Procoralan 7.5mg

Thông tin sản phẩm

[{"title": "Th\u00e0nh ph\u1ea7n", "content": "

Ho\u1ea1t ch\u1ea5t: ivabradin (d\u01b0\u1edbi d\u1ea1ng hydrochloride).

Procoralan 7.5mg: m\u1ed9t viên nén bao phim ch\u1ee9a 7.5mg ivabradin (t\u01b0\u01a1ng \u1ee9ng 8.085mg ivabradin hydrochloride).

Các thành ph\u1ea7n khác trong lõi c\u1ee7a viên nén g\u1ed3m: lactose monohydrate, magiê stearat (E470 B), tinh b\u1ed9t ngô, maltodextrin, silica khan d\u1ea1ng keo (E551).

Bao phim: hypromellose (E464), titan dioxid (E171), macrogol 6000, glycerol (E422), magie stearat (E470 B), s\u1eaft oxyd màu vàng (E172), s\u1eaft oxyd \u0111\u1ecf (E172).

", "index": 1}, {"title": "C\u00f4ng d\u1ee5ng", "content": "", "index": 2}, {"title": "T\u00e1c d\u1ee5ng ph\u1ee5", "content": "

Tóm t\u1eaft h\u1ed3 s\u01a1 an toàn:

Ivabradin \u0111ã \u0111\u01b0\u1ee3c nghiên c\u1ee9u trong các th\u1eed nghi\u1ec7m lâm sàng v\u1edbi g\u1ea7n 45,000 ng\u01b0\u1eddi tham gia.

Tác d\u1ee5ng không mong mu\u1ed1n ph\u1ed5 bi\u1ebfn nh\u1ea5t v\u1edbi ivabradin, hi\u1ec7n t\u01b0\u1ee3ng chói sáng (phosphenes) và ch\u1eadm nh\u1ecbp tim, ph\u1ee5 thu\u1ed9c li\u1ec1u và liên quan \u0111\u1ebfn tác d\u1ee5ng d\u01b0\u1ee3c lý c\u1ee7a thu\u1ed1c.

B\u1ea3ng li\u1ec7t kê các tác d\u1ee5ng b\u1ea5t l\u1ee3i:

Nh\u1eefng tác d\u1ee5ng b\u1ea5t l\u1ee3i \u0111ã \u0111\u01b0\u1ee3c báo cáo trong các th\u1eed nghi\u1ec7m lâm sàng và \u0111\u01b0\u1ee3c x\u1ebfp lo\u1ea1i theo t\u1ea7n su\u1ea5t sau \u0111ây: r\u1ea5t ph\u1ed5 bi\u1ebfn (≥ 1/10); ph\u1ed5 bi\u1ebfn (≥ 1/100 \u0111\u1ebfn < 1/10); không ph\u1ed5 bi\u1ebfn (≥ 1/1,000 \u0111\u1ebfn < 1/100); hi\u1ebfm (≥ 1/10,000 \u0111\u1ebfn < 1/1,000); r\u1ea5t hi\u1ebfm (< 1/10,000); ch\u01b0a \u0111\u01b0\u1ee3c bi\u1ebft \u0111\u1ebfn (không th\u1ec3 \u01b0\u1edbc tính t\u1eeb d\u1eef li\u1ec7u hi\u1ec7n có).

