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Pharmacology:
Hormones and ART
Pharmacology:
Hormones and ART
Tonia
Chase Brexton Health Services
Johns Hopkins School of Public Health
Tonia
Chase Brexton Health Services
Johns Hopkins School of Public Health
Pharmacology:
Hormones and ART
Pharmacology:
Hormones and ART
Tonia Poteat, MMSc, MPH, PA-C
Chase Brexton Health Services
Johns Hopkins School of Public Health
Tonia Poteat, MMSc, MPH, PA-C
Chase Brexton Health Services
Johns Hopkins School of Public Health
HIVHIV--Related Related
Drug InteractionsDrug Interactions
Related Related
Drug InteractionsDrug Interactions
Image: thebody.comImage: thebody.com
Drug MetabolismDrug Metabolism
• Metabolism of some drugs occurs along iso-enzyme pathway (most common = 3A4 and 2D6)
• Two or more drugs using this pathway will interact− Affecting potency, side effects, & effectiveness− Drug concentrations may go up or down− Difficult to predict the effects of multiple drug interactions
• Metabolism of some drugs occurs along iso-enzyme pathway (most common = 3A4 and 2D6)
• Two or more drugs using this pathway will interact− Affecting potency, side effects, & effectiveness− Drug concentrations may go up or down− Difficult to predict the effects of multiple drug interactions
• Enzyme Inducers− Increase metabolism− Decrease amount of drug in bloodstream
• unless it’s a pro-drug
• Enzyme Inhibitors− Decrease metabolism− Increase the amount of drug in bloodstream
• Unless it’s a pro-drug
• Enzyme Inducers− Increase metabolism− Decrease amount of drug in bloodstream
• unless it’s a pro-drug
• Enzyme Inhibitors− Decrease metabolism− Increase the amount of drug in bloodstream
• Unless it’s a pro-drug
Metabolism of some drugs occurs along cytochrome P-450 (most common = 3A4 and 2D6)
Two or more drugs using this pathway will interactpotency, side effects, & effectiveness
Drug concentrations may go up or downDifficult to predict the effects of multiple drug interactions
Metabolism of some drugs occurs along cytochrome P-450 (most common = 3A4 and 2D6)
Two or more drugs using this pathway will interactpotency, side effects, & effectiveness
Drug concentrations may go up or downDifficult to predict the effects of multiple drug interactions
Decrease amount of drug in bloodstreamdrug
Increase the amount of drug in bloodstreamdrug
Decrease amount of drug in bloodstreamdrug
Increase the amount of drug in bloodstreamdrug
Lynch AAFP 2007
Cytochrome (CYP) P450 metabolismCytochrome (CYP) P450 metabolism
• Common inducers
− Smoking
− St. John’s Wort
− All Protease Inhibitors
− NNRTI’s
• Common inducers
− Smoking
− St. John’s Wort
− All Protease Inhibitors
− NNRTI’s− NNRTI’s
• Common inhibitors
− Grapefruit
− Statins
− Azoles (anti-fungals)
• Mixed inducer/inhibitor
− Efavirenz
− NNRTI’s
• Common inhibitors
− Grapefruit
− Statins
− Azoles (anti-fungals)
• Mixed inducer/inhibitor
− Efavirenz
(CYP) P450 metabolism(CYP) P450 metabolism
All Protease InhibitorsAll Protease Inhibitors
)
Mixed inducer/inhibitor
)
Mixed inducer/inhibitor
www.aidsetc.org
ChanelleChanelle
• 28 year old trans woman with HIV
• +THC (no cigarettes), non
• Taking Delestrogenshe can get it. Unsure of dose.
− CD4 count 250 & VL 173,000
• 28 year old trans woman with HIV
• +THC (no cigarettes), non
• Taking Delestrogenshe can get it. Unsure of dose.
− CD4 count 250 & VL 173,000− CD4 count 250 & VL 173,000
− ALT 60, Cr 1.0, Hep
− Rest of CBC and CMP are unremarkable
• Feels ready to start ARVs
• What are her options?
• What else might you want to do?
− CD4 count 250 & VL 173,000
− ALT 60, Cr 1.0, Hep
− Rest of CBC and CMP are unremarkable
• Feels ready to start ARVs
• What are her options?
