AIDS-Related Medications

Chapter 80 AIDS-Related Medications



Alice K. Pau, PharmD, Sarah Robertson, PharmD



INDEX OF MEDICATIONS














































































































































































































































Antiretrovirals 1408
Abacavir 1408
Amprenavir 1409
Atazanavir 1409
Darunavir 1410
Delavirdine 1410
Didanosine 1410
Efavirenz 1411
Emtricitabine 1412
Enfuvirtide 1412
Fosamprenavir 1412
Indinavir 1413
Lamivudine 1413
Lopinavir/Ritonavir 1414
Maraviroc 1414
Nelfinavir 1415
Nevirapine 1415
Ritonavir 1416
Saquinavir 1416
Stavudine 1417
Tenofovir Disoproxil Fumarate 1417
Tipranavir 1417
Zidovudine 1418
Dosing of Antiretrovirals in the Presence of Renal or Hepatic Insufficiency in Adult HIV Patients
Antimycobacterial Drugs 1422
Amikacin 1422
Azithromycin 1422
Clarithromycin 1422
Ethambutol 1423
Isoniazid 1423
Moxifloxacin 1424
Pyrazinamide 1424
Rifabutin 1424
Rifampin 1425
Streptomycin 1425
Agents for Treatment of Pneumocystis Jiroveci (Carinii) Pneumonia (PCP) and Toxoplasma Gondii Infections 1426
Atovaquone 1426
Clindamycin 1426
Dapsone 1426
Pentamidine 1427
Primaquine Phosphate 1427
Pyrimethamine 1428
Sulfadiazine 1428
Trimethoprim/Sulfamethoxazole 1428
Antifungal Agents 1429
Amphotericin B 1429
Anidulofungin 1429
Caspofungin 1430
Clotrimazole 1430
Fluconazole 1430
Flucytosine 1431
Itraconazole 1431
Ketoconazole 1432
Micafungin 1432
Nystatin 1432
Voriconazole 1432
Anticytomegalovirus, Antiherpes Simplex Virus, and Antivaricella-Zoster Virus Agents 1433
Acyclovir 1433
Cidofovir 1434
Famciclovir 1434
Foscarnet 1435
Ganciclovir 1435
Valacyclovir 1436
Valganciclovir 1436
Hepatitis B and Hepatitis C Treatment 1436
Adefovir Dopivoxil 1436
Entecavir 1437
Interferon-alfa 2b 1437
Peginterferon-alfa 2a 1438
Peginterferon-alfa 2b 1438
Ribavirin 1438
Biologics Miscellaneous 1439
Darbepoietin 1439
Erythropoietin 1439
Filgrastim 1439
Miscellaneous – Other Medications 1440
Albendazole 1440
Paromomycin 1440


DEFINITIONS OF FDA PREGNANCY RISK FACTOR CATEGORIES



Category A: Controlled studies in women fail to show risk to fetus during first trimester (with no evidence of risk during later trimesters), and the possibility of fetal harm appears remote.

Category B: Either animal reproduction studies have not demonstrated a fetal risk (with no controlled studies in pregnant women) or animal reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies of women during the first trimester (with no evidence of risk during later trimesters).

Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic, embryocidal, or other), with no controlled studies in pregnant women, or studies in women and animals are not available. Drugs should be given only if potential benefit justifies the potential risk to the fetus.

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Category X: Studies in animals or humans have demonstrated fetal abnormalities, there is evidence of fetal risk based on human experience, or both; and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.






































































Abbreviations  
AUC Area under the concentration–time curve
Cmax Maximum concentration
CMV Cytomegalovirus
CrCl Creatinine clearance
CNS Central nervous system
CSF Cerebrospinal fluid
EC enteric coated
GI Gastrointestinal
HSV Herpes simplex virus
IM Intramuscular
IV Intravenous
LFTs Liver function tests
MAC Mycobacterium avium complex
OTC Over the counter
PCP Pneumocystis jiroveci (carinii) pneumonia
SC Subcutaneous
t1/2 Half-life
Tmax Time to maximum concentration
Toxo Toxoplasmosis
USPHS US Public Health Service
VZV Varicella-zoster virus

Prices listed are approximate and based on 2005 average wholesale price (AWP).



ANTIRETROVIRALS


Note: Please refer to the table at the end of this section for dosing recommendations of antiretroviral agents in patients with renal or hepatic dysfunction.



