KOMPATIBILITAS_training

INTERAKSI, KOMPATIBILITAS & INKOMPATIBILITAS OBAT

 Interaksi obat merupakan satu dari delapan kategori masalah terkait obat (drug-related problem) yang diidentifikasi sebagai kejadian atau keadaan terapi obat yang dapat mempengaruhi outcome klinis pasien.  Sebuah interaksi obat terjadi ketika farmakokinetika atau farmakodinamika obat dalam tubuh diubah oleh kehadiran satu atau lebih zat yang berinteraksi (Piscitelli, 2005).  Dua atau lebih obat yang diberikan pada waktu yang sama dapat berubah efeknya secara tidak langsung atau dapat berinteraksi. Interaksi bisa bersifat potensiasi atau antagonis efek satu obat oleh obat lainnya, atau adakalanya beberapa efek lainnya (BNF 58, 2009).

 Suatu interaksi terjadi ketika efek suatu obat diubah oleh kehadiran obat lain, obat herbal, makanan, minuman atau agen kimia lainnya dalam lingkungannya.  Definisi yang lebih relevan kepada pasien adalah ketika obat bersaing satu dengan yang lainnya, atau apa yang terjadi ketika obat hadir bersama satu dengan yang lainnya (Stockley, 2008).  Interaksi obat dianggap penting secara klinik bila berakibat meningkatkan toksisitas dan atau mengurangi efektivitas obat yang berinteraksi terutama bila menyangkut obat dengan batas keamanan yang sempit (indeks terapi yang rendah), misalnya glikosida jantung, antikoagulan, dan obat-obat sitostatik (Setiawati, 2007).

Interaksi farmakokinetik terdiri dari beberapa tipe :  Interaksi pada absorbsi obat  Interaksi pada distribusi obat  Interaksi pada metabolisme obat  Interaksi pada ekskresi obat Interaksi ini biasanya dapat diprediksi dari pengetahuan tentang farmakologi obat-obat yang berinteraksi (BNF 58, 2009).  Interaksi aditif atau sinergis  Interaksi antagonis atau berlawanan

Hal yang perlu diperhatikan pada interaksi obat :  Tidak semua obat yang berinteraksi signifikan secara klinik.  Interaksi tidak selamanya merugikan.  Jika dua obat berinteraksi tidak berarti tidak boleh diberikan.  Interaksi tidak hanya untuk terapi yang berbeda tetapi kadang untuk mengobati penyakit yang sama.  Interaksi dapat dimanfaatkan untuk meningkatkan pengobatan. Guna interaksi obat, diantaranya yaitu :  Meningkatkan kerja dari obat Contoh : Sulfametoksasol, analgetik dan kafein  Mengurangi efek samping Contoh : Anestetika dan adrenalin  Memperluas spektrum Contoh : Kombinasi antiinfeksi  Memperpanjang kerja obat Probenesid dan penisilin



















NO NAMA OBAT KETERCAMPURAN LARUTAN IV KETERANGAN 1 Acyclovir Larutan Dextrosa, Ringer's Lactat. Tidak kompatibel NOTE: larutan dextrose > 10% dapat menjadikan dengan produk darah, kuning larutan (tidak mempengaruhi potensi obat) larutan yang mengandung protein Jangan simpan di lemari es 2 Albumin NaCl 0.9% (lbh baik) ; kompatibel dengan a 5% dan Jangan gunakan jika 10% larutan keruh. jika kandungan larutan 5%-25% gunakan NS atau Jangan menggunakan D5W sebagai pelarut. SWFI 3 Amikacin Larutan Dextrosa, RL Masukkan > 1 jam Inkompatibel dengan heparin sebelum Penicillin 4 Aminophylline Larutan Dextrose, RL - 5 Amphotericin B Lebih disukai dgn Dekstrosa 5% Tidak kompatibel (Fungizone) dengan NaCl0.9% jangan dicampur dengan obat lain 6 Ampicillin Paling stabil dlm NaCl 0.9% dekstrosa dapat - digunakan tapi tidak dalam konsentrasi tinggi 7 Ampicillin Dalam NaCL 0.9% lebih disukai kompatibel dengan - sulbactam larutan yang mengandung Dextrose dan RL 8 Calcium Kompatibel dengan NaCl 0.9%, dekstrosa, RL -

