methadone hydrochloride

CLINICAL USE

Treatment of opioid drug addiction Analgesic for moderate to severe pain

DOSE IN NORMAL RENAL FUNCTION

Opioid addiction: 10–40 mg per day, increasing by 10 mg per day until there are no signs of withdrawal or intoxication; reduce graduallyAnalgesia: 5–10 mg every 6–8 hours

PHARMACOKINETICS

Molecular weight :346.9

%Protein binding :60–90

%Excreted unchanged in urine : 15–60

Volume of distribution (L/kg) : 3–6

half-life – normal/ESRD (hrs) :13–47/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : 50% of normal dose, and titrate according to response

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 :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antidepressants: concentration possibly increased by fluvoxamine; possible CNS excitation or depression with MAOIs and moclobemide – avoid concomitant use; possibly increased sedative effects with tricyclics

Anti-epileptics: concentration reduced by carbamazepine and phenytoin

Antifungals: concentration increased by voriconazole – may need to reduce methadone dose

Antivirals: methadone possibly increases concentration of zidovudine; concentration reduced by amprenavir, efavirenz, nelfinavir and ritonavir; concentration possibly reduced by abacavir and nevirapine

Atomoxetine: increased risk of ventricular arrhythmiasSodium oxybate: enhanced effect of sodium oxybate – avoid concomitant use

ADMINISTRATION

Reconstition

–

Route

IM, SC, oral

Rate of Administration

–

Comments

Methadone is probably not suitable to be used as an analgesic for patients with severe renal impairment

OTHER INFORMATION

Overdosage with methadone can be reversed using naloxoneRisk of QT interval prolongation especially with high doses and concomitant risk factors

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