Abacavir (ABC)


Trade name: Ziagen (GlaxoSmithKline)




















Available formulations:  
300 mg tablets $7.46
20 mg/mL oral solution, 240 mL $117.71
Epzicom (abacavir 600 mg/lamivudine 300 mg) $26.03
Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg) $19.50

Class: Nucleoside reverse transcriptase inhibitor


Oral dose:


Adults:


As Ziagen: Abacavir 300 mg twice daily or 600 mg once daily


As Epzicom: One tablet once daily


As Trizivir: One tablet twice daily


Children (3 months):–8 mg/kg (max 300 mg) twice daily


Storage and stability: Store at room temperature; oral solution may be refrigerated; do not freeze



Pharmacokinetics


Tmax: 1 h


Bioavailability: 83%


Plasma half-life: 0.9–1.5 h (intracellular 12–26 h)


CSF penetration: Approximately 18% of plasma concentration


Plasma protein binding: Approximately 50%


Metabolism/elimination: Primarily metabolized by alcohol dehydrogenase and glucuronyl transferase


Food effects: Can be taken without regard to meals


Breast milk: Animal studies indicate that abacavir is excreted in breast milk. USPHS recommends that HIV+ mothers not breastfeed, to avoid transmission to infant


Side-effects: Systemic hypersensitivity reaction, associated with constitutional symptoms, fever, rash, gastrointestinal disturbances, and/or respiratory symptoms, reported in 2–9% of patients; reaction is strongly associated with carriage of the MHC class I allele HLA-B*5701. Abacavir should be discontinued and not rechallenged; rechallenge reactions can be severe, even fatal. This reaction has also been reported in patients who discontinue abacavir for reasons other than hypersensitivity. Other side-effects included asthenia, abdominal pain, diarrhea, nausea, vomiting, headache, hepatomegaly with steatosis, lactic acidosis


Pregnancy: Category C



Amprenavir (APV)


Trade name: Agenerase (GlaxoSmithKline)


Available formulations (150 mg capsule formulation is no longer available):











50 mg capsule $0.54
15 mg/mL oral solution, 240 mL $38.77

Note: Oral solution contains propylene glycol, not recommended in children less than 4-years old, pregnant women, patients with renal or liver failure, and patients on metronidazole or disulfiram.


Class: Protease inhibitor (PI)


Oral dose:


Adults:


Capsules: 1200 mg twice daily or (600 mg twice daily 1ritonavir 100 mg twice daily) or (1200 mg once daily + ritonavir 200 mg once daily). Fosamprenavir should be considered for use in place of amprenavir in adults–as amprenavir 150 mg capsule is no longer available


Oral solution: 1400 mg (93.3 mL) twice daily


Children:


Capsules: <50 kg: 20 mg/kg twice daily or 15 mg/kg three times daily


Solution: <50 kg: 22.5 mg/kg twice daily or 17 mg/kg three times daily


Capsules and oral solution doses are not interchangeable on a milligram per milligram basis


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 1–2 h


Bioavailability: Not established


Half-life: 7–10 h


CSF penetration: Not established


Plasma protein binding: 91–95%


Metabolism/elimination: Extensive hepatic metabolism by CYP3A4; inhibitor and inducer of CYP3A4-mediated metabolism


Food effects: Can be taken without regard to meals, but not with a high-fat meal


Breast milk: Animal studies indicate that amprenavir is excreted in breast milk. USPHS recommends that HIV+ mothers not breastfeed, to avoid transmission to infant


Side-effects: Headache, nausea, vomiting, diarrhea, rash. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category C



Atazanavir (ATV)


Trade name: Reyataz (Bristol-Myers Squibb)



















Available formulations:
100 mg $14.29
150 mg $14.29
200 mg $14.29
300 mg $28.57

Class: PI


Oral dose:


Adults: Treatment-naive patients: 400 mg once daily


Treatment-experienced patients and patients on efavirenz or tenofovir: 300 mg once daily + ritonavir 100 mg once daily


Children: Not approved for use in children


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 2.5 h


Bioavailability: Not established


Half-life: 7 h


CSF penetration: CSF to plasma ratio 0.0021–0.0226


Plasma protein binding: 86%


Metabolism/elimination: Substrate and inhibitor of CYP3A4 metabolism


Food effects: Bioavailability increases with food; administer with meals or snack. Avoid taking with antacids


Breast milk: Unknown. USPHS recommends that HIV+ mothers not breastfeed, to avoid transmission to infant


Side-effects: Nausea, headache, indirect hyperbilirubinemia, jaundice, prolonged PR interval (less common), asymptomatic first-degree AV block in some patients. Less hypertriglyceridemia than with other PIs


Pregnancy: Category B



Darunavir (Prezista™)


Class: Protease inhibitor


Oral dose:


Adults: 600 mg bid + ritonavir 100 mg bid (treatment-experienced)


Storage and stability: Tablets stable at room temperature.



