Anti-HIV Drugs Quick Reference Guide

05 AIDS

Quick Reference Guide to Antiretrovirals
23 December 1998

Author: Malte Schutz, M.D.

These tables list all antiretrovirals currently available in US pharmacies and through compassionate use protocols: (May print this in .pdf format - click here )

Nucleoside Analog Reverse Transcriptase Inhibitors (Nucleoside Analogs, NRTIs)

Chemical

Generic

Brand

Dose

Comments and Common Side Effects

AZT

Zidovudine

Retrovir

300 mg twice daily

Initial GI, anemia, neutropenia, neuropathy, myopathy

3TC

Lamivudine

Epivir

150 mg twice daily

Generally well tolerated. Active against HBV

AZT + 3TC

Zidovudine Lamivudine

Combivir

1 tablet twice daily

Combination tablet containing 300 mg of AZT and 150 mg of 3TC

ddI

Didanosine

Videx

200 mg twice daily or 400 mg once daily on empty stomach (>60 kg body weight)

Peripheral neuropathy in 15%, pancreatitis; avoid alcohol. Contains antacid: ok to give at same time as all NRTIs, adefovir, nevirapine and efavirenz; delavirdine and indinavir must be taken at least 1 hour prior to ddI; nelfinavir can be taken 1 hour after ddI

ddC

Zalcitabine

Hivid

0.375-0.75 mg
three times daily

Peripheral neuropathy in 17-31% of trial participants; oral ulcers

d4T

Stavudine

Zerit

20-40 mg twice daily

Peripheral neuropathy (1-4% in early studies; 24% in expanded access patients with CD4 counts <50)

1592U89

Abacavir

Ziagen

300 mg twice daily

Up to 3% hypersensitivity reaction: malaise, fever, possible rash, GI. Resolves within 2 days after discontinuation. DO NOT RECHALLENGE

Non-Nucleoside Analog Reverse Transcriptase Inhibitors (NNRTIs)

Generic

Brand

Dose

Comments and Common Side Effects

Nevirapine

Viramune

200 mg (1 tablet) once daily for 2 weeks, then 200 mg twice daily or 400 mg once daily

Transient rash, hepatitis. P450 3A4 inducer.
Once daily dosing recommendation based on pharmacokinetic data only

Delavirdine

Rescriptor

400 mg (4 tablets) 3 times daily

Transient rash. P450 3A4 inhibitor

Efavirenz

Sustiva

600 mg (3 cap) once daily at bedtime

Initial dizziness, insomnia, transient rash,
P450 3A4 inducer; avoid clarithromycin

Protease Inhibitors (PIs)

Generic

Brand

Dose

Comments and Common Side Effects

Saquinavir hard gel cap

Invirase

600 mg (3 cap) 3 times daily with fatty meals

Well tolerated. Limited potency due to poor absorption. In time will be replaced by Fortovase

Saquinavir soft gel cap

Fortovase

1200 mg (6 cap) 3 times daily with fat containing food (>28 g)

Improved absorption: 8-fold higher SQV level compared to HGC. 1600 mg twice daily promising. Store in refrigerator. Stable at room temperature for about 30 days

Ritonavir

Norvir

600 mg (6 cap/7.5 ml) twice daily; start with 300 mg twice daily and up-taper to full dose over 10 days. Liquid formulation available

Nausea, diarrhea, numb lips for up to 5 weeks; occasional hepatitis. Up to 50% will not tolerate. Capsules require refrigeration; stable at room temperature for about 3 days. Liquid to be stored at room temperature

Indinavir

Crixivan

800 mg (2 cap) every 8 hours on empty stomach or with snack containing <2 g of fat

Kidney stones in 6 to 8%: good hydration essential. Occasional nausea and GI upset. Store in original container which contains dessicant; without this, IDV is stable for only about 3 days

Nelfinavir

Viracept

750 mg (3 tab) 3 times daily or 1250 mg (5 tab) twice daily with food

Diarrhea common, which may respond to Ultrase MT20 enzyme preparations; occasional nausea

Amprenavir
(not FDA approved)

Agenerase

1200 mg (8 cap) twice daily

Rash (20%), diarrhea

Nucleotide Reverse Transcriptase Inhibitors

Generic

Brand

Dose

Comments and Common Side Effects

Adefovir
(not FDA approved)

Preveon

120 mg or 60 mg once daily

Higher dose associated with Fanconi Syndrome after >6 mos. Anti-HIV/HBV/CMV; possible CMV prophylactic. Supplement carnitine

Ribonucleotide Reductase Inhibitors

Generic

Brand

Dose

Comments and Common Side Effects

Hydroxyurea
(not FDA approved)

