Practical Aspects of Practical Aspects of Antiretroviral TherapyAntiretroviral Therapy

Nancy R. Calles,R.N.,B.S.N.Nancy R. Calles,R.N.,B.S.N.

Treatment Goals for Treatment Goals for ChildrenChildren

Promote or restore normal growth Promote or restore normal growth and developmentand development

Prevent complicating infections Prevent complicating infections and cancersand cancers

Improve quality of lifeImprove quality of life Prolong survivalProlong survival

Objectives of this Objectives of this PresentationPresentation

List the names and formulations of List the names and formulations of antiretroviralsantiretrovirals

Describe the dosing of antiretroviralsDescribe the dosing of antiretrovirals Discuss the side effects of Discuss the side effects of

antiretroviralsantiretrovirals List drug interactions of antiretroviralsList drug interactions of antiretrovirals Discuss practical approaches to Discuss practical approaches to

administration of antiretroviralsadministration of antiretrovirals

Nucleoside Reverse Nucleoside Reverse Transcriptase InhibitorsTranscriptase Inhibitors

AZT, zidovudine (RETROVIR)AZT, zidovudine (RETROVIR) d4T, stavudine (ZERIT)d4T, stavudine (ZERIT) ddI, didanosine (VIDEX)ddI, didanosine (VIDEX) ddC, zalcitabine (HIVID)ddC, zalcitabine (HIVID) 3TC, lamivudine (EPIVIR)3TC, lamivudine (EPIVIR) ABC, abacavir (ZIAGEN)ABC, abacavir (ZIAGEN)

Zidovudine (RETROVIR): Zidovudine (RETROVIR): FormulationsFormulations

100 mg capsules100 mg capsules 300 mg tablets300 mg tablets 10 mg/ml yellow liquid, strawberry 10 mg/ml yellow liquid, strawberry

flavoredflavored Intravenous formulationIntravenous formulation

Zidovudine (RETROVIR): Zidovudine (RETROVIR): DosingDosing

Neonatal: Oral: 2 mg/kg q6hNeonatal: Oral: 2 mg/kg q6h

Neonatal: Intravenous: 1.5 mg/kg Neonatal: Intravenous: 1.5 mg/kg q6hq6h

Pediatric: Oral: Pediatric: Oral: 90-180 mg/m90-180 mg/m22 body surface area body surface area tid or bid ( 200 max. qid)tid or bid ( 200 max. qid)

Zidovudine (RETROVIR): Zidovudine (RETROVIR): Side EffectsSide Effects

Most Frequent:Most Frequent:Hematological, including anemia Hematological, including anemia and neutropeniaand neutropenia

Less common:Less common:Myopathy, myositis, and liver Myopathy, myositis, and liver toxicitytoxicity

Zidovudine (RETROVIR):Zidovudine (RETROVIR):Drug InteractionsDrug Interactions

Drugs which can be associated Drugs which can be associated with bone marrow suppression with bone marrow suppression should be avoidedshould be avoided

Drugs which may increase ZDV Drugs which may increase ZDV concentration should be avoided concentration should be avoided (probenecid, atovaquone, (probenecid, atovaquone, methadone, valproic acid, and methadone, valproic acid, and fluconazole)fluconazole)

Zidovudine (RETROVIR):Zidovudine (RETROVIR): Tips for Caregivers Tips for Caregivers

Tablets and capsules should be Tablets and capsules should be stored at room temperaturestored at room temperature

Protect capsules from moistureProtect capsules from moisture May be taken with or without foodMay be taken with or without food

Stavudine (ZERIT):Stavudine (ZERIT):FormulationsFormulations

15 mg, 20 mg, 30 mg, and 40 mg 15 mg, 20 mg, 30 mg, and 40 mg capsulescapsules

1 mg/ml cloudy solution1 mg/ml cloudy solution

Stavudine (ZERIT):Stavudine (ZERIT):DosingDosing

Neonatal:Neonatal:Under investigationUnder investigation

Pediatric: Oral:Pediatric: Oral:1 mg/kg bid (max. 40 mg bid)1 mg/kg bid (max. 40 mg bid)

