diff --git a/libomptarget/plugins-nextgen/amdgpu/CMakeLists.txt b/libomptarget/plugins-nextgen/amdgpu/CMakeLists.txt
index bbf8c0a..68ce634 100644
--- a/libomptarget/plugins-nextgen/amdgpu/CMakeLists.txt
+++ b/libomptarget/plugins-nextgen/amdgpu/CMakeLists.txt
@@ -35,14 +35,6 @@
 # requires changing the original plugins.
 add_definitions(-DDEBUG_PREFIX="TARGET AMDGPU RTL")
 
-if(CMAKE_SYSTEM_PROCESSOR MATCHES "(ppc64le)|(aarch64)$")
-   add_definitions(-DLITTLEENDIAN_CPU=1)
-endif()
-
-if(CMAKE_BUILD_TYPE MATCHES Debug)
-  add_definitions(-DDEBUG)
-endif()
-
 set(LIBOMPTARGET_DLOPEN_LIBHSA OFF)
 option(LIBOMPTARGET_FORCE_DLOPEN_LIBHSA "Build with dlopened libhsa" ${LIBOMPTARGET_DLOPEN_LIBHSA})
 
diff --git a/libomptarget/plugins-nextgen/amdgpu/src/rtl.cpp b/libomptarget/plugins-nextgen/amdgpu/src/rtl.cpp
index 18076f8..b67642e 100644
--- a/libomptarget/plugins-nextgen/amdgpu/src/rtl.cpp
+++ b/libomptarget/plugins-nextgen/amdgpu/src/rtl.cpp
@@ -43,6 +43,18 @@
 #include "llvm/Support/Program.h"
 #include "llvm/Support/raw_ostream.h"
 
+#if !defined(__BYTE_ORDER__) || !defined(__ORDER_LITTLE_ENDIAN__) ||           \
+    !defined(__ORDER_BIG_ENDIAN__)
+#error "Missing preprocessor definitions for endianness detection."
+#endif
+
+// The HSA headers require these definitions.
+#if defined(__BYTE_ORDER__) && (__BYTE_ORDER__ == __ORDER_LITTLE_ENDIAN__)
+#define LITTLEENDIAN_CPU
+#elif defined(__BYTE_ORDER__) && (__BYTE_ORDER__ == __ORDER_BIG_ENDIAN__)
+#define BIGENDIAN_CPU
+#endif
+
 #if defined(__has_include)
 #if __has_include("hsa/hsa.h")
 #include "hsa/hsa.h"