Boldolaxine (Australia); Canthacur-PS (Canda); Cantharone-
Plus (USA, Canada); Opobyl (UK); posalfilin (UK); Salicylin-P
(Australia); Verban (Canda); Verrex (USA); Verrusol (USA);
Wartkil (Australia); Wart-off (Australia)

1.6 Main manufacturers/main importers

Pharmascience (Canada); C. & M. (USA); Cuxson (UK);
Conpharm (Sweden); Norgine (UK).

2. SUMMARY

2.1 Main risk and target organs

Podophyllum resin's major active constituent,
podophyllotoxin, is a lipid-soluble compound that readily
crosses cell membranes. Podophyllotoxin and its derivatives
are potent cytotoxic agents that inhibit cell mitosis and
deoxyribonucleic acid (DNA) synthesis in a manner similar to
that of colchicine. Cell division is arrested and other
cellular processes are impaired, gradually resulting in the
disruption of cells and destruction of the tissue. Topical
podophyllum is easily absorbed systemically and can cross the
placenta. Either local application or oral ingestion may
produce multi-system toxic effects.

2.2 Summary of clinical effects

Features of systemic toxicity include nausea and
vomiting (which may be persistent), tachypnea, fever, stupor,
coma, tachycardia, hypotension, paralytic ileus, oliguria,
renal failure, leucocytosis, leucopenia, peripheral
neuropathy and death.

2.3 Diagnosis

There are no specific analyses for podophyllum.
Clinical diagnosis is difficult due to multiple organ
toxicity. Measurement of HB-Ht-RBC-WBC-platelets.

2.4 First aid measures and management principles

Exposed eyes should be irrigated with copious amounts of
water. Remove contaminated clothing. Decontaminate skin
with soap and copious amounts of water. vomiting is
frequently the first clinical sign to appear and therefore
induced vomiting is seldom required. For recent ingestion,
perform gastric lavage and/or administer activated
charcoal.

No effective treatment is known and only supportive therapy
may be offered whether the exposure was through oral
ingestion or topical application. Rapid transfer to hospital
if symptomatic.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Dried resin from the roots and rhizomes of Podophyllum
peltatum (Mandrake or May apple plant) the North American
variety; active ingredients are lignans including
podophyllotoxins (20%), alpha-peltatin (10%) and beta-
peltatin (5%).

3.2 Chemical structure

Podophyllotoxin:
[5R-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-5,8,8a,9-
Tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)
furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one

The Podophyllum resin extract contains at least 16 active
compounds including podophyllotoxin, picro-podophyllin, alpha
and beta-peltatins and quercetin.

3.3 Physical properties

3.3.1 Colour

Light brown to greenish yellow

3.3.2 State/form

Solid-powder

3.3.3 Description

Amorphous powder, varying in colour from light
brown to greenish yellow, turning darker when
subjected to a temperature exceeding 25°C or when
exposed to light. When dissolved in alcohol, it gives
an acid reaction to moistened litmus paper. It is
soluble in alcohol with slight opalescence. It is
partially soluble in ether and chloroform. It is lipid
soluble.

Podophyllotoxin:

Melting point: 114-118°C (effervescence).
After drying melting point: 183.3-184.0°C
Solubility in water at 23 deg: 120 mg/L.
Solubility in alcohol, chloroform, acetone, warm
benzene, glacial acetic acid.
Budavari (1996).

3.4 Other characteristics

3.4.1 Shelf-life of the substance

Information not found.

Old, discoloured, dried or gritty preparations of
podophyllum should not be used (USPDI, 1990).

3.4.2 Storage Conditions

Commercial podophyllum resin solutions may
contain from 5 to 25% podophyllum resin
concentrations. It has to be stored in a cool place,
in air-tight containers and protected from
light.

4. USES

4.1 Indications

4.1.1 Indications

Wart or corn preparation

4.1.2 Description

Podophyllum resin has an antimitotic action and
is used principally as a topical treatment for ano-
genital warts (condylomata acuminata). Podophyllum
resin has been used on external genital, perianal and
intra-meatal warts, but should not be used on cervical
or urethral warts. Care must be taken to avoid
application to health tissue. Podophyllum resin is
also used in an ointment for plantar warts.

Podophyllum resin has been used as a laxative, but
when taken by mouth, it has a marked purging action
and it is highly irritant to the intestinal mucosa and
produces violent peristalsis. It has been superseded
by less toxic laxatives.

