Names and pronunciation
(meth′a-done) Dolophine, Metadol , Methadose
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Drug reference
(meth′a-done) Dolophine, Metadol , Methadose
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Func. class.: Opioid analgesic
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Chem. class.: Synthetic diphenylhep- tane derivative Controlled Substance Schedule II
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Do not confuse: methadone/methylphenidate /morphine
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ACTION: Depresses pain impulse transmission at the spinal cord level by interacting with opioid receptors; pro- duces CNS depression
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USES: Severe pain, opioid withdrawal
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Unlabeled uses: Neonatal abstinence syndrome
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CONTRAINDICATIONS: Hyper- sensitivity, asthma, ileus
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Black Box Warning: Respiratory depres- sion Precautions: Breastfeeding, children <18 yr, geriatric patients, addictive per- sonality, increased intracranial pressure, MI (acute), severe heart disease, respira- tory depression, pulmonary/renal/ hepatic disease, respiratory insufficiency, torsades de pointes, COPD, seizures Black Box Warning: QT prolongation, pain, substance abuse, potential for over- dose, poisoning, accidental exposure, coadministration with other CNS depres- sants, IV use, pregnancy, requires an ex- perienced clinician Black Box Warning: Respiratory dys- function: respiratory depression, char- acter, rate, rhythm; notify prescriber if respirations are <10/min; avoid use with other CNS depressants (benzodiazepines) Black Box Warning: QT prolongation: may be dose related or use with other products that increase QT; titrate doses carefully, may be fatal Black Box Warning: Accidental expo- sure: make sure product is not acces- sible to children, pets Black Box Warning: Overdose, poison- ing: advise persons involved in correct use Black Box Warning: Substance abuse: may occur but has less psychologic de- pendence than other opiate agonists • Opioid detoxification: goal in detoxifi- cation is only prevention of withdrawal symptoms, not to provide analgesia or pain relief Black Box Warning: B/P, pulse, ECG; hy- potension, palpitations may occur • Bowel changes, bulk, fluids, laxatives should be used for constipation • Beers: avoid in older adults unless safer alternatives are unavailable; may cause ataxia, impaired psychomotor function • Pregnancy/breastfeeding: do not use in pregnancy, neonatal opioid with- drawal syndrome may result; do not use in breastfeeding, serious sedation of the infant may occur, with respiratory depression
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SIDE EFFECTS CNS: Drowsiness, dizziness, confu- sion, headache, sedation, euphoria, seizures CV: Bradycardia, change in B/P, hypo- tension, torsades de pointes, QT prolon- gation EENT: Blurred vision, miosis, diplopia ENDO: adrenal insufficiency MISC: Dependence, tolerance GI: Nausea, vomiting, anorexia, con- stipation GU: Urinary retention INTEG: Rash, flushing, diaphoresis RESP: Respiratory depression
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INTERACTIONS • Unpredictable reactions: MAOIs; do not use together • Do not use within 2 wk of selegiline Increase: serotonin syndrome—linezolid, methylene blue, mirtazapine, tramadol, trazadone, SSRIs, SNRIs, MAOIs, tricyclics, 5-HT3 receptor antagonists Increase: fatal reaction: benzodiazapines Increase: effects with other CNS depres- sants—alcohol, opiates, sedative/hyp- notics, antipsychotics, skeletal muscle relaxants Increase: toxicity—CYP2C9 inhibitors, CYP2C19 inhibitors, CYP2D6 inhibitors, CYP3A4 inhibitors (aprepitant, antiretro- viral protease inhibitors, clarithromycin, danazol, delavirdine, diltiaZEM, erythro- mycin, fluconazole, FLUoxetine, fluvox- aMINE, imatinib, ketoconazole, mibe- fradil, nefazodone, telithromycin, voriconazole) Increase: QT prolongation—class IA anti- arrhythmics (disopyramide, procainamide, quiNIDine), class III antiarrhythmics (ami- odarone, dofetilide, ibutilide, sotalol), astemizole, arsenic trioxide, cisapride, chloroquine, clarithromycin, levometha- dyl, pentamidine, some phenothiazines, pimozide, terfenadine Decrease: analgesia—rifAMPin, phenyt- oin, nalbuphine Decrease: methadone effect—CYP2C9 inducers, CYP2C19 inducers CYP3A4 inducers (barbiturates, bosentan, carBA Mazepine, efavirenz, phenytoins, nevira pine, rifabutin, rifAMPin); withdrawal symp toms may occur Drug/Food • Avoid use with grapefruit juice Drug/Herb • Avoid use with St. John’s wort; with- drawal may result Increase: CNS depression—chamomile, hops, kava, valerian Drug/Lab Test Increase: amylase, lipase
