DRUG COMBINATIONS QUICK REFERENCE GUIDE.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 metabolism, sum of all biochemical processes involved in life. Two subcategories of metabolism are anabolism, the building up of complex organic molecules from simpler precursors, and catabolism, the breakdown of complex substances into simpler molecules, often and in combinations affect each other's drug levels and potency potency /po·ten·cy/ (po´ten-se) 1. the ability of the male to perform coitus. 2. the relationship between the therapeutic effect of a drug and the dose necessary to achieve that effect. 3. . The knowledge on these combinations is still evolving, and few formal dose modification A change or alteration in existing materials. Modification generally has the same meaning in the law as it does in common parlance. The term has special significance in the law of contracts and the law of sales. recommendations are available. Caution and close monitoring are advised. Treating physicians should verify (1) To prove the correctness of data. (2) In data entry operations, to compare the keystrokes of a second operator with the data entered by the first operator to ensure that the data were typed in accurately. See validate. all information with an AIDS specialist and check any dose adjustments with a pharmacist pharmacist /phar·ma·cist/ (fahr´mah-sist) one who is licensed to prepare and sell or dispense drugs and compounds, and to make up prescriptions. phar·ma·cist n. . (*) Comments on each combinations are given below.
Amprenavir Indinavir
Nevirapine No data [arrow down] IDV [1]
Efavirenz [down arrow] J. APV [6] [down arrow] IDV [7]
Delavirdine No data [up arrow] IDV [12]
Saquinavir [down arrow] APV; Antagonistic
[down arrow] SQV [16] in vitro (in
one lab)
Ritonavir [up arrow] APV [20] [up arrow] IDV [21]
Nelfinavir [up arrow] APV [23] [up arrow] IDV [24]
Lopinavir [up arrow] APV [26] No data
Indinavir [up arrow] APV;
[down arrow] IDV [27]
Lopinavir Nelfinavir
Nevirapine No data No significant
interaction [2]
Efavirenz [down arrow] LPV [8] No significant
interaction [9]
Delavirdine No data [up arrow] NFV [13]
Saquinavir [up arrow] SQV-S [up arrow] SQV-S [18]
[17]
Ritonavir No data [up arrow] NFV [22]
Nelfinavir [up arrow] NFV
[25]
Lopinavir
Indinavir
Ritonavir Saquinavir
Nevirapine No significant [down arrow] SQV-H [4]
interaction
noted [3]
Efavirenz Modest [up arrow] in [down arrow] SQV level;
both [10] do not combine
[11]
Delavirdine [up arrow] RTV [14] [up arrow] SQV [15]
Saquinavir [up arrow] SQV [19]
Ritonavir
Nelfinavir
Lopinavir
Indinavir
Delavirdine Efavirenz
Nevirapine No data [down arrow] EFV [5]
Efavirenz No data
Delavirdine
Saquinavir
Ritonavir
Nelfinavir
Lopinavir
Indinavir
Abbreviations RTV Ritonavir NVP Nevirapine IDV Indinavir DLV Delavirdine NFV Nelfinavir EFV Efavirenz APV Amprenavir ADV Adefovir LPV Lopinavir TNV Tenofovir SQV-H Saquinavir hard gel caps (Invirase) SQV-S Saquinavir soft gel caps (Fortovase) Contraindicated Combinations * AZT AZT or zidovudine (zīdō`vy  dēn'), drug used to treat patients infected with the human immunodeficiency virus (HIV), which causes AIDS; also called + d4T d4T Stavudine, Zerit AIDS An anti-HIV reverse transcriptase inhibitor/nucleoside analogue Adverse effects Neuropathies of hands and feet, stomach upset, pancreatitis, liver damage,. See AIDS. Cf AZT, DDC, ddC. combination is antagonistic antagonistic adjective Referring to any combination of 2 or more drugs, which results in a therapeutic effect that is less than the sum of each drug's effect. Cf Additive, Synergism. in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body. in vi·vo adj. Within a living organism. in vivo adv. * ddl and ddC should not be combined due to increased