9 Cefepime Kompatibel dengan NaCl 0.9%, dekstrosa, RL 10 Cefotaxime Kompatibel dengan NaCl 0.9%, dekstrosa, RL 11 Ceftazidime Kompatibel dengan NaCl 0.9%, dekstrosa, RL 12 Ceftiaxone Kompatibel dengan NaCl 0.9%, dekstrosa. 13 Chloramphenicol Kompatibel dengan NaCl 0.9%, dekstrosa, RL 14 Ciprofloxacine Kompatibel dengan NaCl 0.9%, dekstrosa. 15 Clindamycin Kompatibel dengan NaCl 0.9%, dekstrosa, RL 16 Dexamethason Kompatibel dengan NaCl 0.9%, dekstrosa. 17 Diazepam Tidak direkmonedasi untuk dilarutkan tapi NaCl 0.9%dapat digunakan untuk penggunaan darurat 18 Digoxin Dekstros 5% dan NaCl 0.9% 19 Dobutamine Kompatibel dengan NaCl 0.9%, dekstrosa, RL. Tidak kompatibel dengan heparin 20 Dopamine Kompatibel dengan NaCl 0.9%, dekstrosa, RL ( Gunakan N5 bila ada heparin) 21 Epinephrine Kompatibel dengan NaCl 0.9%, dekstrosa. 22 Fentanyl Citrate Kompatibel dengan NaCl 0.9%, dekstrosa. 23 Fluconazole Kompatibel dgn Dextrosa 5%, 10% dan RL 24 Furosemide Kompatibel dng NaCl 0.9% Lebih disukai dgn RL 25 Ganciclovir Kompatibel dgn Dextrosa 5%, NaCl 0.9% dan RL 26 Gentamycin Kompatibel dengan NaCl 0.9%, dekstrosa 27 Heparin Kompatibel dengan NaCl 0.9%, dekstrosa 28 Imipenem-Cilastatin NaCl 0.9% lebih disukai meskipun dekstrose dapat digunakan pada kondisi khusus

29 Ketorolac Kompatibel dengan larutan NaCl 0.9% dan dekstrose, RL - 30 Levofloxacin Kompatibel dengan larutan NaCl 0.9% dan dekstrose, RL - 31 Lorazepam Lebih disukai dgn Dekstrosa 5% Kurang stabil dalam NaCl - 32 MgSO4 Larutan dekstrosa dan NaCl 0.9% - 33 Mannitol Biasanya tdk dilarutkan tetapi Dekstrosa 5%, NaCl telah digunakan - 34 Meropenem Lebih disukai NaCl 0.9%, kurang stabil dalam dekstrose, kompatibel dengan RL - 35 Metronidazole Tdk perlu dilarutkan. Kompatibel dgn larutan dekstrosa dan NaCl 0.9% Jangan dicampur dgn obat lain 36 Midazolam Dekstrose 5%, NaCl 0.9%, RL - 37 Morphine Sulphate Larutan dekstrose dan NaCl 0.9%, bila diinfus bersama dgn heparin gunakan - 38 Ondansentron hanya NaCl 0.9% 39 Penicillin G 40 Phenytoin Larutan dekstrosa dan NaCl 0.9% Tidak tercampur dengan obat dan larutan bersifat basa Larutan dekstrosa dan NaCl 0.9% - NaCl 0.9% Jangan dicampur dgn obat lain 41 Piperacillin-Tazobactam Larutan dekstrosa dan NaCl 0.9% - - tidak tercampur dgn RL - 42 Propranolol Tidak direkomendasi untuk dilarutkan tapi NaCl 0.9% dapat digunakan 43 Ranitidin Kompatibel dengan larutan NaCl 0.9% dan dekstrosa, RL 44 Sodium Bicarbonate Larutan dekstrosa dan NaCl 0.9% - 45 Sodium Valproate Dekstrosa 5%, NaCl 0.9%, RL - 46 Vancomycin Dekstrosa 5%, NaCl 0.9%, RL -