\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n

\n Phân lo\u1ea1i h\u1ec7 th\u1ed1ng c\u01a1 quan \n	\n T\u1ea7n su\u1ea5t \n	\n Tác d\u1ee5ng liên quan \n
\n R\u1ed1i lo\u1ea1n máu và h\u1ec7 b\u1ea1ch huy\u1ebft \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n T\u0103ng b\u1ea1ch c\u1ea7u \n
\n R\u1ed1i lo\u1ea1n chuy\u1ec3n hóa và dinh d\u01b0\u1ee1ng \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n T\u0103ng acid uric máu \n
\n R\u1ed1i lo\u1ea1n h\u1ec7 th\u1ea7n kinh \n	\n Ph\u1ed5 bi\u1ebfn \n	\n \u0110au \u0111\u1ea7u, th\u01b0\u1eddng trong tháng \u0111i\u1ec1u tr\u1ecb \u0111\u1ea7u tiên \n
\n Chóng m\u1eb7t, có th\u1ec3 liên quan \u0111\u1ebfn ch\u1eadm nh\u1ecbp tim \n
\n Không ph\u1ed5 bi\u1ebfn* \n	\n Ng\u1ea5t, có th\u1ec3 liên quan \u0111\u1ebfn ch\u1eadm nh\u1ecbp tim \n
\n R\u1ed1i lo\u1ea1n th\u1ecb giác \n	\n R\u1ea5t ph\u1ed5 bi\u1ebfn \n	\n Hi\u1ec7n t\u01b0\u1ee3ng chói sáng (phosphenes) \n
\n Ph\u1ed5 bi\u1ebfn \n	\n M\u1edd m\u1eaft \n
\n Không ph\u1ed5 bi\u1ebfn* \n	\n Nhìn \u0111ôi \n
\n Suy gi\u1ea3m th\u1ecb giác \n
\n R\u1ed1i lo\u1ea1n tai và mê cung \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n M\u1ea5t th\u0103ng b\u1eb1ng \n
\n R\u1ed1i lo\u1ea1n tim \n	\n Ph\u1ed5 bi\u1ebfn \n	\n Nh\u1ecbp tim ch\u1eadm \n
\n Block nh\u0129 th\u1ea5t \u0111\u1ed9 1 (kéo dài kho\u1ea3ng PQ trên \u0111i\u1ec7n tâm \u0111\u1ed3) \n
\n Ngo\u1ea1i tâm thu th\u1ea5t Rung nh\u0129 \n
\n Không ph\u1ed5 bi\u1ebfn \n	\n \u0110ánh tr\u1ed1ng ng\u1ef1c, ngo\u1ea1i tâm thu trên th\u1ea5t \n
\n R\u1ea5t hi\u1ebfm \n	\n Block nh\u0129 th\u1ea5t \u0111\u1ed9 2, block nh\u0129 th\u1ea5t \u0111\u1ed9 3 \n
\n R\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng nút xoang \n
\n R\u1ed1i lo\u1ea1n m\u1ea1ch \n	\n Ph\u1ed5 bi\u1ebfn \n	\n Huy\u1ebft áp không \u0111\u01b0\u1ee3c ki\u1ec3m soát \n
\n Không ph\u1ed5 bi\u1ebfn* \n	\n H\u1ea1 huy\u1ebft áp, có th\u1ec3 liên quan \u0111\u1ebfn nh\u1ecbp tim ch\u1eadm \n
\n R\u1ed1i lo\u1ea1n hô h\u1ea5p, ng\u1ef1c và trung th\u1ea5t \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n Khó th\u1edf \n
\n R\u1ed1i lo\u1ea1n h\u1ec7 tiêu hóa \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n Bu\u1ed3n nôn \n
\n Táo bón \n
\n Tiêu ch\u1ea3y \n
\n \u0110au b\u1ee5ng \n
\n R\u1ed1i lo\u1ea1n da và mô d\u01b0\u1edbi da \n	\n Không ph\u1ed5 bi\u1ebfn* \n	\n Phù m\u1ea1ch \n
\n Phát ban \n
\n Hi\u1ebfm* \n	\n Ban \u0111\u1ecf \n
\n Viêm da \n
\n N\u1ed5i m\u1ec1 \u0111ay \n
\n R\u1ed1i lo\u1ea1n c\u01a1 x\u01b0\u01a1ng kh\u1edbp và mô liên k\u1ebft \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n Chu\u1ed9t rút \n
\n R\u1ed1i lo\u1ea1n chung và t\u1ea1i v\u1ecb trí \u0111\u01b0a thu\u1ed1c \n	\n Không ph\u1ed5 bi\u1ebfn* \n	\n Suy nh\u01b0\u1ee3c, có th\u1ec3 liên quan \u0111\u1ebfn nh\u1ecbp tim ch\u1eadm \n
\n M\u1ec7t m\u1ecfi, có th\u1ec3 liên quan \u0111\u1ebfn nh\u1ecbp tim ch\u1eadm \n
\n Hi\u1ebfm* \n	\n C\u1ea3m giác b\u1ea5t \u1ed5n, có th\u1ec3 liên quan \u0111\u1ebfn nh\u1ecbp tim ch\u1eadm \n
\n Thông s\u1ed1 \n	\n Không ph\u1ed5 bi\u1ebfn \n	\n T\u0103ng creatinine máu \n
\n Kéo dài kho\u1ea3ng QT trên \u0111i\u1ec7n tâm \u0111\u1ed3 \n

* T\u1ea7n su\u1ea5t \u0111\u01b0\u1ee3c tính t\u1eeb các nghiên c\u1ee9u lâm sàng cho các bi\u1ebfn c\u1ed1 b\u1ea5t l\u1ee3i nh\u1eadn \u0111\u01b0\u1ee3c t\u1eeb các báo cáo t\u1ef1 nguy\u1ec7n

Miêu t\u1ea3 các ph\u1ea3n \u1ee9ng b\u1ea5t l\u1ee3i:

Hi\u1ec7n t\u01b0\u1ee3ng chói sáng (phosphenes) \u0111ã \u0111\u01b0\u1ee3c báo cáo b\u1edfi 14.5% b\u1ec7nh nhân, \u0111\u01b0\u1ee3c mô t\u1ea3 nh\u01b0 m\u1ed9t s\u1ef1 t\u0103ng c\u01b0\u1eddng \u0111\u1ed9 sáng thoáng qua trong khu v\u1ef1c t\u1ea7m nhìn h\u1ea1n ch\u1ebf. Chúng th\u01b0\u1eddng \u0111\u01b0\u1ee3c gây ra b\u1edfi s\u1ef1 thay \u0111\u1ed5i \u0111\u1ed9t ng\u1ed9t v\u1ec1 c\u01b0\u1eddng \u0111\u1ed9 ánh sáng. Phosphenes có th\u1ec3 \u0111\u01b0\u1ee3c mô t\u1ea3 nh\u01b0 m\u1ed9t v\u1ea7ng hào quang, s\u1ef1 phân ly hình \u1ea3nh (hi\u1ec7u \u1ee9ng lóe sáng ho\u1eb7c v\u1ea1n hoa), ánh sáng màu r\u1ef1c r\u1ee1, ho\u1eb7c \u0111a hình \u1ea3nh (kéo dài s\u1ef1 t\u1ed3n t\u1ea1i hình \u1ea3nh trên võng m\u1ea1c). S\u1ef1 kh\u1edfi phát c\u1ee7a hi\u1ec7n t\u01b0\u1ee3ng chói sáng th\u01b0\u1eddng trong vòng hai tháng \u0111\u1ea7u \u0111i\u1ec1u tr\u1ecb sau \u0111ó có th\u1ec3 tái di\u1ec5n. Phosphenes th\u01b0\u1eddng \u0111\u01b0\u1ee3c báo cáo là có c\u01b0\u1eddng \u0111\u1ed9 nh\u1eb9 \u0111\u1ebfn trung bình. T\u1ea5t c\u1ea3 hi\u1ec7n t\u01b0\u1ee3ng chói sáng \u0111\u1ec1u t\u1ef1 h\u1ebft trong ho\u1eb7c sau \u0111i\u1ec1u tr\u1ecb, trong \u0111ó \u0111a s\u1ed1 (77.5%) t\u1ef1 h\u1ebft trong quá trình \u0111i\u1ec1u tr\u1ecb. Ít h\u01a1n 1% s\u1ed1 b\u1ec7nh nhân thay \u0111\u1ed5i thói quen hàng ngày c\u1ee7a h\u1ecd ho\u1eb7c ng\u01b0ng \u0111i\u1ec1u tr\u1ecb liên quan \u0111\u1ebfn hi\u1ec7n t\u01b0\u1ee3ng chói sáng.

