J&J Medical Connect
SYMTUZA®

(darunavir/ cobicistat/ emtricitabine/ tenofovir alafenamide)

J&J Medical Connect

Connect with us

  • Products

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

SYMTUZA® (darunavir/ cobicistat/ emtricitabine/ tenofovir alafenamide)
Medical Information

Splitting/Crushing of SYMTUZA

Last Updated: 08/07/2026

SUMMARY

  • For patients who are unable to swallow the whole tablet, SYMTUZA may be split into two pieces using a tablet-cutter.1
  • The bioavailability of the components of SYMTUZA were not affected when administered orally as a split tablet compared to administration as a tablet swallowed whole.1
  • When administered as a crushed tablet, there was no relevant impact on the bioavailability of darunavir, cobicistat, and emtricitabine, however, there was a decrease (~20%) in the bioavailability of tenofovir alafenamide. Crushing is not recommended.2
  • An additional citation identified during a literature search have been included in the REFERENCES section for your review.3

CLINICAL STUDIES

Phase 1 Study

Brown et al (2019)2 assessed the relative bioavailability of SYMTUZA components after oral administration as a split or crushed tablet versus swallowed as a whole tablet. The study design and methods are depicted in the Figure: Phase 1 Study Design/Methods.

Phase 1 Study Design/Methods2

Abbreviations: C, cobicistat; D, darunavir; F, emtricitabine; TAF, tenofovir alafenamide.

Results

  • A total of 18 men (60%) and 12 women (40%) were enrolled in the study. At screening, the mean±standard deviation age was 36.7±11.0 years, and most participants were white (26 [87%]) and Hispanic or Latino (25 [83%]).
  • There was no relevant impact on the bioavailability of SYMTUZA components when administered as a split versus whole tablet, as depicted in Table: Whole Tablet Versus Split Tablet.
  • When administered as a crushed tablet, there was no relevant impact on the bioavailability of darunavir, cobicistat, and emtricitabine, however, there was a decrease (~20%) in the bioavailability of tenofovir alafenamide.

Whole Tablet Versus Split Tablet2
Darunavir
Cobicistat
Emtricitabine
Tenofovir alafenamide
Whole tablet
Split tablet
Whole tablet
Split tablet
Whole tablet
Split tablet
Whole tablet
Split tablet
na
30
30
30
30
30b
30c
30
30d
Parameter, mean (SD)
Cmax (ng/mL)
8437 (1674)
8963 (2366)
931 (231)
985 (241)
1915 (565)
1892 (537)
163 (71.6)
155 (90.4)
tmaxe (hours)
4.0
(1.0-8.0)
4.0
(1.5-6.0)
4.0
(1.0-5.0)
3.6
(1.5-6.0)
2.0
(0.8-4.0)
2.5
(0.8-5.0)
1.3
(0.3-2.5)
1.0
(0.3-2.5)
AUClast (ng∙hour/mL)
116,139 (38,309)
123,917 (53,827)
7785 (3433)
8297 (4076)
11,830 (2737)
11,742 (2728)
155 (43.2)
153 (51.3)
AUC∞ (ng∙hour/mL)
116,422
(38,652)
124,469
(54,875)
7883
(3497)
8391
(4144)
11,975
(2,806)
12,202
(2,809)
156
(43.2)
156
(52.1)
t1/2term (hours)
5.5 (2.3)
5.3 (2.0)
3.8 (1.0)
3.8 (1.0)
16.7
(4.3)
16.2
(3.4)
0.4
(0.1)
0.4
(0.2)
LS means ratio, n% (90% CI)
Cmax
105 (100-110)
106 (101-110)
100 (93-109)
89 (75-107)
AUClast
103 (97-109)
105 (99-110)
99 (95-103)
97 (90-105)
AUC∞
103 (98-109)
104 (99-110)
99 (94-104)
98 (90-106)
Abbreviations: AUC∞, area under the plasma concentration-time curve from time 0 extrapolated to infinity; AUClast, area under the plasma concentration-time curve from time 0 to the last measurable concentration; CI, confidence interval; Cmax, maximum concentration; LS, least squares; SD, standard deviation; t1/2term, terminal elimination half-life; tmax, time to reach maximum plasma concentration.
aAll exclusions were related to a coefficient of determination <0.90 for the pharmacokinetic parameter estimation.
bn=29 for AUC∞ and t1/2term.
cn=26 for AUC∞ and t1/2term.
dn=28 for AUC∞ and t1/2term.
etmax is reported as median (range).