INKOMPATIBILITAS Inkompatibilitas adalah pencampuran antara dua reaksi atau lebih antara obat-obatan yang menimbulkan ketidakcocokan atau ketidaksesuaian. Inkompatibilitas biasa dikenal dengan OTT (obat tak tercampur) pada sediaan cair biasanya terjadi inkompatibilitas secara fisika atau kimia tergantung pada larutan tersebut ( Syamsuni, 2006). Inkompatibilitas terbagi menjadi beberapa macam, antara lain :  Inkompatibilitas fisika adalah terjadinya perubahan-perubahan yang tidak di inginkan pada percampuran obat dua atau lebih tanpa ada perubahan susunan kimianya.  Inkompatibilitas kimia adalah perubahan-perubahan yang terjadi karena timbulnya reaksi-reaksi kimia pada waktu mencampurkan bahan-bahan obat. Beberapa contoh inkompatibilitas kimia  Inkompatibilitas Farmasetik,Kondisi dimana bahan-bahan obat (bahan aktif maupun bahan tambahan) tidak dapat dicampurkan untuk menghasilkan “pharmaceutically elegant dosage form” karena adanya inkompatibilitas fisika atau/maupun kimia.  Inkompatibilitas Terapetik,Bila obat yang satu dicampur atau dikombinasikan dengan obat lain akan mengalami perubahan-perubahan sedemikian rupa sehingga sifat kerjanya dalam tubuh berlainan dari yg diharapkan.

Drug Compatibility Diluent Comment Atropine √ NaCl 0.9% Atropine may be administered via continuous subcutaneous Clonazepam infusion, but is not commonly used in Australia. Information on compatibility with other drugs is limited therefore not Clonazepam, Glycopyrollate, Oxycodone recommended. Clonazepam, Haloperidol, Methadone Clonazepam, Haloperidol, Morphine sulfate √ NaCl 0.9% WFI There is a significant loss when infused through PVC tubing Clonazepam, Haloperidol, Morphine tartrate Clonazepam, Haloperidol, Oxycodone which can be addressed by using non PVC tubing or titrating Clonazepam, Hydromorphone Clonazepam, Hyoscine butylbromide the dose to desired effect. Clonazepam, Hyoscine butylbromide, Morphine sulfate Clonazepam, Hyoscine butylbromide, Oxycodone √ NaCl 0.9% Clonazepam, Hyoscine butylbromide, Oxycodone Clonazepam, Ketamine, Morphine Tartrate √C NaCl 0.9% Clonazepam, Ketamine, Oxycodone Clonazepam, Levomepromazine, Morphine sulfate √ NaCl 0.9% WFI Clonazepam, Levomepromazine, Oxycodone Clonazepam, Methadone √ NaCl 0.9% Clonazepam, Metoclopramide, Oxycodone √B NaCl 0.9% WFI √ NaCl 0.9% √ NaCl 0.9% WFI √ NaCl 0.9% √B NaCl 0.9% WFI √B NaCl 0.9% WFI √C NaCl 0.9% √C NaCl 0.9% √C NaCl 0.9% WFI √C NaCl 0.9% WFI √C NaCl 0.9% √ NaCl 0.9%

