Naldemedine (Symproic) is a peripherally-acting opioid receptor antagonist that is approved for the treatment of opioid-induced constipation in patients with non-cancer pain.
Naldemedine (Symproic) Uses:
-
Opioid-induced constipation:
- For the management of opioid-induced constipation (OIC) in people with chronic non-cancer discomfort, such as those who endure continuous pain from previously having had cancer or from the therapy for that disease and do not require regular (e.g. weekly) opioid dose escalation.
Naldemedine (Symproic) Dose in Adults
Naldemedine (Symproic) Dose in the treatment of Opioid-induced constipation:
- Oral:
- 0.2 milligrammes once each day.
- If you stop taking your opioid painkillers, stop your therapy.
Naldemedine (Symproic) Dose in Childrens
It has not been studied in children.
Pregnancy Risk Category: B
- In some studies on animal reproduction, adverse events were reported.
- Based on animal data, naldemedine could cross the placenta to cause opioid withdrawal in the foetus if it is administered during pregnancy.
Use during breastfeeding:
- It is unknown if the drug is found in breast milk.
- According to the drug manufacturer breastfeeding during treatment should be considered in light of the risks and harms to infants, as well as the benefits to the mother.
- Breastfeeding may be resumed after 3 days if naldemedine has been stopped to reduce infant exposure.
Naldemedine (Symproic) Dose in Kidney Disease:
- No dosage adjustment is necessary.
Naldemedine (Symproic) Dose in Liver disease:
-
Mild to moderate impairment (Child-Pugh classes A and B):
- No dosage adjustment is necessary.
-
Severe impairment (Child-Pugh class C):
- Avoid use (has not been studied).
Common Side Effects of Naldemedine (Symproic):
-
Gastrointestinal:
- Abdominal pain
- Diarrhea
Less common Side Effects of Symproic:
-
Gastrointestinal:
- Nausea
- Vomiting
- Gastroenteritis
Contraindications to Naldemedine (Symproic):
- Hypersensitivity or hyperresponsiveness to any ingredient in the mix, including naldemedine
- Gastrointestinal blockage (known, suspected, or suspected), or a higher risk of recurring obstruction
Warnings and precautions
-
Perforation of the GI:
- Patients with advanced diseases such as Ogilvie syndrome, peptic disease (PUD), diverticular disorder, infiltrative gastrointestinal malignancies, and peritoneal metastasis have had GI perforation.
- When caring for individuals like these or those with other diseases that might jeopardise the integrity of their GI walls, use additional caution (eg Crohn's disease).
- Keep an eye out for severe, lingering, or intensifying stomach discomfort. If this occurs, stop receiving therapy.
- Those with known or suspected GI blockages or those who are more likely to experience recurring GI problems shouldn't use this product.
-
Withdrawal of Opioid:
- This may cause symptoms of opioid withdrawal, such as abdominal pain, nausea, vomiting, diarrhea, hyperhidrosis and nausea.
- Disturbances of the blood-brain barrier should be taken into account by patients as they may raise the risk of opiate withdrawal and/or reduce analgesia.
- You should keep an eye out for these individuals' opioid withdrawal symptoms.
-
Hepatic impairment
- Avoid severe impairment (Childugh class C).
Naldemedine: Drug Interaction
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
Risk Factor C (Monitor therapy) |
|
| Bosentan | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| CYP3A4 Inducers (Moderate) | May decrease the serum concentration of Naldemedine. |
| CYP3A4 Inhibitors (Moderate) | May increase the serum concentration of Naldemedine. |
| CYP3A4 Inhibitors (Strong) | May increase the serum concentration of Naldemedine. |
| Deferasirox | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Erdafitinib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Erdafitinib | May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
| Ivosidenib | may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). |
| P-glycoprotein/ABCB1 Inhibitors | Naldemedine serum concentration could rise. |
| Ranolazine | Serum levels of ABCB1 substrates and P-glycoprotein can increase. |
| Sarilumab | may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
| Siltuximab | may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
| Tocilizumab | may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
Risk Factor D (Consider therapy modification) |
|
| Dabrafenib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
| Lorlatinib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
| St John's Wort | may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). Management: Take into account a different medication for one of the interacting ones. Specific contraindications for some combinations may exist. Consult the relevant manufacturer labels. |
Risk Factor X (Avoid combination) |
|
| CYP3A4 Inducers (Strong) | May lower the level of naldemedine in the serum. |
| Methylnaltrexone | The negative or hazardous effects of opioid antagonists can be increased. There may be a higher risk of opioid withdrawal in particular. |
| Naloxegol | Opioid antagonists may increase the negative or dangerous effects of Naloxegol. There may be a higher risk of opioid withdrawal in particular. |
| Opioid Antagonists | may lower the level of naldemedine in the serum. may intensify Naldemedine's negative or hazardous effects. Particularly, there may be an increased risk of opioid withdrawal. |
Monitoring parameters:
- Symptoms of opiate withdrawal for signs of GI perforation, such as acute, persistent, or increasing stomach discomfort.
How to administer Naldemedine (Symproic)?
- Administer without regard to meals.
Mechanism of action of Naldemedine (Symproic):
- It functions as an opioid antagonist, preventing the binding of opioids to the mu, delta, and kappa receptors.
- Functions as an antagonist of the muopioid receptor with peripheral action. This comprises procedures performed on the GI tract to prevent a delay in GI transit time.
- By doing this, the constipating effects of opioids will be lessened.
Metabolism:
- UGT1A3 to naldemedine 3-G (minor)
- also undergoes breakdown in the GI tract to form benzamidine and naldemedine carboxylic acid.
- CYP3A to nor-naldemedine (major)
Half-life elimination:
- 11 hours
Excretion:
- feces (35%; 20% as benzamidine metabolite)
- Urine (57%; 16% to 18% in form of unchanged drug; 32% as benzamidine metabolite)
Protein binding:
- 93% to 94%
Time to peak:
0.75 hours & 2.5 hours (with food)
International Brands of Naldemedine:
- Symproic
- Rizmoic
Naldemedine Brand Names in Pakistan:
No Brands Available in Pakistan.