4.2 Therapeutic dosage

4.2.1 Adults

For the treatment of exophytic genital and anal
warts, the US Communicable Disease Center (CDC)
recommends that a 10-25% solution of podophyllum resin
in compound tincture of benzoin be used. The CDC
recommends that each treatment session be limited to
an area less than 10 cm² for genital or perianal

warts. In addition, CDC recommends that the total
volume of 10 to 25% solution be limited to less than
0.5 mL per treatment session. Alternatively, some
clinicians recommend that lower concentrations of the
drug (e.g. a 5% solution) be used for the treatment of
large (i.e. larger than 10 to 20 cm²). genital and
anal warts. The CDC recommends that the solution be
applied to the affected area and then washed off
within 1 to 4 hours for genital and perianal warts and
within 1 to 2 hours for accessible meatal warts. Some
clinicians prefer longer periods of application, but
this must be individualized after patient tolerance
and compliance have been established. Most clinicians
recommend that the duration of therapy not exceed 4 to
6 hours. Therapy may be repeated at weekly intervals
for up to 4 applications; if beneficial effect is not
evident (e.g. regression of warts) after 4
applications, alternate therapies should be used. For
vaginal warts, CDC recommends that each treatment
session be limited to an area less than 2 cm²;
therapy may be repeated at weekly intervals.

Within a few hours after application of the drug, the
lesions become blanched, and they become necrotic
within 24 to 48 hours. After about 72 hours, the
lesions begin to slough and gradually disappear
without scarring.

When used for the treatment of verruca vulgaris
(common warts), one manufacturer suggests that
following application of a solution containing 5%
podophyllum resin, the area be covered with a non-
porous, slightly elastic tape for up to 24 hours. The
wart is then removed with the tape or by curettage
after the tape has been removed. The manufacturer
suggests that the area be treated with a mild topical
anti-infective agent until completely healed
(A.H.F.S., 1990).

4.2.2 Children

See 4.2.1

4.3 Contraindications

- Pregnancy: topical podophyllum is absorbed
systemically and crosses the placental barrier. It has been
associated with the induction of congenital malformations in
humans (Cullis, 1962).

- Breast-feeding
- Pediatrics: No established indication to date
- Friable, bleeding or recently biopsied warts
- Intolerance to podophyllum

5. ROUTES OF EXPOSURE

5.1 Oral

Easily absorbed even if it induces nausea and
vomiting.

5.2 Inhalation

No specific data available but it would be easily
absorbed through mucous membranes

5.3 Dermal

It is absorbed systemically after topical application
especially if the skin surface is not intact.

5.4 Eye

Very well absorbed through mucous membranes

5.5 Parenteral

Should not be used for therapeutic purposes. No such
case is reported.

6. KINETICS

6.1 Absorption by route of exposure

Oral absorption

Podophyllum is very well and rapidly absorbed after
ingestion.

As an example, in the fatal case reported by Cassidy (1982),
the patient ingested between 10 and 11 g of a 25% podophyllum
solution in benzoin tincture in the physician's office. He
was immediately given syrup of Ipecac and vomited 45 minutes
after ingestion. He was also given activated charcoal and
magnesium citrate. He died 39 hours after ingestion despite
hemoperfusion.

Dermal absorption

There are several cases of systemic poisoning following
topical application of podophyllum in the literature. In
such cases, the onset of symptoms is delayed between two and
24 hours.

6.2 Distribution by route of exposure

No data available. Since podophyllumtoxin is water
soluble, a small volume of distribution may be predicted.
Furthermore, no rebound effects were observed after
hemoperfusion.

6.3 Biological half-life by route of exposure

No data available. The clinical effects in systemic
poisoning frequently last for several days.

6.4 Metabolism

No data available. In their case report, Heath et al.
(1982) analyzed podophyllumtoxin in the patient plasma
before, during and after hemoperfusion. A rapid fall in
plasm concentration of podophyllumtoxin occurred in the
period before hemoperfusion was started suggesting rapid
metabolism. The delay of onset of symptoms in several case
reports may suggest that the metabolized of podophyllumtoxin
are more toxic than podophyllumtoxin itself. These authors
were able to identify and measure such a metabolite during
hemoperfusion but several other possible metabolites were
found on analysis and removed by hemoperfusion.

