1. Practical Aspects of Antiretroviral Therapy
Nancy R. Calles,R.N.,B.S.N.

2. Treatment Goals for Children
Promote or restore normal growth and development
Prevent complicating infections and cancers
Improve quality of life
Prolong survival
The goals of antiretroviral treatment for children are to
Promote or restore normal growth and development,
Prevent complicating infections and cancers,
Improve quality of life, and
Prolong survival. Our history with antiretrovirals has proven that these goals can be achieved. It wasn't too many years ago when we didn't have any treatment options for children with HIV. We now have several antiretrovirals available for treating HIV in children. As health care workers it is important that we know as much about these medications as possible to help our patients achieve the goals of antiretroviral therapy with as much ease as possible and with as little disruption in their daily lives as possible.

3. Objectives of this Presentation
List the names and formulations of antiretrovirals
Describe the dosing of antiretrovirals
Discuss the side effects of antiretrovirals
List drug interactions of antiretrovirals
Discuss practical approaches to administration of antiretrovirals
This presentation will not cover pharmacology of the different antiretrovirals but we will discuss some practical approaches to antiretroviral therapy as they relate to the

4. Nucleoside Reverse Transcriptase Inhibitors
AZT, zidovudine (RETROVIR)
d4T, stavudine (ZERIT)
ddI, didanosine (VIDEX)
ddC, zalcitabine (HIVID)
3TC, lamivudine (EPIVIR)
ABC, abacavir (ZIAGEN)

5. Zidovudine (RETROVIR): Formulations
100 mg capsules
300 mg tablets
10 mg/ml yellow liquid, strawberry flavored
Intravenous formulation

6. Zidovudine (RETROVIR): Dosing
Neonatal: Oral: 2 mg/kg q6h
Neonatal: Intravenous: 1.5 mg/kg q6h
Pediatric: Oral: mg/m2 body surface area tid or bid ( 200 max. qid)

7. Zidovudine (RETROVIR): Side Effects
Most Frequent: Hematological, including anemia and neutropenia
Less common: Myopathy, myositis, and liver toxicity

8. Zidovudine (RETROVIR): Drug Interactions
Drugs which can be associated with bone marrow suppression should be avoided
Drugs which may increase ZDV concentration should be avoided (probenecid, atovaquone, methadone, valproic acid, and fluconazole)

9. Zidovudine (RETROVIR): Tips for Caregivers
Tablets and capsules should be stored at room temperature
Protect capsules from moisture
May be taken with or without food

10. Stavudine (ZERIT): Formulations
15 mg, 20 mg, 30 mg, and 40 mg capsules
1 mg/ml cloudy solution

11. Stavudine (ZERIT): Dosing
Neonatal: Under investigation
Pediatric: Oral: 1 mg/kg bid (max. 40 mg bid)

12. Stavudine (ZERIT): Side Effects
Most frequent: Headache, gastrointestinal complaints, skin rash
Less common: Pancreatitis, peripheral neuropathy, increased liver enzymes

13. Stavudine (ZERIT): Drug Interactions
Should not be administered with ZDV because of potential antagonism
Drugs which decrease renal function can decrease clearance and should be avoided

14. Stavudine (ZERIT): Tips for Caregivers
Can be given with or without food
Shake oral solution, keep refrigerated, good for 30 days
Capsules can be opened and sprinkled on mashed potatoes, applesauce or other soft foods

15. Didanosine (VIDEX): Formulations
25 mg, 50 mg, 100 mg, and 150 mg orange flavored, chewable tablets
10 mg/ml white suspension

16. Didanosine (VIDEX): Dosing
Neonatal: Oral: (infants <90 days old) 50 mg/m2 of body surface area
Pediatric: Oral: Dose range: mg/m2 body surface area bid

17. Didanosine (VIDEX): Side Effects
Most frequent: Abdominal pain, nausea, vomiting, diarrhea, constipation
Less common: Peripheral neuropathy, pancreatitis, retinal depigmentation, electrolyte abnormalities

18. Didanosine (VIDEX): Drug Interactions
May decrease the absorption of ketaconazole, itraconazole, and dapsone if administered concomitantly
Tetracycline and fluoroquinolone antibiotic absorption are significantly decreased
Concomitant administration of ddI and DLV decreases the absorption of both