Clonazepam, Morphine sulfate √ NaCl 0.9% WFI Clonazepam, Octreotide, Oxycodone Clonazepam, Oxycodone √ NaCl 0.9% Cyclizine √B NaCl 0.9% WFI Cyclizine, Glycopyrrolate, Haloperidol Cyclizine, Glycopyrrolate, Oxycodone √C WFI Cyclizine may precipitate as the concentration of Cyclizine, Haloperidol chloride ions increase (e.g. With Metoclorpamide Cyclizine, Haloperidol, Hyoscine butylbromide or Oxycodone) or if the pH is greater than 6.8 Cyclizine, Haloperidol, Metoclopramide Cyclizine, Haloperidol, Midazolam √C WFI Risk of precipitation (see above) Cyclizine, Haloperidol, Morphine sulfate √C WFI Risk of precipitation (see above) Cyclizine, Haloperidol, Octreotide Risk of precipitation (see above) Cyclizine, Haloperidol, Oxycodone √C WFI Cyclizine, Hydromorphone X WFI Cyclizine and Levomepromazine are generally not Cyclizine, Hydromorphone, Octreotide administered together due to an increased risk of Cyclizine, Hyoscine butylbromide Caution C WFI adverse effects Cyclizine, Hyoscine butylbromide, Morphine sulfate Cyclizine, Hyoscine butylbromide, Oxycodone √C WFI Cyclizine, Hyoscine butylbromide, Midazolam √A,B,C WFI Cyclizine, Hyoscine butylbromide, Morphine sulfate Cyclizine, Hyoscine butylbromide, Morphine tartrate √C WFI Cyclizine, Levomepromazine √A,B,C WFI Cyclizine, Levomepromazine, Morphine sulfate Caution C WFI √C WFI Caution C WFI Caution C WFI X WFI √C WFI √C WFI √C WFI √C WFI √C WFI Risk of adverse effects (see above)

Cyclizine, Levomepromazine, Octreotide √C WFI Risk of adverse effects (see above) Cyclizine, Levomepromazine, Oxycodone √C WFI Cyclizine may precipitate as the concentration of Cyclizine, Methadone chloride ions increases (e.g. with Cyclizine, Metoclopramide Metoclopramide or Oxycodon). Risk of adverse effects (see above). Cyclizine, Metoclopramide, Octreotide Cyclizine, Midazolam √C WFI The prokinetic effect of Metoclopramide may be √C WFI initiated by Cyclizine. Cyclizine, Midazolam, Morphine sulfate Risk of adverse effects (see above). Cyclizine, Midazolam, Oxycodon √C WFI The prokinetic effect of Metoclopramide may be Cyclizine, Morphine sulfate √C WFI initiated by Cyclizine. Cyclizine, Morphine sulfate, Octreotide Risk of adverse effects (see above). Cyclizine, Morphine tartrate Cyclizine, Ondansetron, Oxycodon √A,B,C WFI Cyclizine may precipitate as the concentration of Cyclizine, Oxycodon √A,B,C WFI chloride ions increases (e.g. with Fentanyl Metoclopramide or Oxycodon). √C WFI Risk of adverse effects (see above). √C WFI √C WFI WFI The volume of fentanyl injection may restrict its X WFI use in the syringe driver. A separate or 12 hourly √A,B,C WFI syringe driver may be required. √ NaCl 0.9%

