METHADONE

category:
135
METHADONE
CALCUTIONS AREA
CLICK ON CALCULATOR

Infant Data

Results


MEDICAL INFORMATIONS

INDICATIONS

  • Neonatal abstinence syndrome (NAS): Sublingual buprenorphine was associated with the largest reduction in length of treatment and length of stay for NAS in a network meta-analysis of 18 randomized controlled trials (n=1072) of buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Morphine was the least effective opioid. The findings should be interpreted with caution due to significant study limitations.
    • Compared with morphine: Methadone outperformed morphine for the treatment of NAS in a multicenter, randomized, double-blind study of 116 term infants (median LOS (16 vs 20 days, p=0.005), LOS attributable to NAS (16 vs 19 days, p=0.005), and length of drug treatment (11.5 vs 15 days, p=0.009)). Initial oral doses were 0.3 mg/kg/day for Finnegan score (FS) of 8 to 10, 0.5 mg/kg/day for FS of 11 to 13, 0.7 mg/kg/day for FS 14 to 16, and 0.9 mg/kg/day for FS of 17 or more. The total daily doses were divided every 4 hours for morphine and every 8 hours for methadone. A nonalcoholic solution of methadone was compounded. Neonatal abstinence syndrome was treated for a median of 14 days with methadone compared with 21 days for morphine (p=0.008) in a double-blind, randomized trial (n=78). All neonates were 35 weeks gestational or more and prenatal exposure was either methadone or buprenorphine.
    • Compared with buprenorphine: A shorter duration of opioid treatment (9.4 vs 14 days) and shorter length of inpatient stay (16.3 vs 20.7 days) with a sublingual buprenorphine protocol compared with oral methadone protocol was demonstrated in a retrospective analysis of 201 infants (34 weeks’ gestation or older) with NAS. Infants exposed in utero to methadone were excluded.

CONTRAINDICATIONS:

  • Significant Respiratory Depression, in The Absence of Resuscitative Equipment or in Unmonitored Settings.
  • Acute or Severe Bronchial Athma in an Unmonitored Setting or in The Absence of Resuscitative Equipment.
  • Known or Suspected Paralytic Ileus.
  • Known or Suspected Gastrointestinal Obstruction.

PRECAUTIONS:

  • ADMINISTRATION
    • Crushing, Chewing, or Dissolving May Result in Uncontrolled Delivery And Increse Risk of Overdose or Death.
    • The Manufacturer Recommends That Methadone Not Be Used as an As-needed(prn) Analgesic.
  • Cardiovascular :
    • Severe Hypotension Orthostatic Hypoteision, AndSyncope Have Been Reported;Incresed Risk in Those With Reduced Blood Volume or Who Use CNS Depressants Concomitantly;
    • Avoid Use in Patients With Circulatory Shock.
  • Concomitant Use :
    • Avoid Concomitant Use Wyh Mixed Agonist/Antagonist or Partial Agonists.
  • Endocrine & Metabolic :
    • Opiods May Rarely Lead to Adrenal Insufficiency
    • Preexisting Hypothyroidism Increse The Risk For Respiratory Depression.
  • Gastrointestinal :
    • Gstrointestinal Obstruction; Avoid Use.
  • Hepatic :
    • Hepatic Disease My Increase Risk of Toxicity And CNS Depressant Effect.Use Lower Initial Dose And Titrate Slowly.
    • Spasm Sphincter of Oddi, And Worsen Biliary Tract Disease, Including Acute Pancreatitis May Occur
  • Neurologic :
    • Potentially Life-treathening Serotonin Syndrome Has Been Reported.Concomitant Use of Seratonergic Drugs Increses The Risk.
    • Seizure Disorder May Be Induced or Aggrevated.
    • Severe Sedation, Coma, And Death Have Been Reported.
    • Avoid Use in Patients With Impaired Conciousenes or Coma
    • Use in Patients at Risk or Who Have Increased Intracranial Pressure(eg: tumore, head injury, intracranial lesions)May Exaggerate Respiratory Depression And Sedation And Furtur Increse Intracranial Pressure.Opioids May Obscure Clinical Course of Hed Injury.
  • Prolonged Use :
    • Long Term Use of Opioids May Be Assiciated With Decresed Sex Hormone Levels And Symptoms Such As Reduced Interest in Sex, Impotence or Infertility.
  • Renal :
    • Renal Disease May Increse Risk of CNS Depressant Effect; Use Lower Dose And Titrate Slowly.
  • Respiratory :
    • Respiratory Depression is More Likely to Occur in Cachectic or Debilitated Patients.
    • Incresed Risk of Decresed Respiratory Drive, Including Apnea, In Patients With a Decresed Respiratory Reserve, Hypoxia, Hypercapnea, or Preexisting Respiratory
    • Sleep Related Breathing Disorders Including Central Sleep Apnea, And Sleep Related Hypoxemia May Occur.
    • Use in Patients With Preexisting Chronic Pulmonary Disease (eg: COPD,corpulmonale, asthma)May Furtue Decrese Respiratory Drive Leading to Apnea Even at Theraputic Doses.
    • Peak Respiratory Depressiant Effect Occur Later And Persist Longer Than Analgesic Effec, Which May Result in Overdose.
  • Withdrawal :
    • Severe Withdrawal Symptoms May Occur With Abrupt Discontinuation or if a Mixed Agonist/Antagonist or Partial Opioid Agonist is Administered or After Full Opioid Agonist Therapy.