6.5 Elimination and excretion

No data available.

7. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

Podophyllum resin is a potent spindle poison
that blocks mitosis metaphase in a manner similar to
colchicine. Human poisoning results from either
topical application or ingestion of the commercial
extract. Overexposure causes neurological,
gastrointestinal and haematological toxicity that
occasionally result in fatalities. Rarely, poisoning
results from consumption of unripe fruit or plant
parts and causes primarily diarrhoea. The ripe fruit
does not produce toxicity.

Podophyllum is a keratolytic agent with caustic and
cathartic actions.

Podophyllum is an antimitotic agent. It binds to
tubulin, the protein subunit of the spindle micro-
tubules, at the same site or greatly overlapping the
same site as colchicine. The antimitotic action of
podophyllumtoxin probably results from interference
with the movement of the chromosomes. The molecular
mechanism of mitosis blockade is the disruption of the
micro-tubules of the mitotic spindle via binding of
podophyllumtoxin to tubulin. Podophyllum is caustic
but its action differs from those of most caustics in
that its effect is neither direct nor immediate:
rather, the disruption of cells and erosion of tissue
occur slowly subsequent to arrest of cell division and
impairment of other cellular processes.

Podophyllumtoxin has an inhibitory effect similar to
that of vinblastine on the release of iodine from the
thyroid gland and catecholamine from the adrenal
medulla (A.H.F.S. 1990).

It is classified as a cell cycle-specific (CCS) agent
(Salmond and Sartorelli, 1987).

7.1.2 Pharmacodynamics

See section 7.1.1

7.2 Toxicity

7.2.1 Human toxicity

7.2.1.1 Adults

Most systemic poisoning cases
following topical application of podophyllum
involved women and some of these were fatal
(Ward, 1954; Fisher, 1981).

Serious systemic toxicity has occurred
following topical application of podophyllum
to large areas or in excessive amounts, or
when the medication was allowed to remain in
contact with the skin or mucous membranes for
a prolonged period of time.

The risk of systemic toxicity may be
increased when podophyllum is applied to
friable bleeding, or recently biopsied warts,

or when the medication is inadvertently
applied to normal skin or mucous membranes
surrounding the affected area.

Renal failure and hepatotoxicity (increased
serum concentrations of lactate dehydrogenase
(LDH), aspartate aminotransferase (AST; SGOT)
and alkaline phospase have occurred following
topical application or ingestion of
podophyllum.

Podophyllum can cause severe systemic
toxicity, which may result from topical
application and ingestion. The toxic effects
are usually reversible but in some instances,
they have been fatal. Death can occur with
ingestion of podophyllum in amounts as small
as 350 mg (Ellenhorn and Barceloux, 1988).

7.2.1.2 Children

Fever and convulsions seem to be
more frequent in children. Most reported
cases followed accidental ingestion.

7.2.2 Animal data

The toxicological properties of
podophyllumtoxin were reviewed by Jardine (1980).

LD50/LC50

1. LD50 (IV) Rat: 8.7 mg/kg
2. LD50 (IP) Rat: 15 mg/kg
3. LD50 (SC) Rat: 8 mg/kg
4. LD50 (IM) Rat: 3 mg/kg
5. LD50 (IP) Mouse: 30 mg/kg
6. LD50 (SC) Mouse: 24.6 mg/kg

7.3 Carcinogenicity

Podophyllum is a suspected human carcinogen (Dukes and
Beeley, 1987).

7.4 Teratogenicity

Podophyllum may be a teratogenic agent in humans. At
least two cases of possible teratogenic effects of
podophyllum have been described (Karol, 1980; Cullis, 1962;
Chamberlain et al., 1972).

7.5 Mutagenicity

Podophyllum is mutagenic in Lalmonella typhimurium
strain of bacteria.

7.6 Interactions

Other keratolytic agents may favour dermal absorption of
podophyllum.

7.7 Main adverse effects

The risk of systemic toxicity may be increased when
podophyllum is applied to friable, bleeding or recently
biopsied warts, or when the medication is inadvertently
applied to normal skin or mucous membranes surrounding the
affected area.

Adverse effects on the nervous system may occur following
topical application of podophyllum; these are usually delayed
in onset and prolonged in duration.

Cerebral toxicity (manifested by altered sensorium ranging
from mild confusion to coma) may occur following topical
application of podophyllum and continue for 7 to 10 days
during which the electorencephalogram (EEG) may show
generalized slowing.

