hepatic
metabolism phenotype.

Sample collection
If required arterial blood for blood gasses.

Biomedical analysis
Arterial blood gasses to determine the degree of ventilatory
depression.

Toxicological analysis
The presence of dextromethorphan may be confirmed by
qualitative determination of the drug in urine or blood, see
Section 8. Plasma levels may be used to determine metabolizer
phenotype.

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Oral ingestion is the most common route of

acute poisoning. The most common clinical effects
involve the central nervous system (CNS).
Neurologic: drowsiness, lethargy, ataxia, nystagmus,
CNS stimulation, vertigo, coma, psychosis and
hyperreflexia (Cetaruk & Aaron, 1995; Wolfe &
 Caravati, 1995; Devlin et al., 1985; Shaul et al.,
1977; Schneider et al., 1991).
Seizures have been reported within 30 minutes of
ingestion.
Respiration: Respiratory depression has been noted
(Katona and Wason, 1986; Shaul et al., 1977).
Cardiovascular: Long-acting preparations may cause
tachycardia (Devlin et al., 1985).
Gastrointestinal: Nausea, vomiting (Versie at al.,
1962) constipation and dry mouth may occur.
Eye: Mydriasis, miosis and nystagmus may be seen.
Genitourinary: Retention of urine may be seen.
Skin: Urticaria was noted after ingestion of a long-
acting preparation in a child (Devlin et al.,
1985).
Long-acting preparations: With 10 mg/Kg or more taken
orally ataxia, lethargy, nystagmus and tachycardia
have been reported.

9.1.2 Inhalation

No data available.

9.1.3 Skin exposure

No data available.

9.1.4 Eye contact

No data available.

9.1.5 Parenteral exposure.

No data available

9.1.6 Other

No data available.

9.2 Chronic Poisoning

9.2.1 Ingestion

The daily abuse of oral dextromethorphan has

been described as causing hallucinations (visual and
auditory), dyspnea, floating and flying sensations,
and increased perception (Wolfe & Caravati, 1995).
Central nervous system (CNS) stimulation has also been
reported (Dodds & Revai, 1967; Orrell & Campbell,
1986). When the drug was stopped no withdrawal
symptoms were noted, however, craving for
dextromethorphan continued.

It should be noted that dextromethorphan may be

marketed as the hydrobromide salt and can produce
bromide toxicity with chronic use.

9.2.2 Inhalation
 No data available.

9.2.3 Skin contact

No data available

9.2.4 Eye contact

No data available

9.2.5 Parental exposure

No data available

9.2.6 Other

It has been reported that sniffing 0.25 g two

to three times a day over 2 to 3 months produced
euphoria and restlessness for up to 2 hours followed
by dizziness, nausea, depression and fatigue (Fleming,
1986). This patient did not demonstrate withdrawal
symptoms on cessation but did complain of continuing
craving for dextromethorphan.

9.3 Course, prognosis, cause of death:

Following overdose of short acting dextromethorphan

patients may become clumsy, hyperkinetic and ataxic a few
hours after the ingestion. There may be vomiting, drowsiness,
dizziness, blurred vision, nystagmus, and visual and auditory
hallucinations. Later unsteadiness and unstable gait are
observed with truncal ataxia. In severe cases, shallow
respirations, urinary retention, stupor, or coma may
supervene, especially if high doses of alcohol have been
ingested. The prognosis for recovery is good (Ellenhorn &
Barceloux, 1988).
Following ingestion of long acting dextromethorphan symptoms
of over use in children include urticaria, restlessness,
lethargy, nystagmus, ataxia, tachycardia and blood pressure
elevation. This may require admission to an intensive care
unit. Long acting preparations may produce a higher rate of
toxic symptoms in children than short-acting
dextromethorphan. There does not appear to be a correlation
between the amount of long-acting dextromethorphan ingested
and the severity of symptoms (Ellenhorn & Barceloux,
1988).

