Methadose


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methadone hydrochloride eptadone (UK)

Dolophine, Metadol, Methadone HCl Intensol, Methadose, Physeptone (UK), Synastone (UK)

Pharmacologic class: Opioid agonist

Therapeutic class: Analgesic, opioid detoxification adjunct

Controlled substance schedule II

Pregnancy risk category C

FDA Box Warning

• Deaths have occurred during drug initiation for opioid dependence. In some cases, deaths apparently resulted from respiratory or cardiac effects of methadone and too-rapid titration without considering drug accumulation. Make sure you understand drug's pharmacokinetics, and be vigilant during treatment initiation and dosage titration. Caution patients against self-medicating with CNS depressants at start of therapy.

• Prolonged QT intervals and serious arrhythmia (torsades de pointes) have occurred. Most cases involved patients being treated for pain with large, multiple daily doses.

• Federal law requires that when drug is used to treat opioid addiction in detoxification or maintenance programs, it can be dispensed only by treatment programs certified by the Substance Abuse and Mental Health Services Administration and approved by designated state authority. Certified treatment programs must dispense and use drug in oral form only and according to treatment requirements stipulated in Federal Opioid Treatment Standards. Failure to abide by regulations may lead to criminal prosecution, drug seizure, revocation of program approval, and injunction precluding program operation.

Action

Binds to and depresses opiate receptors in spinal cord and CNS, altering perception of and response to pain

Availability

Injection: 10 mg/ml

Oral solution: 5 mg/5 ml, 10 mg/5 ml, 10 mg/ml (concentrate)

Tablets: 5 mg, 10 mg

Tablets (dispersible diskettes): 40 mg

Indications and dosages

Opioid detoxification

Adults: Initially, 15 to 20 mg/day P.O. to suppress withdrawal. Additional doses may be necessary if symptoms aren't suppressed or if they reappear. Most patients are adequately stabilized on total daily dosage of 40 mg given in single or divided doses; however, some may need higher dosages. When patient is stable for 2 to 3 days, decrease dosage gradually at 2-day intervals. If patient can't tolerate oral doses, give I.M. or subcutaneously (usually at about 25% of total daily P.O. dosage) in two injections.

To maintain opioid abstinence

Adults: Oral dosage highly individualized based on control of abstinence symptoms without respiratory depression or marked sedation. If patient can't tolerate oral doses, give I.M. or subcutaneously (usually at about 25% of total daily P.O. dosage) in two injections.

Chronic and severe pain

Adults: For chronic pain, 2.5 to 10 mg P.O., I.M., or subcutaneously q 3 to 4 hours as needed; adjust dosage and dosing interval as needed. For severe chronic pain (as in terminal illness), 5 to 20 mg P.O. q 6 to 8 hours.

Children: Dosage individualized.

Contraindications

• Hypersensitivity to drug or other opioid agonists

Precautions

Use cautiously in:

• head trauma; severe renal, hepatic, or pulmonary disease; hypothyroidism; adrenal insufficiency; undiagnosed abdominal pain; prostatic hypertrophy; urethral stricture; toxic psychosis; Addison's disease; cor pulmonale; increased intracranial pressure; severe inflammatory bowel disease; severe CNS depression; hypercapnia; seizures; fever; alcoholism

• recent renal or hepatic surgery

• elderly or debilitated patients

• pregnant patients, patients in labor, or breastfeeding patients.

Administration

• Mix dispersible tablets with 120 ml of water or orange juice, citrus Tang, or other acidic fruit beverage.

• Dilute 10 mg/ml of oral solution with water or other liquid to at least 30 ml. In detoxification and maintenance of opioid withdrawal, dilute solution in at least 90 ml of fluid.

• When used parenterally, I.M. route is preferred. Rotate injection sites.

• For detoxification and maintenance, give oral solution only, to reduce potential for parenteral abuse, hoarding, and accidental ingestion.

• Know that patients who can't take oral drugs because of nausea or vomiting during detoxification or maintenance should be hospitalized and given methadone parenterally.