• What else might you want to do?
28 year old trans woman with HIV
+THC (no cigarettes), non-drinker
Delestrogen on the street whenever she can get it. Unsure of dose.
CD4 count 250 & VL 173,000
28 year old trans woman with HIV
+THC (no cigarettes), non-drinker
Delestrogen on the street whenever she can get it. Unsure of dose.
CD4 count 250 & VL 173,000CD4 count 250 & VL 173,000
Hep C+, Hep A&B immune
Rest of CBC and CMP are unremarkable
Feels ready to start ARVs
What are her options?
What else might you want to do?
CD4 count 250 & VL 173,000
Hep C+, Hep A&B immune
Rest of CBC and CMP are unremarkable
Feels ready to start ARVs
What are her options?
What else might you want to do?
Available Antiretroviral Agents: Available Antiretroviral Agents:
Abacavir (Ziagen)Didanosine (Videx)Emtricitabine (Emtriva)Lamivudine (Epivir)Stavudine (Zerit)Tenofovir (Viread)Zidovudine (Retrovir)3TC/ABC (Epzicom)
NRTIs
NNRTIs
Delavirdine (Rescriptor)Efavirenz (Sustiva) Nevirapine (Viramune)Etravirine (Intelence)Rilpivirine (Edurant)
3TC/ABC/ZDV (Trizivir)3TC/ZDV (Combivir)FTC/TDF (Truvada)
Multiple Class
Atripla (EFV/FTC/TDF)
Available Antiretroviral Agents: June 2011Available Antiretroviral Agents: June 2011
PIs
Atazanavir (Reyataz)Darunavir (Prezista)Fosamprenavir (Lexiva)Indinavir (Crixivan)Lopinavir/ritonavir (Kaletra)Nelfinavir (Viracept)Ritonavir (Norvir)Saquinavir (Invirase)Tipranavir (Aptivus)
Fusion Inhibitors (FIs)
Enfuvirtide (Fuzeon)
CCR5 Inhibitor
Raltegravir (Isentress)
Integrase Inhibitor
Maraviroc (Selzentry)
Chanelle - 3 months laterChanelle - 3 months later
• Switched to oral estradiol100mg twice daily of
• Started on TDF/FTC + ATV + RTV
• Denies any side effects
− CD4 increased to 400, UDVL
• Switched to oral estradiol100mg twice daily of
• Started on TDF/FTC + ATV + RTV
• Denies any side effects
− CD4 increased to 400, UDVL− CD4 increased to 400, UDVL
− ALT increased to 100, Cr 1.45
− Complains of hot flashes
• What drug interactions may be at play?
• What might you want to do?
− CD4 increased to 400, UDVL
− ALT increased to 100, Cr 1.45
− Complains of hot flashes
• What drug interactions may be at play?
• What might you want to do?
3 months later3 months later
estradiol 4mg daily plus 100mg twice daily of spironolactone.
Started on TDF/FTC + ATV + RTV
Denies any side effects
CD4 increased to 400, UDVL
estradiol 4mg daily plus 100mg twice daily of spironolactone.
Started on TDF/FTC + ATV + RTV
Denies any side effects
CD4 increased to 400, UDVLCD4 increased to 400, UDVL
ALT increased to 100, Cr 1.45
Complains of hot flashes
What drug interactions may be at play?
What might you want to do?
CD4 increased to 400, UDVL
ALT increased to 100, Cr 1.45
Complains of hot flashes
What drug interactions may be at play?
What might you want to do?