Hydrea

500 mg twice daily

Bone marrow suppression, aphthous ulcers, hair loss. Augments nucleoside analogs. No direct antiviral effect

Two-Drug Combinations

This table gives an overview of current knowledge of drug-drug combinations. The NRTIs are not listed since they do not require dose adjustments when combined. In contrast, PIs and NNRTIs tend to have complex metabolism and in combinations affect each other’s drug levels and potency. The knowledge on these combinations is still evolving, and few formal dose modification recommendations are available. Caution and close monitoring are advised. Treating physicians should verify all information with an AIDS specialist and check any dose adjustments with a pharmacist.
* Comments on each combination are given overleaf.

Abbreviations

RTV Ritonavir NVP Nevirapine

IDV Indinavir DLV Delavirdine

NFV Nelfinavir EFV Efavirenz

APV Amprenavir

SQV-H Saquinavir hard gel caps (Invirase)

SQV-S Saquinavir soft gel caps (Fortovase)

RTV IDV NFV APV NVP DLV EFV

Substantial increase in SQV level (1)

Antagonistic in vitro; do not combine

Increase in SQV-S level (3)

No significant interaction noted (4)

Decrease in SQV-H level; do not combine (5)

Increase in SQV level (6)

Decrease in SQV level; do not combine (7)
SQV

Increase in IDV level (8)

Increase in NFV level (9)

No data

No significant interaction noted (11)

Increase in RTV level (12)

Modest increase in levels of both (13)
RTV

Increase in IDV level (14)

Increase in APV level; decrease in IDV level (15)

Decrease in IDV level (16)

Increase in IDV level (17)

Decrease in IDV level (18)
IDV

No significant interaction noted (19)

No significant interaction noted (20)

Increase in NFV level (21)

No significant interaction noted (22)
NFV

No data

No data

Decrease in APV level (25)
APV

Contraindicated Combinations
These medications should not be combined:

AZT + d4T combination is antagonistic in vivo
ddI and ddC are chemically very similar and should not be combined
IDV + SQV combination is antagonistic in vitro and in practice extremely difficult to dose
There are virtually no data on NNRTI combinations with each other and they should generally be avoided at this time

Comments on Two-Drug Combinations

1

Ritonavir & Saquinavir

RTV increases SQV levels 3-fold or higher. No food effect on SQV level in this combination. RTV level not affected, but generally same clinical efficacy with reduced RTV dose with considerably less GI side effects. Good results from studies of 400 mg twice daily for each drug.

3

Nelfinavir & Saquinavir

NFV increases SQV-S levels 3-fold or higher. Consider dosing of NFV 750 mg + SQV-S 800 mg three times daily, or NFV 1250 mg + SQV-S 1200 mg twice daily (under study) (ICAAC 1998)

4

Amprenavir & Saquinavir

Decrease in APV AUC by -36% and SQV AUC by -18% (Geneva Conference 1998)

5

Saquinavir & Nevirapine

SQV-H AUC decreased by -27%, which is of concern as SQV-H by itself reaches marginal levels only. No effect on NVP level. No data on nevirapine and SQV-S

6

Saquinavir & Delavirdine

3-fold or higher increase in SQV peak level, mild decrease in DLV peak level. Increased hepato-toxicity observed – monitor especially during first 6 weeks and in patients with hepatitis B or C

7

Efavirenz & Saquinavir

EFV lowers SQV-S AUC by 62% and Cmax by 50%. Avoid combination with SQV as sole PI. Co-administration with RTV under investigation (ICAAC 1998)

8

Indinavir & Ritonavir

RTV increases IDV AUC up to 480%, and increases IDV trough levels. Levels not affected by food. Studies are investigating 400 mg twice daily of both drugs with a light meal (ICAAC 97). Other IDV/RTV twice daily dose combinations under study: 800/100; 800/200; 800/400; 400/400

9

Nelfinavir & Ritonavir

RTV increases level of NFV and NFV M8 metabolite. RTV 400 mg with NFV 500 mg or 750 mg (all twice daily) resulted in NFV AUC equivalent to standard dosing. Higher dose resulted in higher AUC of M8 metabolite, but also lower RTV level. Clinical data pending (Geneva Conference 1998)

11

Ritonavir & Nevirapine

NVP decreases RTV levels by 11%

12

Ritonavir & Delavirdine

DLV increases RTV levels by 70%. May merit RTV dose reduction e.g. 400 mg twice daily. Limited data only (5^th Retrovirus Conference 1998, Pharmacia & Upjohn data 8/98)