Pharmacokinetics


Tmax: 2.5–4 hours


Bioavailability: 37% (82% with ritonavir)


Half-life: approximately 10 hours (unboosted); 15 hours (with ritonavir)


CSF penetration: Unknown


Plasma protein binding: 95%


Metabolism/elimination: Darunavir is almost exclusively metabolized by CYP3A4. Both darunavir and ritonavir are inhibitors of CYP3A4.


Food effects: When administered with food, the Cmax and AUC of darunavir, co-administered with ritonavir, increases 30% relative to the fasting state. Darunavir/ritonavir should be administered with meals.


Breast milk: Darunavir is secreted into the milk of lactating rats; extent of secretion in human milk is unknown. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant.


Dosage adjustment for organ failure: No dosage adjustment in the setting of renal impairment is necessary, as the renal clearance of darunavir is limited. No recommendations for patients with hepatic impairment; use with caution.


Side-effects: Diarrhea, headache, nausea, fatigue, nasopharyngitis, increased liver enzymes, increased pancreatic enzymes, and increased cholesterol and triglycerides.


Pregnancy: Category B



Delavirdine


Trade name: Rescriptor (Agouron)














Available formulations:  
100 mg tablets $0.88
200 mg tablets $1.76

Class: Non-nucleoside reverse transcriptase inhibitor


Oral dose (adults): 400 mg three times daily


Storage and stability: Keep in tightly closed container at room temperature away from high humidity



Pharmacokinetics


Tmax: 1 h


Bioavailability: 85%, increased when in slurry of water


Half-life: 5.8 h


CSF penetration: 0.4% of plasma concentration


Plasma protein binding: 98%


Metabolism/elimination: Extensively metabolized in liver by CYP3A4 and possibly CYP2D6. Inhibitor of CYP3A4-mediated metabolism


Food effects: Can be taken without regard to meals


Breast milk: Unknown. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Rash in 18% and severe in 3.6%, usually appears within 1–3 weeks of therapy initiation; nausea; increased serum transaminases


Pregnancy: Category C



Didanosine (ddI)


Trade name: Videx and Videx EC (Bristol-Myers Squibb); generic enteric-coated didanosine


















































Available formulations:  
25 mg buffered tablets $0.47
50 mg buffered tablets $0.95
100 mg buffered tablets $1.89
150 mg buffered tablets $2.84
200 mg buffered tablets $3.79
2 g/100 mL pediatric powder $34.70
4 g/200 mL pediatric powder $78.61
100 mg sachet $1.89
167 mg sachet $3.16
250 mg sachet $4.74
125 mg EC capsules $3.60
200 mg EC capsules $4.96
250 mg EC capsules $6.19
400 mg EC capsules $9.91

Class: Nucleoside reverse transcriptase inhibitor


Oral doses:


EC capsules:


>60 kg: 400 mg once daily on an empty stomach


<60 kg: 250 mg once daily on an empty stomach


Buffered tablets:


>60 kg: 200 mg twice daily or 400 mg once daily on an empty stomach


<60 kg: 125 mg twice daily or 250 mg once daily on an empty stomach


Note: Two buffered tablets must be administered at each dose to ensure adequate buffering. Tablets should be chewed, crushed, or dispersed in water or clear apple juice


Sachet:


>60 kg: 250 mg twice daily on an empty stomach


<60 kg: 167 mg twice daily on an empty stomach


Mix with 4 ounces of water; stir until dissolved


Oral dose suspension (children):


Age 2 weeks to 8 months: 100 mg/m2 twice daily


Age > 8 months: 120 mg/m2 twice daily


Suspension is dissolved in water and then mixed with equal amount of antacid


Storage and stability:


EC capsules: Store at room temperature


Tablets: Store at room temperature in tightly closed bottles. If dispersed in water or apple juice, stable for 1 h at room temperature


Sachet: Store at room temperature. If dissolved in water, stable for 4 h at room temperature


Suspension: Store bottles at room temperature. After reconstitution, store in refrigerator in tightly closed container for up to 30 days



Pharmacokinetics


Tmax: 0.6–1.0 h


Bioavailability: Buffered tablet and EC capsule 40%; sachet 30%


Plasma half-life: 1.6 h (Intracellular >20 h)


CSF penetration: 21% of serum concentration (children 46%)