Stavudine (ZERIT):Stavudine (ZERIT):Side EffectsSide Effects

Most frequent:Most frequent:Headache, gastrointestinal Headache, gastrointestinal complaints, skin rashcomplaints, skin rash

Less common:Less common:Pancreatitis, peripheral Pancreatitis, peripheral neuropathy, increased liver neuropathy, increased liver enzymesenzymes

Stavudine (ZERIT):Stavudine (ZERIT):Drug InteractionsDrug Interactions

Should not be administered with Should not be administered with ZDV because of potential ZDV because of potential antagonismantagonism

Drugs which decrease renal Drugs which decrease renal function can decrease clearance function can decrease clearance and should be avoidedand should be avoided

Stavudine (ZERIT):Stavudine (ZERIT):Tips for CaregiversTips for Caregivers

Can be given with or without foodCan be given with or without food Shake oral solution, keep Shake oral solution, keep

refrigerated, good for 30 daysrefrigerated, good for 30 days Capsules can be opened and Capsules can be opened and

sprinkled on mashed potatoes, sprinkled on mashed potatoes, applesauce or other soft foodsapplesauce or other soft foods

Didanosine (VIDEX): Didanosine (VIDEX): FormulationsFormulations

25 mg, 50 mg, 100 mg, and 150 25 mg, 50 mg, 100 mg, and 150 mg orange flavored, chewable mg orange flavored, chewable tabletstablets

10 mg/ml white suspension10 mg/ml white suspension

Didanosine (VIDEX): Didanosine (VIDEX): Dosing Dosing

Neonatal: Oral: (infants <90 days Neonatal: Oral: (infants <90 days old)old)50 mg/m50 mg/m22 of body surface area of body surface area

Pediatric: Oral: Dose range: Pediatric: Oral: Dose range: 90-150 mg/m90-150 mg/m22 body surface area body surface area bidbid

Didanosine (VIDEX):Didanosine (VIDEX):Side EffectsSide Effects

Most frequent:Most frequent:Abdominal pain, nausea, vomiting, Abdominal pain, nausea, vomiting, diarrhea, constipationdiarrhea, constipation

Less common:Less common:Peripheral neuropathy, Peripheral neuropathy, pancreatitis, retinal pancreatitis, retinal depigmentation, electrolyte depigmentation, electrolyte abnormalitiesabnormalities

Didanosine (VIDEX):Didanosine (VIDEX):Drug InteractionsDrug Interactions

May decrease the absorption of May decrease the absorption of ketaconazole, itraconazole, and ketaconazole, itraconazole, and dapsone if administered concomitantlydapsone if administered concomitantly

Tetracycline and fluoroquinolone Tetracycline and fluoroquinolone antibiotic absorption are significantly antibiotic absorption are significantly decreaseddecreased

Concomitant administration of ddI and Concomitant administration of ddI and DLV decreases the absorption of bothDLV decreases the absorption of both

Didanosine (VIDEX):Didanosine (VIDEX): Tips for Caregivers Tips for Caregivers

Give on an empty stomach 1 hour Give on an empty stomach 1 hour before or 2 hours after a mealbefore or 2 hours after a meal

Shake suspension well, keep Shake suspension well, keep refrigeratedrefrigerated

Give two tablets to ensure adequate Give two tablets to ensure adequate buffering, may be dissolved in waterbuffering, may be dissolved in water

Do not give at the same time as Do not give at the same time as indinavir, ritonavir, or delavirdineindinavir, ritonavir, or delavirdine

Lamivudine (EPIVIR):Lamivudine (EPIVIR):FormulationsFormulations

150 mg white tablets150 mg white tablets 10 mg/ml clear solution10 mg/ml clear solution

Lamivudine (EPIVIR):Lamivudine (EPIVIR):DosingDosing

Neonatal: Oral: (< 30 days old)Neonatal: Oral: (< 30 days old)2 mg/kg bid2 mg/kg bid