PI’s and Hormonal ContraceptivesPI’s and Hormonal Contraceptives
Ritonavir-boosted Protease Inhibitors
Atazanavir/r EE
Darunavir/r EE
Fosamprenavir/r EE
DHHS Guidelines
Lopinavir/r EE
Saquinavir/r EE
Tipranavir/r EE no
Protease Inhibitors without Ritonavir
Atazanavir EE norethindrone
Fosamprenavir APV EE and
EE APV by 20%
PI’s and Hormonal ContraceptivesPI’s and Hormonal Contraceptives
Protease Inhibitors
EE norgestimate Use OCP >35mcg EE
EE norethindrone Use alternative method
EE norethindrone Use alternative method
DHHS Guidelines – January 10, 2011
EE norethindrone Use alternative method
Use alternative method
EE no ∆ norethindrone Use alternative method
Ritonavir
norethindrone Use OCP >35mcg EE
APV EE and norethindrone
EE APV by 20%
Use alternative method
NNRTI’s and Hormonal ContraceptivesNNRTI’s and Hormonal Contraceptives
Efavirenz EE
Levenorgestrel
Norelgestromin
Etravirine EE
No ∆ Norethindrone
Nevirapine EE
Norethindrone
No ∆ DMPA
NNRTI’s and Hormonal ContraceptivesNNRTI’s and Hormonal Contraceptives
Use alternative methods.
Norelgestromin & levonorgestrel are
active metabolites of norgestimate.
Norethindrone
No dose adjustment necessary
Use alternative methods
No dose adjustment necessary
DHHS Guidelines – January 10, 2011
Other ARVs & Hormonal ContraceptionOther ARVs & Hormonal Contraception
CCR5 Antagonist
Maraviroc No ∆ EE or levonorgestrel
Integrase Inhibitor
Raltegravir No clinically significant effectRaltegravir No clinically significant effect
Other ARVs & Hormonal ContraceptionOther ARVs & Hormonal Contraception
levonorgestrel Safe to use together
No clinically significant effect Safe to use togetherNo clinically significant effect Safe to use together
DHHS Guidelines – January 10, 2011
Chanelle - 6 months laterChanelle - 6 months later
• Pt was switched back to 40mg IM every other spironalactone at previous doses.
• She returns with resolution of symptoms
• Stable on ARVs and hormone therapy
• Pt was switched back to 40mg IM every other spironalactone at previous doses.
• She returns with resolution of symptoms
• Stable on ARVs and hormone therapy• Stable on ARVs and hormone therapy
• Wants to address her Hepatitis C
− CD4 count 500, UDVL,
− HCV RNA 750,000; ALT 80; Cr 1.2
− No known contraindications to treatment
• What drug interactions concern you?
• Stable on ARVs and hormone therapy
• Wants to address her Hepatitis C
− CD4 count 500, UDVL,
− HCV RNA 750,000; ALT 80; Cr 1.2
− No known contraindications to treatment
• What drug interactions concern you?
6 months later6 months later
Pt was switched back to Delestrogen at 40mg IM every other week and continues
at previous doses.
She returns with resolution of symptoms
Stable on ARVs and hormone therapy
Pt was switched back to Delestrogen at 40mg IM every other week and continues
at previous doses.
She returns with resolution of symptoms
Stable on ARVs and hormone therapyStable on ARVs and hormone therapy
Wants to address her Hepatitis C
CD4 count 500, UDVL, Hep C genotype 1
HCV RNA 750,000; ALT 80; Cr 1.2
No known contraindications to treatment
drug interactions concern you?
Stable on ARVs and hormone therapy
Wants to address her Hepatitis C
CD4 count 500, UDVL, Hep C genotype 1
HCV RNA 750,000; ALT 80; Cr 1.2
No known contraindications to treatment
drug interactions concern you?
Drug InteractionDrug Interaction
• Rifampin• Dexamethasone• Rifampin• Dexamethasone
Estradiol levels are
• Dexamethasone• Naphthoflavone• Smoking cigarettes
• Dexamethasone• Naphthoflavone• Smoking cigarettes
Drug InteractionDrug Interaction
• Carbamazepine• Phenytoin• Carbamazepine• Phenytoin
levels are DECREASED by:
Smoking cigarettesSmoking cigarettes
• Phenytoin• Phenobarbital• Telaprevir
• Phenytoin• Phenobarbital• Telaprevir
www.hivwebstudy.orgwww.hivwebstudy.org
Chanelle – 4 weeks laterChanelle – 4 weeks later
• She has started Peg
• She complains of depressive symptoms; denies suicidal ideation
• She doesn’t want twants to try something natural like St. John’s
• She has started Peg
• She complains of depressive symptoms; denies suicidal ideation
• She doesn’t want twants to try something natural like St. John’s wants to try something natural like St. John’s Wort.