Nh\u1ecbp tim ch\u1eadm \u0111ã \u0111\u01b0\u1ee3c báo cáo b\u1edfi 3.3% s\u1ed1 b\u1ec7nh nhân, \u0111\u1eb7c bi\u1ec7t là trong 2 - 3 tháng \u0111\u1ea7u \u0111i\u1ec1u tr\u1ecb. 0.5% b\u1ec7nh nhân có nh\u1ecbp tim ch\u1eadm nh\u1ecf h\u01a1n ho\u1eb7c b\u1eb1ng 40 nh\u1ecbp/phút.

Trong nghiên c\u1ee9u SIGNIFY, hi\u1ec7n t\u01b0\u1ee3ng rung nh\u0129 \u0111ã \u0111\u01b0\u1ee3c quan sát \u1edf 5.3% b\u1ec7nh nhân s\u1eed d\u1ee5ng ivabradin so v\u1edbi 3.8% b\u1ec7nh nhân thu\u1ed9c nhóm ch\u1ee9ng. Trong m\u1ed9t phân tích g\u1ed9p trên t\u1ea5t c\u1ea3 các th\u1eed nghi\u1ec7m lâm sàng mù \u0111ôi có ki\u1ec3m soát Pha II/III kéo dài ít nh\u1ea5t 3 tháng v\u1edbi s\u1ef1 tham gia c\u1ee7a trên 40,000 b\u1ec7nh nhân, t\u1ec9 lê m\u1eafc ch\u1ee9ng rung nh\u0129 là 4.86% \u1edf b\u1ec7nh nhân \u0111i\u1ec1u tr\u1ecb b\u1eb1ng ivabradin so v\u1edbi 4.08% \u1edf nhóm \u0111\u1ed1i ch\u1ee9ng, t\u01b0\u01a1ng \u1ee9ng v\u1edbi t\u1ec9 lê nguy c\u01a1 là 1.26, 95% Cl [1.15 -1.39].

Báo cáo ph\u1ea3n \u1ee9ng b\u1ea5t l\u1ee3i nghi ng\u1edd:

Báo cáo các ph\u1ea3n \u1ee9ng b\u1ea5t l\u1ee3i có nghi ng\u1edd sau khi thu\u1ed1c \u0111ã \u0111\u01b0\u1ee3c c\u1ea5p phép là quan tr\u1ecdng. \u0110i\u1ec1u này cho phép ti\u1ebfp t\u1ee5c theo dõi s\u1ef1 cân b\u1eb1ng gi\u1eefa l\u1ee3i ích/nguy c\u01a1 c\u1ee7a thu\u1ed1c. Chuyên gia y t\u1ebf \u0111\u01b0\u1ee3c yêu c\u1ea7u báo cáo b\u1ea5t c\u1ee9 ph\u1ea3n \u1ee9ng b\u1ea5t l\u1ee3i có nghi ng\u1edd nào qua h\u1ec7 th\u1ed1ng thông tin thu\u1ed1c qu\u1ed1c gia.

L\u01afU Ý KHI S\u1eec D\u1ee4NG

C\u1ea3nh báo \u0111\u1eb7c bi\u1ec7t:

Thi\u1ebfu l\u1ee3i ích v\u1ec1 k\u1ebft qu\u1ea3 lâm sàng trên b\u1ec7nh nhân \u0111au th\u1eaft ng\u1ef1c \u1ed5n \u0111\u1ecbnh mãn tính có tri\u1ec7u ch\u1ee9ng:

Ivabradin ch\u1ec9 \u0111\u01b0\u1ee3c ch\u1ec9 \u0111\u1ecbnh \u0111i\u1ec1u tr\u1ecb tri\u1ec7u ch\u1ee9ng cho b\u1ec7nh nhân \u0111au th\u1eaft ng\u1ef1c \u1ed5n \u0111\u1ecbnh mãn tính do thu\u1ed1c này không \u0111em t\u1edbi l\u1ee3i ích tác \u0111\u1ed9ng trên tim m\u1ea1ch (ví d\u1ee5 nh\u1ed3i máu c\u01a1 tim ho\u1eb7c t\u1eed vong do tim m\u1ea1ch).