Pediatric: Oral:Pediatric: Oral:4 mg/kg bid (max. 150 mg bid)4 mg/kg bid (max. 150 mg bid)

Lamivudine (EPIVIR):Lamivudine (EPIVIR):Side EffectsSide Effects

Most frequent:Most frequent:Headache, fatigue, nausea, Headache, fatigue, nausea, diarrhea, skin rash, abdominal paindiarrhea, skin rash, abdominal pain

Less common:Less common:Pancreatitis, peripheral Pancreatitis, peripheral neuropathy, increased liver neuropathy, increased liver enzymesenzymes

Lamivudine (EPIVIR):Lamivudine (EPIVIR):Drug InteractionsDrug Interactions

No known negative drug No known negative drug interactionsinteractions

Lamivudine (EPIVIR):Lamivudine (EPIVIR):Tips for CaregiversTips for Caregivers

Can be given with or without foodCan be given with or without food Store oral solution at room Store oral solution at room

temperaturetemperature Dosage should be decreased in Dosage should be decreased in

patients with impaired renal patients with impaired renal functionfunction

Abacavir (ZIAGEN):Abacavir (ZIAGEN):FormulationsFormulations

300 mg yellow, capsule-shaped 300 mg yellow, capsule-shaped tabletstablets

20 mg/ml yellow oral solution20 mg/ml yellow oral solution

Abacavir (ZIAGEN):Abacavir (ZIAGEN):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not approved for children < 3 Not approved for children < 3 months of agemonths of age

Pediatric: Oral:Pediatric: Oral:8 mg/kg bid (max. 300 mg bid)8 mg/kg bid (max. 300 mg bid)

Abacavir (ZIAGEN):Abacavir (ZIAGEN):Side EffectsSide Effects

Most frequent:Most frequent:Nausea, fever, vomiting, headache, Nausea, fever, vomiting, headache, rash, anorexia, and fatiguerash, anorexia, and fatigue

Less common:Less common:Hypersensitivity reaction, diarrhea, Hypersensitivity reaction, diarrhea, pancreatitis, increased liver enzymes, pancreatitis, increased liver enzymes, elevated blood glucose, elevated elevated blood glucose, elevated triglycerides, and lactic acidosistriglycerides, and lactic acidosis

Abacavir (ZIAGEN):Abacavir (ZIAGEN):Drug InteractionsDrug Interactions

No known significant drug No known significant drug interactions interactions

Abacavir (ZIAGEN):Abacavir (ZIAGEN):Tips for CaregiversTips for Caregivers

Give with or without foodGive with or without food Store at room temperatureStore at room temperature Teach the signs and symptoms of a Teach the signs and symptoms of a

hypersensitivity reactionhypersensitivity reaction Instruct parents to call immediately Instruct parents to call immediately

if rash occursif rash occurs Provide a medication guide and Provide a medication guide and

warning card warning card

Non-Nucleoside Reverse Non-Nucleoside Reverse Transcriptase InhibitorsTranscriptase Inhibitors

NVP, nevirapine (VIRAMUNE)NVP, nevirapine (VIRAMUNE) EFV, efavirenz (SUSTIVA)EFV, efavirenz (SUSTIVA) DLV, delavirdine (RESCRIPTOR)DLV, delavirdine (RESCRIPTOR)

Nevirapine (VIRAMUNE):Nevirapine (VIRAMUNE):FormulationsFormulations

200 mg white, oval tablets200 mg white, oval tablets 50 mg/5 ml solution50 mg/5 ml solution

Nevirapine (VIRAMUNE):Nevirapine (VIRAMUNE):DosingDosing

Neonatal: Oral:Neonatal: Oral:Under investigationUnder investigation

Pediatric: Oral:Pediatric: Oral:(>3 months - 8 years of of age)(>3 months - 8 years of of age)7 mg/kg bid7 mg/kg bid(> 8 years of age)(> 8 years of age)4 mg/kg bid (max. 200 mg bid)4 mg/kg bid (max. 200 mg bid)