19. Didanosine (VIDEX): Tips for Caregivers
Give on an empty stomach 1 hour before or 2 hours after a meal
Shake suspension well, keep refrigerated
Give two tablets to ensure adequate buffering, may be dissolved in water
Do not give at the same time as indinavir, ritonavir, or delavirdine

20. Lamivudine (EPIVIR): Formulations
150 mg white tablets
10 mg/ml clear solution

21. Lamivudine (EPIVIR): Dosing
Neonatal: Oral: (< 30 days old) 2 mg/kg bid
Pediatric: Oral: 4 mg/kg bid (max. 150 mg bid)

22. Lamivudine (EPIVIR): Side Effects
Most frequent: Headache, fatigue, nausea, diarrhea, skin rash, abdominal pain
Less common: Pancreatitis, peripheral neuropathy, increased liver enzymes

23. Lamivudine (EPIVIR): Drug Interactions
No known negative drug interactions

24. Lamivudine (EPIVIR): Tips for Caregivers
Can be given with or without food
Store oral solution at room temperature
Dosage should be decreased in patients with impaired renal function

25. Abacavir (ZIAGEN): Formulations
300 mg yellow, capsule-shaped tablets
20 mg/ml yellow oral solution

26. Abacavir (ZIAGEN): Dosing
Neonatal: Oral: Not approved for children < 3 months of age
Pediatric: Oral: 8 mg/kg bid (max. 300 mg bid)

27. Abacavir (ZIAGEN): Side Effects
Most frequent: Nausea, fever, vomiting, headache, rash, anorexia, and fatigue
Less common: Hypersensitivity reaction, diarrhea, pancreatitis, increased liver enzymes, elevated blood glucose, elevated triglycerides, and lactic acidosis

28. Abacavir (ZIAGEN): Drug Interactions
No known significant drug interactions

29. Abacavir (ZIAGEN): Tips for Caregivers
Give with or without food
Store at room temperature
Teach the signs and symptoms of a hypersensitivity reaction
Instruct parents to call immediately if rash occurs
Provide a medication guide and warning card

30. Non-Nucleoside Reverse Transcriptase Inhibitors
NVP, nevirapine (VIRAMUNE)
EFV, efavirenz (SUSTIVA)
DLV, delavirdine (RESCRIPTOR)

31. Nevirapine (VIRAMUNE): Formulations
200 mg white, oval tablets
50 mg/5 ml solution

32. Nevirapine (VIRAMUNE): Dosing
Neonatal: Oral: Under investigation
Pediatric: Oral: (>3 months - 8 years of of age) 7 mg/kg bid (> 8 years of age) 4 mg/kg bid (max. 200 mg bid)

33. Nevirapine (VIRAMUNE): Side Effects
Most frequent: Skin rash, sedative effect, headache, diarrhea, nausea
Less common: Elevated liver enzymes

34. Nevirapine (VIRAMUNE): Drug Interactions
Lowers the levels of rifampin and rifabutin
Should not be administered with ketoconazole or oral contraceptives
Decreases levels of indinavir (recommended indinavir dose in adults is 1000 mg q8h)

35. Nevirapine (VIRAMUNE): Tips for Caregivers
Give with or without food
Tablets may be broken in half
Shake solution well
Discuss potential for rash
Medication profile should be reviewed carefully prior to starting NVP for potential of multiple drug interactions

36. Efavirenz (SUSTIVA): Formulations
50 mg, 100 mg and 200 mg capsules

37. Efavirenz (SUSTIVA): Dosing
Neonatal: Oral: Not approved for children < 3 years old
Pediatric: Oral: mg qd (exact dose is dependent on weight)

38. Efavirenz (SUSTIVA): Side Effects
Most frequent: Rash, CNS symptoms (somnolence, insomnia, abnormal dreams, confusion, abnormal thinking, impaired concentration, hallucinations, euphoria)
Less common: Elevated liver enzymes, hepatitis