ADVERSE EFFECTS

Respiratory depression in excessive doses. Ileus and delayed gastric emptying. In a single case report, QTc prolongation was noted in a term infant born to a mother receiving methadone maintenance therapy (50 mg/day). After birth, the infant’s resting HR was 80 to 90 beats per minute and ECG showed a QTc of 510 msec. This resolved spontaneously over 5 days.

BLACK BOX WARNING

Warning: Addiction, Abuse And Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Life-Threatening QT Prolongation; Neonatal Opioid Withdrawal Syndrome; Interactions With Drugs Affecting Cytochrome P450 Isoenzymes; Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants; And Treatment For Opioid Addiction.

  • Addiction, Abuse, and Misuse
  • Methadone hydrochloride tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing methadone hydrochloride tablets, and monitor all patients regularly for the development of these behaviors and conditions.
  • Life-Threatening Respiratory Depression.
  • Serious, life-threatening, or fatal respiratory depression may occur with use of methadone hydrochloride tablets. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak analgesic effect, especially during the initial dosing period or following a dose increase. Monitor for respiratory depression, especially during initiation of methadone hydrochloride tablets or following a dose increase.
  • Accidental Ingestion.
  • Accidental ingestion of even one dose of methadone hydrochloride tablets, especially by children, can result in a fatal overdose of methadone.
  • Life-Threatening QT Prolongation.
  • QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration of methadone hydrochloride tablets.
  • Neonatal Opioid Withdrawal Syndrome.
  • Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of methadone hydrochloride tablets during pregnancy. NOWS may be lifethreatening if not recognized and treated in the neonate. The balance between the risks of NOWS and the benefits of maternal methadone hydrochloride use may differ based on the risks associated with the mother’s underlying condition, pain, or addiction. Advise the patient of the risk of NOWS so that appropriate planning for management of the neonate can occur.
  • Cytochrome P450 Interaction
  • The concomitant use of methadone hydrochloride tablets with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. In addition, discontinuation of concomitantly used cytochrome P450 3A4, 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes of concomitant medications that can result in an increase in methadone levels.
  • Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants.
  • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death..
  • Reserve concomitant prescribing of methadone benzodiazepines or other CNS depressants for use in patients in methadone treatment for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation. If the patient is visibly sedated, evaluate the cause of sedation, and consider delaying or omitting the daily methadone dose.
  • Conditions For Distribution And Use Of Methadone Products For The Treatment Of Opioid Addiction.
  • For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.

MONITORING

Monitor respiratory, central nervous system, and cardiac status closely, especially during drug initiation and titration. A 12-lead ECG should be obtained on methadone-exposed infants experiencing bradycardia or tachycardia. Assess for gastric residuals, abdominal distention, and loss of bowel sounds. For infants experiencing neonatal abstinence syndrome, monitor and score signs of drug withdrawal using a published abstinence assessment tool such as the modified Neonatal Abstinence Scoring System (Finnegan) or the Lipsitz tool.

Tags: , , , , ,