Nevirapine (VIRAMUNE):Nevirapine (VIRAMUNE):Side EffectsSide Effects

Most frequent:Most frequent:Skin rash, sedative effect, Skin rash, sedative effect, headache, diarrhea, nauseaheadache, diarrhea, nausea

Less common:Less common:Elevated liver enzymesElevated liver enzymes

Nevirapine (VIRAMUNE):Nevirapine (VIRAMUNE):Drug InteractionsDrug Interactions

Lowers the levels of rifampin and Lowers the levels of rifampin and rifabutinrifabutin

Should not be administered with Should not be administered with ketoconazole or oral ketoconazole or oral contraceptivescontraceptives

Decreases levels of indinavir Decreases levels of indinavir (recommended indinavir dose in (recommended indinavir dose in adults is 1000 mg q8h)adults is 1000 mg q8h)

Nevirapine (VIRAMUNE):Nevirapine (VIRAMUNE):Tips for CaregiversTips for Caregivers

Give with or without foodGive with or without food Tablets may be broken in halfTablets may be broken in half Shake solution wellShake solution well Discuss potential for rashDiscuss potential for rash Medication profile should be Medication profile should be

reviewed carefully prior to starting reviewed carefully prior to starting NVP for potential of multiple drug NVP for potential of multiple drug interactions interactions

Efavirenz (SUSTIVA):Efavirenz (SUSTIVA):FormulationsFormulations

50 mg, 100 mg and 200 mg 50 mg, 100 mg and 200 mg capsulescapsules

Efavirenz (SUSTIVA):Efavirenz (SUSTIVA):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not approved for children < 3 Not approved for children < 3 years oldyears old

Pediatric: Oral:Pediatric: Oral:200-600 mg qd (exact dose is 200-600 mg qd (exact dose is dependent on weight)dependent on weight)

Efavirenz (SUSTIVA):Efavirenz (SUSTIVA):Side EffectsSide Effects

Most frequent:Most frequent:Rash, CNS symptoms (somnolence, Rash, CNS symptoms (somnolence, insomnia, abnormal dreams, insomnia, abnormal dreams, confusion, abnormal thinking, confusion, abnormal thinking, impaired concentration, impaired concentration, hallucinations, euphoria)hallucinations, euphoria)

Less common:Less common:Elevated liver enzymes, hepatitisElevated liver enzymes, hepatitis

Efavirenz (SUSTIVA):Efavirenz (SUSTIVA):Drug InteractionsDrug Interactions

Should not be taken with Should not be taken with midazolam, triazolam, cisapride, midazolam, triazolam, cisapride, and ergot derivativesand ergot derivatives

Reduces levels of clarithromycin Reduces levels of clarithromycin and rifampinand rifampin

Reduces level of rifabutinReduces level of rifabutin Decreases levels of saquinavir, Decreases levels of saquinavir,

indinavir, lopinavirindinavir, lopinavir

Efavirenz (SUSTIVA): Efavirenz (SUSTIVA): Tips for CaregiversTips for Caregivers

Give with or without food, but Give with or without food, but avoid high fat mealavoid high fat meal

Capsules may be opened and Capsules may be opened and sprinkled on foodsprinkled on food

Tolerability of CNS side effects can Tolerability of CNS side effects can be improved by bedtime dosingbe improved by bedtime dosing

Delavirdine (RESCRIPTOR):Delavirdine (RESCRIPTOR):FormulationsFormulations

100 mg white, capsule-shaped 100 mg white, capsule-shaped tabletstablets

Delavirdine (RESCRIPTOR):Delavirdine (RESCRIPTOR):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not approved for use in neonatesNot approved for use in neonates

Pediatric: Oral:Pediatric: Oral:Not approved for use in children Not approved for use in children less than 16 years oldless than 16 years old

Protease InhibitorsProtease Inhibitors

NFV, nelfinavir (VIRACEPT)NFV, nelfinavir (VIRACEPT) RTV, ritonavir (NORVIR)RTV, ritonavir (NORVIR) IDV, indinavir (CRIXIVAN)IDV, indinavir (CRIXIVAN) SQV, saquinavir (FORTOVASE)SQV, saquinavir (FORTOVASE) APV, amprenavir (AGENERASE)APV, amprenavir (AGENERASE) LPV, lopinavir/r (KALETRA)LPV, lopinavir/r (KALETRA)

