METHADONE Oral Solution – Exir Pharmaceutical Company

METHADONE

Oral Solution Methadone 25 mg/5ml ( 250 ml )

Generic Name of Product	Brand Name	Dosage Form	Strength	Pharmacologic Group	Therapeutic Group	Unit Per Pack
Methadone	-	Oral Solution	5 mg/ml (250 ml)	Narcotic analgesics	Narcotics	1

Indications And Usage

anagement of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Detoxification treatment of opioid addiction (heroin or other morphine-like drugs).

Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.

Administration

Methadone Hydrochloride Oral Solution should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Consider the following important factors that differentiate methadone from other opioid analgesics:

There is high interpatient variability in absorption, metabolism, and relative analgesic potency of methadone.
The duration of analgesic action of methadone is 4 to 8 hours (based on single-dose studies) but the plasma elimination half-life is 8 to 59 hours.
With repeated dosing, the potency of methadone increases due to systemic accumulation.
Steady-state plasma concentrations, and full analgesic effects, are not attained until at least 3 to 5 days on a dose, and may take longer in some patients.

Conversion Factors to Methadone Hydrochloride Oral Solution:

Total Daily Baseline Oral Morphine Equivalent Dose	Estimated Daily Oral Methadone Requirement as Percent of Total Daily Morphine Equivalent Dose
< 100 mg	20% to 30%
100 to 300 mg	10% to 20%
300 to 600 mg	8% to 12%
600 mg to 1000 mg	5% to 10%
> 1000 mg	< 5 %

For patients on a single opioid, sum the current total daily dose of the opioid, convert it to a Morphine Equivalent Dose according to specific conversion factor for that specific opioid, then multiply the Morphine Equivalent Dose by the corresponding percentage in the above table to calculate the approximate oral methadone daily dose. Divide the total daily methadone dose derived from the table above to reflect the intended dosing schedule (i.e., for administration every 8 hours, divide total daily methadone dose by 3).
For patients on a regimen of more than one opioid, calculate the approximate oral methadone dose for each opioid and sum the totals to obtain the approximate total methadone daily dose. Divide the total daily methadone dose derived from the table above to reflect the intended dosing schedule (i.e., for administration every 8 hours, divide total daily methadone dose by 3).
For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.

Contraindications

Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus

Hypersensitivity (e.g., anaphylaxis) to methadone

Precautions

Risk of Accidental Overdose and Death due to Medication Errors, Addiction, Abuse and Misuse, Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS), Life-Threatening Respiratory Depression, Life-Threatening QT Prolongation6 Neonatal Opioid Withdrawal Syndrome, Risks of Concomitant Use of Cytochrome P450 3A4, 2B6, 2C19, 2C9, or 2D6 Inhibitors or Discontinuation of P450 3A4, 2B6, 2C19, or 2C9 Inducers, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants, Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, and Debilitated Patients, Serotonin Syndrome with Concomitant Use of Serotonergic Drugs, Adrenal Insufficiency, Severe Hypotension, Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness, Risks of Use in Patients with Gastrointestinal Conditions, Increased Risk of Seizures in Patients with Seizure Disorders, Withdrawal, Risks Driving and Operating Machinery, Laboratory Test Interactions

Adverse Reactions

Addiction, Abuse, and Misuse, Life Threatening Respiratory Depression, QT Prolongation, Neonatal Opioid Withdrawal Syndrome, Interactions with Benzodiazepines and other CNS Depressants, Serotonin Syndrome, Adrenal Insufficiency, Severe Hypotension, Gastrointestinal Adverse Reactions, Seizures, Withdrawal

Pregnancy and lactation

Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.

There are no adequate and well-controlled studies in pregnant women.

Renal and liver Impairment

Methadone pharmacokinetics have not been extensively evaluated in patients with hepatic insufficiency. Methadone is metabolized by hepatic pathways; therefore, patients with liver impairment may be at risk of increased systemic exposure to methadone after multiple dosing. Start these patients on lower doses and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression.

Methadone pharmacokinetics have not been extensively evaluated in patients with renal insufficiency. Since un metabolized methadone and its metabolites are excreted in urine to a variable degree, start these patients on lower doses and with longer dosing intervals and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression.

Laboratory Tests

Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with Methadone Hydrochloride.