Digoxin (Digoksin) Bagian 4

DIGOXIN (DIGOKSIN) Bagian 4

INTERAKSI DIGOXIN :

Obat dan Radiasi Mempengaruhi GI Penyerapan

Sejumlah obat yang mampu mengikat glikosida jantung dan / atau menghambat penyerapan glikosida dari saluran GI, yang dapat mengakibatkan konsentrasi glikosida plasma rendah.

Penyerapan GI tablet digoxin oral dapat dikurangi secara substansial pada pasien yang menerima terapi radiasi, agen antineoplastik tertentu, atau berbagai rejimen kemoterapi kombinasi, mungkin sebagai akibat dari kerusakan sementara pada mukosa usus yang disebabkan oleh radiasi atau agen sitotoksik, Penggunaan digoxin oral elixir atau berisi cairan kapsul dapat memperkecil potensi interaksi.

Obat yang mengubah GI waktu transit dan / atau motilitas saluran pencernaan (misalnya, antimuscarinics, difenoksilat) dapat mengubah tingkat penyerapan digoxin. Penggunaan bersamaan antimuscarinics dan lambat-melarutkan tablet digoksin dapat menyebabkan konsentrasi digoxin meningkat. Interaksi ini dapat dihindari dengan menggunakan larutan oral digoxin atau tablet yang larut dengan cepat (misalnya, Lanoxin®). Pasien menerima antimuskarinik dan digoxin harus diperhatikan dengan seksama tanda-tanda toksisitas digitalis.