39. Efavirenz (SUSTIVA): Drug Interactions
Should not be taken with midazolam, triazolam, cisapride, and ergot derivatives
Reduces levels of clarithromycin and rifampin
Reduces level of rifabutin
Decreases levels of saquinavir, indinavir, lopinavir

40. Efavirenz (SUSTIVA): Tips for Caregivers
Give with or without food, but avoid high fat meal
Capsules may be opened and sprinkled on food
Tolerability of CNS side effects can be improved by bedtime dosing

41. Delavirdine (RESCRIPTOR): Formulations
100 mg white, capsule-shaped tablets

42. Delavirdine (RESCRIPTOR): Dosing
Neonatal: Oral: Not approved for use in neonates
Pediatric: Oral: Not approved for use in children less than 16 years old

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

44. Nelfinavir (VIRACEPT): Formulations
250 mg blue, capsule-shaped tablets
50 mg/scoop white powder

45. Nelfinavir (VIRACEPT): Dosing
Neonatal: Oral: Under investigation
Pediatric: Oral: 30 mg/kg tid

46. Nelfinavir (VIRACEPT): Side Effects
Most frequent: Diarrhea
Less common: Abdominal pain, rash, exacerbation of liver disease, hyperglycemia, diabetes, metabolic abnormalities

47. Nelfinavir (VIRACEPT): Drug Interactions
Do not give with simvastatin, lovastatin, rifampin, cisapride, midazolam, triazolam, dihydroergotamine, ergotamine
Concominant Rifabutin should be reduced to 150 mg qd and nelfinavir increased to 1000 mg tid
Decreases level of oral contraceptives

48. Nelfinavir (VIRACEPT): Tips for Caregivers
Give with a meal or light snack
Tablets can be crushed or pulverized
Do not give with citrus juice or apple sauce
Powder may be put on food or in liquids
Improve taste by mixing with milk, chocolate milk, pudding or vanilla ice cream

49. Ritonavir (NORVIR): Formulations
100 mg white, soft-gelatin capsule
80 mg/ml orange colored solution

50. Ritonavir (NORVIR): Dosing
Neonatal: Oral: Under investigation
Pediatrics: Oral: 400 mg/m2 body surface area bid (max. 600 mg bid)

51. Ritonavir (NORVIR): Side Effects
Most frequent: Nausea, vomiting, diarrhea, abdominal pain, anorexia
Less common: Paresthesias, increased liver enzymes, pancreatitis, increased triglycerides and cholesterol, hyperglycemia, diabetes, metabolic abnormalities

52. Ritonavir (NORVIR): Drug Interactions
Should not be used with bepridil, amiodarone, flecainide, propafenone, quinidine, simvastatin, lovastatin, cisapride, clozapine, midazolam, ergotamine
Lowers the level of oral contraceptives

53. Ritonavir (NORVIR): Tips for Caregivers
Give with or without food, but food seems to make it more tolerable
Keep refrigerated
Tips for making it more palatable: mix with milk or chocolate milk, or vanilla or chocolate pudding, dull taste buds by giving ice or popsicles prior to dosing, coat the mouth with peanut butter

54. Ritonavir (NORVIR): Tips for Caregivers
Give gradually increasing amounts over 5 days until the full dose is achieved to help prevent nausea and vomiting
Obtain a medication history prior to starting therapy

55. Indinavir (CRIXIVAN): Formulations
200 mg, 400 mg capsules

56. Indinavir (CRIXIVAN): Dosing
Neonatal: Oral: Not recommended
Pediatric: Oral: 500 mg/m2 body surface area q8h (max. 800 mg q8h)

57. Indinavir (CRIXIVAN): Side Effects
Most frequent: Nausea, abdominal pain, headache, metallic taste, dizziness, asymptomatic hyperbilirubinemia
Less common: Nephrolithiasis, hyperglycemia, ketoacidosis, diabetes, metabolic abnormalities

58. Indinavir (CRIXIVAN): Drug Interactions
Do not give with cisapride, triazolam, midazolam, ergot derivatives, simvastatin, lovastatin
Reduce to 800 mg tid when used in combination with ketoconazole
Reduce rifabutin 50% when used together