Plasma protein binding: Less than 5%


Metabolism/elimination: Primarily eliminated by renal excretion


Food effects: Requires administration on empty stomach, at least 30 min before or 2 h after a meal


Breast milk: Unknown. The USPHS recommends that HIV+ women not breastfeed to avoid transmission to infants


Side-effects: Nausea, diarrhea (mainly with buffered formulations), abdominal pain, peripheral neuropathy (12–34%, dose-related), pancreatitis (1–7%, dose-related), headache, rash, hepatomegaly with steatosis, lactic acidosis, retinal pigmentation


Pregnancy: Category B. Fatal lactic acidosis has been reported in pregnant women treated with a combination of ddI and stavudine



Efavirenz (EFV)


Trade name: Sustiva (Bristol-Meyers Squibb)























Available formulations:  
50 mg capsules $1.33
100 mg capsules $2.66
200 mg capsules $5.33
600 mg tablets $15.98
Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg) $47.95

Class: Non-nucleoside reverse transcriptase inhibitor


Oral dose:


Adults: 600 mg once daily, recommended to be given at bedtime or before bedtime on an empty stomach.


As Atripla: One tablet at bedtime or before bedtime on an empty stomach


Children (3 years of age or older):


























Weight (lbs) Dose (mg)
22 to <33 200
33 to <44 250
44 to <55 300
55 to <71.5 350
71.5 to <88 400
≥88 600

Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 3–5 h


Bioavailability: Not established


Half-life: 40–55 h with multiple dosing


CSF penetration: 0.65–1.20% of plasma concentration


Plasma protein binding: 99.5–99.75%


Metabolism/elimination: Primarily hepatic metabolism by CYP2B6 and CYP3A4; mixed inducer and inhibitor of CYP3A4


Food effects: Administer on an empty stomach; food increases EFV absorption and may result in increased toxicity


Breast milk: Animal studies indicate that EFV is excreted in breast milk. USPHS recommends that HIV+ women not breastfeed to avoid transmission to infants


Side-effects: Dizziness, paresthesias, headache, lightheadedness, confusion, vivid dreams (CNS-related symptoms may be minimized by administering drug at bedtime), nausea, rash (26% in adults, 40% in children), elevated LFTs, liver failure, elevated serum lipids


Pregnancy: Category D. EFV has been shown to cause major congenital anomalies in nonhuman primates following first trimester exposure; there are case reports of neural tube defects in humans following first trimester exposure



Emtricitabine (FTC)


Trade name: Emtriva (Gilead Sciences)




















Available formulations:  
200 mg capsule $10.60
10 mg/mL oral solution 170 mL $81.96
Truvada (FTC 200 mg/tenofovir 300 mg) $26.03
Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg) $47.95

Class: Nucleoside reverse transcriptase inhibitor active against HIV and hepatitis B


Oral dose:


Adults: 200 mg capsule once daily or 240 mg oral solution (24 mL) once daily


As Atripla: One tablet at bedtime or before bedtime on an empty stomach


Children (3 months to 17 years): 6 mg/kg (max 240 mg) oral solution once daily; capsules (for weight >33 kg): 200 mg once daily


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 1–2 h


Bioavailability: 93% capsules; 75% oral solution


Plasma half-life: 10 h (intracellular >20 h)


CSF penetration: Unknown


Plasma protein binding: <4%


Metabolism/elimination: Renal excretion by glomerular filtration and active tubular secretion


Food effects: Administer without regards to meals


Breast milk: Unknown. The USPHS recommends that HIV+ women not breastfeed to avoid transmission to infants


Side-effects: Minimal toxicity; nausea, headache, diarrhea, hyperpigmentation, lactic acidosis with hepatic steatosis (rare). Potential exacerbation of hepatitis B in co-infected patients following discontinuation of FTC change to alternative agent with activity against hepatitis B virus (HBV)


Pregnancy: Category B



Enfuvirtide (T20)


Trade name: Fuzeon (Hoffmann-LaRoche)











Available formulations:  
Single-use vial of 108 mg enfuvirtide, to be reconstituted with 1.1 mL sterile water for delivery of 90 mg/1 mL $35.29

Class: Fusion inhibitor


Dose:


Adults: 90 mg (1 mL) subcutaneous (SC) injection twice daily


Children: Not approved for children <6 years of age. In children 6 years of age: 2 mg/kg (max 90 mg) twice daily by subcutaneous injection


Storage and stability: Store vials at room temperature. Reconstituted solution should be stored under refrigeration and used within 24 h



