Download Marked Elevation of the Creatine Phosphokinase Level in a Patient

Marked Elevation of the
Creatine Phosphokinase
Level in a Patient
Receiving Tenofovir
Table 1. Findings of analyses of blood samples obtained from an HIV-infected man
whose HAART regimen was changed to include tenofovir.
Sir—Tenofovir is the most recent nucleoside analogue to have been approved by
the US Food and Drug Administration for
the treatment of HIV-infected patients. We
describe a 47-year-old HIV-infected man
with a history of hepatitis B, hypertension,
and peripheral neuropathy who developed elevations in creatine phosphokinase
(CPK), aspartate aminotransferase (AST),
and alanine aminotransferase (ALT) levels
after the addition of tenofovir and acyclovir to a stable regimen. The patient’s
HAART regimen was changed from efavirenz, stavudine, and didanosine to efavirenz, stavudine, and tenofovir. On the
day of the switch, acyclovir therapy was
started for treatment of anogenital herpes.
He was concurrently receiving atorvastatin, enalapril, furosemide, zolpidem,
gabapentin, and methadone. The patient
had been receiving atorvastatin for 3.5
months before he presented with elevated
CPK, AST, and ALT levels. Although he
complained of having mild muscle cramps
after he started receiving atorvastatin, he
denied having any symptoms during the
month before presentation.
On day 2 of the new HAART regimen,
the patient developed severe lower back
pain and lower extremity swelling and tenderness. On day 3, he reported his symptoms and was told to stop taking his antiretroviral medications and to increase his
fluid intake. He continued taking his other
medications. He denied performing vigorous exercise or drinking grapefruit juice.
On day 5 of the new HAART regimen, a
blood sample was obtained for analysis
(table 1). The findings of a complete blood
cell count and the ratio of blood urea nitrogen to creatine were normal. Myoglobin was not present in the urine. That
evening, the patient took another dose of
acyclovir and noted recurrence of his
symptoms. On day 6, he felt markedly
improved, and additional blood samples
were obtained for chemical analysis (table
Laboratory measurement
Creatine phosphokinase, U/L
Aspartate aminotransferase, U/L
Alanine aminotransferase, U/L
Alkaline phosphatase, U/L
Total bilirubin, mg/dL
Lactate, mM
NOTE.
Baseline
value
Concentration, by day
after HAART switch
5
6
7
8
NA
15,830
11,392
5830
3368
108
645
629
404
301
39
158
169
126
105
167
133
128
109
110
1.7
NA
1.1
1.3
1.8
—
1.0
—
0.9
—
NA, not available.
1). The patient was admitted to the hospital for intravenous hydration.
Moderate elevations in CPK, AST, and
ALT levels have been noted in patients
who receive tenofovir [1]. In our patient,
the elevation in the CPK level was unusually marked—it was ∼100 times the upper limit of normal. It is possible that this
elevation was caused by an interaction between tenofovir and another medication
in the patient’s regimen. One possibility
is that tenofovir interacted with acyclovir.
Acyclovir has not been associated with
elevated CPK levels; the only reported interaction between acyclovir and a nucleoside analogue is a case in which concomitant administration of zidovudine
and acyclovir resulted in a change in mental status [2]. However, the manufacturers
of tenofovir caution against the use of
tenofovir with drugs that reduce renal
function or compete for active tubular secretion, such as cidofovir, acyclovir, valacyclovir, ganciclovir, and valganciclovir,
because these agents may increase serum
concentrations of tenofovir [3]. The possible interaction between tenofovir and
acyclovir is supported by evidence of the
recurrence of symptoms associated with
acyclovir use on day 5 of the new HAART
regimen.
Another possibility is that there was an
interaction between tenofovir and atorvastatin. The 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors, or “statins,” are associated with elevations in
CPK levels and rhabdomyolysis. Although
interactions between protease inhibitors
and statins have been well described, to
our knowledge, there have been no reports
of interactions between nucleoside analogues and statins. In addition, tenofovir
is not a substrate of CYP450 enzymes, so
it is unclear how these drugs would affect
each other [3].
It is unknown how greatly the CPK level would have increased or whether rhabdomyolysis would have developed had
our patient not been so quick to report
his symptoms. Physicians prescribing tenofovir with acyclovir and/or atorvastatin
should be aware of the possible risk of
elevation in the CPK level and the potential risk for rhabdomyolysis.
K. D. Shere-Wolfe and J. R. Verley
Division of Infectious Diseases, Nassau University
Medical Center, East Meadow, New York
References
1. Barditch-Crovo P, Deeks SG, Collier A, et al.
Phase I/II trial of the pharmacokinetics, safety,
and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency
virus–infected adults. Antimicrob Agents Chemother 2001; 45:2733–9.
2. Bach MC. Possible drug interaction during
therapy with azidothymidine and acyclovir for
AIDS. N Engl J Med 1987; 316:547.
3. Tenofovir [product insert]. Foster City, CA: Gilead Sciences, 2001.
Reprints or correspondence Dr. K. D. Shere-Wolfe, Nassau
University Medical Center, 2201 Hempstead Turnpike, East
Meadow, NY 11554 ([email protected]).
Clinical Infectious Diseases 2002; 35:1137
2002 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2002/3509-0019$15.00
CORRESPONDENCE • CID 2002:35 (1 November) • 1137