• What do you recommend?
wants to try something natural like St. John’s Wort.
• What do you recommend?
*Telaprevir
co-infected patients. This is an off
4 weeks later4 weeks later
She has started Peg-IFN, RBV, and Telaprevir*
She complains of depressive symptoms; denies suicidal ideation
t to take pharmaceuticals and wants to try something natural like St. John’s
She has started Peg-IFN, RBV, and Telaprevir*
She complains of depressive symptoms; denies suicidal ideation
t to take pharmaceuticals and wants to try something natural like St. John’s wants to try something natural like St. John’s
What do you recommend?
wants to try something natural like St. John’s
What do you recommend?
Telaprevir has not been FDA-approved for use in HIV-HCV
infected patients. This is an off-label use of this medication.
Cytochrome (CYP) P450 metabolismCytochrome (CYP) P450 metabolism
• Common inducers
− Smoking
− St. John’s Wort
− All Protease Inhibitors
− NNRTI’s
• Common inducers
− Smoking
− St. John’s Wort
− All Protease Inhibitors
− NNRTI’s− NNRTI’s
• Common inhibitors
− Grapefruit
− Statins
− Azoles (anti-fungals)
• Mixed inducer/inhibitor
− Efavirenz
− NNRTI’s
• Common inhibitors
− Grapefruit
− Statins
− Azoles (anti-fungals)
• Mixed inducer/inhibitor
− Efavirenz
(CYP) P450 metabolism(CYP) P450 metabolism
All Protease InhibitorsAll Protease Inhibitors
)
Mixed inducer/inhibitor
)
Mixed inducer/inhibitor
www.aidsetc.org
Drug InteractionDrug Interaction
• Isoniazid• Fluvoxamine• Fluoxetine• Sertraline
• Isoniazid• Fluvoxamine• Fluoxetine• Sertraline
Estradiol levels are
• Sertraline• Paroxetine• Diltiazem• Verapamil• Cimetidine
• Sertraline• Paroxetine• Diltiazem• Verapamil• Cimetidine
Drug InteractionDrug Interaction
• Astemizole• Itraconazole• Ketoconazole
• Astemizole• Itraconazole• Ketoconazole
levels are INCREASED by:
• Ketoconazole• Fluconazole• Miconazole• Clarythromycin• Erythromycin• Grapefruit
• Ketoconazole• Fluconazole• Miconazole• Clarythromycin• Erythromycin• Grapefruit
www.hivwebstudy.orgwww.hivwebstudy.org
Chanelle – 8 weeks laterChanelle – 8 weeks later
• She was started on citalopramsymptoms have improved
• Her labs are stable and she continues on the following medications:
− Peg-IFN, RBV, and
• She was started on citalopramsymptoms have improved
• Her labs are stable and she continues on the following medications:
− Peg-IFN, RBV, and
− Tenofovir/Emtricitabine
− Delestrogen, Spironolactone
• While she doesn’t like the pill burden, she is tolerating meds well and happy to be able to get her all her care in the same place.
− Tenofovir/Emtricitabine
− Delestrogen, Spironolactone
• While she doesn’t like the pill burden, she is tolerating meds well and happy to be able to get her all her care in the same place.
8 weeks later8 weeks later
citalopram and depressive symptoms have improved
Her labs are stable and she continues on the following medications:
IFN, RBV, and Telaprevir
citalopram and depressive symptoms have improved
Her labs are stable and she continues on the following medications:
IFN, RBV, and Telaprevir
Emtricitabine, Atazanavir, Norvir
Spironolactone
While she doesn’t like the pill burden, she is tolerating meds well and happy to be able to get her all her care in the same place.
Emtricitabine, Atazanavir, Norvir
Spironolactone
While she doesn’t like the pill burden, she is tolerating meds well and happy to be able to get her all her care in the same place.