9.4 Systematic description of clinical effects:

9.4.1 Cardiovascular

Long-acting preparations may cause tachycardia

(Devlin et al., 1985). No reports of chronic effects
were found in the literature.

9.4.2 Respiratory

Respiratory depression has been noted following

large doses (Katona and Wason, 1986; Shaul et al.,
1977). No reports of chronic effects were found in the
literature.
9.4.3 Neurologic

9.4.3.1 Central nervous system (CNS)

In acute overdose ataxia, drowsiness

(Devlin et al., 1985; Shaul et al., 1977)
vertigo and coma (Schneider et al.,
1991).
CNS stimulation may be noted. Restlessness,
increased muscle tone with body rigidity have
been reported (Benson et al., 1953).
Seizures have been reported within 30 minutes
of ingestion.
In the abuse situation it can cause CNS
stimulation and visual and/or auditory
hallucinations (Dodds & Revai, 1967; Orrell &
Campbell, 1986). It has been reported that
sniffing 0.25 g two to three times a day over
2 to 3 months produced euphoria and
restlessness for up to 2 hours followed by
dizziness, nausea, depression and fatigue
(Fleming, 1986).
Cognitive deterioration resulting from
prolonged abuse has been reported (Hinsberger
et al., 1994).

9.4.3.2 Peripheral nervous system

No data available

9.4.3.3 Autonomic

No data available

9.4.3.4 Skeletal and smooth muscle

No data available

9.4.4 Gastrointestinal

After acute overdose nausea, vomiting (Versie

et al., 1962), constipation and dry mouth may occur.
No chronic effects were found.

9.4.5 Hepatic

No data available.

9.4.6 Urinary

9.4.6.1 Renal

No data available.

9.4.6.2 Others

Urinary retention has been seen.

9.4.7 Endocrine and reproductive systems

 No data available.

9.4.8 Dermatologic

Urticaria was reported in a child after acute

overdose of a long-acting preparation (Devlin et
al.,1985).

9.4.9 Eye, ear, throat: local effects

After acute overdose mydriasis or miosis

(Schneider et al., 1991) and nystagmus (Katona &
Wason, 1986; Devlin et al., 1985) may be noted.
Nystagmus may persist from 7 to 8 hours with long-
acting preparations (Devlin et al., 1985). No chronic
effects were found.

9.4.10 Hematological

No data available.

9.4.11 Immunologic

No data available.

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

No data available.

9.4.12.2 Fluid and electrolyte disturbances

No data available.

9.4.12.3 Others

No data available.

9.4.13 Allergic reactions

A cutaneous lesion consistent with a fixed-

drug reaction was reported after ingestion over 2 to 3
weeks in therapeutic doses (Stubb & Reitamo,
1990).

9.4.14 Other clinical effects

No data available.

9.4.15 Special risks

Pregnancy:
Ingesting dextromethorphan during the first trimester
demonstrated no association between the drug and
malformations (Heinonen, 1989). Dextromethorphan is
generally considered safe during pregnancy (Berkowitz,
1981).

Breast feeding:
No data available.
 Enzyme deficiencies:
No data available.

Serotonergic Syndrome (see 4.3)

9.5 Others

Dextromethorphan has been used for abuse however there

were no withdrawal symptoms on cessation but there was a
continued craving for the drug.

10. MANAGEMENT

10.1 General principles

Assess and support airway, ventilation, and

circulation. Naloxone may antagonize respiratory depression.
Gastric decontamination is recommended for recent ingestions
of more than 10 mg/kg of dextromethorphan. Patients with
respiratory depression may require admission to an intensive
care unit. Others can be observed in the emergency facility
for 4 to 6 hours and then discharged. A small number of
patients with minor symptoms (such as ataxia or restlessness)

may be sent home under careful supervision. (Ellenhorn &

Barceloux, 1988) Children who have ingested a long-acting
preparation should be hospitalized.