\u0110o nh\u1ecbp tim:

\u0110o nh\u1ecbp tim có th\u1ec3 dao \u0111\u1ed9ng \u0111áng k\u1ec3 theo th\u1eddi gian, c\u1ea7n cân nh\u1eafc ti\u1ebfn hành \u0111o nh\u1ecbp tim, ki\u1ec3m soát \u0111i\u1ec7n tâm \u0111\u1ed3 ho\u1eb7c theo dõi ngo\u1ea1i trú 24 gi\u1edd khi xác \u0111\u1ecbnh t\u1ea7n s\u1ed1 tim lúc ngh\u1ec9 tr\u01b0\u1edbc khi b\u1eaft \u0111\u1ea7u \u0111i\u1ec1u tr\u1ecb b\u1eb1ng ivabradin và khi cân nh\u1eafc \u0111i\u1ec1u ch\u1ec9nh li\u1ec1u \u1edf b\u1ec7nh nhân \u0111ang \u0111i\u1ec1u tr\u1ecb b\u1eb1ng ivabradin. Vi\u1ec7c ki\u1ec3m soát nh\u01b0 v\u1eady c\u0169ng có th\u1ec3 áp d\u1ee5ng cho b\u1ec7nh nhân có t\u1ea7n s\u1ed1 tim th\u1ea5p, \u0111\u1eb7c bi\u1ec7t khi nh\u1ecbp tim gi\u1ea3m d\u01b0\u1edbi 50 nh\u1ecbp/phút, ho\u1eb7c sau khi gi\u1ea3m li\u1ec1u.

R\u1ed1i lo\u1ea1n nh\u1ecbp tim:

Ivabradin không hi\u1ec7u qu\u1ea3 trong vi\u1ec7c \u0111i\u1ec1u tr\u1ecb ho\u1eb7c phòng ng\u1eeba r\u1ed1i lo\u1ea1n nh\u1ecbp tim và có th\u1ec3 không có tác d\u1ee5ng trong tr\u01b0\u1eddng h\u1ee3p lo\u1ea1n nh\u1ecbp nhanh (ví d\u1ee5 nh\u1ecbp tim nhanh th\u1ea5t ho\u1eb7c trên th\u1ea5t). Ivabradin do \u0111ó không \u0111\u01b0\u1ee3c khuy\u1ebfn cáo \u1edf các b\u1ec7nh nhân rung nh\u0129 ho\u1eb7c lo\u1ea1n nh\u1ecbp tim khác gây c\u1ea3n tr\u1edf ch\u1ee9c n\u0103ng nút xoang.

\u1ede b\u1ec7nh nhân \u0111i\u1ec1u tr\u1ecb b\u1eb1ng ivabradin có s\u1ef1 t\u0103ng nguy c\u01a1 ti\u1ebfn tri\u1ec3n rung nh\u0129. Rung nh\u0129 ph\u1ed5 bi\u1ebfn h\u01a1n \u1edf b\u1ec7nh nhân s\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi amiodaron ho\u1eb7c thu\u1ed1c ch\u1ed1ng lo\u1ea1n nh\u1ecbp m\u1ea1nh nhóm I. Các b\u1ec7nh nhân \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin \u0111\u01b0\u1ee3c khuy\u1ebfn cáo th\u01b0\u1eddng xuyên theo dõi lâm sàng s\u1ef1 xu\u1ea5t hi\u1ec7n c\u1ee7a rung nh\u0129 (duy trì ho\u1eb7c k\u1ecbch phát), trong \u0111ó nên bao g\u1ed3m theo dõi \u0111i\u1ec7n tâm \u0111\u1ed3 n\u1ebfu có ch\u1ec9 \u0111\u1ecbnh lâm sàng (ví d\u1ee5 trong tr\u01b0\u1eddng h\u1ee3p \u0111au th\u1eaft ng\u1ef1c tr\u1ea7m tr\u1ecdng h\u01a1n, \u0111ánh tr\u1ed1ng ng\u1ef1c, m\u1ea1ch b\u1ea5t th\u01b0\u1eddng). B\u1ec7nh nhân c\u1ea7n \u0111\u01b0\u1ee3c thông báo v\u1ec1 các d\u1ea5u hi\u1ec7u và tri\u1ec7u ch\u1ee9ng c\u1ee7a rung nh\u0129 và \u0111\u01b0\u1ee3c khuy\u1ebfn cáo liên h\u1ec7 v\u1edbi bác s\u0129 c\u1ee7a h\u1ecd n\u1ebfu tri\u1ec7u ch\u1ee9ng này x\u1ea3y ra.

N\u1ebfu tình tr\u1ea1ng rung nh\u0129 ti\u1ebfn tri\u1ec3n trong quá trình \u0111i\u1ec1u tr\u1ecb, c\u1ea7n cân nh\u1eafc c\u1ea9n th\u1eadn s\u1ef1 cân b\u1eb1ng gi\u1eefa l\u1ee3i ích và nguy c\u01a1 c\u1ee7a vi\u1ec7c ti\u1ebfp t\u1ee5c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng ivabradin. B\u1ec7nh nhân suy tim m\u1ea1n tính có khi\u1ebfm khuy\u1ebft v\u1ec1 d\u1eabn truy\u1ec1n tâm th\u1ea5t (block nhánh trái, block nhánh ph\u1ea3i) và r\u1ed1i lo\u1ea1n \u0111\u1ed3ng b\u1ed9 tâm th\u1ea5t nên \u0111\u01b0\u1ee3c theo dõi ch\u1eb7t ch\u1ebd.

S\u1eed d\u1ee5ng \u1edf các b\u1ec7nh nhân block nh\u0129 th\u1ea5t \u0111\u1ed9 2:

Ivabradin không \u0111\u01b0\u1ee3c khuy\u1ebfn cáo cho các b\u1ec7nh nhân block nh\u0129 th\u1ea5t \u0111\u1ed9 2.

