NEODOSE

INDICATIONS

• Neonatal abstinence syndrome, adjunct: CloNIDine has been used as an adjunct to tincture of opium in neonates with intrauterine exposure to heroin or methadone. In a prospective, randomized, double-blind, placebo-controlled trial, infants 35 weeks GA and older receiving tincture of opium with oral cloNIDine experienced fewer treatment failures, a shorter duration of treatment and observation, and required less tincture of opium than infants receiving tincture of opium with placebo. There were no clinically important changes in blood pressure and heart rate in the cloNIDine group. In a prospective, randomized, open-label trial, infants 35 weeks gestational age or older treated with morphine for NAS experienced shorter morphine treatment days (4.6 less days (95% CI, 0.3 to 8.9 days)) and no difference in morphine total dose with adjunctive phenobarbital compared with cloNIDine. However, the total duration of phenobarbital therapy continued for an average of 3.8 months (range 1 8 months). 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 (number of participants=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.
• Neonatal abstinence syndrome (NAS), monotherapy: Overall, cloNIDine monotherapy for NAS appeared to be as effective as morphine in a randomized, double-blind, pilot study of 31 neonates younger than 7 days (gestational age, 35 weeks or more). Rescue drugs were not necessary in any neonate. The initial cloNIDine dose was 0.625 mcg/kg/dose orally every 3 hours with dose titrations up to a maximum of 12 mcg/kg/day.
• Sedation and analgesia, Adjunct; Mechanical ventilation: There is a lack of evidence to support the use in term and preterm newborn infants. There was no improvement in mortality, duration of mechanical ventilation or intensive care unit stay between the cloNIDine (1 mcg/kg/hr) and placebo group in a study of 112 term infants.

CONTRAINDICATIONS

Epidural Injection Contraindicated in patients with an injection site infection, patients with a bleeding diathesis, and patients on concurrent anticoagulant therapy. Epidural administration above the C4 dermatome is also contraindicated.

PRECAUTIONS

Abrupt discontinuation may result in symptoms of withdrawal (eg, agitation, headache, tremor, rapid rise of blood pressure); a gradual reduction of dosage is recommended when therapy is discontinued.

ADVERSE EFFECTS

• Local anesthetics; adjunct: The use of cloNIDine as an adjunct with local anesthetics for caudal or spinal anesthesia/analgesia has been associated with apnea and respiratory depression in neonates and premature infants.
• Neonatal abstinence syndrome (NAS): The use of cloNIDine for treatment of NAS has not been associated with clinically important changes in blood pressure or heart rate; however, close monitoring is imperative. Adjunct cloNIDine up to doses of 24 mcg/kg/day in neonates at least 35 weeks’ gestation resulted in a heart rate decrease between 7 to 10 beats per minute compared with baseline in a retrospective study (n=64). Systolic blood pressure did not significantly change during cloNIDine treatment with any dose, but diastolic blood pressure was significantly increased 5 mm Hg with doses between 1.5 and 2 mcg/kg/dose every 3 hours. After discontinuation of clonidine the blood pressure (systolic and diastolic) increased (8 and 4 mm Hg, respectively) compared with baseline.

ADMINISTRATION

Oral: Oral: Some experts recommend using a dilution of the epidural formulation of cloNIDine for use in neonates with NAS due to concerns about extemporaneous compounded oral suspensions and accuracy of dosing . The epidural formulation (100 mcg/mL) was diluted in NS to a concentration of 5 mcg/mL and used orally in a randomized controlled trial.

MONITORING

Monitor heart rate and blood pressure every 4 hours the first 2 days of therapy and every 12 hours thereafter; monitor blood pressure closely for 48 hours after discontinuing cloNIDine to access for rebound hypertension. Monitor NAS scores every 3 to 4 hours during treatment using a published abstinence assessment tool such as the modified Neonatal Abstinence Scoring System (Finnegan) or the Lipsitz tool.