Adverse Reactions & Antiretroviral Therapy
Kirsten B. Balano, PharmD October 26, 2002
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?
The most effective regimen for HIV infected individuals is the one they will take.
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
Common Adverse Effects
• • • • Nausea/Vomiting Diarrhea Rash Fatigue
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
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
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
Nausea: Other possible causes
• Drug Related
– Acute hepatitis – Acute pancreatitis
• Gastrointestinal Disease • CNS Disease
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
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
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
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
Common Adverse Effects
• • • • Nausea/Vomiting Diarrhea Rash Fatigue
Diarrhea:
• Antiretrovirals most likely to cause diarrhea
– – – – – – ddI (tablet/powder formulation) Abacavir Nelfinavir Ritonavir Amprenavir Lopinavir
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
Diarrhea Management cont.
• • • • Psyllium (metamucil) Calcium Carbonate Iron Pancrelipase (i.e. Ultrase) 1-2 capsules with meals and snacks.
Common Adverse Effects
• • • • Nausea/Vomiting Diarrhea Rash Fatigue
Rash:
• Antiretrovirals commonly associated with rash:
– Nevirapine – Delavirdine – Amprenavir
• Rash also seen with (but less likely)
– Abacavir, 3TC, Nelfinavir, Efavirenz
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.
Common Adverse Effects
• • • • Nausea/Vomiting Diarrhea Rash Fatigue
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?
Fatigue
• Antiretrovirals most associated with fatigue:
– Zidovudine – Efavirenz
• Pill Fatigue
– Protease Inhibitors
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
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.
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)
Questions?