S\u1eed d\u1ee5ng \u1edf các b\u1ec7nh nhân có t\u1ea7n s\u1ed1 tim th\u1ea5p:

Ivabradin không \u0111\u01b0\u1ee3c kh\u1edfi tr\u1ecb \u1edf các b\u1ec7nh nhân có t\u1ea7n s\u1ed1 tim lúc ngh\u1ec9 tr\u01b0\u1edbc khi \u0111i\u1ec1u tr\u1ecb th\u1ea5p h\u01a1n 70 nh\u1ecbp/phút.

N\u1ebfu trong quá trình \u0111i\u1ec1u tr\u1ecb, t\u1ea7n s\u1ed1 tim lúc ngh\u1ec9 gi\u1ea3m liên t\u1ee5c d\u01b0\u1edbi 50 nh\u1ecbp/phút ho\u1eb7c b\u1ec7nh nhân có các tri\u1ec7u ch\u1ee9ng liên quan \u0111\u1ebfn nh\u1ecbp tim ch\u1eadm nh\u01b0 chóng m\u1eb7t, m\u1ec7t m\u1ecfi ho\u1eb7c h\u1ea1 huy\u1ebft áp, li\u1ec1u \u0111i\u1ec1u tr\u1ecb c\u1ea7n ph\u1ea3i gi\u1ea3m xu\u1ed1ng ho\u1eb7c ng\u01b0ng \u0111i\u1ec1u tr\u1ecb n\u1ebfu t\u1ea7n s\u1ed1 tim d\u01b0\u1edbi 50 nh\u1ecbp/phút ho\u1eb7c các tri\u1ec7u ch\u1ee9ng c\u1ee7a nh\u1ecbp tim ch\u1eadm v\u1eabn t\u1ed3n t\u1ea1i.

Ph\u1ed1i h\u1ee3p v\u1edbi thu\u1ed1c ch\u1eb9n kênh canxi:

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi ivabradin v\u1edbi thu\u1ed1c làm gi\u1ea3m t\u1ea7n s\u1ed1 tim thu\u1ed9c nhóm thu\u1ed1c ch\u1eb9n kênh canxi nh\u01b0 verapamil ho\u1eb7c diltiazem là ch\u1ed1ng ch\u1ec9 \u0111\u1ecbnh. Ch\u01b0a có v\u1ea5n \u0111\u1ec1 liên quan \u0111\u1ebfn an toàn \u0111\u01b0\u1ee3c ghi nh\u1eadn khi ph\u1ed1i h\u1ee3p ivabradin v\u1edbi nitrate ho\u1eb7c thu\u1ed1c ch\u1eb9n kênh canxi nhóm dihydropyridine nh\u01b0 amlodipine. Hi\u1ec7u qu\u1ea3 hi\u1ec7p \u0111\u1ed3ng c\u1ed9ng c\u1ee7a ivabradin khi ph\u1ed1i h\u1ee3p v\u1edbi thu\u1ed1c ch\u1eb9n kênh canxi nhóm dihydropyridine ch\u01b0a \u0111\u01b0\u1ee3c thi\u1ebft l\u1eadp.

Suy tim m\u1ea1n tính:

B\u1ec7nh suy tim c\u1ea7n ph\u1ea3i \u1edf giai \u0111o\u1ea1n \u1ed5n \u0111\u1ecbnh tr\u01b0\u1edbc khi cân nh\u1eafc \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin. Ivabradin nên \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng th\u1eadn tr\u1ecdng \u1edf các b\u1ec7nh nhân suy tim NYHA \u0111\u1ed9 IV do d\u1eef li\u1ec7u còn gi\u1edbi h\u1ea1n trên nh\u1eefng \u0111\u1ed1i t\u01b0\u1ee3ng này.

\u0110\u1ed9t qu\u1ef5:

Không khuy\u1ebfn cáo s\u1eed d\u1ee5ng ivabradin ngay sau khi \u0111\u1ed9t qu\u1ef5 do ch\u01b0a có d\u1eef li\u1ec7u cho nh\u1eefng tr\u01b0\u1eddng h\u1ee3p này.

Ch\u1ee9c n\u0103ng th\u1ecb giác:

Ivabradin \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn ch\u1ee9c n\u0103ng võng m\u1ea1c. Cho \u0111\u1ebfn nay, không có b\u1eb1ng ch\u1ee9ng v\u1ec1 \u0111\u1ed9c tính c\u1ee7a ivabradin trên võng m\u1ea1c, nh\u01b0ng nh\u1eefng \u1ea3nh h\u01b0\u1edfng c\u1ee7a vi\u1ec7c \u0111i\u1ec1u tr\u1ecb dài h\u1ea1n trên m\u1ed9t n\u0103m c\u1ee7a ivabradin trên ch\u1ee9c n\u0103ng võng m\u1ea1c hi\u1ec7n t\u1ea1i ch\u01b0a \u0111\u01b0\u1ee3c bi\u1ebft \u0111\u1ebfn. Vi\u1ec7c ng\u01b0ng \u0111i\u1ec1u tr\u1ecb c\u1ea7n \u0111\u01b0\u1ee3c xem xét n\u1ebfu x\u1ea3y ra b\u1ea5t k\u1ef3 s\u1ef1 suy gi\u1ea3m ch\u1ee9c n\u0103ng th\u1ecb giác nào. C\u1ea7n th\u1eadn tr\u1ecdng \u1edf nh\u1eefng b\u1ec7nh nhân viêm s\u1eafc t\u1ed1 võng m\u1ea1c.