Adverse reactions

CNS: amnesia, anxiety, confusion, poor concentration, delirium, delusions, depression, dizziness, drowsiness, euphoria, fever, hallucinations, headache, insomnia, lethargy, light-headedness, malaise, psychosis, restlessness, sedation, clouded sensorium, syncope, tremor, seizures, coma

CV: hypotension, palpitations, edema, bradycardia, shock, cardiac arrest

EENT: visual disturbances

GI: nausea, vomiting, constipation, ileus, biliary tract spasm, gastroesophageal reflux, indigestion, dysphagia, dry mouth, anorexia

GU: urinary hesitancy, urinary retention, prolonged labor, difficult ejaculation, erectile dysfunction

Hematologic: anemia, leukopenia, thrombocytopenia

Musculoskeletal: joint pain

Respiratory: depressed cough reflex, hypoventilation, wheezing, asthma exacerbation, atelectasis, pulmonary edema, bronchospasm, respiratory depression or arrest, apnea

Skin: urticaria, pruritus, flushing, pallor, diaphoresis

Other: allergic reaction, hiccups, facial or injection site edema, pain, physical or psychological drug dependence, withdrawal symptoms

Interactions

Drug-drug. Amitriptyline, antihistamines, chloral hydrate, clomipramine, glutethimide, methocarbamol, MAO inhibitors, nortriptyline: increased CNS and respiratory depression

Anticholinergics: increased risk of severe constipation leading to ileus

Antiemetics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers: coma, hypotension, respiratory depression, severe sedation

Ascorbic acid, phenytoin, phosphate, potassium, rifampin: decreased methadone blood level

Cimetidine, fluvoxamine, protease inhibitors: increased analgesia, CNS and respiratory depression

Diuretics: increased diuresis

Hydroxyzine: increased analgesia, CNS depression, and hypotension

Paregoric, loperamide: increased CNS depression, severe constipation

Naloxone: antagonism of methadone's analgesic, CNS, and respiratory effects

Naltrexone: induction or worsening of withdrawal symptoms (when given within 7 days of methadone)

Neuromuscular blockers: increased or prolonged respiratory depression

Drug-diagnostic tests. Amylase, liver function tests: increased levels

Drug-behaviors. Alcohol use: increased CNS and respiratory depression

Patient monitoring

• Assess patient for relief of severe, chronic pain requiring around-the-clock dosing. Tailor dosage to patient's pain level and drug tolerance.

• Monitor CNS, respiratory, and cardiovascular status.

• Watch for deepening sedation, which may increase with successive doses.

• Evaluate bowel and bladder function. Give laxatives if appropriate.

• Monitor detoxification treatment closely. Short-term detoxification shouldn't exceed 30 days; long-term detoxification, 180 days.

• Assess patient on maintenance therapy for successful rehabilitation. Know that maintenance therapy should be part of comprehensive treatment plan that includes medical, vocational rehabilitative, employment, educational, and counseling services.

Patient teaching

Instruct patient to promptly report severe adverse reactions.

• Tell patient he may take drug with food if GI upset occurs.

• Tell ambulatory patient to change positions slowly to avoid orthostatic hypotension.

Caution patient not to discontinue drug abruptly.

• Advise patient to avoid driving and other hazardous activities, because drug may cause drowsiness or dizziness.

• Tell female patient to inform prescriber if she's pregnant or breastfeeding.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

methadone

(meth-a-done) ,

Dolophine

(trade name),

Metadol

(trade name),

Methadose

(trade name)

Classification

Therapeutic: opioid analgesics
Pharmacologic: opioid agonists
Pregnancy Category: C

Indications

Management of moderate to severe chronic pain in patients requiring use of a continuous around-the-clock opioid analgesic for an extended period of time.Detoxification and maintenance therapy for opioid use disorder.Neonatal abstinence syndrome.

Action

Binds to opiate receptors in the CNS.
Alters the perception of and response to painful stimuli, while producing generalized CNS depression.

Therapeutic effects

Decrease in severity of pain.
Suppression of withdrawal symptoms during detoxification and maintenance from heroin and other opioids.

Pharmacokinetics

Absorption: Well absorbed from all sites (50% absorbed following oral administration).
Distribution: Widely distributed. Crosses the placenta; enters breast milk.
Protein Binding: High.
Metabolism and Excretion: Mostly metabolized by the liver; some metabolites are active and may accumulate with chronic administration.
Half-life: 15–25 hr; ↑ with chronic use.

Time/action profile (analgesic effect)

ROUTEONSETPEAKDURATION
PO30–60 min90–120 min4–12 hr
IM, subcut10–20 min60–120 min4–6 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Significant respiratory depression;Acute or severe bronchial asthma;Paralytic ileus;Known alcohol intolerance (some oral solutions);Concurrent MAO inhibitor therapy.
Use Cautiously in: Structural heart disease, concomitant diuretic use, hypokalemia, hypomagnesemia, history of arrhythmia/syncope, or other risk factors for arrhythmias;Concurrent use of drugs that prolong the QTc interval or are CYP3A4 inhibitors;Head trauma;Seizure disorders;↑ intracranial pressure;Severe renal, hepatic, or pulmonary disease;Hypothyroidism;Adrenal insufficiency;Alcoholism;Undiagnosed abdominal pain;Prostatic hyperplasia or ureteral stricture; Obstetric: Use with addiction control: weigh risk against potential for illicit drug use. Counsel mother about potential harm to fetus; Lactation: Appears in breast milk. Weigh risks against potential for illicit drug use. Counsel mother about potential harm to infant and to wean breast feeding slowly to prevent abstinence syndrome; Geriatric: Dose ↓ suggested.