Nelfinavir (VIRACEPT):Nelfinavir (VIRACEPT):FormulationsFormulations

250 mg blue, capsule-shaped 250 mg blue, capsule-shaped tabletstablets

50 mg/scoop white powder50 mg/scoop white powder

Nelfinavir (VIRACEPT):Nelfinavir (VIRACEPT):DosingDosing

Neonatal: Oral:Neonatal: Oral:Under investigationUnder investigation

Pediatric: Oral:Pediatric: Oral:30 mg/kg tid30 mg/kg tid

Nelfinavir (VIRACEPT):Nelfinavir (VIRACEPT):Side EffectsSide Effects

Most frequent:Most frequent:DiarrheaDiarrhea

Less common:Less common:Abdominal pain, rash, Abdominal pain, rash, exacerbation of liver disease, exacerbation of liver disease, hyperglycemia, diabetes, hyperglycemia, diabetes, metabolic abnormalitiesmetabolic abnormalities

Nelfinavir (VIRACEPT):Nelfinavir (VIRACEPT):Drug InteractionsDrug Interactions

Do not give with simvastatin, Do not give with simvastatin, lovastatin, rifampin, cisapride, lovastatin, rifampin, cisapride, midazolam, triazolam, midazolam, triazolam, dihydroergotamine, ergotaminedihydroergotamine, ergotamine

Concominant Rifabutin should be Concominant Rifabutin should be reduced to 150 mg qd and nelfinavir reduced to 150 mg qd and nelfinavir increased to 1000 mg tidincreased to 1000 mg tid

Decreases level of oral contraceptivesDecreases level of oral contraceptives

Nelfinavir (VIRACEPT):Nelfinavir (VIRACEPT):Tips for CaregiversTips for Caregivers

Give with a meal or light snackGive with a meal or light snack Tablets can be crushed or pulverizedTablets can be crushed or pulverized Do not give with citrus juice or apple Do not give with citrus juice or apple

saucesauce Powder may be put on food or in liquidsPowder may be put on food or in liquids Improve taste by mixing with milk, Improve taste by mixing with milk,

chocolate milk, pudding or vanilla ice chocolate milk, pudding or vanilla ice creamcream

Ritonavir (NORVIR):Ritonavir (NORVIR):FormulationsFormulations

100 mg white, soft-gelatin capsule100 mg white, soft-gelatin capsule 80 mg/ml orange colored solution80 mg/ml orange colored solution

Ritonavir (NORVIR):Ritonavir (NORVIR): Dosing Dosing

Neonatal: Oral:Neonatal: Oral:Under investigationUnder investigation

Pediatrics: Oral:Pediatrics: Oral:400 mg/m400 mg/m22 body surface area bid body surface area bid (max. 600 mg bid)(max. 600 mg bid)

Ritonavir (NORVIR):Ritonavir (NORVIR):Side EffectsSide Effects

Most frequent:Most frequent:Nausea, vomiting, diarrhea, Nausea, vomiting, diarrhea, abdominal pain, anorexiaabdominal pain, anorexia

Less common:Less common:Paresthesias, increased liver Paresthesias, increased liver enzymes, pancreatitis, increased enzymes, pancreatitis, increased triglycerides and cholesterol, triglycerides and cholesterol, hyperglycemia, diabetes, metabolic hyperglycemia, diabetes, metabolic abnormalitiesabnormalities

Ritonavir (NORVIR):Ritonavir (NORVIR):Drug InteractionsDrug Interactions

Should not be used with bepridil, Should not be used with bepridil, amiodarone, flecainide, amiodarone, flecainide, propafenone, quinidine, propafenone, quinidine, simvastatin, lovastatin, cisapride, simvastatin, lovastatin, cisapride, clozapine, midazolam, ergotamineclozapine, midazolam, ergotamine