Th\u1eadn tr\u1ecdng khi s\u1eed d\u1ee5ng:

B\u1ec7nh nhân huy\u1ebft áp th\u1ea5p:

D\u1eef li\u1ec7u hi\u1ec7n có \u1edf m\u1ee9c gi\u1edbi h\u1ea1n trên nh\u1eefng b\u1ec7nh nhân huy\u1ebft áp th\u1ea5p t\u1eeb nh\u1eb9 \u0111\u1ebfn trung bình, do \u0111ó ivabradin c\u1ea7n \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng th\u1eadn tr\u1ecdng trên nh\u1eefng b\u1ec7nh nhân này. Ch\u1ed1ng ch\u1ec9 \u0111\u1ecbnh dùng ivabradin \u1edf nh\u1eefng b\u1ec7nh nhân h\u1ea1 huy\u1ebft áp m\u1ee9c \u0111\u1ed9 n\u1eb7ng (huy\u1ebft áp < 90/50mmHg).

Rung nh\u0129 - Lo\u1ea1n nh\u1ecbp tim:

Không có b\u1eb1ng ch\u1ee9ng v\u1ec1 nguy c\u01a1 c\u1ee7a nh\u1ecbp xoang ch\u1eadm (quá m\u1ee9c) khi b\u1eaft \u0111\u1ea7u s\u1ef1 kh\u1eed dung d\u01b0\u1ee3c lý \u1edf nh\u1eefng b\u1ec7nh nhân \u0111ang \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin. Tuy nhiên, do thi\u1ebfu các d\u1eef li\u1ec7u m\u1edf r\u1ed9ng, vi\u1ec7c kh\u1eed dung không c\u1ea5p c\u1ee9u nên \u0111\u01b0\u1ee3c cân nh\u1eafc 24 gi\u1edd sau li\u1ec1u cu\u1ed1i cùng c\u1ee7a ivabradin.

S\u1eed d\u1ee5ng \u1edf b\u1ec7nh nhân có h\u1ed9i ch\u1ee9ng QT b\u1ea9m sinh ho\u1eb7c \u0111i\u1ec1u tr\u1ecb v\u1edbi thu\u1ed1c kéo dài kho\u1ea3ng QT:

Nên tránh s\u1eed d\u1ee5ng ivabradin \u1edf các b\u1ec7nh nhân có h\u1ed9i ch\u1ee9ng QT b\u1ea9m sinh ho\u1eb7c \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb v\u1edbi thu\u1ed1c kéo dài kho\u1ea3ng QT. N\u1ebfu ph\u1ed1i h\u1ee3p này là c\u1ea7n thi\u1ebft, c\u1ea7n theo dõi ch\u1eb7t ch\u1ebd tình tr\u1ea1ng tim m\u1ea1ch.

Gi\u1ea3m nh\u1ecbp tim, do ivabradin, có th\u1ec3 làm tr\u1ea7m tr\u1ecdng thêm s\u1ef1 kéo dài kho\u1ea3ng QT, có th\u1ec3 d\u1eabn \u0111\u1ebfn lo\u1ea1n nh\u1ecbp nghiêm tr\u1ecdng, \u0111\u1eb7c bi\u1ec7t là xo\u1eafn \u0111\u1ec9nh.

B\u1ec7nh nhân t\u0103ng huy\u1ebft áp c\u1ea7n ph\u1ea3i thay \u0111\u1ed5i \u0111i\u1ec1u tr\u1ecb v\u1ec1 huy\u1ebft áp:

Trong th\u1eed nghi\u1ec7m SHIFT, nhi\u1ec1u b\u1ec7nh nhân có c\u01a1n t\u0103ng huy\u1ebft áp khi \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin h\u01a1n (7.1%) khi so sánh v\u1edbi b\u1ec7nh nhân \u0111i\u1ec1u tr\u1ecb v\u1edbi gi\u1ea3 d\u01b0\u1ee3c (6.1%). Nh\u1eefng giai \u0111o\u1ea1n này ch\u1ee7 y\u1ebfu x\u1ea3y ra thoáng qua trong th\u1eddi gian ng\u1eafn ngay sau khi thay \u0111\u1ed5i \u0111i\u1ec1u tr\u1ecb huy\u1ebft áp, và không \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn hi\u1ec7u qu\u1ea3 \u0111i\u1ec1u tr\u1ecb c\u1ee7a ivabradin. Khi thay \u0111\u1ed5i \u0111i\u1ec1u tr\u1ecb trên nh\u1eefng b\u1ec7nh nhân suy tim m\u1ea1n tính \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin, nên theo dõi huy\u1ebft áp trong kho\u1ea3ng th\u1eddi gian thích h\u1ee3p.

Tá d\u01b0\u1ee3c:

Do viên nén có ch\u1ee9a lactose, các b\u1ec7nh nhân có v\u1ea5n \u0111\u1ec1 di truy\u1ec1n hi\u1ebfm g\u1eb7p v\u1ec1 không dung n\u1ea1p galactose, thi\u1ebfu h\u1ee5t Lapp lactase ho\u1eb7c kém h\u1ea5p thu glucose - galactose không nên s\u1eed d\u1ee5ng s\u1ea3n ph\u1ea9m này.

T\u01af\u01a0NG TÁC V\u1edaI CÁC THU\u1ed0C KHÁC

T\u01b0\u01a1ng tác d\u01b0\u1ee3c l\u1ef1c h\u1ecdc:

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi không \u0111\u01b0\u1ee3c khuy\u1ebfn cáo:

Các thu\u1ed1c kéo dài kho\u1ea3ng QT:

- Các thu\u1ed1c tim m\u1ea1ch làm kéo dài kho\u1ea3ng QT (ví d\u1ee5 quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone).