The following side/adverse effects have been selected on the
basis of their potential clinical significance (presenting
signs and symptoms in parentheses where appropriate - not
necessarily inclusive).

Those indicating need for medical attention:

Skin rash or itching - allergic reaction to benzoin, which
may be present in some preparations.
Redness, burning or other irritation of affected area or
skin.
Abdominal pain
Nausea or vomiting
Diarrhoea, sometimes severe and prolonged
Clumsiness or unsteadiness
Confusion
Reduced reflexes
Excitement, irritability or nervousness
Hallucinations
Muscle weakness
Leucopenia (sore throat and fever)
Thrombocytopenia (unusual bleeding or bruising)

Delayed symptoms of systemic toxicity

Autonomic neuropathy (difficult or painful urination;
dizziness or lightheadedness, especially when getting from a
lying or sitting position; fast heartbeat).
Difficulty in breathing.
Drowsiness.
Paralytic ileus (constipation, nausea and vomiting; pain in
upper abdomen or stomach, mild dull and continuing)
Peripheral neuropathy (numbness, tingling, pain or weakness
in hands or feet).
If peripheral neuropathy occurs, it usually appears about 2
weeks after podophyllum application, may worsen progressively
for up to 3 months and may persist for up to 9 months or
longer.
Seizures.
USPDI (1990).

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

Leucocytosis followed by leucopenia
and thrombocytopenia are common and therefore
should be closely monitored until full
recovery.

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

Renal and hepatic function must be monitored

Electrolytes and calcium should be monitored especially if
severe diarrhoea or paralytic ileus occurs. Creatinine
phosphokinase and myoglobin should be monitored to detect
rhabdomyolysis.

Chest X-Ray
EEG
EMG and peripheral nerve conduction in late phase of the
clinical course.
ECG especially to detect conduction defects and cardiac
arrhythmias.

8.5 Overall interpretation of all toxicological analyses and
toxicological investigations

Since there are no specific toxicological analyses
available and the fact that podophyllumtoxin is a non-
specific cell poison, it is essential to monitor the various
biochemical and physiological parameters in order to detect
early complications and rapidly correct any significant
disturbances.

Sample collection
Blood and urine for haematological and biochemical analysis.
Blood may be collected for later toxicological analysis
especially for medico-legal reasons.

Other investigations
EEG, EMG with nerve conduction measurements and psychometric
testing may be useful in the later phase of poisoning.

8.6 References

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Ingestion may cause: nausea and vomiting, which
may be severe and persistent and occur rapidly after
ingestion. Abdominal pain, ileus (paralytic),
lethargy, coma, tachypnoea, respiratory failure,
tachycardia, hypotension, cardiac arrhythmia,
cardiovascular collapse, oliguria, renal failure,
fever, metabolic acidosis, leucocytosis, leucopenia,
thrombocytopenia, pancytopenia, peripheral neuropathy,
death.

9.1.2 Inhalation

Not applicable

9.1.3 Skin exposure

In contrast to ingestion, there will be a delay
of up to 24 hours before appearance of signs. These
are similar to those occurring after ingestion (see
9.1.1).

9.1.4 Eye contact

Podophyllum may be absorbed through this route
but severe systemic poisoning seldom occurs. Local
irritation and lesions of cornea and conjunctiva may
occur.

9.1.5 Parenteral exposure

Not reported to date.

9.1.6 Other

None

9.2 Chronic poisoning by

9.2.1 Ingestion

This type of poisoning occurred when
podophyllum was used as a cathartic or slimming aid.
It has not been reported in recent years.

In such cases, poisoning was sometimes difficult to
diagnose since the clinical picture did not resemble
that of acute poisoning.

The first clinical signs are either haematological,
gastro-intestinal or peripheral neuropathy.

9.2.2 Inhalation

Not applicable

9.2.3 Skin exposure

Repeated local treatment of warts or condyloma
may produce systemic poisoning or local lesions of the
skin (erosion, pain, bleeding, infection).

9.2.4 Eye contact

Chronic poisoning not reported.

9.2.5 Parenteral exposure

Not reported

9.2.6 Other

Not applicable

9.3 Course, prognosis, cause of death

The precise course following overdose is difficult to
predict since we seldom have good indicators of the absorbed
dose. It should be noted that some severely intoxicated
patients (especially children) have survived while others
either died or developed permanent sequelae (peripheral
neuropathy) with lower doses.