Adverse Reactions/Side Effects

Central nervous system

  • confusion (most frequent)
  • sedation (most frequent)
  • dizziness
  • dysphoria
  • euphoria
  • floating feeling
  • hallucinations
  • headache
  • unusual dreams

Ear, Eye, Nose, Throat

  • blurred vision
  • diplopia
  • miosis

Respiratory

  • respiratory depression

Cardiovascular

  • torsades de pointes (life-threatening)
  • hypotension (most frequent)
  • bradycardia
  • QT interval prolongation

Gastrointestinal

  • constipation (most frequent)
  • nausea
  • vomiting

Genitourinary

  • urinary retention

Dermatologic

  • flushing
  • sweating

Miscellaneous

  • physical dependence
  • psychological dependence
  • tolerance

Interactions

Drug-Drug interaction

Use with extreme caution in patients receiving MAO inhibitors (may result in severe, unpredictable reactions—↓ initial dose of methadone to 25% of usual dose).Use with extreme caution with any drug known to potentially prolong QT interval, including class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers.Use with extreme caution with CYP3A4 inhibitors, including ketoconazole, itraconazole, erythromycin, clarithromycin, calcium channel blockers, or voriconazole.Concurrent use with laxatives, diuretics, or mineralocorticoids may ↑ risk of hypomagnesemia or hypokalemia and ↑ risk of arrhythmias.↑ CNS depression with alcohol, antihistamines, and sedative/hypnotics.Administration of agonist/antagonist opioids may precipitate opioid withdrawal in physically dependent patients.Nalbuphine or pentazocine may ↓ analgesia.Interferons (alpha) may ↓ metabolism and ↑ effects.Nevirapine, efavirenz, ritonavir, ritonavir/lopinavir, phenobarbital, carbamazepinephenytoin, and rifampin may ↑ metabolism and ↓ analgesia; withdrawal may occur.Fluvoxamine may ↑ CNS depression; with fluvoxamine, opioid withdrawal may occur.May ↑ blood levels and effects of zidovudine and desipramine.May ↓ level and effects of didanosine and stavudine. St. John’s wort ↑ metabolism and ↓ blood levels, concurrent use may result in withdrawal.Kava-kava, valerian, or chamomile, can ↑ CNS depression.

Route/Dosage

Larger doses may be required for analgesia during chronic therapy; interval may be ↓/dose ↑ if pain recurs
Oral (Adults and Children ≥ 50 kg) Analgesic—20 mg q 6–8 hr. Opioid detoxification—15–40 mg once daily or amount needed to prevent withdrawal. Dose may be decreased q 1–2 days; maintenance dose is determined on an individual basis.
Oral (Adults and Children < 50 kg) Analgesic—0.1 mg/kg/dose q 4 hr for 2–3 doses then q 6–8 hr prn; maximum: 10 mg/dose. Iatrogenic narcotic dependency—0.05–0.1 mg/kg/dose q 6 hr; ↑ by 0.05 mg/kg/dose until withdrawal symptoms controlled; after 1–2 days lengthen dosing interval to q 12–24 hr; taper by ↓ dose by 0.05 mg/kg/day.
Oral Intravenous (Neonates) Initial 0.05–0.2 mg/kg/dose q 12–24 hr or 0.5 mg/kg/day divided q 8 hr; taper dose by 10–20% per week over 1–1 1/2 mo.
Intravenous Intramuscular Subcutaneous (Adults and Children ≥50 kg) Analgesic—10 mg q 6–8 hr. Opioid detoxification—15–40 mg once daily or amount needed to prevent withdrawal. Dose may be ↓ q 1–2 days; maintenance dose is determined on an individual basis.
Intravenous Intramuscular Subcutaneous (Adults and Children <50 kg) Analgesic–0.1 mg/kg q 6–8 hr; maximum: 10 mg/dose.

