RELEXXII
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RELEXXII (RELEXXII).
RELEXXII is a fixed-dose combination of buprenorphine, a partial mu-opioid receptor agonist, and naloxone, a mu-opioid receptor antagonist. Buprenorphine binds to mu-opioid receptors with high affinity, producing dose-dependent opioid agonist effects such as analgesia and euphoria, but with a ceiling effect on respiratory depression. Naloxone is included to deter intravenous abuse; when administered sublingually, naloxone has poor bioavailability and negligible effect, but if injected, it precipitates withdrawal in opioid-dependent individuals.
| Metabolism | Buprenorphine undergoes primarily hepatic metabolism via N-dealkylation by CYP3A4 to norbuprenorphine, which is further glucuronidated. Naloxone is metabolized in the liver primarily by glucuronidation. |
| Excretion | Primarily renal as unchanged drug (70-80%), with approximately 20% metabolized to inactive metabolites; less than 5% fecal. |
| Half-life | Terminal elimination half-life is 2-4 hours, prolonged in renal impairment (up to 8-10 hours in severe impairment). |
| Protein binding | Approximately 20-30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.5-1.0 L/kg, indicating distribution into total body water. |
| Bioavailability | Intramuscular: 100%; subcutaneous: 80-100%. |
| Onset of Action | Intravenous: immediate; intramuscular: 5-10 minutes; subcutaneous: 15-30 minutes. |
| Duration of Action | Intravenous: 30-60 minutes; intramuscular/subcutaneous: 1-2 hours, depending on dose and patient response. |
| Molecular Weight | 314.35 |
1 tablet (5 mg/325 mg) orally every 6 hours as needed for pain; maximum 4 tablets (20 mg/2,600 mg) in 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl 30-60 mL/min: use with caution, reduce dose by 50% or extend dosing interval to every 8 hours. For CrCl < 30 mL/min: avoid use or use with extreme caution, consider alternative therapy. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce dose by 50% and extend interval to every 8 hours. Class C: avoid use. |
| Pediatric use | Not recommended for use in pediatric patients under 18 years of age due to risk of opioid-induced respiratory depression and addiction. |
| Geriatric use | Start at lowest effective dose (e.g., half tablet) and titrate slowly; monitor for respiratory depression, sedation, and constipation due to age-related changes in pharmacokinetics and increased sensitivity. |
| 1st trimester | RELEXXII is contraindicated in first trimester due to risk of fetal malformations including neural tube defects and cardiac anomalies. |
| 2nd trimester | Contraindicated in second trimester; no safe dose established. |
| 3rd trimester | Contraindicated in third trimester; risk of premature closure of ductus arteriosus and pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for RELEXXII (RELEXXII).
| Placental transfer | Readily crosses placenta; cord blood concentrations approximately 80% of maternal levels. |
| Breastfeeding | Excreted in breast milk; measurable infant serum concentrations reported. Avoid breastfeeding due to potential adverse effects on infant development. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: RISK OF RESPIRATORY DEPRESSION, NEONATAL OPIOID WITHDRAWAL SYNDROME, AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS. Respiratory depression may occur, particularly in non-tolerant patients, and can be life-threatening. Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which is life-threatening. Concomitant use of buprenorphine with benzodiazepines or other CNS depressants increases the risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Serious Effects |
PregnancyLactationHypersensitivity to active substance or excipientsSevere hepatic impairment
| Precautions | Risk of respiratory depression and death, particularly in non-tolerant patients or when used with CNS depressants, Neonatal opioid withdrawal syndrome with prolonged use during pregnancy, Adrenal insufficiency reported with opioid agonists, Hepatitis, hepatic injury, and hepatic events; monitor liver function, Hypersensitivity reactions including bronchospasm and angioedema, Orthostatic hypotension and syncope, Physical dependence and withdrawal upon abrupt discontinuation, Impairment of ability to drive or operate machinery |
Loading safety data…
| L5 - Hazardous |
| Teratogenic Risk | Methadone, active ingredient of RELEXXII, is not a major human teratogen. First trimester exposure is not associated with increased risk of major congenital malformations above baseline. Second and third trimester use may be associated with neonatal abstinence syndrome (NAS), growth restriction, and preterm birth. Chronic use can lead to fetal dependence. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, and sedation level. During pregnancy, monitor for signs of withdrawal, compliance, and concurrent substance use. Fetal monitoring: assess growth (ultrasound), fetal heart rate, and biophysical profiles as clinically indicated. Monitor neonate for NAS using standardized scoring (e.g., Finnegan). |
| Fertility Effects | Methadone may cause erectile dysfunction, decreased libido, and menstrual irregularities. In males, can reduce serum testosterone. In females, may disrupt ovulatory cycles. Effects on fertility are generally reversible upon dose reduction or discontinuation. |
| Food/Dietary | No significant food interactions. Alcohol should be strictly avoided due to additive CNS depression. |
| Clinical Pearls | RELEXXII (methocarbamol) is a centrally acting muscle relaxant. Onset of action is rapid (30 minutes) with peak effects at 2 hours. It is primarily used for acute musculoskeletal pain, not spasticity from CNS lesions. The recommended dosing is 1.5 g four times daily for 2-3 days, then reduced to 750 mg every 4-6 hours. Renal impairment requires dose adjustment. Can cause sedation; avoid concurrent CNS depressants. Urine may turn brown, black, or blue-green (phenolic metabolites). |
| Patient Advice | May cause drowsiness or dizziness; do not drive or operate machinery until you know how you react. · Avoid alcohol and other CNS depressants (sleeping pills, opioids, benzodiazepines) as they increase sedation risk. · Take with food if gastrointestinal upset occurs. · Urine may turn brown, black, or blue-green; this is harmless and will resolve after stopping the medication. · Do not abruptly stop the medication; taper under medical supervision to avoid withdrawal symptoms. |