Death generally results from the cerebral; cardiovascular;
renal; or haematological complications.

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

Tachycardia, cardiac, arrhythmias, hypotension
and cardiovascular collapse.

9.4.2 Respiratory

Tachypnoea
Respiratory failure
Pneumonitis (resembling chemical pneumonitis)
Pulmonary oedema (rarely)

9.4.3 Neurological

9.4.3.1 Central Nervous System (CNS)

- Confusion
- Lethargy
- Coma
- Convulsions

9.4.3.2 Peripheral nervous system

Peripheral neuropathy which develops
over several days and may take weeks or
months to regress. There may be permanent
sequelae.

9.4.3.3 Autonomic nervous system

- Paralytic ileus

9.4.3.4 Skeletal and smooth muscle

Rhabdomyolysis may occur with
myoglobinuria. This may aggravate the renal
failure. Phosphokinase (CPK) should be
monitored.

9.4.4 Gastrointestinal

- Nausea and vomiting which may be persistent
and severe;
- abdominal pain;
- paralytic ileus;
- diarrhoea which may produce water and electrolyte
imbalance.

9.4.5 Hepatic

Elevation of hepatic enzymes: (ast; GOT), (alt;
GPT), alkaline phosphatase.

9.4.6 Urinary

9.4.6.1 Renal

- Oliguria
- Renal insufficiency

9.4.6.2 Other

- Cystitis
- Painful micturition

9.4.7 Encodrine and reproductive system

- Fetal death
- Abortion
- Premature labour
- Fetal malformations

9.4.8 Dermatologic

- Pruritus around the treated sites especially
if the skin has not been protected by petroleum jelly
- Irritation
- Urticaria
- Skin necrosis
- Bleeding
- Scarring of tissue, especially of anogenital regions
- Paraphimosis that may require circumcision
- Pseudo-epitheliomatosis hyperplasia

9.4.9 Eye, ear, nose, throat: local effects

- Irritation
- Skin or mucous membrane
- Necrosis
- Scarring of tissues
- Bleeding
- Corneal erosion

9.4.10 Haematological

- Leucocytosis followed by leucopenia
- Anaemia
- Thrombocytopenia
- Pancytopenia

9.4.11 Immunologic

No data available.

9.4.12 Metabolic

9.4.12.1 Acid base disturbances

Metabolic acidosis

9.4.12.2 Fluid and electrolyte disturbances

They may occur secondary to
vomiting or diarrhoea.

9.4.13 Allergic reactions

Urticaria

9.4.14 Other clinical effects

9.4.15 Special risks:

The use of podophyllum is contraindicated in
pregnant or lactating women.

9.5 Other

No data available.

9.6 Summary

10. MANAGEMENT

10.1 General principles

Perform gastric lavage if patient is seen early.
Administer activated charcoal.

If topical contact: wash with soap and water. Repeat until
pain disappears. Remove any residual solid podophyllum
material.

No specific treatment is available. Intensive supportive
therapy may be required.

10.2 Life supportive procedures and symptomatic treatment

Maintain vital signs

10.3 Decontamination

Wash with soap and water if skin contact has occurred.
Irrigate eyes with water after eye contact.

10.4 Enhanced elimination

Haemoperfusion should be used for severe systemic
poisoning since it has been shown to be effective in reducing
the plasma fraction of podophyllumtoxin and other active
metabolites but its real impact on the course of the disease
has not been sufficiently documented to date. Haemodialysis
is unlikely to be effective in removing podophyllumtoxin or
its metabolites.

10.5 Antidote treatment

10.5.1 Adults

None available.

10.5.2 Children

None available

10.6 Management discussion

Further research is required on toxicokinetics and
elimination procedures.

