Dihydrocodeine tartate

CLINICAL USE

Supraventricular arrhythmias Heart failure

DOSE IN NORMAL RENAL FUNCTION

Digitalisation: 1–1.5 mg in divided doses over 24 hours, followed by 62.5–500 mcg daily, adjusted according to responseEmergency loading (IV): 0.75–1 mg over at least 2 hours

PHARMACOKINETICS

Molecular weight :780.9

%Protein binding :25

%Excreted unchanged in urine : 50–75

Volume of distribution (L/kg) :5–8

half-life – normal/ESRD (hrs) :30–40/100

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : 125–250 micrograms per day

10 to 20 : 125–250 micrograms per day. Monitor levels

<10 : Dose commonly 62.5 micrograms alternate days, or 62.5 micrograms daily. Monitor levels

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Not dialysed. Dose as in GFR <10 mL/min

CAV/VVHD :Not dialysed. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAngiotensin-II antagonists: concentration increased by telmisartanAnti-arrhythmics: concentration increased by amiodarone and propafenone (half maintenance dose of digoxin)Antidepressants: concentration reduced by St John’s wort – avoid concomitant useAntifungals: increased toxicity if hypokalaemia occurs with amphotericin; concentration increased by itraconazoleAntimalarials: concentration possibly increased by quinine, hydroxychloroquine and chloroquine; increased risk of bradycardia with mefloquineCalcium-channel blockers: concentration increased by diltiazem, lercanidipine, nicardipine, verapamil and possibly nifedipine; increased risk of AV block and bradycardia with verapamilCiclosporin: concentration increased by ciclosporinDiuretics: increased toxicity if hypokalaemia occurs; concentration increased by spironolactone

ADMINISTRATION

Reconstition

–

Route

Oral, IV

Rate of Administration

Loading dose: infuse over

10 to 20 : minutes

Comments

IV administration: dilute dose to 4 times volume with sodium chloride 0.9% or glucose 5%IV dosing may be used for very rapid control

OTHER INFORMATION

Complex kinetics in renal impairment: Volume of distribution and total body clearance reduced in CKD 5Steady-state plasma monitoring advisable: normal range 0.8–2 nanograms/mL; take at least 8 hours post-dose, ideally before dose in the morningIf changing from oral to IV reduce dose by a thirdHypokalaemia, hypomagnesaemia, marked hypercalcaemia and hypothyroidism increase toxicityIncreases uraemic gastrointestinal symptomsOnly 3% of dose is removed after a 5 hour

HD : sessionConcomitant administration of phosphate binders reduces GI absorption by up to 25%Digitalisation using 750 micrograms – 1 mg. Interval between normal or reduced doses may need to be lengthened.

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