INVAGESIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVAGESIC (INVAGESIC).

How it works

INVAGESIC is a combination of pregabalin, an alpha2-delta ligand that inhibits presynaptic calcium channels to reduce excitatory neurotransmitter release, and meloxicam, a COX-2 selective NSAID that decreases prostaglandin synthesis via cyclooxygenase inhibition.

What the body does with it

Metabolism	Pregabalin: Negligible metabolism; excreted renally (~90% unchanged). Meloxicam: Primarily metabolized by CYP2C9 and CYP3A4; also undergoes glucuronidation.
Excretion	Renal: ~70% as unchanged drug; biliary/fecal: ~30% as metabolites
Half-life	Terminal elimination half-life: 4-6 hours in adults; prolonged to 8-12 hours in elderly or mild renal impairment
Protein binding	~95% bound primarily to albumin; also binds to alpha-1-acid glycoprotein
Volume of Distribution	0.3-0.5 L/kg, indicating moderate tissue distribution; increases in inflammation or sepsis due to altered protein binding
Bioavailability	Oral: ~85-90%; IM: 100%; Rectal: ~70%
Onset of Action	IV: 2-5 minutes; IM: 10-15 minutes; Oral: 30-60 minutes
Duration of Action	Analgesic effect: 4-6 hours after therapeutic doses; duration may be prolonged with repeated dosing due to tissue accumulation

Classification & Brands

Dosing & administration

Adults: 1-2 tablets (325 mg acetaminophen/5 mg hydrocodone) orally every 4-6 hours as needed for pain, not to exceed 12 tablets per day.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: Administer every 6-8 hours; GFR 15-29 mL/min: Administer every 8-12 hours; GFR <15 mL/min: Use not recommended due to accumulation of metabolites.
Liver impairment	Child-Pugh Class A: No adjustment; Class B: Reduce dose by 50% or extend interval; Class C: Avoid use due to risk of hepatotoxicity.
Pediatric use	Children ≥2 years: 0.1-0.2 mg hydrocodone/kg/dose orally every 4-6 hours, maximum 6 doses/day; dose based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours, max 75 mg/kg/day.
Geriatric use	Initiate at low end of dosing range (e.g., 1 tablet every 6 hours), monitor for sedation and respiratory depression; reduce total daily dose if creatinine clearance <30 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INVAGESIC (INVAGESIC).

Breastfeeding	Excreted in human milk; M/P ratio unknown. Due to potential adverse effects (e.g., kernicterus in neonates, renal toxicity), use only if benefit outweighs risk. Monitor infant for jaundice, drowsiness, poor feeding.
Teratogenic Risk	First trimester: Increased risk of neural tube defects (evidence from animal studies, limited human data). Second trimester: No specific malformation risk reported. Third trimester: Risk of premature closure of ductus arteriosus, oligohydramnios, fetal renal impairment, and persistent pulmonary hypertension of the newborn (PPHN) if used >48 hours near term.

Warnings & precautions

■ FDA Black Box Warning

NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular risk factors. INVAGESIC is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; in the setting of CABG surgery; advanced renal disease; patients with a history of hypersensitivity to pregabalin, meloxicam, or any component of the formulation.

Clinical Precautions

Precautions

Cardiovascular thrombotic events; GI bleeding, ulceration, and perforation; hepatotoxicity; renal toxicity; anaphylactoid reactions; serious skin reactions; fetal toxicity; central nervous system depression (dizziness, somnolence); seizure risk with abrupt discontinuation; respiratory depression with concomitant opioids.

Clinical Tips & Counseling

Drug interactions

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INVAGESIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVAGESIC (INVAGESIC).

How it works

What the body does with it

Metabolism	Pregabalin: Negligible metabolism; excreted renally (~90% unchanged). Meloxicam: Primarily metabolized by CYP2C9 and CYP3A4; also undergoes glucuronidation.
Excretion	Renal: ~70% as unchanged drug; biliary/fecal: ~30% as metabolites
Half-life	Terminal elimination half-life: 4-6 hours in adults; prolonged to 8-12 hours in elderly or mild renal impairment
Protein binding	~95% bound primarily to albumin; also binds to alpha-1-acid glycoprotein
Volume of Distribution	0.3-0.5 L/kg, indicating moderate tissue distribution; increases in inflammation or sepsis due to altered protein binding
Bioavailability	Oral: ~85-90%; IM: 100%; Rectal: ~70%
Onset of Action	IV: 2-5 minutes; IM: 10-15 minutes; Oral: 30-60 minutes
Duration of Action	Analgesic effect: 4-6 hours after therapeutic doses; duration may be prolonged with repeated dosing due to tissue accumulation

Classification & Brands

Dosing & administration

Adults: 1-2 tablets (325 mg acetaminophen/5 mg hydrocodone) orally every 4-6 hours as needed for pain, not to exceed 12 tablets per day.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: Administer every 6-8 hours; GFR 15-29 mL/min: Administer every 8-12 hours; GFR <15 mL/min: Use not recommended due to accumulation of metabolites.
Liver impairment	Child-Pugh Class A: No adjustment; Class B: Reduce dose by 50% or extend interval; Class C: Avoid use due to risk of hepatotoxicity.
Pediatric use	Children ≥2 years: 0.1-0.2 mg hydrocodone/kg/dose orally every 4-6 hours, maximum 6 doses/day; dose based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours, max 75 mg/kg/day.
Geriatric use	Initiate at low end of dosing range (e.g., 1 tablet every 6 hours), monitor for sedation and respiratory depression; reduce total daily dose if creatinine clearance <30 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INVAGESIC (INVAGESIC).

Breastfeeding	Excreted in human milk; M/P ratio unknown. Due to potential adverse effects (e.g., kernicterus in neonates, renal toxicity), use only if benefit outweighs risk. Monitor infant for jaundice, drowsiness, poor feeding.
Teratogenic Risk	First trimester: Increased risk of neural tube defects (evidence from animal studies, limited human data). Second trimester: No specific malformation risk reported. Third trimester: Risk of premature closure of ductus arteriosus, oligohydramnios, fetal renal impairment, and persistent pulmonary hypertension of the newborn (PPHN) if used >48 hours near term.