Lowers the level of oral Lowers the level of oral contraceptivescontraceptives

Ritonavir (NORVIR):Ritonavir (NORVIR):Tips for CaregiversTips for Caregivers

Give with or without food, but food Give with or without food, but food seems to make it more tolerableseems to make it more tolerable

Keep refrigeratedKeep refrigerated Tips for making it more palatable: mix Tips for making it more palatable: mix

with milk or chocolate milk, or vanilla with milk or chocolate milk, or vanilla or chocolate pudding, dull taste buds or chocolate pudding, dull taste buds by giving ice or popsicles prior to by giving ice or popsicles prior to dosing, coat the mouth with peanut dosing, coat the mouth with peanut butter butter

Ritonavir (NORVIR):Ritonavir (NORVIR):Tips for CaregiversTips for Caregivers

Give gradually increasing amounts Give gradually increasing amounts over 5 days until the full dose is over 5 days until the full dose is achieved to help prevent nausea achieved to help prevent nausea and vomitingand vomiting

Obtain a medication history prior Obtain a medication history prior to starting therapyto starting therapy

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):FormulationsFormulations

200 mg, 400 mg capsules200 mg, 400 mg capsules

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not recommendedNot recommended

Pediatric: Oral:Pediatric: Oral:500 mg/m500 mg/m22 body surface area q8h body surface area q8h(max. 800 mg q8h)(max. 800 mg q8h)

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):Side EffectsSide Effects

Most frequent:Most frequent:Nausea, abdominal pain, Nausea, abdominal pain, headache, metallic taste, dizziness, headache, metallic taste, dizziness, asymptomatic hyperbilirubinemiaasymptomatic hyperbilirubinemia

Less common:Less common:Nephrolithiasis, hyperglycemia, Nephrolithiasis, hyperglycemia, ketoacidosis, diabetes, metabolic ketoacidosis, diabetes, metabolic abnormalitiesabnormalities

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):Drug InteractionsDrug Interactions

Do not give with cisapride, Do not give with cisapride, triazolam, midazolam, ergot triazolam, midazolam, ergot derivatives, simvastatin, lovastatinderivatives, simvastatin, lovastatin

Reduce to 800 mg tid when used in Reduce to 800 mg tid when used in combination with ketoconazolecombination with ketoconazole

Reduce rifabutin 50% when used Reduce rifabutin 50% when used togethertogether

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):Tips for CaregiversTips for Caregivers

Give 1 hour before or 2 hours after Give 1 hour before or 2 hours after a meala meal

Encourage 48 ounces of fluid q24hEncourage 48 ounces of fluid q24h Do not take with grapefruit juice;Do not take with grapefruit juice;

may take with water, skim milk, or may take with water, skim milk, or apple juiceapple juice

Keep capsules moisture freeKeep capsules moisture free

Indinavir (CRIXIVAN):Indinavir (CRIXIVAN):Tips for CaregiversTips for Caregivers

Decrease dose in patients with Decrease dose in patients with hepatic insufficiencyhepatic insufficiency

Give 1 hour apart from ddI on an Give 1 hour apart from ddI on an empty stomachempty stomach

Saquinavir (FORTOVASE):Saquinavir (FORTOVASE):FormulationsFormulations

200 mg beige, soft-gel capsules200 mg beige, soft-gel capsules

Saquinavir (FORTOVASE):Saquinavir (FORTOVASE):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not approvedNot approved

Pediatric: Oral:Pediatric: Oral:50 mg/kg tid50 mg/kg tid

Saquinavir (FORTOVASE):Saquinavir (FORTOVASE):Side EffectsSide Effects

Most frequent:Most frequent:Diarrhea, abdominal discomfort, Diarrhea, abdominal discomfort, headache, nausea, paresthesias, skin headache, nausea, paresthesias, skin rashrash

Less common:Less common:Exacerbation of chronic liver disease, Exacerbation of chronic liver disease, hyperglycemia, ketoacidosis, hyperglycemia, ketoacidosis, diabetes, metabolic abnormalitiesdiabetes, metabolic abnormalities