Fentanyl, Haloperidol, Midazolam √ NaCl 0.9% WFI Fentanyl, Hyoscine butylbromide, Midazolam √A,B NaCl 0.9% Fentanyl, Ketamine WFI Fentanyl, Metoclopramide √B,C NaCl 0.9% WFI Fentanyl, Metoclopramide, Midazolam √ WFI Fentanyl, Midazolam NaCl 0.9% The prokinetic effect of Metoclopramide may be initiated by Fentanyl, Ondansetron √A,B NaCl 0.9% Glycipyrrolate Glycipyrrolate √A,B NaCl 0.9% WFI The prokinetic effect of Metoclopramide may be initiated by Glycipyrrolate, Haloperidol, Ondansetron √A,B NaCl 0.9% Glycipyrrolate, Ketamine Oxycodone Glycipyrrolate Glycipyrrolate, Levomepromazine, Midazolam √ NaCl 0.9% Glycipyrrolate, Levomepromazine, Morphine sulfate WFI Glycipyrrolate, Levomepromazine, Ocreotide √ NaCl 0.9% WFI Glycipyrrolate, Levomepromazine, Oxycodone NaCl 0.9% Glycipyrrolate, Methadone, Midazolam √C WFI Glycipyrrolate, Metoclorpamide, Morphine sulfate √C NaCl 0.9% WFI At concentrations greater than 1 mg/ml, Haloperidol may Glycipyrrolate, Metoclorpamide, Oxycodone √C NaCl 0.9% precipitate in NaCl 0.9% Increased risk of extrapyramidal adverse effects when Glycipyrrolate, Midazolam √C NaCl 0.9% combining with dopaime activity, e.g. Haloperidol, Glycipyrrolate, Midazolam, Morphine sulfate Metocorpamide and Levomepromazine Glycipyrrolate, Midazolam, Oxycodone √C NaCl 0.9% Glycipyrrolate, Ondansetron Glycipyrrolate, Oxycodone √C NaCl 0.9% Haloperidol √ NaCl 0.9% Haloperidol, Hydromorphone √ NaCl 0.9% NaCl 0.9% √ √ NaCl 0.9% √ NaCl 0.9% NaCl 0.9% √A,B √ NaCl 0.9% √ √ NaCl 0.9% WFI

Haloperidol, Hydromorphone, Ketamine √C NaCl 0.9% WFI Haloperidol, Hydromorphone, Metoclorpamide Haloperidol, Hydromorphone, Midazolam √ NaCl 0.9% Increased risk of adverse effects (see above) Haloperidol, Hydromorphone, Ranitidin Haloperidol, Hyoscine butylbromide √ NaCl 0.9% WFI Haloperidol, Hyoscine butylbromide, Oxycodone Haloperidol, Hyoscine butylbromide, Metoclorpamide √ NaCl 0.9% Haloperidol, Hyoscine butylbromide, Midazolam √B NaCl 0.9% Haloperidol, Hyoscine butylbromide, Morphine sulfate Haloperidol, Hyoscine butylbromide, Ranitidine √B NaCl 0.9% WFI Haloperidol, Hyoscine butylbromide Haloperidol, Hyoscine butylbromide, Morphine sulfate √ NaCl 0.9% The prokinetic effect of Metoclopramide may be Haloperidol, Hyoscine butylbromide, Ocreotide initiated by Hyoscine butylbromide. Haloperidol, Hyoscine butylbromide, Oxycodone Increased risk of extrapyramidal adverse effects when Haloperidol, Ketamine combining drugs with dopamine activity e.g. Haloperidol, Ketamine, Midazolam Haloperidol, Metoclopramide and Levomepromazine Haloperidol, Ketamine, Morphine sulfate Haloperidol, Ketamine, Oxycodone √B NaCl 0.9% WFI √ NaCl 0.9% √ NaCl 0.9% WFI Caution A,B NaCl 0.9% WFI √ NaCl 0.9% WFI √ NaCl 0.9% √B NaCl 0.9% √C NaCl 0.9% √C NaCl 0.9% √C NaCl 0.9% √B,C NaCl 0.9%