Interaksi Obat atau Tes Laboratorium khusus terhadap Digoxin

Obat dan Test Lab	Interaksi	Comments
Amiodarone	MEningkatkan serum konsentrasi digoxin dan toksisitas. Besarnya peningkatan mungkin lebih besar pada anak.	Kebutuhan melanjutkan terapi glikosida jantung harus dinilai ulang ketika memulai amiodaron, dan digoxin dihentikan jika sesuai; jika terapi bersamaan diperlukan, mengurangi digoxin sebesar 50% bila terapi amiodarone adalah begun.a Memantau konsentrasi digoxin serum dengan hati-hati dan mengurangi dosis digoxin yang diperlukan; mengamati dari dekat tanda-tanda toksisitas glikosida jantung.
Asam Aminosalicylic	Mengurangi penyerapan GI digoxin (yang mengakibatkan konsentrasi digoxin plasma rendah), terutama bila diberikan pada waktu yang sama seperti digoxin	Harus jarak terpisah sejauh mungkin
Antiarrhythmic Agents	Quinidine, procainamide, disopyramide, phenytoin, propranolol, and lidocaine may have negative inotropic effects with larger than usual doses, especially in patients with cardiac glycoside toxicity (propranolol has negative inotropic effects with usual doses).a	Such combined therapy may be useful in controlling atrial fibrillation, but digoxin dosage in patients receiving such therapy should be carefully individualized given the considerable interaction variability.379, 380
β-Adrenergic blocking agents	Concomitant use of digoxin and β-adrenergic blocking agents can have additive negative effects on AV conduction, which can result in complete heart block.379, 380
Antacids (i.e., aluminum hydroxide, magnesium hydroxide, magnesium trisilicate)	Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin	Should be spaced as far apart as possiblea
Anti-infectives	In patients who form substantial amounts of reduced metabolites, alteration of enteric bacterial flora by some anti-infective agents (e.g., oral erythromycin or tetracycline hydrochloride) may result in increased bioavailability of active drug and up to a twofold increase in serum digoxin concentrations.254	The clinical importance of this interaction remains to be determined, but be alert to possible need for digoxin dosage adjustment.254, 256
Calcium-channel blocking agents	Concomitant use can have additive negative effects on AV conduction.379, 380, 381, 382 (See Diltiazem.)
Calcium salts	Inotropic and toxic effects of digoxin and calcium are synergistic and arrhythmias may occur if used concomitantly (particularly when calcium is given IV).379	IV administration of calcium should be avoided in patients receiving digoxin; if necessary, calcium should be given slowly in small amounts.a
Captopril	Serum digoxin concentrations may increase by about 15-30% when captopril and digoxin are used concomitantly for CHF.366, 367, 368	Captopril has been administered concomitantly with digoxin in patients with congestive heart failure without unusual adverse effects366, 367 or apparent increased risk of cardiac glycoside toxicity.366, 367, 368 Captopril-induced increases in serum potassium may offset the potential toxic effects of increased serum digoxin concentrations.366, 368 Reduction in digoxin dosage does not appear to be necessary when captopril is initiated;366 however, serum digoxin concentrations should be monitored and the patient observed for signs of glycoside toxicity when the drugs are used concomitantly.366, 368
Cholestyramine and colestipol	May bind digoxin in the GI tract and impair its absorption (resulting in low plasma digoxin concentrations), particularly if the glycoside and bile acid sequestrant are administered simultaneously or close together.a	Orally, digoxin should be given at least 1.5-2 hours before cholestyramine or colestipol.a
Diltiazem	Conflicting reports on whether diltiazem substantially affects the pharmacokinetics of digoxin when the drugs are administered concomitantly.313, 314, 315, 316, 317, 318, 319, 320, 321 In some studies, diltiazem reportedly increased average steady-state serum digoxin concentrations by about 20-50%,313, 315, 316, 317 possibly by decreasing the renal and nonrenal clearance of the glycoside, but not in others.313, 314, 315, 317, 318, 319, 320, 321 Concomitant use can have negative effects on AV conduction, which can result in complete heart block.379, 380	Despite conflicting reports, serum digoxin concentrations should be carefully monitored and the patient observed closely for signs of digoxin toxicity when diltiazem and digoxin are administered concomitantly.313, 315, 317, 318, 322 Although such combined therapy may be useful in controlling atrial fibrillation, digoxin dosage should be carefully individualized when such therapy is used because of the considerable variability of these interactions.379, 380
Electrolyte balance, drugs affecting	Electrolyte disturbances produced by diuretics (primarily hypokalemia but also hypomagnesemia and, with the thiazides, hypercalcemia) predispose to digoxin toxicity, including fatal cardiac arrhythmias. Other drugs that deplete body potassium (e.g., amphotericin B, corticosteroids, corticotropin, edetate disodium, laxatives, sodium polystyrene sulfonate) or that reduce extracellular potassium (e.g., glucagon, large doses of dextrose, dextrose-insulin infusions) also may predispose digitalized patients to toxicity.	Periodic electrolyte determinations must be performed during concomitant therapy and corrective measures undertaken if warranted.a
Flecainide	Plasma digoxin concentrations may be increased when used concomitantly.304, 305, 306, 307, 308	Flecainide-induced increases in plasma digoxin concentration generally appear to be of a small magnitude and are unlikely to be clinically important in most cases; however, patients with AV nodal dysfunction,306 plasma digoxin concentrations in the upper end of the therapeutic range, and/or high plasma flecainide concentrations may be at increased risk of digoxin toxicity.305, 306 Patients receiving flecainide and digoxin should be monitored for signs of digoxin toxicity.305, 306
Indomethacin	May prolong elimination half-life and increase serum concentrations of digoxin372, 373, 374	Monitor serum digoxin concentrations carefully.372
Itraconazole	Concomitant use of digoxin and itraconazole may result in increased serum digoxin concentrations;263, 377, 378 digoxin toxicity may occur.263, 377, 378	Monitor serum digoxin concentrations carefully, observe for clinical signs and symptoms of digoxin toxicity,377, 378 and decrease digoxin dosage as necessary.377, 378
Metoclopramide	Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin	Should be spaced as far apart as possible.
Neomycin	Oral neomycin may cause malabsorption of digoxin, resulting in low plasma digoxin concentrations.a
Nifedipine	Most evidence indicates that nifedipine does not substantially affect the pharmacokinetics of digoxin,303, 324, 325, 326, 327 but some data suggest increased serum digoxin concentrations.328, 329	Isolated reports of increased serum digoxin concentrations during concomitant use warrant monitoring of serum digoxin concentrations and toxicity when nifedipine therapy is initiated or discontinued or dosage of nifedipine is adjusted in patients receiving digoxin.303, 328, 330
Propafenone	Concomitant use may result in increased serum digoxin concentrations.a	Monitor for possible toxicity.a
Quinidine	Concomitant use produces increased plasma digoxin concentrations.303, 308, 311, 312 Although variability exists in the magnitude of the increase, plasma digoxin concentrations usually increase twofold to threefold when quinidine therapy is initiated in patients digitalized with digoxin.303, 308, 311	When quinidine therapy is initiated in a patient receiving digoxin, serum digoxin concentrations should be carefully monitored and the digoxin dosage reduced as needed; the patient should be observed closely for signs of toxicity.302, 303, 308 Reduce digoxin dosage by one-half when quinidine therapy is initiated;302, 303, 308 additional dosage adjustments are likely.303, 308 If severe toxicity occurs or if digoxin dosage adjustment is difficult, an alternative antiarrhythmic drug should be used instead of quinidine (e.g., procainamide).303 If digoxin therapy is initiated in a patient receiving quinidine, lower than usual dosages of digoxin may be sufficient to produce desired plasma concentrations.302, 303, 308 If quinidine is discontinued in a patient stabilized on therapy with both drugs, the patient should be observed for signs of decreased response to digoxin and dosage of the cardiac glycoside adjusted as necessary.302, 303, 308
Quinine	Possible interaction similar to that reported with quinidine could occur with concomitant digoxin and quinine (or another cinchona alkaloid)a
Rauwolfia alkaloids	Concomitant use may predispose to the development of cardiac arrhythmias.a	Consider possible interaction in patients prone to arrhythmias; large parenteral doses of reserpine should be avoided
Succinylcholine	Potentiates effects of digoxin on conduction and ventricular irritability.	Cardiac arrhythmias have occurred; succinylcholine should be administered with caution in digitalized patients.
Sulfasalazine	Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin	Should be spaced as far apart as possible.
Sympathomimetics (ephedrine, epinephrine, isoproterenol)		Sympathomimetics should be used with caution in digitalized patients, since the risk of arrhythmias may be increased.
Test, exercise testing	Digoxin may cause false-positive ST-T changes during exercise testing.a
Verapamil	Oral verapamil may increase serum digoxin concentrations by 50-75% during the first week of verapamil therapy; may be more pronounced in patients with underlying hepatic disease (e.g., cirrhosis).a	When verapamil is administered, dosage of digoxin should generally be reduced and the patient monitored closely for clinical response and cardiac glycoside toxicity.a Combined therapy with the drugs (e.g., for control of ventricular rate in patients with atrial fibrillation and/or flutter) usually is well tolerated if digoxin dosage is properly adjusted.a Whenever toxicity is suspected, digoxin dosage should be further reduced and/or temporarily withheld.a If verapamil is discontinued in a patient stabilized on digoxin, monitor closely and increase digoxin dosage as necessary to avoid underdigitalization.