risk of peripheral neuropathy Peripheral Neuropathy Definition The term peripheral neuropathy encompasses a wide range of disorders in which the nerves outside of the brain and spinal cord—peripheral nerves—have been damaged. * ADV ADV Advertisement ADV Adverb ADV Advance/Advanced ADV Advantage (tennis) ADV Advise ADV Advocate ADV Advancement ADV Advent ADV Arbeitsgemeinschaft für Datenverarbeitung ADV Adversus (Latin: Against) + DLV DLV Deflection Limiting Volume DLV Demonstration of Lower Value DLV Date of Last Visit DLV Discharge Line Volume may result in significantly [arrow down] DLV levels, undermining DLV's efficacy efficacy /ef·fi·ca·cy/ (ef´i-kah-se) 1. the ability of an intervention to produce the desired beneficial effect in expert hands and under ideal circumstances. 2. and ability to [arrow up] PI levels (ACTG ACTG Acting ACTG AIDS Clinical Trial Group ACTG Actuating/Actuator 359) * IDV IDV intermittent demand ventilation. + SQV SQV Scottish Vocational Qualification SQV Standard Quality Voice (aircraft cockpit voice recorder audio quality rating) SQV Site Quality Verification SQV Sediment Quality value SQV Sports Q-tility Vehicle combination is antagonistic in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment. in vi·tro adj. In an artificial environment outside a living organism. and in practice extremely difficult to dose * Limited data on NNRTI NNRTI Non-nucleoside reverse transcriptase inhibitor, see there combinations with each other; they should generally be avoided, pending results of ongoing clinical trials Comments on Drug-Drug Combinations
1 IDV & NVP NVP decreases IDV levels by 30%.
(Indinavir decrease is most pronounced
in patients with a high IDV level
within the interpatient variability
of IDV levels). Consider IDV dosage
increase eg, 1000 mg every 8 hours
(5th CROI, 1998)
2 NFV & NVP Steady state studies indicate no
significant changes in NVP or
NVP levels (5th CROI, 1998)
3 RTV & NVP NVP decreases RTV levels by 11%
4 SQV & NVP 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 NVP and SQV-S
5 NVP & EFV Decrease in EFV AUC by 22% and EFV
Cmin by 36%; NVP levels unchanged;
Dose increase of EFV to 800 mg
daily being discussed, but no safety
data are available for this dose
(7th CROI, 2000)
6 APV & EFV Decrease in APV Cmax by -36%, AUC
-39% and Cmin -43% (5th CROI, 1998).
See comments #19 and #22 for
dosing options
7 IDV & EFV EFV reduces IDV AUC by 31% and Cmax
by 16%; consider dose increase to 1000
mg every 8 hours. Combination under
investigation (ICAAC 1998)
8 LPV & EFV Decrease in LPV Cmin by -40% and AUC
by -20%; considered not significant in
patients naive to Pls. If PI resistance
suspected, consider LPV dose increase
to 433/133 mg (4 cap) 2x/d (Abbott
data, 2000)
9 NFV & EFV EFV increases NFV level by 20%. No change
in EFV level. Clinical efficacy documented
in several studies (6th CROI, 1999)
10 RTV & EFV 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). See comment
19 for further dosing options
11 SQV & EFV EFV lowers SQV-S AUC by 62% and Cmax by
50%. Avoid combination with SQV as
sole PI (ICAAC 1998). See comment 19 for
further dosing options
12 IDV & DLV IDV 400 or 600 mg with DLV 400 mg 3x/d
leads to increase in IDV Cmin of 140%
and 400% respectively, compared with
standard IDV dosing. Clinical studies
use IDV 600 mg with DLV 400 mg 3x/d
(ICAAC 1999)
13 NFV & DLV Increase in NFV levels by 113%. 40%
decrease in DLV AUC (Pharmacia &
Upjohn data 8/98)
14 RTV & DLV DLV increases RTV levels by 70%. May
merit RTV dose reduction eg, 400 mg
twice daily. Limited data only (5th
CROI, 1998, Pharmacia & Upjohn data 8/98)
15 SQV & DLV DLV dosed 400 mg 3x/d or 600mg 2x/d
decreases SQV clearance by 63%,
resulting in increase in SQV AUC/Cmin/Cmax.