Summary: Estrogens & Summary: Estrogens &
• DHHS evidence based on oral contraceptives− Oral contraceptives use
contraceptive doses− Hormones for transgender patients usually are 17
estradiol or conjugated equine estrogen (CEE)
• Most PI interactions decrease
• DHHS evidence based on oral contraceptives− Oral contraceptives use
contraceptive doses− Hormones for transgender patients usually are 17
estradiol or conjugated equine estrogen (CEE)
• Most PI interactions decrease• Most PI interactions decrease− If estrogen is continued and
stopped, this may llevels with associated risk of adverse effects
• Non-nucleosides (NNRTI)− Nevirapine decreases estrogen levels− Efavirenz may increase
• Most PI interactions decrease− If estrogen is continued and
stopped, this may llevels with associated risk of adverse effects
• Non-nucleosides (NNRTI)− Nevirapine decreases estrogen levels− Efavirenz may increase
Summary: Estrogens & AntiretroviralsSummary: Estrogens & Antiretrovirals
DHHS evidence based on oral contraceptivesOral contraceptives use ethinyl estradiol at contraceptive dosesHormones for transgender patients usually are 17-β
or conjugated equine estrogen (CEE)
decrease estrogen levels
DHHS evidence based on oral contraceptivesOral contraceptives use ethinyl estradiol at contraceptive dosesHormones for transgender patients usually are 17-β
or conjugated equine estrogen (CEE)
decrease estrogen levelsdecrease estrogen levelsIf estrogen is continued and antiretrovirals are
y lead to dangerously high estrogen levels with associated risk of adverse effects
nucleosides (NNRTI)decreases estrogen levels
may increase or decrease estrogen levels
decrease estrogen levelsIf estrogen is continued and antiretrovirals are
y lead to dangerously high estrogen levels with associated risk of adverse effects
nucleosides (NNRTI)decreases estrogen levels
may increase or decrease estrogen levels
Take Home MessageTake Home Message
� Amprenavir and Fosamprenavironly antiretroviralsadministered with estrogen due to risk of virologic failure.
� Amprenavir and Fosamprenavironly antiretroviralsadministered with estrogen due to risk of virologic failure.
� Several HIV medications change the levels of estrogens, therefore estrogen dose adjustment may be necessary
� Gender confirming hormone therapy is not contraindicated with antiretroviral therapy.
� Several HIV medications change the levels of estrogens, therefore estrogen dose adjustment may be necessary
� Gender confirming hormone therapy is not contraindicated with antiretroviral therapy.
Take Home MessageTake Home Message
Fosamprenavir are the antiretrovirals that should not be co-
administered with estrogen due to risk of
Fosamprenavir are the antiretrovirals that should not be co-
administered with estrogen due to risk of
Several HIV medications change the levels of estrogens, therefore estrogen dose adjustment may be necessary
Gender confirming hormone therapy is not contraindicated with antiretroviral therapy.
Several HIV medications change the levels of estrogens, therefore estrogen dose adjustment may be necessary
Gender confirming hormone therapy is not contraindicated with antiretroviral therapy.
Web Resources for Drug InteractionsWeb Resources for Drug Interactions
http://www.healthline.com/druginteractions
http://reference.medscape.com/druginteractionchecker
http://www.healthline.com/druginteractions
http://reference.medscape.com/druginteractionchecker
http://www.drugs.com/drug_interactions.htmlhttp://www.drugs.com/drug_interactions.html
Web Resources for Drug InteractionsWeb Resources for Drug Interactions
http://www.healthline.com/druginteractions
http://reference.medscape.com/drug-
http://www.healthline.com/druginteractions
http://reference.medscape.com/drug-
http://www.drugs.com/drug_interactions.htmlhttp://www.drugs.com/drug_interactions.html
Expert Advice at Your FingertipsExpert Advice at Your Fingertips
HIV/AIDS Clinical Consultation 1-800-933-3413Mon-Fri 8am to 8pm ESTwww.ucsf.edu/hivcntr
HIV/AIDS Clinical Consultation 1-800-933-3413Mon-Fri 8am to 8pm ESTwww.ucsf.edu/hivcntr
Expert Advice at Your FingertipsExpert Advice at Your Fingertips
HIV/AIDS Clinical Consultation 3413
Fri 8am to 8pm ESTwww.ucsf.edu/hivcntr
HIV/AIDS Clinical Consultation 3413
Fri 8am to 8pm ESTwww.ucsf.edu/hivcntr