Haloperidol, Levomepromazine, Morphine sulfate √C NaCl 0.9% WFI Increased risk of extrapyramidal adverse effects when Haloperidol, Metoclorpamide combining drugs with dopamine activity (e.g. Haloperidol, Metoclorpamide, Midazolam Haloperidol, Metoclorpamide, Morphine sulfate Haloperidol, Metoclopramide and Levomepromazine). Haloperidol, Metoclorpamide, Morphine tartrate Haloperidol, Metoclorpamide, Ocreotide √B NaCl 0.9% WFI Increased risk of adverse effects (see above) Haloperidol, Metoclorpamide, Oxycodone Increased risk of adverse effects (see above) Haloperidol, Metoclorpamide, Ranitidine √B NaCl 0.9% WFI Increased risk of adverse effects (see above) Haloperidol, Midazolam Increased risk of adverse effects (see above) Haloperidol, Midazolam, Morphine sulfate √ NaCl 0.9% WFI Increased risk of adverse effects (see above) Haloperidol, Midazolam, Octreotide WFI Increased risk of adverse effects (see above) Haloperidol, Midazolam, Oxycodone √ NaCl 0.9% WFI Increased risk of adverse effects (see above) Haloperidol, Morphine Sulfate WFI Haloperidol, Morphine Sulfate, Ocreotide √ NaCl 0.9% WFI Haloperidol, Morphine Tartrate WFI Haloperidol, Ocreotide √ WFI Haloperidol, Ocreotide, Oxycodone Haloperidol, Ondansetron √ NaCl 0.9% Haloperidol, Oxycodone Hydromorphone √A,B NaCl 0.9% Hydromorphone, Hyoscine Butylbromide √A,B NaCl 0.9% NaCl 0.9% √ NaCl 0.9% √A,B NaCl 0.9% √ NaCl 0.9% √ NaCl 0.9% √ NaCl 0.9% √ NaCl 0.9% √ NaCl 0.9% √ NaCl 0.9% √ A, B NaCl 0.9% √ NaCl 0.9% √

Hydromorphone, Hyoscine Butylbromide, Levomepromazine √C NaCl 0.9% WFI Hydromorphone, Hyoscine Butylbromide, Midazolam √ NaCl 0.9% Hydromorphone, Ketamine √ A, B, C NaCl 0.9% Increased risk of extrapyramidal adverse effects when Hydromorphone, Ketamine, Levomepromazine √C NaCl 0.9% combining drugs with dopamine activity e.g. Haloperidol, Hydromorphone, Ketamine, Midazolam √C NaCl 0.9% Metoclopramide, Levomepromazine Hydromorphone, Levomepromazine √C NaCl 0.9% Hydromorphone, Levomepromazine, Metoclopramide √C NaCl 0.9% Hydromorphone, Levomepromazine, Midazolam √C NaCl 0.9% WFI Hydromorphone, Levomepromazine, Ranitidine √C Hydromorphone, Metoclopramide √ NaCl 0.9% WFI Hydromorphone, Metoclopramide, Midazolam √ NaCl 0.9% WFI Hydromorphone, Metoclopramide, Ocreotide √ NaCl 0.9% Hydromorphone, Metoclopramide, Ondansetron √ NaCl 0.9% WFI Hydromorphone, Midazolam √ A, B NaCl 0.9% WFI Hydromorphone, Ocreotide, Ondansetron √ NaCl 0.9% Hydromorphone, Ondansetron √ A, B NaCl 0.9% The prokinetic effect of metoclopramide may be inhibited by Hyoscine Butylbromide (Hyoscine BBr) √ NaCl 0.9% hyoscine butylbromide Hyoscine BBr, Ketamine, Levomepromazine √C NaCl 0.9% Hyoscine BBr, Levomepromazine, Morphine Sulfate √ A, B, C NaCl 0.9% Hyoscine BBr, Levomepromazine, Ocreotide √C NaCl 0.9% Hyoscine BBr, Levomepromazine, Ondansetron √C NaCl 0.9% Hyoscine BBr, Levomepromazine, Oxycodone √ A, B, C NaCl 0.9% Hyoscine BBr, Methadone, Ranitidine √C NaCl 0.9% Hyoscine BBr, Metoclopramide √B WFI