Pharmacokinetics


Tmax: 4 h


Bioavailability: 84.3%


Half-life: 3.8 h


CSF penetration: Unknown


Plasma protein binding: 92%


Metabolism/elimination: Catabolism to constituent amino acids


Food effects: Administer without regards to meals


Breast milk: Animal studies indicate that enfuvirtide is excreted in breast milk. The USPHS recommends that HIV+ women not breastfeed, to avoid transmission to infants


Side-effects: Local injection site reaction seen in almost all patients (pain, erythema, induration, nodules, pruritis); increased rate of bacterial pneumonia in patients receiving enfuvirtide was observed in clinical trials; hypersensitivity reaction (<1%)


Pregnancy: Category B



Fosamprenavir (f-APV)


Trade name: Lexiva (GlaxoSmithKline)














Available formulations:  
700 mg tablet $11.09
50 mg/mL oral suspension, 225 mL  

Class: PI


Oral dose:


Adult treatment-naive patients:


f-APV 1400 mg twice-daily OR


(f-APV1400 mg + ritonavir 200 mg) once-daily OR


(f-APV 700 mg + ritonavir 100 mg) twice daily


Adult treatment-experienced patients:


f-APV 700 mg twice daily + ritonavir 100 mg twice daily


Children:


Therapy-naive 2–5 years old:


30 mg/kg twice daily, not to exceed 1,400 mg twice daily


Therapy-naive ≥ 6 years old:


30 mg/kg twice daily not to exceed 1,400 mg twice daily or


18 mg/kg plus ritonavir 3 mg/kg twice daily not to exceed 700 mg + ritonavir 100 mg twice daily


Therapy-experienced ≥ 6 Years of Age:


18 mg/kg plus ritonavir 3 mg/kg administered twice daily not to exceed fosamprenavir 700 mg + ritonavir 100 mg twice daily


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 1.5–2.5 h


Bioavailability: Not established


Half-life: 7.7 h


CSF penetration: Unknown


Plasma protein binding: 90%


Metabolism/elimination: f-APV is rapidly and almost completely hydrolyzed to APV in the gut epithelium. The parent drug, APV, is extensively metabolism by CYP3A4, and is an inhibitor and inducer of CYP3A4-mediated metabolism


Food effects: Administer without regards to meals


Breast milk: Animal studies indicate that APV is excreted in breast milk. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Skin rash (19%), headache, nausea, vomiting, diarrhea. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category C



Indinavir (IDV)


Trade name: Crixivan (Merck)




















Available formulations:  
100 mg $0.76
200 mg $1.52
333 mg $2.54
400 mg $3.05

Class: PI


Oral doses:


800 mg every 8 h on an empty stomach, OR


IDV 800 mg + ritonavir (100 or 200 mg) twice daily with or without food


Storage and stability: Store at room temperature in original, tightly closed container with desiccant



Pharmacokinetics


Tmax: 0.8 h


Bioavailability: 65%


Half-life: 1.5–2.0 h


CSF penetration: 2.2–76.0% in limited number of patients


Plasma protein binding: Approximately 60%


Metabolism/elimination: Hepatic metabolism by CYP3A4; less than 20% excreted unchanged in urine; inhibitor of CY3A4-mediated metabolism


Food effects: High-caloric, high-fat meal reduces bioavailability. Administer on empty stomach or with a low-fat, light meal. It can be administered with food when taken with ritonavir. Patients are advised to drink at least 1.5 L of fluid daily to avoid crystalluria and nephrolithiasis


Breast milk: Available data suggest distribution into milk. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Nephrolithiasis/urolithiasis, nausea, GI intolerance, indirect hyperbilirubinemia, headache, dizziness, rash, hemolytic anemia. PIs have been associated with metabolic effects, including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category C



Lamivudine (3TC)


Trade name: Epivir (GlaxoSmithKline)


























Available formulations:  
150 mg tablet $5.55
300 mg tablet $11.11
10 mg/mL, 240 mL oral solution $88.86
Combivir (3TC 150 mg + zidovudine 300 mg) $12.04
Epzicom (3TC 300 mg + ABC 600 mg) $26.03
Trizivir (3TC 150 mg + ABC 300 mg + zidovudine 300 mg) $19.05

Class: Nucleoside reverse transcriptase inhibitor active against HIV and HBV


Oral dose:


Adults: 150 mg twice daily or 300 mg once daily


Children:


Neonatal/infants (<30 days): 2 mg/kg twice daily


Pediatric (<50 kg): 4 mg/kg twice daily (up to 150 mg twice daily)