Saquinavir (FORTOVASE):Saquinavir (FORTOVASE):Drug InteractionsDrug Interactions

Should not be taken with cisapride, Should not be taken with cisapride, triazolam, midazolam, ergot, triazolam, midazolam, ergot, simvastatin, lovastatin, rifampin, simvastatin, lovastatin, rifampin, rifabutin, efavirenz, indinavir, rifabutin, efavirenz, indinavir, ketoconazole, clarithromycinketoconazole, clarithromycin

Ritonavir increases levels of Ritonavir increases levels of saquinavir by 3 fold or greatersaquinavir by 3 fold or greater

Saquinavir (FORTOVASE):Saquinavir (FORTOVASE):Tips for CaregiversTips for Caregivers

Give with a meal or up to 2 hours Give with a meal or up to 2 hours after a mealafter a meal

Avoid grapefruit juiceAvoid grapefruit juice Sunscreen or protective clothing is Sunscreen or protective clothing is

recommended recommended Review the patient’s medication Review the patient’s medication

profile for potential drug profile for potential drug interactionsinteractions

Amprenavir (AGENERASE):Amprenavir (AGENERASE):FormulationsFormulations

50 mg and 150 mg cream-white, 50 mg and 150 mg cream-white, soft-gelatin capsulessoft-gelatin capsules

Yellow colored oral solutionYellow colored oral solution

Amprenavir (AGENERASE):Amprenavir (AGENERASE):DosingDosing

Neonatal: Oral:Neonatal: Oral:Not approved for children < 4 years Not approved for children < 4 years oldold

Pediatric: Oral:Pediatric: Oral:Capsule: 20 mg/kg bid or 15 mg/kg Capsule: 20 mg/kg bid or 15 mg/kg tidtidSolution: 22.5 mg/kg bid or Solution: 22.5 mg/kg bid or 17 mg/kg tid17 mg/kg tid(max. 2,800 mg daily)(max. 2,800 mg daily)

Amprenavir (AGENERASE):Amprenavir (AGENERASE):Side EffectsSide Effects

Most frequent:Most frequent:Headache, nausea, upset stomach, Headache, nausea, upset stomach, tirednesstiredness

Less common:Less common:Hyperglycemia, Stevens-Johnson Hyperglycemia, Stevens-Johnson syndromesyndrome

Amprenavir (AGENERASE):Amprenavir (AGENERASE):Drug InteractionsDrug Interactions

Should not be given with bepridil, Should not be given with bepridil, cisapride, dihydroergotamine, cisapride, dihydroergotamine, ergotamine, midazolam, triazolam, ergotamine, midazolam, triazolam, rifampin, simvastatin, lovastatinrifampin, simvastatin, lovastatin

Reduce concomitant Rifabutin by Reduce concomitant Rifabutin by 50% 50%

Give 1 hour before ddIGive 1 hour before ddI Interacts with other antiretroviralsInteracts with other antiretrovirals

Amprenavir (AGENERASE):Amprenavir (AGENERASE):Tips for CaregiversTips for Caregivers

Give with or without foodGive with or without food Do not give supplemental vitamin Do not give supplemental vitamin

EE Solution is bitter but well toleratedSolution is bitter but well tolerated Get comprehensive medication Get comprehensive medication

history prior to starting treatmenthistory prior to starting treatment

Lopinavir/r (KALETRA):Lopinavir/r (KALETRA):FormulationsFormulations

133.3 mg lopinavir/ 33.3 mg 133.3 mg lopinavir/ 33.3 mg ritonavir orange, soft gelatin ritonavir orange, soft gelatin capsulecapsule

80 mg lopinavir/ 20 mg ritonavir/ 80 mg lopinavir/ 20 mg ritonavir/ ml light, yellow/orange oral ml light, yellow/orange oral solutionsolution

Lopinavir/r (KALETRA) Lopinavir/r (KALETRA) DosingDosing

Neonatal: oral: Not approved for Neonatal: oral: Not approved for children less than 6 months of agechildren less than 6 months of age

