TARGINIQ
Clinical safety rating
cautionComprehensive clinical and safety monograph for TARGINIQ (TARGINIQ).
TARGINIQ combines naloxegol, a peripherally acting mu-opioid receptor antagonist (PAMORA), with oxycodone, a full mu-opioid receptor agonist. Naloxegol reduces opioid-induced constipation by blocking opioid effects in the gastrointestinal tract without affecting central analgesia.
| Metabolism | Oxycodone: primarily hepatic via CYP3A4 and CYP2D6. Naloxegol: primarily hepatic via CYP3A4. |
| Excretion | Oxycodone is primarily excreted renally as noroxycodone and free oxycodone; naloxone undergoes extensive hepatic metabolism and is excreted renally as naloxone-3-glucuronide. For TARGINIQ, approximately 87% of the dose is eliminated in urine: 19% as unchanged oxycodone, 1% as unchanged naloxone, and the remainder as metabolites. Fecal excretion accounts for ~10%. |
| Half-life | Oxycodone terminal half-life is 3.5-4.0 hours; naloxone half-life is 1-1.5 hours. The prolonged-release formulation yields a longer apparent half-life, supporting twice-daily dosing. |
| Protein binding | Oxycodone: 45% bound primarily to albumin. Naloxone: approximately 40% bound predominantly to albumin. |
| Volume of Distribution | Oxycodone: Vd 2.6 L/kg, indicating extensive tissue distribution. Naloxone: Vd 2.1 L/kg. |
| Bioavailability | Oral bioavailability of oxycodone: 60-87% (first-pass metabolism). Naloxone oral bioavailability: <2% due to extensive first-pass hepatic metabolism, allowing local gastrointestinal effect without significant systemic opioid antagonism. |
| Onset of Action | Oral: analgesia onset within 20-30 minutes for immediate-release, but TARGINIQ is extended-release, with peak plasma concentrations at 3-4 hours. |
| Duration of Action | Extended-release TARGINIQ provides analgesia for approximately 12 hours; the naloxone component acts locally in the gut to reduce opioid-induced constipation. |
| Molecular Weight | 634.76 |
1 tablet orally every 12 hours, each tablet containing oxycodone hydrochloride 10 mg and naloxone hydrochloride 5 mg (as naloxone hydrochloride dihydrate). Dose may be titrated based on analgesic requirements; maximum daily dose: oxycodone 80 mg and naloxone 40 mg.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For GFR <60 mL/min: initiate at 50% of usual dose and titrate cautiously. For GFR <30 mL/min: consider alternative therapy; if used, reduce starting dose by 50% and monitor closely. Not recommended in end-stage renal disease (GFR <15 mL/min). |
| Liver impairment | Child-Pugh Class A: no adjustment required. Child-Pugh Class B: initiate at 50% of usual dose and titrate cautiously. Child-Pugh Class C: contraindicated due to risk of naloxone accumulation and CNS effects. |
| Pediatric use | Not recommended for use in pediatric patients (≤18 years) due to lack of safety and efficacy data. |
| Geriatric use | Initiate at the lower end of the dosing range (e.g., 1 tablet every 12 hours) and titrate cautiously. Monitor for signs of CNS depression, constipation, and respiratory depression. Consider baseline renal and hepatic function for dose adjustments. |
| 1st trimester | Avoid. Naloxegol is an opioid antagonist; potential for fetal harm based on animal studies. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid. Limited human data; animal studies show fetal toxicity. Consider alternative therapies. |
| 3rd trimester | Avoid. May precipitate opioid withdrawal in mother or fetus; risk of premature labor. |
Clinical note
Comprehensive clinical and safety monograph for TARGINIQ (TARGINIQ).
| Placental transfer | Likely minimal due to high molecular weight and P-glycoprotein efflux; however, no direct human data. |
| Breastfeeding | Naloxegol is likely excreted into breast milk in low amounts due to high molecular weight and low oral bioavailability. However, no human data available. Caution recommended; monitor infant for signs of opioid withdrawal. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS). First trimester: Limited data; animal studies show increased risk of neural tube defects at high doses. Second and third trimesters: Chronic use may lead to fetal dependence and withdrawal at birth. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and signs of opioid withdrawal. Fetal monitoring: Nonstress test and biophysical profile in third trimester if chronic use. Assess for neonatal withdrawal after delivery. |
| Fertility Effects | Opioids may suppress gonadotropin-releasing hormone (GnRH), leading to decreased libido, amenorrhea, and reduced fertility. Reversible upon discontinuation. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of even one dose of TARGINIQ, especially by children, can cause fatal respiratory depression; neonatal opioid withdrawal syndrome; opioid-induced hyperalgesia and allodynia; concomitant use with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may increase naloxegol exposure and risk of adverse reactions.
| Serious Effects |
Known hypersensitivity to naloxegol or any componentConcurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)Gastrointestinal obstruction or risk of recurrent obstructionConcurrent use with opioid analgesics for acute postoperative pain (risk of withdrawal)
| Precautions | Addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion, Neonatal opioid withdrawal syndrome, Opioid-induced hyperalgesia and allodynia, CYP3A4 inhibitor/inducer interactions with naloxegol, Gastrointestinal obstruction: naloxegol is contraindicated in patients with known or suspected gastrointestinal obstruction, Risk of severe opioid withdrawal symptoms with abrupt discontinuation or naloxegol dose increase |
| Food/Dietary | Take on an empty stomach at least 1 hour before or 2 hours after a meal. Avoid grapefruit juice and other CYP3A4 inhibitors in food, as they may increase naloxegol levels. |
| Clinical Pearls | TARGINIQ (naloxegol) is a peripherally acting mu-opioid receptor antagonist (PAMORA) indicated for opioid-induced constipation (OIC) in adults with chronic non-cancer pain. It does not cross the blood-brain barrier, so it does not reverse central analgesia or precipitate opioid withdrawal. Contraindicated in patients with known or suspected gastrointestinal obstruction. Administer on an empty stomach at least 1 hour before or 2 hours after a meal. Avoid use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) as they increase naloxegol exposure. Dose adjustments needed for moderate or severe hepatic impairment. |
| Patient Advice | Take TARGINIQ on an empty stomach, at least 1 hour before or 2 hours after eating. · Do not crush or chew the tablet; swallow it whole with water. · If you miss a dose, skip it and take the next dose at the regular time. Do not take two doses at once. · Common side effects include abdominal pain, diarrhea, nausea, gas, and headache. Call your doctor if you have severe or persistent symptoms. · Seek immediate medical attention if you have severe stomach pain, vomiting, or if you are unable to pass stool (possible bowel obstruction). · Inform your doctor about all medications you take, especially strong CYP3A4 inhibitors like certain antibiotics or antifungals. · TARGINIQ does not affect the pain relief from your opioid medication; continue taking your pain medicine as prescribed. · Store at room temperature away from moisture and heat. |
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