Whole Tablet Versus Crushed Tablet2
Darunavir
Cobicistat
Emtricitabine
Tenofovir alafenamide
Whole tablet
Crushed tablet
Whole tablet
Crushed tablet
Whole tablet
Crushed tablet
Whole tablet
Crushed tablet
na
30
29
30
29
30b
29c
30
29
Parameter, mean (SD)
Cmax (ng/mL)
8437 (1674)
9484 (1867)
931 (231)
937 (242)
1915 (565)
1599 (472)
163 (71.6)
121 (69.9)
tmaxd (hours)
4.0
(1.0-8.0)
3.0
(1.5-5.0)
4.0
(1.0-5.0)
3.0
(2.0-6.0)
2.0
(0.8-4.0)
2.0
(1.0-4.0)
1.3
(0.3-2.5)
0.6
(0.3-2.0)
AUClast (ng∙hour/mL)
116,139 (38,309)
130,532 (48,649)
7785 (3433)
8062 (3786)
11,830 (2737)
11,013 (2690)
155 (43.2)
126 (37.5)
AUC∞ (ng∙hour/mL)
116,422
(38,652)
130,940
(49,458)
7883
(3497)
8180
(3898)
11,975
(2,806)
10,956
(2682)
156
(43.2)
128
(37.4)
t1/2term (hours)
5.5 (2.3)
5.0 (1.7)
3.8 (1.0)
3.8 (1.3)
16.7
(4.3)
16.0 (3.7)
0.4
(0.1)
0.5 (0.2)
LS means ratio, n% (90% CI)
Cmax
113 (108-119)
100 (96-104)
83 (77-90)
71 (59-86)
AUClast
111 (105-118)
101 (96-107)
92 (88-96)
81 (75-88)
AUC∞
111 (105-118)
101 (96-107)
93 (88-97)
82 (75-88)
Abbreviations: AUC∞, area under the plasma concentration-time curve from time 0 extrapolated to infinity; AUClast, area under the plasma concentration-time curve from time 0 to the last measurable concentration; CI, confidence interval; Cmax, maximum concentration; LS, least squares; SD, standard deviation; t1/2term, terminal elimination half-life; tmax, time to reach maximum plasma concentration.
aAll exclusions were related to a coefficient of determination <0.90 for the pharmacokinetic parameter estimation.
bn=29 for AUC∞ and t1/2term.
cn=27 for AUC∞ and t1/2term.
dtmax is reported as median (range).
  • All adverse events were grade 1 or 2, aside from one adverse event which was grade 4 (increased lipase, which was considered possibly related to drug).
  • The most frequent adverse events across all treatments were nausea (40%), headache (30%), and vomiting (17%).
  • The incidence of adverse events was generally comparable between treatments.

Safety2
Parameter, n (%)
Whole tablet
(n=30)
Split tablet
(n=30)
Crushed tablet
(n=29)
All treatments
(n=30)
≥1 AE
14 (47)
15 (50)
10 (34)
22 (73)
≥1 grade 3 or 4 AE
1 (3)a
0
0
1 (3)a
≥1 serious AE
0
0
0
0
Death
0
0
0
0
≥1 AE for which study drug was permanently stopped
1 (3)a
0
0
1 (3)a
≥1 AE possibly related to any study drug
12 (40)
15 (50)
9 (31)
22 (73)
Most common AEsb
   Nausea
4 (13)
6 (20)
5 (17)
12 (40)
   Headache
5 (17)
3 (10)
2 (7)
9 (30)
   Vomiting
3 (10)
2 (7)
0
5 (17)
Abbreviation: AE, adverse event.
aOne participant prematurely discontinued study drug because of an AE (increased lipase), which was grade 4 in severity and considered to be possibly related to the study drug. It was deemed nonserious by the investigator.
bBy preferred term and occurring in ≥15% of participants (all-treatments population).

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 09 April 2025.

References

Show
1 SYMTUZA (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide) [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SYMTUZA-pi.pdf.  
2 Brown K, Thomas D, McKenney K, et al. Impact of splitting or crushing on the relative bioavailability of the darunavir/cobicistat/emtricitabine/tenofovir alafenamide single-tablet regimen. Clin Pharmacol Drug Dev. 2019;8(4):541-548.  
3 Van Hemelryck S, Van Landuyt E, Hufkens V, et al. Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1–infected children aged ≥6 to <12 years, using matching placebo tablets: a randomized study. Antivir Ther. 2024;29(2):13596535241248282.  

Would you like to clear and leave your conversation? Message history will be lost.