Storage and stability: Store at room temperature in tightly closed containers



Pharmacokinetics


Tmax: Approximately 1 h (fasting), 3.2 h (fed)


Bioavailability: 86% (66–68% in children)


Half-life: 5–7 h (intracellular 18–22 h)


CSF penetration: Unknown


Plasma protein binding: Less than 36%


Metabolism/elimination: Primarily eliminated unchanged in the urine


Food effects: Food delays absorption but not overall extent; give without regard to meals


Breast milk: Available data suggest that lamivudine is readily excreted in milk. USPHS recommends that HIV+ women not breastfeed to avoid transmission to infants


Side-effects: Nausea, headache, malaise, nasal congestion, pancreatitis in children (14%), hepatomegaly with steatosis, lactic acidosis. Potential exacerbation of hepatitis B in co-infected patients following discontinuation of 3TC–change to alternative agent with activity against HBV


Pregnancy: Category C



Lopinavir/Ritonavir (LPV/RTV)


Trade name: Kaletra (Abbott)














Available formulations:  
Lopinavir 200 mg + ritonavir 50 mg tablet $6.64
Lopinavir 80 mg/ritionavir 20 mg/mL oral solution, 180 mL $351.75

Class: PI


Oral dose:


Adults, adolescents (>12 years): 400/100 mg twice daily or 800/200 mg once daily (treatment-naive patients only)


Children (6 months to 12 years):














7 to <15 kg 12/3 mg/kg twice daily
15 to 40 kg 10/2.5 mg/kg twice daily
>40 kg Use adult dose

Storage and stability: Solution is stable in refrigerator until date on label; at room temperature, use within2 months. Tablets are stored at room temperature



Pharmacokinetics


Tmax: 4 h


Bioavailability: Not determined


Half-life: 5–6 h


CSF penetration: Negligible


Plasma protein binding: Approximately 98–99%


Metabolism/elimination: Substrate and inhibitor of CYP3A4 metabolism


Food effects: Food significantly increases plasma concentrations of the solution; administer with food. Tablets may be administered without regard to meals


Breast milk: Animal data suggest distribution into milk. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Nausea, diarrhea (higher incidence with once-daily dosing), abdominal pain, asthenia, headache, elevated LFTs. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category C



Maraviroc


Trade name: Selzentry (Pfizer)


Available formulation:


150 mg tablet


300 mg tablet


Class: Entry Inhibitor


Mechanism of Action: CCR5 Antagonist


Oral dose:


Adults:














When given with strong CYP3A inhibitors (with or without CYP3A inducers), including protease inhibitors (except tipranavir/ritonavir) and delavirdine 150 mg twice daily
With NRTIs, tipranavir/ritonavir, nevirapine and other drugs that are not strong CYP3A inhibitors or CYP3A inducers 300 mg twice daily
With CYP3A inducers including efavirenz (without a strong CYP3A inhibitor) 600 mg twice daily

Storage and stability: Room temperature



Pharmacokinetics


Tmax: 0.5–4 h


Bioavailability: 33% (predicted, following a 300 mg dose)


Half-life: 14–18 h


CSF penetration: Unknown


Plasma protein binding: 76%


Metabolism/elimination: Maraviroc is principally metabolized by CYP3A, and is also a substrate for P-glycoprotein (P-gp). Renal clearance accounts for approximately 25% of maraviroc total clearance. When administered with CYP3A/P-gp inhibitors, maraviroc exposure is significantly increased, while CYP3A inducers rifampin and efavirenz significantly decrease maraviroc exposure. Tipranavir/ritonavir does not affect the PK of maraviroc


Food effects: Maraviroc may be taken with or without food


Breast milk: Maraviroc is extensively secreted into the milk of lactating rats; the extent of secretion into human milk is unknown. USPHS recommends that HIV+ mothers not breastfeed to avoid HIV transmission to infant


Dosage adjustment for organ failure: Maraviroc exposure may be increased in patients with renal impairment, especially when CYP3A inhibitors are coadministered. Patients with a CrCl < 50 mL/min should take maraviroc with a CYP3A inhibitor only if the potential benefit outweighs the risk of toxicity; monitor for side-effects. Maraviroc exposure is expected to be increased in patients with hepatic impairment; use with caution


Side-effects: The most common adverse events reported in clinical trials were cough, pyrexia, upper respiratory tract infection, rash, musculoskeletal symptoms, abdominal pain and dizziness. Laboratory abnormalities reported in clinical trials included increases in AST, ALT, total bilirubin, amylase and lipase, and decreased absolute neutrophil count


