Dosing and uses of Sprix (ketorolac intranasal)
Adult dosage forms and strengths
intranasaL
- 15.75mg per 100 microL spray; 8 sprays/1.7g bottle
Pain
Indicated for short-term (up to 5 days) management of moderate to moderately severe pain
<65 years: 31.5 mg (ie, 1 spray in each nostril) q6-8h; not to exceed 126 mg/day
<50 kg or ≥65 years: 15.75 mg (ie, 1 spray in only 1nostril) q6-8h; not to exceed 63 mg/day
Renal Impairment
1 spray (15.75 mg) in 1 nostriL
Total dose: 15.75 mg intranasal q6-8hr; not to exceed 4 doses (63 mg/day)
Hepatic Impairment
Use caution; may cause elevation of liver enzymes; discontinued if symptoms of liver toxicity develop
Administration
Store refrigerated until use, then may keep at room temperature during use
Discard bottle within 24 hr after first dose, even if bottle still contains medication (will not deliver intended dose after 24 hr)
Pediatric dosage forms and strengths
Safety and efficacy not established
Sprix (ketorolac intranasal) adverse (side) effects
>10%
Nasal discomfort (15%)
Rhinalgia (13%)
1-10%
Increased lacrimation (5%)
Throat irritation (4%)
Oliguria (3%)
Rash (3%)
Bradycardia (2%)
Decreased urine output (2%)
Increased ALT and/or AST (2%)
Hypertension (2%)
Rhinitis (2%)
Warnings
Black box warnings
Limitations of use
- Total duration of use of intranasal alone or sequentially with and other ketorolac formulations should not exceed 5 days
Cardiovascular risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal; risk may increase with duration of use; patients with risk factors for or existing cardiovascular disease may be at greater risk; contraindicated for perioperative pain in the setting of CABG surgery (increased risk of MI and stroke)
Gastrointestinal risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal; GI adverse events may occur at any time during use and without warning symptoms; elderly patients are at greater risk for serious GI events
Bleeding risk
- Inhibits platelet function and is contraindicated with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high risk of bleeding
Renal risk
- Contraindicated with advanced renal impairment and patients at risk for renal failure due to volume depletion
Contraindications
Hypersensitivity to ketorolac, other NSAID, aspirin, ethylenediamine tetraacetic acid (EDTA)
Active peptic ulcer disease, recent GI bleeding or perforation, or history of peptic ulcer disease or GI bleeding
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
Prophylactic analgesic before any major surgery; during the perioperative period in the setting of coronary artery bypass graft (CABG) surgery; advanced renal disease or patients at risk for renal failure due to volume depletion
Labor and delivery
Breastfeeding women
Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or those for whom hemostasis is criticaL
Coadministration with probenecid or pentoxifylline
Cautions
May lead to onset of new hypertension or exacerbate existing hypertension
NSAIDs may cause serious skin reactions (eg, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis)
Common local adverse effects include mild and transient nasal discomfort and irritation
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs
Pregnancy and lactation
Pregnancy category: C prior to 30 weeks gestation; D starting at 30 weeks gestation, risk of premature closure of ductus arteriosus near term
The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)
Lactation: Distributed in human breast milk, caution not advised
Limited data from 1 published study involving 10 breastfeed women 2-6 days postpartum showed low levels of ketorolac in breast milk; levels were undetectable (<5 ng/mL) in 4 of the patients
After a single 10 mg dose, the maximum milk concentration observed was 7.3 ng/mL, and the maximum milk to plasma ratio was 0.037; after 1 day of dosing (10 mg q6hr), the maximum milk concentration was 7.9 ng/mL, and the maximum milk-to-plasma ratio was 0.025
Assuming an infant daily intake of 400-1000 mL/day and a maternal body weight of 60 kg, the calculated maximum daily infant exposure was 0.00263 mg/kg/day, which is 0.4% of the maternal weight adjusted dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sprix (ketorolac intranasal)
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2)
May inhibit chemotaxis, may alter lymphocyte activity, decrease proinflammatory cytokine activity, and may inhibit neutrophil aggregation. These effects may contribute to its anti-inflammatory activity
Pharmacokinetics
Bioavailability: 60% (compared with 30 mg IM)
Peak plasma time: 0.75 hr
Peak plasma concentration: 1805.8 ng/mL
Protein bound: 99% (5% to albumin)
Vd: 13 L
Metabolism: By liver via hydroxylation and conjugation
Half-life: 5.24 hr; 6-19 hr with renal impairment
Excretion: 92% urine (~40% as metabolites); 6% feces