59. Indinavir (CRIXIVAN): Tips for Caregivers
Give 1 hour before or 2 hours after a meal
Encourage 48 ounces of fluid q24h
Do not take with grapefruit juice; may take with water, skim milk, or apple juice
Keep capsules moisture free

60. Indinavir (CRIXIVAN): Tips for Caregivers
Decrease dose in patients with hepatic insufficiency
Give 1 hour apart from ddI on an empty stomach

61. Saquinavir (FORTOVASE): Formulations
200 mg beige, soft-gel capsules

62. Saquinavir (FORTOVASE): Dosing
Neonatal: Oral: Not approved
Pediatric: Oral: 50 mg/kg tid

63. Saquinavir (FORTOVASE): Side Effects
Most frequent: Diarrhea, abdominal discomfort, headache, nausea, paresthesias, skin rash
Less common: Exacerbation of chronic liver disease, hyperglycemia, ketoacidosis, diabetes, metabolic abnormalities

64. Saquinavir (FORTOVASE): Drug Interactions
Should not be taken with cisapride, triazolam, midazolam, ergot, simvastatin, lovastatin, rifampin, rifabutin, efavirenz, indinavir, ketoconazole, clarithromycin
Ritonavir increases levels of saquinavir by 3 fold or greater

65. Saquinavir (FORTOVASE): Tips for Caregivers
Give with a meal or up to 2 hours after a meal
Avoid grapefruit juice
Sunscreen or protective clothing is recommended
Review the patient’s medication profile for potential drug interactions

66. Amprenavir (AGENERASE): Formulations
50 mg and 150 mg cream-white, soft-gelatin capsules
Yellow colored oral solution

67. Amprenavir (AGENERASE): Dosing
Neonatal: Oral: Not approved for children < 4 years old
Pediatric: Oral: Capsule: 20 mg/kg bid or 15 mg/kg tid Solution: 22.5 mg/kg bid or 17 mg/kg tid (max. 2,800 mg daily)

68. Amprenavir (AGENERASE): Side Effects
Most frequent: Headache, nausea, upset stomach, tiredness
Less common: Hyperglycemia, Stevens-Johnson syndrome

69. Amprenavir (AGENERASE): Drug Interactions
Should not be given with bepridil, cisapride, dihydroergotamine, ergotamine, midazolam, triazolam, rifampin, simvastatin, lovastatin
Reduce concomitant Rifabutin by 50%
Give 1 hour before ddI
Interacts with other antiretrovirals

70. Amprenavir (AGENERASE): Tips for Caregivers
Give with or without food
Do not give supplemental vitamin E
Solution is bitter but well tolerated
Get comprehensive medication history prior to starting treatment

71. Lopinavir/r (KALETRA): Formulations
133.3 mg lopinavir/ 33.3 mg ritonavir orange, soft gelatin capsule
80 mg lopinavir/ 20 mg ritonavir/ ml light, yellow/orange oral solution

72. Lopinavir/r (KALETRA) Dosing
Neonatal: oral: Not approved for children less than 6 months of age
Pediatric: oral:
12 mg LPV/ 3 mg RTV/kg for children 7-15 kg bid with food
10 mg LPV/ 2.5 mg RTV/kg for children kg bid with food

73. Lopinavir/r (KALETRA) Side Effects
Most frequent:
Diarrhea, nausea, vomiting, headache, fatigue
Less Common:
Pancreatitis, hyperglycemia, diabetes,
metabolic abnormalities

74. Lopinavir/r (KALETRA) Drug Interactions
Should not be taken with ergotamine, triazolam, astemizole, pinozide, cisapride, propafenone, terfenadine, flecainide, midazolam, rifampin, lovastatin, simvastatin, St. John’s Wort
May reduce effectiveness of oral contraceptives
Increase dose if used with NNRTI’s

75. Lopinavir/r (KALETRA): Tips for Caregivers
Give with food
Stable unrefridgerated for 2 months
Review patients medication profile for potential drug interactions

76. Drug Interactions of NRTIs

77. Drug Interactions of NNRTIs

78. Drug Interactions of PIs

79. Drug Interactions of PIs

80. Serious Side Effects of NRTIs in Children

81. Serious Side Effects of NNRTIs

82. Side Effects of PIs