Hyoscine BBr, Metoclopramide, Midazolam √ B NaCl 0.9% The prokinetic effect of metoclopramide may be inhibited by hyoscine butylbromide Hyoscine BBr, Midazolam Hyoscine BBr, Midazolam, Morphine Sulfate √B NaCl 0.9% WFI Hyoscine BBr, Midazolam, Oxycodone √ NaCl 0.9% Hyoscine BBr, Morphine Sulfate, Ocreotide WFI Hyoscine BBr, Morphine Sulfate, Ondansetron √ NaCl 0.9% WFI Hyoscine BBr, Oxycodone √ NaCl 0.9% √ Hyoscine Hydrobromide (Hyoscine HBr) NaCl 0.9% WFI √ A, B WFI Hyoscine HBr, Ketorolac, Ranitidine NaCl 0.9% Hyoscine HBr, Levomepromazine, Morphine Sulfate √ WFI NaCl 0.9% WFI Hyoscine HBr, Levomepromazine, Oxycodone √ NaCl 0.9% WFI Hyoscine HBr, Midazolam √C Hysocine HBr, Midazolam, Morphine Sulfate NaCl 0.9% Increased risk of extrapyramidal adverse effects √ A, B, C NaCl 0.9% Hysocine HBr, Midazolam, Morphine Tartrate NaCl 0.9% Hyoscine HBr, Midazolam, Oxycodone √ A, B √ NaCl 0.9% Hyoscine HBr, Morphine Sulfate, Ocreotide NaCl 0.9% Hyoscine HBr, Oxycodone √ NaCl 0.9% Ketamine √ NaCl 0.9% Ketamine, Levomepromazine Ketamine, Levomepromazine, Metoclopramide √ NaCl 0.9% √ A, B NaCl 0.9% NaCl 0.9% √C √C √C when combining drugs with dopamine activity e.g haloperidol, metoclopramide and levomepromazine

Ketamine, Levomepromazine, Oxycodone √C NaCl 0.9% Ketamine, Methadone √C NaCl 0.9% WFI Ketamine, Metoclopramide √C NaCl 0.9% WFI Ketamine, Midazolam √C NaCl 0.9% Ketamine, Midazolam, Morphine Sulfate √C NaCl 0.9% Ketamine, Midazolam, Oxycodone √C NaCl 0.9% WFI Ketamine, Morphine Sulfate √ A, B, C NaCl 0.9% WFI Ketamine, Oxycodone √ A, B, C NaCl 0.9% Ketorolac √ NaCl 0.9% WFI Ketorolac, Methadone √ A, B, C NaCl 0.9% Ketorolac, Oxycodone NaCl 0.9% Ketorolac, Oxycodone, Ranitidine √B NaCl 0.9% √B Ketorolac, Ranitidine NaCl 0.9% WFI Increased risk of extrapyramidil adverse Levomepromazine √ NaCl 0.9% effects when combining drugs with dopamine √C activity, eg haloperidol, metoclopramide and levo,epromazine Levomepromazine, Methadone, Midazolam √C NaCl 0.9% Increase risk of adverse effect (see above) Levomepromazine, Metoclopramide √C NaCl 0.9% WFI Levomepromazine, Metoclopramide, Morphine Sulphate √A,B,C NaCl 0.9% Increase risk of adverse effect (see above) Levomepromazine, Metoclopramide, Octreotide √C NaCl 0.9% WFI Increased risk of extrapyramidil adverse effects when combining drugs with dopamine activity, eg haloperidol, metoclopramide and levo,epromazine