- Các thu\u1ed1c không thu\u1ed9c nhóm tim m\u1ea1ch làm kéo dài kho\u1ea3ng QT (ví d\u1ee5 pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin dùng \u0111\u01b0\u1eddng t\u0129nh m\u1ea1ch).

Nên tránh s\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi các thu\u1ed1c tim m\u1ea1ch và thu\u1ed1c không thu\u1ed9c nhóm tim m\u1ea1ch làm kéo dài kho\u1ea3ng QT v\u1edbi ivabradin do s\u1ef1 kéo dài kho\u1ea3ng QT có th\u1ec3 tr\u1ea7m tr\u1ecdng h\u01a1n do gi\u1ea3m t\u1ea7n s\u1ed1 tim. N\u1ebfu s\u1ef1 ph\u1ed1i h\u1ee3p này là c\u1ea7n thi\u1ebft, c\u1ea7n theo dõi ch\u1eb7t ch\u1ebd ch\u1ee9c n\u0103ng tim m\u1ea1ch.

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi yêu c\u1ea7u th\u1eadn tr\u1ecdng:

Thu\u1ed1c l\u1ee3i ti\u1ec3u làm gi\u1ea3m kali (thu\u1ed1c l\u1ee3i ti\u1ec3u thiazid và thu\u1ed1c l\u1ee3i ti\u1ec3u quai): h\u1ea1 kali máu có th\u1ec3 làm t\u0103ng nguy c\u01a1 r\u1ed1i lo\u1ea1n nh\u1ecbp tim. Do ivabradin có th\u1ec3 gây ch\u1eadm nh\u1ecbp tim, k\u1ebft qu\u1ea3 c\u1ee7a s\u1ef1 ph\u1ed1i h\u1ee3p h\u1ea1 kali máu và gi\u1ea3m nh\u1ecbp tim là m\u1ed9t y\u1ebfu t\u1ed1 n\u1ec1n kh\u1edfi phát r\u1ed1i lo\u1ea1n nh\u1ecbp tim nghiêm tr\u1ecdng, \u0111\u1eb7c bi\u1ec7t \u1edf các b\u1ec7nh nhân có h\u1ed9i ch\u1ee9ng QT kéo dài b\u1ea9m sinh hay do dùng thu\u1ed1c.

T\u01b0\u01a1ng tác d\u01b0\u1ee3c \u0111\u1ed9ng h\u1ecdc:

Cytochrome P450 3A4 (CYP3A4):

Ivabradin \u0111\u01b0\u1ee3c chuy\u1ec3n hóa ch\u1ec9 b\u1edfi CYP3A4 và nó là m\u1ed9t ch\u1ea5t \u1ee9c ch\u1ebf r\u1ea5t y\u1ebfu c\u1ee7a cytochrome này. Ivabradin \u0111\u01b0\u1ee3c ch\u1ee9ng minh là không \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn s\u1ef1 chuy\u1ec3n hóa và n\u1ed3ng \u0111\u1ed9 trong huy\u1ebft t\u01b0\u01a1ng c\u1ee7a các ch\u1ea5t n\u1ec1n CYP3A4 khác (các ch\u1ea5t \u1ee9c ch\u1ebf nh\u1eb9, v\u1eeba và m\u1ea1nh). Các ch\u1ea5t \u1ee9c ch\u1ebf và các ch\u1ea5t gây c\u1ea3m \u1ee9ng CYP3A4 t\u01b0\u01a1ng tác v\u1edbi ivabradin và \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn s\u1ef1 chuy\u1ec3n hóa và d\u01b0\u1ee3c \u0111\u1ed9ng h\u1ecdc c\u1ee7a ivabradin m\u1ed9t cách \u0111áng k\u1ec3 trên lâm sàng. Các nghiên c\u1ee9u v\u1ec1 t\u01b0\u01a1ng tác thu\u1ed1c - thu\u1ed1c \u0111ã cho th\u1ea5y các ch\u1ea5t \u1ee9c ch\u1ebf CYP3A4 làm t\u0103ng n\u1ed3ng \u0111\u1ed9 ivabradin trong huy\u1ebft t\u01b0\u01a1ng, trong khi các ch\u1ea5t gây c\u1ea3m \u1ee9ng làm gi\u1ea3m n\u1ed3ng \u0111\u1ed9 này. T\u0103ng n\u1ed3ng \u0111\u1ed9 c\u1ee7a ivabradin trong huy\u1ebft t\u01b0\u01a1ng có th\u1ec3 liên quan \u0111\u1ebfn nguy c\u01a1 ch\u1eadm nh\u1ecbp tim quá m\u1ee9c.

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi là ch\u1ed1ng ch\u1ec9 \u0111\u1ecbnh:

Ph\u1ed1i h\u1ee3p v\u1edbi các ch\u1ea5t \u1ee9c ch\u1ebf m\u1ea1nh CYP3A4 nh\u01b0 thu\u1ed1c kháng n\u1ea5m nhóm azole (ketoconazole, itraconazole), thu\u1ed1c kháng sinh macrolide (clarithromycin, erythromycin \u0111\u01b0\u1eddng u\u1ed1ng, josamycin, telithromycin), các ch\u1ea5t \u1ee9c ch\u1ebf HIV protease (nelfinavir, ritonavir) và nefazodone là ch\u1ed1ng ch\u1ec9 \u0111\u1ecbnh. Các ch\u1ea5t \u1ee9c ch\u1ebf m\u1ea1nh CYP3A4 nh\u01b0 ketoconazole (200mg m\u1ed9t l\u1ea7n m\u1ed7i ngày) và josamycin (1g hai l\u1ea7n m\u1ed7i ngày) làm t\u0103ng n\u1ed3ng \u0111\u1ed9 ivabradin trong huy\u1ebft t\u01b0\u01a1ng lên 7 \u0111\u1ebfn 8 l\u1ea7n.