13

Efavirenz & Ritonavir

EFV increases RTV AUC by 18% and Cmax by 24%. No dose adjustment for EFV necessary. Consider dose reduction of RTV. Monitor LFTs (ICAAC 1998)

14

Indinavir & Nelfinavir

NFV increases IDV level by 51%; IDV does not affect NFV level. Pharmacokinetic studies of NFV 1250 mg with IDV 1200 mg dosed twice daily show sufficient levels of both drugs. Administer with a low fat snack on an empty stomach to ensure absorption (Merck 1998)

15

Amprenavir & Indinavir

+26% increase in APV, -38% decrease in IDV AUC. Combination under investigation (Geneva Conference 1998)

16

Indinavir & Nevirapine

NVP decreases IDV levels by 30%. (Indinavir decrease is most pronounced in patients with a high IDV level within the inter-patient variability of IDV levels). Consider IDV dosage increase e.g.
1000 mg every 8 hours (5^th Retrovirus Conference 1998)

17

Indinavir & Delavirdine

IDV AUC increased 40%. Consider dosage reduction of IDV. Combination under investigation
(5^th Retrovirus Conference 1998)

18

Efavirenz & Indinavir

EFV reduces IDV AUC by 31% and Cmax by 16%; consider indinavir dose increase to 1000 mg every 8 hours. Combination under investigation (ICAAC 1998)

19

Amprenavir & Nelfinavir

Combination increases NFV AUC by 15%. APV AUC unchanged (Geneva Conference 1998)

20

Nelfinavir & Nevirapine

Steady state studies indicate no significant changes in NVP or NLV levels (5^th Retrovirus Conference 1998)

21

Nelfinavir & Delavirdine

Increase in NFV levels by 113%. 40% decrease in DLV AUC (Pharmacia & Upjohn data 8/98)

22

Efavirenz & Nelfinavir

EFV increases NFV level by 20%. No change of EFV level. No dose adjustment recommended
(5^th Retrovirus Conference 1998)

25

Amprenavir & Efavirenz

EFV decreases APV AUC by 36%. EFV levels slightly increased compared to historical data. Combination under investigation (5^th Retrovirus Conference 1998)

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Chemical	Generic	Brand	Dose	Comments and Common Side Effects
AZT	Zidovudine	Retrovir	300 mg twice daily	Initial GI, anemia, neutropenia, neuropathy, myopathy
3TC	Lamivudine	Epivir	150 mg twice daily	Generally well tolerated. Active against HBV
AZT + 3TC	Zidovudine Lamivudine	Combivir	1 tablet twice daily	Combination tablet containing 300 mg of AZT and 150 mg of 3TC
ddI	Didanosine	Videx	200 mg twice daily or 400 mg once daily on empty stomach (>60 kg body weight)	Peripheral neuropathy in 15%, pancreatitis; avoid alcohol. Contains antacid: ok to give at same time as all NRTIs, adefovir, nevirapine and efavirenz; delavirdine and indinavir must be taken at least 1 hour prior to ddI; nelfinavir can be taken 1 hour after ddI
ddC	Zalcitabine	Hivid	0.375-0.75 mg three times daily	Peripheral neuropathy in 17-31% of trial participants; oral ulcers
d4T	Stavudine	Zerit	20-40 mg twice daily	Peripheral neuropathy (1-4% in early studies; 24% in expanded access patients with CD4 counts <50)
1592U89	Abacavir	Ziagen	300 mg twice daily	Up to 3% hypersensitivity reaction: malaise, fever, possible rash, GI. Resolves within 2 days after discontinuation. DO NOT RECHALLENGE

RTV	Ritonavir	NVP	Nevirapine
IDV	Indinavir	DLV	Delavirdine
NFV	Nelfinavir	EFV	Efavirenz
APV	Amprenavir
SQV-H	Saquinavir hard gel caps (Invirase)
SQV-S	Saquinavir soft gel caps (Fortovase)

RTV	IDV	NFV	APV	NVP	DLV	EFV
Substantial increase in SQV level (1)	Antagonistic in vitro; do not combine	Increase in SQV-S level (3)	No significant interaction noted (4)	Decrease in SQV-H level; do not combine (5)	Increase in SQV level (6)	Decrease in SQV level; do not combine (7)	SQV
	Increase in IDV level (8)	Increase in NFV level (9)	No data	No significant interaction noted (11)	Increase in RTV level (12)	Modest increase in levels of both (13)	RTV
		Increase in IDV level (14)	Increase in APV level; decrease in IDV level (15)	Decrease in IDV level (16)	Increase in IDV level (17)	Decrease in IDV level (18)	IDV
			No significant interaction noted (19)	No significant interaction noted (20)	Increase in NFV level (21)	No significant interaction noted (22)	NFV
				No data	No data	Decrease in APV level (25)	APV