Pregnancy: Pregnancy Category B. Maraviroc has not been studied in pregnant women. Ensure adequate contraception in women of childbearing potential



Nelfinavir (NFV)


Trade name: Viracept (Agouron)

















Available formulations:  
250 mg tablet $2.52
625 mg tablet $6.05
50 mg/g oral powder, 144 g $66.48

Class: PI


Oral dose:


Adults: 750 mg three times daily or 1250 mg twice daily with food


Children (≤2 years): 45–55 mg/kg twice daily with food or 25–35 mg/kg three times daily with food


Storage and stability: Oral powder may be mixed with water, milk/formula, soy milk/formula, and dietary supplements. Mixed powder may be stored in refrigerator up to 6 h. Store tablets at room temperature



Pharmacokinetics


Tmax: 2–4 h


Bioavailability: 20–80%


Half-life: 3.5–5.0 h


CSF penetration: Negligible


Plasma protein binding: More than 98%


Metabolism/elimination: Extensive hepatic metabolism by CYP3A4 and CYP2C19, with metabolites excreted in feces. Inhibitor of CYP3A4-mediated metabolism


Food effects: Bioavailability increased with food. Administer with meals or snack


Breast milk: Animal data suggest that nelfinavir is distributed into breast milk USPHS recommends that HIV mothers do not breastfeed to avoid transmission to infant


Side-effects: Diarrhea, nausea, elevated serum transaminases, abdominal pain. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category B



Nevirapine (NVP)


Trade name: Viramune (Boeringer-Ingelheim)














Available formulations:  
200 mg tablet $12.97
10 mg/mL suspension, 240 mL $91.98

Class: Non-nucleoside reverse transcriptase inhibitor


Oral dose:


Adults: 200 mg once daily for 14 days, then 200 mg twice daily


Children:


Neonatal/infant (through 2 months of age): 120 mg/m2 once 3 14 days, then 120 mg/m2 twice a day 3 14 days, then 200 mg/m2 twice daily


2 months to <8 years: 4 mg/kg once daily 3 14 days, then 7 mg/kg twice daily


≥ 8 years: 4 mg/kg once daily 3 14 days, then 4 mg/kg once daily (max 200 mg twice a day)


Do not increase dosage if rash appears during escalation phase. If therapy is stopped for more than 7 days, reinitiate dose escalation


Storage and stability: Store at room temperature in tightly closed bottles



Pharmacokinetics


Tmax: Within 4 h


Bioavailability: More than 90%


Half-life: 25–30 h


CSF penetration: 45% of concentration in plasma


Plasma protein binding: 60%


Metabolism/elimination: Substrate and inducer of CYP3A metabolism


Food effects: Not affected by food; administer without regard to meals


Breast milk: Detectable in breast milk. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Rash (17%) usually appears within the first 6 weeks of therapy; Stevens–Johnson syndrome has been reported. Nausea, fever, headache. Hepatotoxicity–can be severe, close monitoring of serum transaminases is recommended, particularly during first 18 weeks of therapy. Women have threefold greater risk of hepatotoxicity than men;contraindicated in women with CD4+ T-lymphocyte count >250 cells/mL and men with CD4+ T-lymphocyte count >400 cells/mL. Do not restart after severe hepatic, skin or hypersensitivity reaction


Pregnancy: Category C



Ritonavir (RTV)


Trade name: Norvir (Abbott)














Available formulations:  
100 mg capsule $10.29
80 mg/mL oral solution, 240 mL $1728.24

Class: PI


Oral dose:


Adults: 600 mg twice daily (when used as sole PI); dose escalation required to reduce gastrointestinal side-effects


Doses of 100–400 mg/day (in 1–2 divided doses) are used as pharmacokinetic enhancer with other PIs. Solution may be mixed with Advera, Ensure, or chocolate milk to increase palatability


Children (>1 month): 350–400 mg/m2; dose escalation required. Initiate with 250 mg/m2 and increase in 50 mg/m2 twice-daily increments every 2–3 days


Storage and stability: Store capsules in refrigerator; stable at room temperature for up to 30 days. Solution should not be refrigerated. Avoid exposure to extreme heat and protect from light



Pharmacokinetics


Tmax: 2–4 h


Bioavailability: 60–80%


Half-life: 3–5 h


CSF penetration: Negligible


Plasma protein binding: 98–99%


Metabolism/elimination: Extensive hepatic metabolism by hepatic CYP3A4; potent inhibitor of CYP3A4-mediated metabolism


Food effects: Recommended to be administered with food: 15% increase in AUC with food