Dose of SQV 1400 mg 2x/d or 1000mg 3x/d
with DLV 600 mg 2x/d or 400 mg 3x/d being
evaluated CROI, 2000)
16 APV & SQV Decrease in APV Cmax/AUC/Cmin by
37%/32%/14% respectively and increase
in SQV Cmax by +21%, but decrease of SQV
AUC by 19% and Cmin by 48% (Geneva, 1998)
17 SQV & LPV Single dose PK suggests increase in SQV
AUC and Cmin; SQV 800 mg 2x/d with
standard dose LPV suggested (Abbott data)
18 NFV & SQV NFV increases SQV-S levels 3-fold or
higher. Consider dosing of NFV 750 mg +
SQV-S 800 mg 3x/d, or NFV 1250 mg+ SQV-S
1200 mg 2x/d (under study) (6th CROI, 1999)
19 RTV, SQV RTV increases SQV levels 3-fold or higher.
&EFV No food effect on SQV level in this
combination. RTV level not affected,
but generally same clinical efficacy
with reduced RTV dose with considerably
fewer GI side effects. Good results
from studies of 400 mg 2x/d for each
drug. Once daily dosing of SQV with low
dose RTV as pharmacokinetic enhancer
being studied. The addition of EFV to
RTV/SQV 400 mg 2x/d does not
significantly change levels CROI, 2000)
20 APV, RTV APV 1200 mg with RTV 200 mg 2x/d increases
&EFV APV Cmax/AUC/Cmin by +33%/+131%/+680%.
The addition of EFV 600 mg qd to this
combination results in Cmax -9%, AUC +8%
and Cmin +27%. Consider dosing
APV 1200 mg 2x/d + EFV 600 mg qd +
RTV 200 mg 2x/d. No antiviral activity
of RTV in this dose. Studies evaluating
qd dosing of APV/RTV with or without
EFV are under way (NIH/GW data, 1999).
Doses of APV 900 mg with RTV 300
mg qd are being studied.
21 IDV & RTV RTV increases IDV AUC up to 480%. Compared
to IDV alone, 400 mg of both drugs 2x/d
leads to same IDV peak and higher
trough levels and acts as true dual
PI combo. No reports of nephrolithiasis
in this combination yet. IDV/RTV 800/100
mg or 800/200 mg 2x/d augments IDV
to higher peak and trough levels without
antiviral activity of RTV. No significant
food effect on IDV absorption with
either dose combination. Other dose
combinations under study (6th CROI, 1999)
22 NFV & RTV RTV increases level of NFV and NFV M8
metabolite. RTV 400 mg with NFV 500 mg
or 750 mg (all 2x/d) results in NFV AUC
equivalent to standard dosing. Higher
dose results in higher AUC of M8, but
lower RTV level. Limited clinical
data CROI, '99)
23 APV, NFV Full dose of APV+NFV results in decrease
& EFV in APV Cmax by -14%, but increase in AUC
by +46% and Cmin by +235%. No
significant effect on NFV levels. The
addition of EFV 600 mg qd resulted in
same APV Cmax and AUC and mild
reduction of Cmin by -14%. Consider
dosing APV/NFV or APV/NFV/EFV at full
dose of each drug (7th CROI, 2000)
24 IDV & NFV NFV increases IDV level by 51%; IDV does
not affect NFV level. NFV 1250 mg with
IDV 1200 mg 2x/d with a low fat snack on
empty stomach shows good drug levels and
clinical efficacy (6th CROI, 1999)
25 NFV & LPV Limited data from single dose PK suggests
unchanged NFV AUC, but increase in NFV
Cmin and M8 metabolite; consider
dose reduction of NFV to 750 mg 2x/d
with standard dose LPV (Abbott data)
26 LPV & APV LPV increases APV AUC and Cmin; dose
reduction of APV to 750 mg 2x/d with
standard dose LPV suggested (NIH, unpubl.)
27 APV & IDV Increase in APV Cmax/AUC/Cmin by
18%/32%/25% respectively and decrease
in IDV Cmax by 22%, AUC by 38% and
Cmin by 27% (GW data, 1999)
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