FARMAKOKINETIK DIGOXIN :

ABSORPSI

Bioavailabilitas

Terutama dari usus kecil, mungkin oleh pasif, proses nonsaturable

Tablet atau elixir:

Sekitar 60-85% dari dosis biasanya diabsorpsi.

Kapsul Yang berisi cairan:

Sekitar 90-100% diabsorpsi.

IM:

Sekitar 80% diabsorpsi

Onset

Pasien Undigitalized, Oral: 0,5-2 jam; efek maksimal: 2-6 jam.

Pasien Undigitalized, IV: 5-30 menit;  efek maksimal: 1-4 jam.

Pasien Undigitalized, IM: 30 menit; efek maksimal: 4-6 jam

Durasi

3-4 hari setelah penghentian obat di pasien digitaliz

Makanan

Pengosongan lambung Tertunda atau adanya makanan di saluran pencernaan dapat memperlambat kecepatan tapi tidak tingkat penyerapan digoxin oral lisan.

Konsentrasi plasma

Tentukan konsentrasi plasma dengan mendapatkan sampel darah setidaknya 6-8 jam setelah dosis harian dan sebaiknya sesaat sebelum dosis berikutnya dijadwalkan setiap hari,

Konsentrasi plasma terapeutik pada orang dewasa umumnya 0,5-2 ng / mL.

Pada orang dewasa, keracunan biasanya, namun tidak selalu, berhubungan dengan konsentrasi digoxin plasma steady-state> 2 ng / mL.

Pada beberapa pasien dengan atrial fibrilasi, memperlambat laju ventrikel mungkin memerlukan konsentrasi plasma steady-state dari 2-4 ng / mL.