Breast milk: Unknown. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Predominantly GI side-effects (nausea and vomiting, diarrhea, abdominal pain) especially during first month of treatment, circumoral paresthesias, taste perversion, elevated serum transaminases, hypertriglyceridemia. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category B



Saquinavir (SQV)


Trade name: Invirase (Roche)














Available formulations:  
200 mg hard gel capsule $2.40
500 mg tablet $5.99

Class: PI


Oral dose:


Adults: Unboosted SQV not recommended


Recommended RTV-boosted dose: (SQV 1000 mg + RTV 100 mg) twice daily


Not approved for use in children


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: Approximately 3 h


Bioavailability: Approximately 4% with full meal (when sole PI)


Half-life: 1–2 h


CSF penetration: Negligible


Plasma protein binding: 98%


Metabolism/elimination: Metabolized primarily by CYP3A4; extensive first-pass metabolism. Inhibitor of CYP3A4


Food effects: Administer within 2 h of a full meal


Breast milk: Secreted in milk of laboratory animals; no data in humans. USPHS recommends that HIV+ mothers not breastfeed to avoid transmission to infant


Side-effects: Nausea and vomiting, abdominal pain, diarrhea, elevated serum transaminases, headache. PIs have been associated with metabolic effects including hyperglycemia, increased triglycerides and cholesterol, and fat redistribution


Pregnancy: Category B



Stavudine (d4T)


Trade name: Zerit (Bristol Myers Squibb)























Available formulations:  
15 mg capsule $5.49
20 mg capsule $5.70
30 mg capsule $6.06
40 mg capsule $6.17
1 mg/mL, 200 mL $69.64

Class: Nucleoside reverse transcriptase inhibitor


Oral dose:


Adults:


>60 kg: 40 mg twice daily; <60 kg: 30 mg twice daily


Children: <30 kg: 1 mg/kg per dose every 12 h. Weight ≤30 kg, follow adult recommendations


Storage and stability:


Capsules: store at room temperature in tightly closed bottles


Suspension: After reconstitution with water, store in refrigerator in tightly closed original container for up to 30 days



Pharmacokinetics


Tmax: Within 1 h


Bioavailability: 86%


Half-life: 1.0–1.4 h (intracellular 7.5 h)


CSF penetration: 30% of serum levels


Plasma protein binding: Negligible


Metabolism/elimination: Primarily excreted renally (50%)


Food effects: AUC unchanged with food; give without regard to meals


Breast milk: Animal studies suggest d4T is excreted in breast milk. USPHS recommends that HIV+ women not breastfeed to avoid transmission to infants


Side-effects: Peripheral neuropathy (>20%), lipodystrophy, hypertriglyceridemia, rapidly progressive ascending neuromuscular weakness (rare), pancreatitis (especially if used with ddI), hepatomegaly with steatosis, lactic acidosis (can be severe, even fatal)


Pregnancy: Category C. Fatal lactic acidosis has been reported in pregnant women treated with a combination of d4T and ddI



Tenofovir Disoproxil Fumarate (TDF)


Trade name: Viread (Gilead)
















Available formulations:
300 mg tablet $16.75
Truvada (tenofovir 300 mg + emtricitabine 200 mg) $26.03
Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg) $47.95

Class: Nucleotide reverse transcriptase inhibitor with activities against HIV and HBV


Oral dose (adults): 300 mg once dailyAs Truvada: one tablet once dailyAs Atripla: One tablet at bedtime or before bedtime on an empty stomach


Not approved for use in children


Storage and stability: Store at room temperature



Pharmacokinetics


Tmax: 1 h under fasting condition, and 2 h when taken with food


Bioavailability: 25% in fasting state; 39% with high-fat meal


Half-life: 17 h (intracellular >60 h)


Metabolism/elimination: Primarily renal excretion by glomerular filtration and active tubular secretion


Food effects: Take without regard to meals


Breast milk: Animal studies suggest tenofovir is excreted in breast milk. USPHS recommends that HIV+ women not breastfeed, to avoid transmission to infants


Side-effects: Nausea, vomiting, headache, asthenia, increased serum creatinine, renal insufficiency, diabetes insipidus (rare), Fanconi-like syndrome


Pregnancy: Category C

Related posts:

Abacavir Human Herpesvirus-6 and Herpesvirus-7 Infections Cryptosporidia, Isospora, and Cyclospora Infections Saquinavir Acute HIV Infection Adult Antiretroviral Dosing Guidelines

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Aug 11, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on AIDS-Related Medications

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