adverse reactions & antiretroviral therapy kirsten b. balano, pharmd october 26, 2002
TRANSCRIPT
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Adverse Reactions & Antiretroviral Therapy
Kirsten B. Balano, PharmD
October 26, 2002
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Challenges associated with antiretroviral therapy:
When to start medications?When to change medications?What medications to start with?What medications to change to when fail?
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The most effective regimen for HIV infected individuals is the
one they will take.
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How to achieve 100% adherence?
Prior to therapy educate client on therapeutic goals
Review regimen, how to take, how to store
Review and manage side-effects as they occur
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Common Adverse Effects
• Nausea/Vomiting
• Diarrhea
• Rash
• Fatigue
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Case Report:• 38 yo man with AIDS, history of several antiretroviral
regimens in the past, including AZT, 3TC, IDV and was non-adherent with these regimens, primarily due to intolerance.
• Current CD4 150, VL 400,000 Has been working closely with his NP and case manager over the past 1.5 years to consider restarting ARV.
• Three days ago was begun on salvage regimen: Abacavir, Combivir, Amprenavir, Ritonavir, Efavirenz, continues Septra.
• Comes in for adherence check with new regimen, complaining of intolerable dizziness and nausea
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Nausea
• Antiretroviral agents most commonly associated with nausea:– Zidovudine (AZT, ZDV, Retrovir)– Didanosine (ddI, Videx)– Abacavir (ABC, Ziagen)– All of the protease inhibitors– Tenofovir – gas/bloating & flatulence
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Abacavir Hypersensitivity
• Occurs in 3-5% of pts• Most commonly by day 10 of start• Associated with fever, nausea, GI
symptoms, respiratory symptoms and possibly a rash
• Increasing intensity of symptoms with subsequent doses
• DO NOT RECHALLENGE
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Nausea: Other possible causes
• Drug Related– Acute hepatitis– Acute pancreatitis
• Gastrointestinal Disease
• CNS Disease
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Nausea Counseling• Reassure pt symptoms decrease over first month
• Don’t stop meds without advice from physician
• Double check dosage and administration– IDV can be given with lite snacks if alone and with
food if with RTV– ddI with very cold water can decrease nausea
• Consider holding supplements/vitamins or other less vital medications
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Nausea Management• Avoid greasy, fried foods• Eat small, frequent snacks or meals• Ginger - Ginger Tea, Ginger Ale, Ginger Snaps• Mint and/or simethicone for gas/bloating• Consider antiemetics (i.e. prochorperazine
10mg BID – TID, marinol, marijuana)• If anticipatory nausea is part of the origin,
consider adjust regimen to decrease number of pills (if clinically appropriate) or lorazepam 0.5mg 30 min before meds
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Strategies to Limit Pill Burden
• Ritonavir Boosted Regimens– IDV 800 + RTV 100/200 twice daily– APV 600 + RTV 100/200 twice daily– Lopinavir/ritonavir – Kaletra
• Once Daily Regimens – may increase pill burden– SQV 1200/1600 +RTV 100/200– APV 1200 + RTV 200
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Case Report:• Three days ago was begun on salvage regimen: Abacavir,
Combivir, Amprenavir, Ritonavir, Efavirenz, continues Septra.
• Comes in for adherence check with new regimen, complaining of intolerable dizziness and nausea
• Pill Burden:– Abacavir 1 BID, Combivir 1 BID, Amprenavir 8 BID, Ritonavir 2
BID, Efavirenz 3 Qhs, Septra 1 QD– 13 pills AM, 15 pill PM
• Switch Indinavir 2 BID, Ritonavir 2 BID, Trizivir 1 BID, Nevirapine 1 BID– 7 pills AM, 6 pills PM
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Common Adverse Effects
• Nausea/Vomiting
• Diarrhea
• Rash
• Fatigue
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Diarrhea:
• Antiretrovirals most likely to cause diarrhea– ddI (tablet/powder formulation)– Abacavir– Nelfinavir– Ritonavir– Amprenavir– Lopinavir
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Diarrhea Management
• Nelfinavir: Access to lomotil or loperamide before starting nelfinavir. Usually will lessen within 1 month of continued treatment
• Dose escalation of ritonavir, even if using 400mg BID, can decrease adverse effects in first 2 weeks of treatment
• ddI: related to buffer in tablet. Make sure number of tablets appropriately minimal or switch formulations - Videx EC.
• Abacavir – concern related to hypersensitivity reaction – need to monitor carefully
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Diarrhea Management cont.
• Psyllium (metamucil)
• Calcium Carbonate
• Iron
• Pancrelipase (i.e. Ultrase) 1-2 capsules with meals and snacks.
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Common Adverse Effects
• Nausea/Vomiting
• Diarrhea
• Rash
• Fatigue
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Rash:
• Antiretrovirals commonly associated with rash:– Nevirapine– Delavirdine– Amprenavir
• Rash also seen with (but less likely)– Abacavir, 3TC, Nelfinavir, Efavirenz
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Rash Management• Rule out SJS rash - painful & involve conjunctiva & mucosa)• Most are self-limiting with continued treatment and will
resolve w/in 2-3 weeks. • Supportive care including creams for dryness and antipruitics
for itching (i.e. diphenhydramine or doxepin)• Use of sunscreen can decrease likelihood of
rash/phonosensitivity• Nevirapine – dose escalation decreases likelihood rash
(200mg QD x 2wk then 200 mg BID)• Abacavir – r/o hypersensitivity reaction, with other
symptoms present.
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Common Adverse Effects
• Nausea/Vomiting
• Diarrhea
• Rash
• Fatigue
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Case Report:
• Switch Indinavir 2 BID, Ritonavir 2 BID, Trizivir 1 BID, Nevirapine 1 BID, Continue Septra
• Several weeks later, partner calls complaining of being so tired taking so many meds
• Is it possible to stop one medicine?
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Fatigue
• Antiretrovirals most associated with fatigue:– Zidovudine– Efavirenz
• Pill Fatigue– Protease Inhibitors
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Strategies to Limit Pill Burden
• Ritonavir Boosted Regimens– IDV 800 + RTV 100/200 twice daily– APV 600 + RTV 100/200 twice daily– Lopinavir/ritonavir – Kaletra
• Once Daily Regimens– SQV 1200/1600 +RTV 100/200– APV 1200 + RTV 200
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Fatigue Management
• Symptoms should resolve after 4-6 weeks of a new regimen
• Zidovudine: need to rule out anemia, especially if associated with SOB, palpitations, loss of color
• Efavirenz: Consider splitting dose or taking early in evening rather than bedtime. CNS symptoms usually resolve by 2-4 weeks continued treatment.
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Case Report:
• Switch Indinavir 2 BID, Ritonavir 2 BID, Trizivir 1 BID, Nevirapine 1 BID, Continue Septra
• Several weeks later, partner calls complaining of being so tired taking so many meds
• Is it possible to stop one medicine?
• So tired, short of breath walking up stairs and across parking lot.
• Hct 32 - 24• Transfusion• Switch Trizivir to D4T(Zerit), 3TC (Epivir), Abacavir
(Ziagen)
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Questions?