Report-1 Imatinib and Ginseng

8/2/2019 Report-1 Imatinib and Ginseng

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Imatinib and Panaxginseng: A Potential

InteractionResulting in LiverToxicity

Naveen Bilgi, Kim Bell, Ashwin NAnanthakrishnan, and Ehab Atallah

Annals of PharmacotherapyMay 2010


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Philadelphia

Chromosome A shortened

chromosome 22

resulting from thetranslocation betweenchromosome 9 andchromosome 22

Produces BCR-ABLoncogene


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Structure of Imatinib (Gleevec)

Class: Phenylaminopyrimidines,

C30H35N7SO4

MW=589.7

CH3SO3HN

N

N

HN

HN

O

N

N


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Mechanism ofGleevec


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Side Effects

Mild: Nausea, vomiting, diarrhea,heart burn, headache, and musclecramps

Severe: Ascites, Pulmonary Edema,Neutropenia, Thrombocytopenia, etc

Uncommon: Hepatotoxicity(usually manifests within the first1-2 years of therapy


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Imatinib

Specifically targets an enzyme incancer cells, not normal healthy cells

Given orally instead of injections

Dosage 400 mg/day in Chronic Phase CML

600 mg/day in Accelerated/Blast

Crisis Metabolized in the liver via the

Cytochrome P450 system,

primarily by CYP3A4


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What is Ginseng? Low-growing, shade-

loving perennial herb oftheAralianceaefamily

(http://www.bccancer.bc.ca/PPI/UnconventionalTherapies/Ginseng.htm)

Latin name= Panax

The scientific names

Panax Ginseng

Derived from the Greek

word for cure-all,

related to the wordPanacea.


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Active Components Ginsenosides

or PanaxosidesMajor ginsenosides:

Rg1, Re, Rf, Rb1, Rc, Rg2, Rb2, Rb

Panaxans

Ginsenans


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Forms of Ginseng Root itself

Dried root

Teas, capsules, tablets,tinctures, powders.


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DosageWell tolerated orally

usually provide 100mg to400mg of dried extract

(equivalent to 0.5g to 2g of

ginseng root.)-A Cytochrome P450inhibitor


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Traditional and modern uses Improving the health of people

recovering form illness

Memory and energy

enhancement Heightens bodys response to

stress, fatigue, trauma and

anxiety


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Side Effects Bleeding disorders

Diarrhea Edema Headache Hypoglycemia

Hyperpyrexia Menstrual abnormalities Nausea and vomiting Nervous excitation

Palpitations Itchiness Dizziness Rose spots


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Side Effects (contd)Large doses over an extended period of

time

Diarrhea

Estrogenic effectHTN

Hypertonicity

Decreased libido

Insomnia

Menstruation in menopausal women

Nervousness


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Case Report

A 26-year-old man with CML (CP-MMR)

On Imatinib 400mg daily for 7 years withno complications

Presented with 2 day history of RUQ pain sharp, stabbing, exacerbated withmovement

(-)Heavy lifting, alcohol intake,acetaminophen ingestion

3 month history of using energy drink thatcontained Panaxginseng.


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Diagnostics

Liver enzyme tests - elevated

Abdominal and Pelvic CT scan -unremarkable

Hepatitis profile negative/non-reactive(NON-VIRAL)

Autoimmune work-up - negative

Enzymatic deficiency workup negative


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Liver Biopsy

Resolving or Late-Stage LobularHepatitis, Most likely

drug-induced
http://upload.wikimedia.org/wikipedia/commons/6/6d/Drug-induced_hepatitis_intermed_mag.jpg


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Therapeutics

Both Imatinib and ginseng werediscontinued.

The patient was treated witha short

course of corticosteroids. Imatinib was later restartedat the same

dose, and liver enzymelevels remainednormal.


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Dilemma

Toxic Reaction:

Due to a previously tolerated drug?

Due to a newly added medication? Due to interaction of previously

tolerated drug and newly added

medication?


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Hypothesis

Hepatotoxicity due to ginseng-mediated inhibition of Imatinibmetabolism

Pharmacologic studies providesupport for this hypothesis


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What is known?

Imatinib is metabolized byCYP3A4, CYP2D6, 1A2, 2C9,

2C9Ginseng has an inhibitoryeffect on CYP3A4 but not onisoenzymes that play a role inthe metabolism of of

Imatinib.


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Pathophysiology of LiverToxicity


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What is known?

Imatinib is a P-GP Substrate

Ginseng has an inhibitory

effect on P-GP


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Pathophysiology of livertoxicity
http://www.drugdevelopment-technology.com/projects/tesmilifene/


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Conclusions

Importance of continuousmonitoring of liver function tests inpatients on Imatinib therapy evenafter several years

Importance of counseling patientsto avoid ginseng and any other

over-the-counter herbalsupplements that may interact withImatinib

Documents

Report-1 Imatinib and Ginseng