1	Ritonavir & Saquinavir	RTV increases SQV levels 3-fold or higher. No food effect on SQV level in this combination. RTV level not affected, but generally same clinical efficacy with reduced RTV dose with considerably less GI side effects. Good results from studies of 400 mg twice daily for each drug.
3	Nelfinavir & Saquinavir	NFV increases SQV-S levels 3-fold or higher. Consider dosing of NFV 750 mg + SQV-S 800 mg three times daily, or NFV 1250 mg + SQV-S 1200 mg twice daily (under study) (ICAAC 1998)
4	Amprenavir & Saquinavir	Decrease in APV AUC by -36% and SQV AUC by -18% (Geneva Conference 1998)
5	Saquinavir & Nevirapine	SQV-H AUC decreased by -27%, which is of concern as SQV-H by itself reaches marginal levels only. No effect on NVP level. No data on nevirapine and SQV-S
6	Saquinavir & Delavirdine	3-fold or higher increase in SQV peak level, mild decrease in DLV peak level. Increased hepato-toxicity observed – monitor especially during first 6 weeks and in patients with hepatitis B or C
7	Efavirenz & Saquinavir	EFV lowers SQV-S AUC by 62% and Cmax by 50%. Avoid combination with SQV as sole PI. Co-administration with RTV under investigation (ICAAC 1998)
8	Indinavir & Ritonavir	RTV increases IDV AUC up to 480%, and increases IDV trough levels. Levels not affected by food. Studies are investigating 400 mg twice daily of both drugs with a light meal (ICAAC 97). Other IDV/RTV twice daily dose combinations under study: 800/100; 800/200; 800/400; 400/400
9	Nelfinavir & Ritonavir	RTV increases level of NFV and NFV M8 metabolite. RTV 400 mg with NFV 500 mg or 750 mg (all twice daily) resulted in NFV AUC equivalent to standard dosing. Higher dose resulted in higher AUC of M8 metabolite, but also lower RTV level. Clinical data pending (Geneva Conference 1998)
11	Ritonavir & Nevirapine	NVP decreases RTV levels by 11%
12	Ritonavir & Delavirdine	DLV increases RTV levels by 70%. May merit RTV dose reduction e.g. 400 mg twice daily. Limited data only (5^th Retrovirus Conference 1998, Pharmacia & Upjohn data 8/98)
13	Efavirenz & Ritonavir	EFV increases RTV AUC by 18% and Cmax by 24%. No dose adjustment for EFV necessary. Consider dose reduction of RTV. Monitor LFTs (ICAAC 1998)
14	Indinavir & Nelfinavir	NFV increases IDV level by 51%; IDV does not affect NFV level. Pharmacokinetic studies of NFV 1250 mg with IDV 1200 mg dosed twice daily show sufficient levels of both drugs. Administer with a low fat snack on an empty stomach to ensure absorption (Merck 1998)
15	Amprenavir & Indinavir	+26% increase in APV, -38% decrease in IDV AUC. Combination under investigation (Geneva Conference 1998)
16	Indinavir & Nevirapine	NVP decreases IDV levels by 30%. (Indinavir decrease is most pronounced in patients with a high IDV level within the inter-patient variability of IDV levels). Consider IDV dosage increase e.g. 1000 mg every 8 hours (5^th Retrovirus Conference 1998)
17	Indinavir & Delavirdine	IDV AUC increased 40%. Consider dosage reduction of IDV. Combination under investigation (5^th Retrovirus Conference 1998)
18	Efavirenz & Indinavir	EFV reduces IDV AUC by 31% and Cmax by 16%; consider indinavir dose increase to 1000 mg every 8 hours. Combination under investigation (ICAAC 1998)
19	Amprenavir & Nelfinavir	Combination increases NFV AUC by 15%. APV AUC unchanged (Geneva Conference 1998)
20	Nelfinavir & Nevirapine	Steady state studies indicate no significant changes in NVP or NLV levels (5^th Retrovirus Conference 1998)
21	Nelfinavir & Delavirdine	Increase in NFV levels by 113%. 40% decrease in DLV AUC (Pharmacia & Upjohn data 8/98)
22	Efavirenz & Nelfinavir	EFV increases NFV level by 20%. No change of EFV level. No dose adjustment recommended (5^th Retrovirus Conference 1998)
25	Amprenavir & Efavirenz	EFV decreases APV AUC by 36%. EFV levels slightly increased compared to historical data. Combination under investigation (5^th Retrovirus Conference 1998)