Neonatus dan bayi tampaknya mentolerir konsentrasi plasma sedikit lebih tinggi, namun konsentrasi plasma> 2 ng / mL berhubungan dengan sedikit, jika ada, tambahan manfaat terapi. Konsentrasi plasma steady-state tambahan 1.1 -1,7 ng / mL umumnya berhubungan dengan efek terapi yang memadai pada neonatus dan infants.

Menafsirkan konsentrasi plasma dalam konteks klinis secara keseluruhan; dengan demikian, tidak menggunakan pengukuran konsentrasi plasma terisolasi sendiri sebagai dasar untuk menyesuaikan dosis.

DISTRIBUSI

Luasnya

Luas di jaringan tubuh; konsentrasi tertinggi di jantung, ginjal, usus, lambung, hati, dan otot skeletal

Dalam miokardium, digoxin ditemukan dalam sistem sarcolemma-T terikat reseptor.

Protein Plasma Binding

Sekitar 20-30%  

Populasi khusus

Persilangan placenta (melewati plasenta).

Masuk ke dalam ASI.

METABOLISME

Biasanya, hanya sejumlah kecil dimetabolisme, tetapi tingkat metabolisme adalah variabel dan mungkin substansial dalam beberapa pasien.

Beberapa mungkin terjadi di hati, tetapi digoxin juga rupanya dimetabolisme oleh bakteri dalam lumen usus besar berikut pemberian oral dan mungkin setelah eliminasi empedu berikut penggunaan parenteral.

ELIMINASI

Rute eliminasi

Terutama dalam urin, terutama sebagai bentuk berubah

Sejumlah kecil metabolit dan obat tidak berubah juga diekskresikan dalam empedu dan feces.

Waktu Paruh

34-44 jam di fungsi ginjal normal.

Populasi Khusus

Gangguan ginjal: ekskresi feses mungkin meningkat.

Gagal ginjal dan hipotiroidisme: eliminasi Terminal waktu paruh diperpanjang.

Digoxin overdosis akut dan hipertiroidisme: eliminasi Terminal paruh adalah menurun.

STABILITAS DIGOXIN :

Penyimpanan

Lindungi dari cahaya pada 15-25 ° C.

Parenteral

Injeksi

Kompatibel dengan sebagian besar tersedia secara komersial cairan infus IV.

Sebelum pemberian IV, injeksi digoxin dapat diencerkan dengan volume yang ≥4 kali lipat dari air steril untuk injeksi, injeksi dekstrosa 5%, atau 0,9% injeksi natrium klorida; penggunaan <volume 4 kali lipat dari pengencer dapat menyebabkan pengendapan digoxin.

Larutan digoxin hasil pengenceran harus digunakan secara langsung.

Kompatibilitas

Untuk informasi tentang interaksi sistemik yang disebabkan dari penggunaan bersamaan, lihat Interaksi.

Parenteral

Kompatibilitas Larutan

                                           

Kompatibel

Dextrose 5% natrium klorida 0,45% dengan kalium klorida 20 mEq

Dekstrosa 5% dalam air

Injeksi Ringer, laktat

Natrium klorida 0,45 atau 0,9%

Kompatibilitas obat

> Kompatibilitas Campuran

Kompatibel

Bretylium tosylate

cimetidine HCl

furosemide

lidocaine HCl

ranitidine HCl

verapamil HCl

tidak kompatibel

dobutamin HCl

> Y-Site Compatibility  

Kompatibel

bivalirudin

ciprofloxacin

Dexmedetomidine HCl

diltiazem HCl

famotidine

fenoldopam mesylate

Natrium heparin dengan hidrokortison natrium suksinat

Hetastarch dalam injeksi elektrolit laktat (Hextend)

Inamrinone laktat

linezolid

meperidin HCl

meropenem

midazolam HCl

milrinone laktat

morfin sulfat

kalium klorida

remifentanil HCl

tacrolimus

Vitamin B kompleks dengan C

Tidak Kompatibel

amiodarone HCl

Amfoterisin B kolesterol sulfat kompleks

flukonazol

natrium foscarnet

lansoprazole

propofol

variabel

Insulin, teratur (Humulin R)

Informasi Obat di Obat dRug Informasi

Baca Bagian sebelumnya di Digoxin (Digoksin) Bagian 1
Baca Bagian sebelumnya di Digoxin (Digoksin) Bagian 3