Levomepromazine, Metoclopramide, Oxycodone √A,B,C NaCl 0.9% Increase risk of adverse effect (see above) Levomepromazine, Midazolam √C Levomepromazine, Midazolam, Morphine Sulphate NaCl 0.9% WFI Combination appears to be physicaly incompatible Levomepromazine, Midazolam, Octreotide √A,B,C with increasing levemepromazine concentration Levomepromazine, Midazolam, Oxucodone √C NaCl 0.9% Levomepromazine, Morphine Sulphate √C Levomepromazine, Morphine Sulphate. Octreotide √C NaCl 0.9% Levomepromazine, Octreotide √C Levomepromazine, Octreotide, Ondansetron √C NaCl 0.9% WFI Levomepromazine, Octreotide, Oxycodone √C Levomepromazine, Ondansetron √B,C NaCl 0.9% WFI Levomepromazine, Ondansetron, Oxycodone √C Levomepromazine, Oxycodone √C NaCl 0.9% WFI Levomepromazine, Ranitidine √A,B,C NaCl 0.9% WFI Lignocaine √C Methadone NaCl 0.9% Methadone, Midazolam Methadone, Octreotide, Ranitidine NaCl 0.9% WFI Metoclopramide NaCl 0.9% WFI NaCl 0.9% NaCl 0.9% WFI NaCl 0.9% WFI √ NaCl 0.9% √C NaCl 0.9% WFI √C NaCl 0.9% WFI √C NaCl 0.9% √ NaCl 0.9% WFI

Metoclopramide, Midazolam √B NaCl 0.9% Metoclopramide, Midazolam, Morphine Sulphate √A,B NaCl 0.9% Metoclopramide, Midazolam, Oxycodone √A,B NaCl 0.9% WFI Metoclopramide, Midazolam, Ranitidine √ NaCl 0.9% Metoclopramide, Morphine Sulphate √ NaCl 0.9% Metoclopramide, Morphine Sulphate, Octreotide √ NaCl 0.9% Metoclopramide, Morphine Sulphate, Ranitidine √ NaCl 0.9% Metoclopramide, Morphine Sulfate, Ondansetron √ NaCl 0.9% Metoclopramide, Morphine Tartrate √ NaCl 0.9% WFI Metoclopramide, Octreotide √ NaCl 0.9% Metoclopramide, Octreotide, Oxycodone √ NaCl 0.9% WFI Metoclopramide, Ondansetron √A,B NaCl 0.9% Metoclopramide, Ondansetron, Oxycodone √ NaCl 0.9% Metoclopramide, Oxycodone √A,B NaCl 0.9% WFI Metoclopramide, Ranitidine √ NaCl 0.9% WFI Midazolam √ NaCl 0.9% Midazolam, Morphine Sulfate √ NaCl 0.9% WFI Midazolam, Morphine Sulfate, Octreotide √ NaCl 0.9% Midazolam, Morphine Sulfate, Ondansetron √ NaCl 0.9% Midazolam, Octreotide, Oxycodone √ NaCl 0.9% WFI Midazolam, Olanzapine √ NaCl 0.9% Midazolam, Ondansetron √A,B NaCl 0.9% Midazolam, Ondansetron, Oxycodone √ NaCl 0.9% Midazolam, Oxycodone √A,B NaCl 0.9%

Morphine Sulphate √ NaCl 0.9% WFI Morphine Sulphate, Octreotide √ Morphine Sulphate, Ondansetron √A,B NaCl 0.9% WFI Octreotide √ Octreotide, Ondansetron √B NaCl 0.9% WFI Octreotide, Ondansetron, Oxycodone √B Octreotide, Oxycodone √B NaCl 0.9% WFI Olanzapine √ Ondansetron √ NaCl 0.9% WFI Ondansetron, Oxycodone √ Oxycodone √ NaCl 0.9% WFI Oxycodone, Ranitidine √B Ranitidine √ NaCl 0.9% WFI Sulfentanil √ NaCl 0.9% WFI Initial dilution of powder with WFI prior to further dilution NaCl 0.9% WFI NaCl 0.9% WFI NaCl 0.9% WFI NaCl 0.9% WFI NaCl 0.9% WFI NaCl 0.9% Little compatibility data is available. Incompatibility has not been observed in combination with clonazepam, ketamine, methadone, levomepAromazine, metoclopramide, midazolam and octreotide