10.2 Life supportive procedures and symptomatic treatment

Assess and support airway, ventilation, and

circulation. Naloxone may antagonize respiratory depression.
Patients with respiratory depression may require admission to
an intensive care unit. Other patients can be observed in the
emergency facility for 4 to 6 hours and then discharged.
Patients with minor symptoms (such as ataxia or restlessness)
may be sent home under supervision. (Ellenhorn & Barceloux,
1988) Children who have ingested a long-acting preparation
should be hospitalized for 24 observation.

10.3 Decontamination

Gastric decontamination is recommended for a recent

ingestion of more than 10 mg/kg. Seizures and/or central
nervous system (CNS) depression have occurred within 30
minutes of ingesting dextromethorphan.

GASTRIC LAVAGE followed by activated charcoal may be used

within 1 to 2 hours of ingestion and may be indicated in
recent large ingestions or in patients who are comatose or at
risk of convulsing. Gastric lavage in a comatose patient
should be preceded by intubation.

ACTIVATED CHARCOAL/CATHARTIC. Activated charcoal may be given

alone or with a cathartic such as sorbitol or magnesium
citrate, even though at this time there is no data concerning
the adsorption of dextromethorphan by charcoal.
Because there is no data concerning the adsorption of
dextromethorphan by charcoal if routine gastric emptying is
 omitted the patient may receive inadequate treatment if
charcoal alone is used. A reasonable approach might be to
consider gastric lavage in patients ingesting more than 10
mg/Kg of dextromethorphan, those with clinical features of
overdose, or those where the time and quantity of ingestion
is unknown.
The optimum dose of activated charcoal has not been
established, but as a guide 1 g to 2 g/kg of activated
charcoal is recommended, particularly in infants. The adult
dose may therefore be 30 g to 100 g and the dose in children
15 g to 30 g. If a patient vomits the dose it may be
repeated. Do not use charcoal tablets or universal antidote
as a substitute for activated charcoal.

WHOLE BOWEL LAVAGE. If a long-acting dextromethorphan

preparation has been ingested whole bowel lavage may be
considered.

CATHARTIC. A saline cathartic or sorbitol may be administered

with the first dose of activated charcoal or it may be given
separately. Although there is little evidence to support the
use of cathartics (McNamara, 1988; Stewart, 1983) their use
would seem logical to shorten transit time and avoid the
constipation caused by charcoal. Repeated doses of cathartics
is not recommended especially in children. If the dose is
repeated this should be done with extreme caution.

10.4 Enhancd elimination

There is no information currently available on the

effectiveness of forced diuresis, alkalinization,
acidification, haemoperfusion, or dialysis for the treatment
of dextromethorphan overdose. The use of these methods of
potentially increasing drug elimination are not recommended
for the treatment of dextromethorphan poisonings.

10.5 Antidote

10.5.1 Adults

NALOXONE may be of benefit to reverse the

respiratory and CNS effects of dextromethorphan.
Although there have been reports concerning the
response to naloxone (Katona & Wason, 1986; Shaul et
al, 1977), in most cases improvement in, and
resolution of, neurologic symptoms occurred over three
to eight hours after naloxone administration, and this
may represent the natural course of dextromethorphan
toxicity rather than a response to naloxone
(Pender,1991). There is currently no evidence which
suggests significant efficacy associated with naloxone
administration (Wolfe & Caravati, 1995).

10.5.2 Children

No data available.

10.6 Management discussion

Many references still recommend the use of Ipecac to

 induce emesis in dextromethorphan overdose. However there
have been reports of seizures following overdose and thus
this monograph does not advocate the induction of emesis.
Also, most dextromethorphan ingestions are the liquid
formulation which are most likely absorbed quickly. Emesis
may thus be ineffective and contraindicated due to rapid CNS
depression, and may delay the administration of activated
charcoal. Charcoal has been recommended without reports
proving or disproving its efficacy. However it is commonly

used for dextromethorphan overdose and is likely to be

effective and safe. Research on this matter would determine
if this is so.
Further information is required before naloxone can be
accepted as an antidote for dextromethorphan toxicity. The
cases presented to date do not support reversal of
dextromethorphan toxicity by naloxone. This is supported by
the pharmacology of dextromethorphan (Wolfe & Caravati, 1995;
Hardman et al., 1996).