Availability (generic available)

Tablets: 5 mg, 10 mg
Dispersible tablets (diskettes): 40 mg (available only to licensed detoxification/maintenance programs)
Injection: 10 mg/mL
Oral solution (contains alcohol)citrus: 5 mg/5 mL, 10 mg/5 mL
Oral concentratecherry and unflavored: 10 mg/mL

Nursing implications

Nursing assessment

  • Pain: Assess type, location, and intensity of pain prior to and 1–2 hr (peak) following administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient’s pain rating on a numeric or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal. Cumulative effects of this medication may require periodic dose adjustments.
    • Doses of methadone for patients on methadone maintenance only prevent withdrawal symptoms; no analgesia is provided. Additional opioid doses are required for treatment of pain.
  • An equianalgesic chart (see ) should be used when changing routes or when changing from one opioid to another.
  • Assess BP, pulse, and respirations before and periodically during administration. If respiratory rate is < 10/min, assess level of sedation. Dose may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use.
  • Assess bowel function routinely. Prevention of constipation should be instituted with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Stimulant laxatives should be administered routinely if opioid use exceeds 2–3 days, unless contraindicated.
  • Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Most patients who receive methadone for pain do not develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.
  • Assess for history of structural heart disease, arrhythmia, and syncope. Obtain a pretreatment ECG to measure QTc interval and follow-up ECG within 30 days and annually. Additional ECGs recommended if dose >100 mg/day or if patients have unexplained syncope or seizures. If QTc interval is >450 ms but <500 ms, discuss potential risks and benefits with patients and monitor more frequently. If the QTc interval >500 ms, consider discontinuing or reducing dose; eliminating contributing factors (drugs that promote hypokalemia) or using an alternative therapy.
  • Opioid Detoxification: Assess patient for signs of opioid withdrawal (irritability, runny nose and eyes, abdominal cramps, body aches, sweating, loss of appetite, shivering, unusually large pupils, trouble sleeping, weakness, yawning). Methadone maintenance is undertaken only by federally approved treatment centers. This does not preclude maintenance for addicts hospitalized for other conditions and who require temporary maintenance during their care.
  • Lab Test Considerations: May ↑ plasma amylase and lipase levels.
  • If an opioid antagonist is required to reverse respiratory depression or coma, naloxone is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by direct IV push every 2 min. For children and patients weighing < 40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain.

Potential Nursing Diagnoses

Acute pain (Indications)
Disturbed sensory perception(visual, auditory) (Side Effects)
Risk for injury (Side Effects)

Implementation

  • high alert: Accidental overdose of opioid analgesics has resulted in fatalities. Before administering, clarify all ambiguous orders; have second practitioner independently check original order and dose calculations.
  • Do not confuse methadone with dexmethylphenidate, ketorolac, Mephyton (phytonadione), Metadate ER/CD (methylphenidate), or methylphenidate.
  • Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
    • Regularly administered doses may be more effective than prn administration. Analgesic is more effective if administered before pain becomes severe. For patients in chronic severe pain, the oral solution containing 5 or 10 mg/5 mL is recommended on a fixed dose schedule.
    • Coadministration with nonopioid analgesics may have additive analgesic effects and may permit lower doses.
    • Medication should be discontinued gradually after long-term use to prevent withdrawal symptoms.
  • Oral: Doses may be administered with food or milk to minimize GI irritation.
    • Dilute each dose of 10 mg/mL oral concentrate with at least 30 mL of water or other liquid prior to administration.
    • Diskettes (dispersible tablets) are to be dissolved and used for detoxification and maintenance treatment only. Available only to licensed detoxification/maintenance programs.
  • Subcutaneous: Intramuscular: IM is the preferred parenteral route for repeated doses. Subcut administration may cause tissue irritation.

Patient/Family Teaching

  • Instruct patient on how and when to ask for and take pain medication.
  • Instruct patient to take methadone exactly as directed. If dose is less effective after a few weeks, do not increase dose without consulting health care professional.
  • May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating or smoking and to avoid driving or other activities requiring alertness until response to medication is known.
  • Inform patient of the potential for arrhythmias and emphasize the importance of regular ECGs.
  • Caution patient to notify health care professional if signs of overdose (difficult or shallow breathing, extreme tiredness or sleepiness, blurred vision, inability to think, talk, or walk normally, and feelings of faintness, dizziness, or confusion) occur. Methadone has a prolonged action causing increased risk of overdose.
  • Advise patient to change positions slowly to minimize orthostatic hypotension.
  • Advise patient to tell health care professional what medications they are taking and to avoid taking new Rx, OTC, vitamins, or herbal products without consulting health care professional. Caution patient to avoid concurrent use of alcohol or other CNS depressants with this medication.
  • Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.

Evaluation/Desired Outcomes

  • Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.
  • Prevention of withdrawal symptoms in detoxification from heroin and other opioid analgesics.

Methadose

Dosed methadone for treating heroin addiction.