KETOROLAC TROMETHAMINE AND PHENYLEPHRINE HYDROCHLORIDE
Clinical safety rating: avoid
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious bleeding and renal impairment.
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis. Phenylephrine is a selective alpha-1 adrenergic receptor agonist, causing vasoconstriction.
| Metabolism | Ketorolac: Hepatic metabolism primarily via CYP2C9 and conjugation to inactive metabolites. Phenylephrine: Metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) in the liver and extrahepatic tissues. |
| Excretion | Ketorolac: ~92% renal (60% as unchanged drug, 32% as metabolites), 6% fecal. Phenylephrine: primarily renal as metabolites (sulfate conjugates) with <1% unchanged. |
| Half-life | Ketorolac: 2.4-8.6 hours (mean 5.3 hours) in young adults; prolonged in elderly (up to 13.9 hours) and renal impairment. Phenylephrine: 2-3 hours. |
| Protein binding | Ketorolac: 99.4% bound to albumin. Phenylephrine: ~95% bound to albumin and α-1-acid glycoprotein. |
| Volume of Distribution | Ketorolac: 0.15-0.3 L/kg (rapid and extensive tissue distribution). Phenylephrine: 0.5-1.0 L/kg (primarily in extracellular fluid). |
| Bioavailability | Ketorolac: oral ~80-100%, IM ~100%, ophthalmic: negligible systemic (≤1%). Phenylephrine: ophthalmic: negligible systemic; oral: 38% (first-pass effect). |
| Onset of Action | Ophthalmic: within 30 minutes for mydriasis; systemic ketorolac: IV 1-30 min, IM 10 min, oral 30-60 min. |
| Duration of Action | Ophthalmic: mydriasis persists 2-4 hours; ketorolac: analgesic effect 4-6 hours (IM/IV) to 6-8 hours (oral). |
Ophthalmic: 1 drop of the combination (ketorolac tromethamine 0.45% and phenylephrine hydrochloride 1%) into the operative eye three times daily, beginning 1 day prior to surgery and continuing on the day of surgery and for 2 weeks postoperatively.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment guidelines available for ophthalmic use. Systemic absorption is minimal; however, caution is advised in patients with severe renal impairment (CrCl <30 mL/min) due to potential for increased systemic exposure. |
| Liver impairment | No specific dose adjustment guidelines available for ophthalmic use. Caution in severe hepatic impairment (Child-Pugh class C) due to potential for increased systemic exposure, though absorption is minimal. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. Not recommended for use in children. |
| Geriatric use | No specific dose adjustment required; use same dose as for younger adults. Monitor for adverse effects due to potential age-related renal or hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious bleeding and renal impairment.
| FDA category | Contraindicated |
| Breastfeeding | Ketorolac is excreted in breast milk in low amounts; relative infant dose is approximately 0.4% of maternal weight-adjusted dose. M/P ratio not reported. Avoid use in nursing mothers due to potential adverse effects on infant's cardiovascular system (including ductus arteriosus closure) and renal function. Phenylephrine excretion in breast milk is likely minimal; however, oral bioavailability is low. Use caution; monitor infant for irritability and changes in blood pressure. |
■ FDA Black Box Warning
Ketorolac: Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke; increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation. Phenylephrine: No black box warning.
| Common Effects | Skin peeling Application site reactions burning irritation itching and redness Nausea Vomiting Abdominal pain Increased liver enzymes Application site redness Itching Diarrhea Abnormal liver function tests Adrenal insufficiency Application site burning |
| Serious Effects |
Hypersensitivity to ketorolac, phenylephrine, or any component; patients with active bleeding or bleeding disorders; advanced renal disease; patients on anticoagulants (including low-dose heparin); history of asthma, urticaria, or allergic-type reactions after aspirin or other NSAIDs; patients with narrow-angle glaucoma (phenylephrine).
| Precautions | Bleeding risk (due to inhibition of platelet aggregation), ocular infection risk with topical use, delayed wound healing, hypersensitivity reactions, renal toxicity, hypertension, and rebound congestion with prolonged use. |
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| Teratogenic Risk |
| First trimester: Ketorolac, like other NSAIDs, is associated with increased risk of spontaneous abortion and cardiac defects. Avoid use. Second trimester: Use only if clearly needed; may cause oligohydramnios. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus and pulmonary hypertension in the neonate. Phenylephrine is a sympathomimetic; animal studies show fetal abnormalities at high doses, but human data are limited. Avoid in first trimester due to potential teratogenicity; in second and third trimesters, use only if benefit outweighs risk, as it may reduce uteroplacental blood flow. |
| Fetal Monitoring | Monitor maternal blood pressure and fetal heart rate during administration. Assess for signs of oligohydramnios with prolonged ketorolac use; perform ultrasound if indicated. Monitor neonatal status for ductus arteriosus patency if used near term. |
| Fertility Effects | Ketorolac may impair female fertility by inhibiting prostaglandin synthesis, affecting ovulation and implantation; reversible upon discontinuation. Phenylephrine effects on fertility are not well studied; high doses may impair spermatogenesis in animal models. |