Symproic (naldemedine tosylate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Naldemedine tosylate is a peripherally acting micro-opiate receptor antagonist.
Naldemedine tosylate, a derivative of naltrexone, is a peripherally acting micro-opiate receptor antagonist that also binds to and exhibits antagonistic activity at delta- and kappa-opiate receptors. The mechanism of action of naldemedine in the management of opiate-induced constipation stems from the drug's ability to block micro-opiate receptors in the GI tract, thereby reversing opiate-induced constipating effects (e.g., slowing of GI transit). Naldemedine differs structurally from naltrexone by the addition of a large polar side chain that decreases the ability of the drug to cross the blood-brain barrier.
In addition, naldemedine is a substrate of the P-glycoprotein (P-gp) efflux transporter. Because of these properties, CNS penetration of naldemedine is expected to be negligible at the recommended dosage, limiting the potential for interference with centrally mediated opiate analgesia.
Following oral administration in the fasted state, peak plasma concentrations of naldemedine are attained in approximately 45 minutes. Peak plasma concentration and area under the plasma concentration-time curve (AUC) increase in a dose-proportional or almost dose-proportional manner. Administration of naldemedine with a high-fat meal decreases the peak plasma concentration by approximately 35% and delays the time to peak plasma concentration by approximately 1.75 hours, but does not affect the extent of absorption.
Naldemedine is 93-94% bound to plasma proteins and has a terminal elimination half-life of 11 hours. Naldemedine is metabolized principally by cytochrome P-450 isoenzyme 3A4 (CYP3A4), with minor contribution by uridine diphosphate-glucuronosyltransferase (UGT) isoenzyme 1A3 (UGT1A3), to form metabolites (nornaldemedine and naldemedine 3-glucuronide, respectively) that are less-potent opiate receptor antagonists. At usual clinical concentrations, these metabolites are not expected to contribute to the drug's pharmacologic effects.
Naldemedine also is cleaved in the GI tract to form benzamidine and naldemedine carboxylic acid. Following oral administration of a radiolabeled dose of naldemedine, 57% of the dose was excreted in urine and 35% in feces, with 16-18% of the administered dose excreted as unchanged drug in urine. Benzamidine was the principal metabolite excreted in urine and feces, accounting for 32 and 20%, respectively, of the administered dose.
USES: This medication is used to treat constipation caused by opioid medication. It blocks the effect of opioids on the gut without blocking the effect on pain. Naldemedine belongs to a class of medications known as opioid antagonists.
Generic name: naldemedine tosylate
Pronunciation: (nal-DEM-e-deen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Symproic
Indications
The following indications are listed for Symproic:
- Opioid-Induced Constipation
Dosing
Dosage of naldemedine tosylate is expressed in terms of naldemedine.
The recommended adult dosage of naldemedine for the management of opiate-induced constipation in patients with chronic non-cancer-related pain is 0.2 mg once daily.
Naldemedine tosylate is administered orally without regard to food.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Naldemedine is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 (CYP3A4), with minimal contribution from uridine diphosphate-glucuronosyltransferase (UGT) 1A3; naldemedine also is a substrate of P-glycoprotein (P-gp). Naldemedine did not inhibit CYP isoenzyme 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A11 in vitro at clinically relevant concentrations. The drug also did not substantially induce CYP isoenzyme 1A2, 2B6, or 3A4 or UGT 1A2, 1A6, or 2B7.
Naldemedine does not inhibit organic anion transport protein (OATP) 1B1 or 1B3, organic cation transporter (OCT) 1 or 2, organic anion transporter (OAT) 1 or 3, breast cancer resistance protein (BCRP), or P-gp.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Because of the potential for GI perforation, naldemedine is contraindicated in patients with known or suspected GI obstruction and in patients at increased risk for recurrent GI obstruction. (See GI Perforation under Cautions: Warnings/Precautions.)
Naldemedine also is contraindicated in patients with known hypersensitivity to the drug.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 2% or more of patients receiving naldemedine and at a greater incidence than that observed with placebo include abdominal pain, diarrhea, nausea, vomiting, and gastroenteritis.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of naldemedine have not been established in pediatric patients.
Naldemedine should be used in pregnant women only if the potential benefits justify the potential risk to the fetus. There are no adequate and well-controlled studies of naldemedine in pregnant women. Naldemedine crosses the placenta; because of the immature fetal blood-brain barrier, use of naldemedine during pregnancy may precipitate opiate withdrawal in the fetus. No adverse effects of the drug on embryofetal development have been observed in animal reproduction studies.
It is not known whether naldemedine is distributed into human milk, affects milk production, or affects the breast-fed infant. Naldemedine is distributed into milk in rats. Because of the potential for serious adverse effects, including opiate withdrawal, in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. If naldemedine is discontinued, nursing may be resumed 3 days after the final dose of the drug.
In clinical studies, 16% of patients who received naldemedine were 65 years of age and older, while 3% were 75 years of age and older. Although no overall differences in safety and efficacy were observed between geriatric patients and younger adults, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. A population pharmacokinetic analysis revealed no age-related differences in the pharmacokinetics of naldemedine.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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