11. ILLUSTRATIVE CASES

11.1 Case reports from the literature

Age/ Dose: Onset of Nausea/ Peripheral Lethargy Tachypnea Respiratory Hematologic Other Outcome
sex topical/ symptoms vomit neuropathy (L) failure findings
ingested Coma (C)

60 F 325mg Few X C X haematuria Death
topical hours at 31 h
18 F ?, <12 h X X C X Renal Death at
topical failure, 7 d
ileus
25 F 2.8g <24 h X X C Minimal
ingested neuropathy
at 16 months
19 F ?, 4.5 h X X No
topical sequelae
and 1 g
ingested
2 F 350 mg, 3 h X L Leukocytosis Fever Survived
ingested anaemia seizure
25 M 160mg, 2 h X X X Survived
ingested
71 M ?, < 24 h X Survived
topical
on tongue
18 F 1.88g, Few X X X Neuropathy
topical hours resolved at
9 months
20 F ?, 13.5 h X X C X Leukocytosis High Discharged
topical amylase at 25 d with
neuropathy
16 F 1 g, 7 h X X C X Leukocytosis Abdominal Neuropathy
topical pain at 4 months
15 F ?, Few X L X Pancytopenia Survived
topical hours

Age/ Dose: Onset of Nausea/ Peripheral Lethargy Tachypnea Respiratory Hematologic Other Outcome
sex topical/ symptoms vomit neuropathy (L) failure findings
ingested Coma (C)

20 F 150 mg, <24 h X X L X Pancytopenia Minimal
topical neuropathy
at 4 yr
17 F 400 mg, 20 h X X C X X Leukocytosis, Complete
topical then leukopenia, recovery at
thrombocytopenia 10 months
2 F 1 g, 9 h X C Fever Neuropathy
ingested seizure at discharge
59 M 10 g, 10 h X C X X Leukocytosis Renal Death at
ingested with abnormal failure 39 h
morphology

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

No data available.

12.2 Other

No data available.

13. REFERENCES

American Society of Hospital Pharmacists (1990) American
Hospital Formulary Service, p. 2055-57.

Association Pharmaceutique Canadienne (1990) Compendium des
produits et spécialités pharmaceutiques (25ième ed.) p. 969-70.

Budavari S ed. (1996) The Merck Index: An Encyclopedia of
Chemicals, Drugs, and Biologicals. 12th ed. Merck & Co., Inc,
Whitehouse Station, NJ.

Chamberlain MJ, Reynolds AL & Yeoman WB (1972) Toxic effect of
podophyllum application in pregnancy. Brit Med J, 8549: 391-392.

Cassidy DE, Drewry J & Fanning JP (1982) Podophyllum toxicity: A
report of a fatal case and a review of the literature. J Toxicol,
19 (1): 35-44.

Cullis JE (1962) Congenital deformities and herbal "slimming
tablets". Lancet 2: 511-512.

Dukes MNG & Beeley L (1987) In: Side effects of drugs annual 11.
Elsevier, Amsterdam, New York, Oxford. p. 516.

Ellenhorn MJ & Barceloux DG (1988) Medical toxicology. Elsevier,
New York, Amsterdam, London. p. 1268-69.

Fisher AA (1981) Severe systemic and local reactions to topical
podophyllum resin. CUTIS, 28: 233-248 & 266.

Heath A, Mellstrans T & Alhmen J (1982) Treatment of podophyllum
poisoning with resin hemoperfusion. Human toxicol, 1: 373-378.

Jardine I (1980) Podophyllumtoxin. In: Anticancer agents based on
natural product models (Academic Press), 319-351.

Karol MD, Conner CS, Watanabe AS & Murphrey KJ (1980) Podophyllum:
suspected teratogenicity from topical application. Clin Toxicol
16(3):283-286.

Salmon SE & Sartorelli AC (1987) Cancer Chemotherapy. In: Basic
and clinical pharmacology, Katzung BG, ed. Lange 3rd ed., 665-78.

United States Pharmacopoeial Convention, Inc. (1990) USPDI. Drug
information for the health care professional, p. 2270-72.

Ward JW, Clifford WS, Monaco AR & Bickerstaff HJ (1954) Fatal
systemic poisoning following podophyllum treatment of condyloma
acuminatum. Southern Med J, 75(10): 1204-1206.

14. AUTHOR(S), REVIEWER(S), DATE (S)

Author: A.J. Nantel
directeur
Centre de Toxicologie du Québec
Le Centre Hospitalier de l'Université Laval
2705, boul. Laurier, local 800
Sainte-Foy (Québec)
GIV 4G2 Canada

Tél. 654-2254
Fax. 654-2754

Peer review: Newcastle, U.K. (Janvier 15-19, 1991)
Adelaide, Autralie (Avril 8-12, 1991)

Editor: Dr M. Ruse (August, 1997)

    See Also:
       Toxicological Abbreviations