SPRIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPRIX (SPRIX).
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, thereby decreasing inflammation, pain, and fever.
| Metabolism | Primarily hepatic via conjugation (glucuronidation) and oxidation (CYP2C9 minor). Metabolites are inactive. |
| Excretion | Renal excretion of unchanged drug and metabolites; after intravenous administration, approximately 92% of the dose is recovered in urine (50% as unchanged ketorolac, 40% as glucuronide conjugates) and 6% in feces. |
| Half-life | Terminal elimination half-life is 5-6 hours in adults with normal renal function; may be prolonged to 13-14 hours in elderly patients and 15-20 hours in patients with renal impairment. |
| Protein binding | 99% bound to plasma proteins, primarily albumin (saturable at high concentrations). |
| Volume of Distribution | 0.2-0.3 L/kg; indicates distribution primarily into extracellular fluid. |
| Bioavailability | Intranasal: approximately 75-80% relative to intravenous administration. |
| Onset of Action | Intranasal: 30 minutes to first perceptible pain relief, with peak analgesic effect at 1-2 hours. |
| Duration of Action | Duration of analgesic effect is 6-8 hours after intranasal administration; multi-dose studies show sustained efficacy with dosing every 6-8 hours. |
| Molecular Weight | 376.4 Da |
Intranasal: 31.5 mg (1 spray) in one nostril, may repeat after 30 minutes; maximum 63 mg (2 sprays) per dose. Subsequent doses every 6-8 hours as needed; maximum 126 mg (4 sprays) per day.
| Dosage form | SPRAY, METERED |
| Renal impairment | Contraindicated in patients with severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-60 mL/min), reduce total daily dose by 50% and monitor for renal toxicity. |
| Liver impairment | Contraindicated in Child-Pugh Class C cirrhosis. For mild to moderate hepatic impairment (Child-Pugh A or B), reduce total daily dose by 50% and monitor for signs of bleeding or hepatic toxicity. |
| Pediatric use | Not recommended for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | Elderly patients may have increased risk of GI bleeding and renal toxicity. Use lowest effective dose and shortest duration; monitor renal function and adjust dose based on estimated glomerular filtration rate (eGFR). |
| 1st trimester | Avoid in first trimester due to risk of cardiac malformations and gastroschisis; NSAIDs are generally not recommended unless necessary. |
| 2nd trimester | Avoid unless benefit clearly outweighs risk; may be used with caution if no alternative, but monitor for oligohydramnios. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature ductus arteriosus closure and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for SPRIX (SPRIX).
| Placental transfer | Ketorolac crosses the placenta; limited data suggest low transfer, but NSAIDs are known to cross freely, especially in later pregnancy. |
| Breastfeeding | Minimal excretion into breast milk; unlikely to cause adverse effects in infant due to short half-life and low oral bioavailability. However, use with caution in breastfeeding women, especially if infant has thrombocytopenia or renal impairment. |
■ FDA Black Box Warning
Risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk is increased with duration of use and in patients with cardiovascular risk factors. Contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Active peptic ulcer diseaseHistory of gastrointestinal bleeding or perforationAdvanced renal impairment (CrCl < 30 mL/min)Risk of bleeding (e.g., hemorrhagic diathesis, incomplete hemostasis)Cerebrovascular bleedingHypersensitivity to ketorolac or any componentPatients with aspirin/NSAID-induced asthma, urticaria, or allergic reactionsConcurrent use with other NSAIDs or probenecidThird trimester of pregnancyPatients with confirmed or suspected coronary artery bypass graft surgery (CABG)Labor and delivery (due to risk of uterine atony and fetal ductus arteriosus closure)
| Precautions | Cardiovascular risk: May increase risk of serious cardiovascular thrombotic events., Gastrointestinal risk: Can cause serious GI adverse events including bleeding, ulceration, and perforation., Renal toxicity: Monitor renal function; avoid in patients with advanced renal disease., Hepatic effects: Elevations in liver enzymes; discontinue if signs of hepatic injury occur., Anaphylactoid reactions: Can occur in patients without prior exposure., Pregnancy: Avoid in late pregnancy due to risk of premature closure of ductus arteriosus. |
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| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Pregnancy Category C. Avoid in third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. No adequate studies in first two trimesters; use only if potential benefit justifies risk. |
| Fetal Monitoring | Monitor renal function, platelet count, and bleeding times in mother. Fetal ultrasound for oligohydramnios if used beyond 48 hours or after 32 weeks gestation. |
| Fertility Effects | May impair female fertility via inhibition of prostaglandin synthesis affecting ovulation. Reversible upon discontinuation. |
| Food/Dietary | No specific food interactions. Avoid alcohol as it may increase risk of GI bleeding. Take with food or milk to minimize GI upset. |
| Clinical Pearls | SPRIX (ketorolac tromethamine) is an NSAID nasal spray for acute pain. Use lowest effective dose for shortest duration. Avoid in patients with active peptic ulcer, recent GI bleeding, renal impairment (CrCl <30 mL/min), or at risk of bleeding. Contraindicated in patients with aspirin or NSAID allergy, and in patients with or at risk of intracranial bleeding. Monitor renal function and GI symptoms. Not for use in pediatric patients. Maximum duration is 5 days. |
| Patient Advice | Use exactly as prescribed; do not exceed 5 days of therapy. · Spray into nostril; do not sniff deeply after spraying. · Avoid alcohol and other NSAIDs while using this medication. · Seek medical help if you experience signs of bleeding, stomach pain, or allergic reaction. · Store at room temperature; do not refrigerate or freeze. · Tell your doctor about all other medications you take, especially blood thinners or other NSAIDs. |