Pediatric: oral: Pediatric: oral: 12 mg LPV/ 3 mg RTV/kg for children 12 mg LPV/ 3 mg RTV/kg for children

7-15 kg bid with food7-15 kg bid with food10 mg LPV/ 2.5 mg RTV/kg for 10 mg LPV/ 2.5 mg RTV/kg for

children 15-40 kg bid with foodchildren 15-40 kg bid with food

Lopinavir/r (KALETRA)Lopinavir/r (KALETRA)Side EffectsSide Effects

Most frequent:Most frequent: Diarrhea, nausea, vomiting, Diarrhea, nausea, vomiting,

headache, fatigueheadache, fatigue Less Common:Less Common: Pancreatitis, hyperglycemia, Pancreatitis, hyperglycemia,

diabetes, diabetes, metabolic abnormalitiesmetabolic abnormalities

Lopinavir/r (KALETRA)Lopinavir/r (KALETRA)Drug InteractionsDrug Interactions

Should not be taken with ergotamine, Should not be taken with ergotamine, triazolam, astemizole, pinozide, triazolam, astemizole, pinozide, cisapride, propafenone, terfenadine, cisapride, propafenone, terfenadine, flecainide, midazolam, rifampin, flecainide, midazolam, rifampin, lovastatin, simvastatin, St. John’s Wortlovastatin, simvastatin, St. John’s Wort

May reduce effectiveness of oral May reduce effectiveness of oral contraceptivescontraceptives

Increase dose if used with NNRTI’sIncrease dose if used with NNRTI’s

Lopinavir/r (KALETRA):Lopinavir/r (KALETRA):Tips for CaregiversTips for Caregivers

Give with foodGive with food Stable unrefridgerated for 2 Stable unrefridgerated for 2

monthsmonths Review patients medication profile Review patients medication profile

for potential drug interactionsfor potential drug interactions

Drug Interactions of NRTIsDrug Interactions of NRTIsDrug Interactions

AZT Drugs associated with bone marrowsuppressionDrugs which increase ZDVconcentration

d4T Should not be administered with AZTbecause of potential antagonism

ddI Decreases the absorption ofketaconazole, itraconazole, anddapsone

3TC No known drug interactions

ABC No known drug interactions

Drug Interactions of Drug Interactions of NNRTIsNNRTIs

Drug Interactions

NVP Lowers levels of rifampinShould not be administeredwith ketoconazole or oralcontraceptives

EFV Decreases levels of rifampin,rifabutin, clarithromycin,saquinavir, indinavir, lopinavir

Drug Interactions of PIsDrug Interactions of PIsDrug Interactions*

NFV Decreases level of oralcontraceptives

RTV Decreases level of oralcontraceptivesIncreases metabolism oftheophylline

IDV Reduces rifabutin 50% when usedconcomitantly

*All PIs have multiple drug interactions because they are metabolized by ctyochrome

P450 3A

Drug Interactions of PIsDrug Interactions of PIs

Drug InteractionsSQV Levels are increased 3 fold

or greater by RitonavirAPV Reduces Rifabutin 50%

when used concomitantly

Serious Side Effects of Serious Side Effects of NRTIs in ChildrenNRTIs in Children

Drug Side Effects

3TC Pancreatitis, peripheral neuropathy

ABC Hypersensitivity reactions, pancreatitis

AZT Bone marrow suppression

d4t Pancreatitis, peripheral neuropathy

ddC Peripheral neuropathy

ddI Pancreatitis, peripheral neuropathy, retinaldepigmentation

Serious Side Effects of Serious Side Effects of NNRTIsNNRTIs

Drug Side Effects

NVP Rash, fever, nausea, headache,diarrhea

EFV Rash, diarrhea, fever, cough, nausea

DLV Not approved for use in children

Side Effects of PIsSide Effects of PIsDrug Side Effects

NFV Diarrhea

RTV Nausea, vomiting

IDV Nausea, vomiting, hematuria,kidney stones, hyperbilrubinemia

SQV Diarrhea

APV Nausea, vomiting, diarrhea