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TREATMENT OF OVERDOSE: Naloxone (Narcan) 0.2-0.8 mg IV, O2, IV fluids, vasopressors
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DOSAGE AND ROUTES Severe pain • Adult: PO 2.5 mg q8-12hr in opioid- naive, titrate; IV/IM/SUBCUT 2.5-10 mg q8-12hr in opioid-naive Opioid withdrawal • Adult including pregnant woman: PO 20-30 mg initially unless low opioid tolerance expected; additional 5-10 mg q2-4hr as needed after initial dose; if symptoms continue, may give for ≤5 days Analgesic • Adult/child <50 kg: PO 0.1 mg/kg/ dose q4hr × 2-3 doses, then q6-8hr prn, max 10 mg q6-8hr; ≥50 kg IM/ IV/SUBCUT 10 mg q6-8hr, max 10 mg/ dose Narcotic dependency • Adult/child <50 kg: PO 0.05-0.1 mg/ kg/dose q6hr, increase by 0.05 mg/kg/ dose until withdrawal, if controlled after 1-2 days lengthen dosing interval to q12- 24hr, taper by 0.05 mg/kg/day; ⬧50 kg IM/IV SUBCUT 15-40 mg daily, decrease dose q1-2days
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Available forms: Inj 10 mg/mL; tabs 5, 10 mg; oral sol 5, 10 mg/5 mL; 10 mg/ mL (concentrate); dispersible tabs 40 mg
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Administer: PO route • When using during a methadone main- tenance program, use only PO according to NATA guidelines • PO is half as potent as parenteral IM route • Rotating inj sites, give deep in large muscle mass (IM) • Protect from light IV route • Used as PCA • Protect from light SUBCUT route • Pain and induration may occur at site
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Assess: • Pain: type, location, intensity, grimac- ing before, 1½-2 hr after administration; use pain scoring; monitor for cumulative reactions; use during entire 24-hr period for severe pain • I&O ratio; check for decreasing out- put; may indicate urinary retention • CNS changes: dizziness, drowsiness, hallucinations, euphoria, LOC, pupil re- action • Allergic reactions: rash, urticaria
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Evaluate: • Therapeutic response: decrease in pain, successful opioid withdrawal
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CLINICAL CONSIDERATIONS M
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Patient and caregiver information: • To report any symptoms of CNS changes, allergic reactions, extreme se- dation, trouble breathing • That physical dependency may result from extended use • That withdrawal symptoms may occur: nausea, vomiting, cramps, fever, faintness, anorexia • To maintain proper hydration; to avoid alcohol use • To avoid use with other products with- out approval of prescriber; many drug interactions • To use correctly, exactly as directed; not to increase unless directed by pre- scriber • That drowsiness, dizziness may occur; not to perform hazardous tasks until ef- fect is known; to ask for assistance when getting out of bed • That regular ECGs will be needed • To change positions slowly to mini- mize orthostatic hypotension • To advise all providers of product taken • Pregnancy/breastfeeding: not to use in pregnancy, breastfeeding
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PHARMACOKINETICS Metabolized by liver; excreted by kid- neys; crosses placenta; excreted in breast milk; half-life 15-23 hr, extended interval with continued dosing; 90% bound to plasma proteins PO: Onset 30-60 min, peak 1-1.5 hr, duration 6-8 hr, cumulative 22-48 hr; PO half as active as INJ SUBCUT/IM: Onset 10-20 min, peak 1½-2 hr, duration 4-6 hr, cumulative 22-48 hr
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• Adult/child <50 kg: PO 0.1 mg/kg/ dose q4hr × 2-3 doses, then q6-8hr prn, max 10 mg q6-8hr; ≥50 kg IM/ IV/SUBCUT 10 mg q6-8hr, max 10 mg/ dose Narcotic dependency
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• Adult/child <50 kg: PO 0.05-0.1 mg/ kg/dose q6hr, increase by 0.05 mg/kg/ dose until withdrawal, if controlled after 1-2 days lengthen dosing interval to q12- 24hr, taper by 0.05 mg/kg/day; ⬧50 kg IM/IV SUBCUT 15-40 mg daily, decrease dose q1-2days
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