Các ch\u1ea5t \u1ee9c ch\u1ebf trung bình CYP3A4: các nghiên c\u1ee9u \u0111\u1eb7c hi\u1ec7u v\u1ec1 t\u01b0\u01a1ng tác thu\u1ed1c ti\u1ebfn hành trên ng\u01b0\u1eddi tình nguy\u1ec7n kh\u1ecfe m\u1ea1nh và b\u1ec7nh nhân \u0111ã ch\u1ee9ng minh s\u1ef1 ph\u1ed1i h\u1ee3p ivabradin v\u1edbi các thu\u1ed1c làm gi\u1ea3m t\u1ea7n s\u1ed1 tim diltiazem ho\u1eb7c verapamil d\u1eabn \u0111\u1ebfn k\u1ebft qu\u1ea3 làm t\u0103ng n\u1ed3ng \u0111\u1ed9 ivabradin (t\u0103ng 2 \u0111\u1ebfn 3 l\u1ea7n di\u1ec7n tích d\u01b0\u1edbi \u0111\u01b0\u1eddng cong (AUC)) và làm gi\u1ea3m t\u1ea7n s\u1ed1 tim thêm 5 nh\u1ecbp/phút. Vi\u1ec7c s\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi ivabradin v\u1edbi nh\u1eefng thu\u1ed1c này là ch\u1ed1ng ch\u1ec9 \u0111\u1ecbnh.

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi không \u0111\u01b0\u1ee3c khuy\u1ebfn cáo:

N\u01b0\u1edbc ép b\u01b0\u1edfi chùm: n\u1ed3ng \u0111\u1ed9 ivabradin t\u0103ng 2 l\u1ea7n khi s\u1eed d\u1ee5ng cùng v\u1edbi n\u01b0\u1edbc ép b\u01b0\u1edfi chùm. Do \u0111ó nên tránh s\u1eed d\u1ee5ng n\u01b0\u1edbc ép b\u01b0\u1edfi chùm trong quá trình \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin.

S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi yêu c\u1ea7u th\u1eadn tr\u1ecdng:

- Các ch\u1ea5t \u1ee9c ch\u1ebf trung bình CYP3A4: s\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi ivabradin v\u1edbi các ch\u1ea5t \u1ee9c ch\u1ebf trung bình CYP3A4 khác (ví d\u1ee5 fluconazole) có th\u1ec3 \u0111\u01b0\u1ee3c cân nh\u1eafc \u1edf li\u1ec1u kh\u1edfi \u0111\u1ea7u 2.5mg hai l\u1ea7n m\u1ed7i ngày và n\u1ebfu t\u1ea7n s\u1ed1 tim lúc ngh\u1ec9 trên 70 nh\u1ecbp/phút, v\u1edbi s\u1ef1 giám sát t\u1ea7n s\u1ed1 tim.

- Các ch\u1ea5t gây c\u1ea3m \u1ee9ng CYP3A4: Các ch\u1ea5t gây c\u1ea3m \u1ee9ng CYP3A4 (ví d\u1ee5 rifampicin, barbiturates, phenytoin, Hypericum perforatum [St John’s Wort] có th\u1ec3 làm gi\u1ea3m n\u1ed3ng \u0111\u1ed9 và m\u1ee9c \u0111\u1ed9 ho\u1ea1t \u0111\u1ed9ng c\u1ee7a ivabradin. Vi\u1ec7c s\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi các ch\u1ea5t gây c\u1ea3m \u1ee9ng CYP3A4 có th\u1ec3 c\u1ea7n ph\u1ea3i \u0111i\u1ec1u ch\u1ec9nh li\u1ec1u c\u1ee7a ivabradin. S\u1eed d\u1ee5ng \u0111\u1ed3ng th\u1eddi ivabradin 10mg hai l\u1ea7n m\u1ed9t ngày v\u1edbi St John’s Wort \u0111ã cho th\u1ea5y di\u1ec7n tích d\u01b0\u1edbi \u0111\u01b0\u1eddng cong (AUC) c\u1ee7a ivabradin gi\u1ea3m m\u1ed9t n\u1eeda. S\u1eed d\u1ee5ng St John’s Wort nên \u0111\u01b0\u1ee3c gi\u1edbi h\u1ea1n trong khi \u0111i\u1ec1u tr\u1ecb v\u1edbi ivabradin.

Nh\u1eefng ph\u1ed1i h\u1ee3p khác:

Các nghiên c\u1ee9u \u0111\u1eb7c hi\u1ec7u trên t\u01b0\u01a1ng tác thu\u1ed1c - thu\u1ed1c \u0111ã ch\u1ee9ng minh không có \u1ea3nh h\u01b0\u1edfng \u0111áng k\u1ec3 nào trên lâm sàng c\u1ee7a các thu\u1ed1c sau trên d\u01b0\u1ee3c \u0111\u1ed9ng h\u1ecdc và d\u01b0\u1ee3c l\u1ef1c h\u1ecdc c\u1ee7a ivabradin: các thu\u1ed1c \u1ee9c ch\u1ebf b\u01a1m proton (omeprazole, lansoprazole), sildenafil, các ch\u1ea5t \u1ee9c ch\u1ebf HMG CoA reductase (simvastatin), các thu\u1ed1c ch\u1eb9n kênh canxi nhóm dihydropyridine (amlodipine, lacidipine), digoxin và warfarin. Thêm vào \u0