11. ILLUSTRATIVE CASES

11.1 Case report from the literature

Case 1
A 41 year old female ingested 720 mg of dextromethorphan over
a 36 hour period. She presented lethargic and responding only
to painful stimuli. Respirations were shallow and sporadic,
pupils pinpoint and minimally reactive to light. Because of
her decreased level of consciousness and miosis, 1 mg of
naloxone intravenous (IV) was administered with some
improvement of consciousness. An additional 2 mg naloxone was
administered with further improvement and ultimate return to
normal mental status. Serum samples showed dextromethorphan
level of 100 ng/mL (Schneider et al., 1991).

Case 2
A report is given of two young adults who died after overdose
of dextromethorphan. How much was taken is uncertain (Rammer
at al 1988).

Case 3
A 23 year old male presented with psychosis after an acute
overdose of dextromethorphan. He demonstrated
hyperexcitability and hallucinations which he compared to his
experience with LSD.(Dodds & Revai, 1967).

Case 4
A 26 year old female took approximately 60ml of a cough
medicine containing dextromethorphan about six hours after
ingesting 30 mg of phenelzine (Nardil). Thirty minutes later
she felt nauseated, dizzy and collapsed. Within one hour she
was brought to the hospital unconscious with rigid
extremities and fixed, dilated pupils. She was severely
hypotensive with a systolic blood pressure that did not rise
above 70 mm of mercury and a temperature that ranged from
42°C to 42.2°C. Despite vasopressors, anti-arrhythmics and
adrenaline, approximately four hours after arriving at the
hospital she had a cardiac arrest and died (Rivers & Horner,
1970).
 Case 5
An 11 week old infant was given inappropriate doses of a
dextromethorphan/guaifenesin mixture over a period of 24
hours. Doses were more frequent and larger than those
recommended, but the exact amount was unable to be
determined. The infant was alert and noted to be
hyperexcitable with intermittent periods of extremity
stiffening and cutaneous mottling. He was given naloxone 0.1
mg/Kg intravenously. Within 30 minutes of the naloxone he
was noted to be calmer and within two hours all signs had
resolved (Pender & Parks, 1991).

Case 6
A 3 year old boy ingested an unknown amount of
dextromethorphan and presented with lethargy, somnolence,
ataxia and nystagmus. Vital signs were normal, and
respirations adequate. He awoke after he was given
intravenous naloxone (0.4 mg). Twenty five grams of charcoal
was given and during the next three hours his condition
steadily improved and he was discharged (Katona & Wason,
1986).

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

Dextromethorphan must not be used with monoamine

oxidase inhibitors (MAOIs) since death has occurred.
Dextromethorphan should not be used with other CNS
depressants.
Dextromethorphan should not be used with serotonin re-uptake
inhibitors.
Care should be taken that dextromethorphan is not given in
overdose, especially to children.
Medicines containing dextromethorphan are best store in child
resistant containers.
Dextromethorphan has been abused and care should be taken not
to supply it to susceptible individuals.

12.2 Other

No data available.

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14. AUTHOR(S), REVIEWER(S) DATES (INCLUDING EACH UPDATING), COMPLETE

ADDRESSES

Author: Jim Magarey

Poisons Information Centre
Royal Childrens Hospital
Flemington Rd, Parkville
Melbourne, Victoria
AUSTRALIA 3052

Telephone 03 93455680 Fax 03 93491261

Date of writing: 1992

Updated by same author August 1996

Peer review: Dr. A.N.P. van Heijst, August 1996

Dr. W. Watson August, 1996

PIM review group: Intox 9, September, 1996, Cardif, Wales

Editor: Dr M. Ruse (August, 1997)

See Also:
Toxicological Abbreviations