Why can oral ketorolac not be used as the first dose?

[peebinrx]

I have been searching as part of a drug information response for the answer to this question. I cannot find any literature to explain this distinction for drug administration and the package insert does not have any more information. Does anyone know the reason and have a source to prove it?
Thank you

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[farmadiazepine]

No freakin idea. It seems so dumb and I wondered this myself. It must be one of those old pharmacy sayings which get passed down from generation to generation without any data to back it up. "Oral ketorolac is only for those who continue it after IV or IM therapy" and "Don't drink alcohol with metronidzole because you will have a violent reaction and throw up." All bullshi* to me.

Pharmacodynamics/Kinetics
Onset of action: Analgesic: Oral: 30-60 minutes; IM, IV: ~30 minutes
Peak effect: Analgesic: Oral: 2 to 3 hours; IM, IV: ≤2-3 hours
Duration: Analgesic: 4-6 hours
Absorption: Oral: Well absorbed (100%); IM: Rapid and complete
Distribution: Poor penetration into CSF; Vd beta:
Children 4-8 years: 0.19-0.44 L/kg (mean: 0.26 L/kg)
Adults: 0.11-0.33 L/kg (mean: 0.18 L/kg)
Protein binding: 99%
Metabolism: Hepatic; undergoes hydroxylation and glucuronide conjugation; in children 4-8 years, Vdss and plasma clearance were twice as high as adults
Bioavailability: Oral, IM: 100%
Half-life elimination:
Infants 6-18 months of age (n=25): S-enantiomer: 0.83 ± 0.7 hours; R-enantiomer: 4 ± 0.8 hours (Lynn 2007)
Children:
1-16 years (n=36): Mean: 3 ± 1.1 hours (Dsida 2002)
3-18 years (n=24): Mean: 3.8 ± 2.6 hours
4-8 years (n=10): Mean: ~6 hours; Range: 3.5-10 hours
Adults:
Mean: ~5 hours; Range: 2-9 hours [S-enantiomer ~2.5 hours (biologically active); R-enantiomer ~5 hours]; Prolonged 30% to 50% in elderly
With renal impairment: Scr 1.9-5 mg/dL: Mean: ~11 hours; Range: 4-19 hours
Renal dialysis patients: Mean: ~14 hours; Range: 8-40 hours
Time to peak, serum: Oral: ~45 minutes; IM: 30-60 minutes; IV: 1-3 minutes
Excretion: Urine (92%, ~60% as unchanged drug); feces ~6%

 

[Promethean]

Maybe because there are other, less expensive, less problematic oral NSAIDS available?

What on earth would be the indication for prescribing ketorolac as an oral agent over ibuprofen? If someone can't take ibuprofen, say because they are NPO, then you have ketorolac as a viable parenteral alternative. If that has worked well for them, then it might be reasonable to stick with it when they can take oral, rather than changing them to a different drug. But why would you ever reach for the more costly drug with greater risk of adverse effects, if there were no particular benefit, such as needing a particular route of admin?

I think that is all that is being conveyed in the admonition not to start oral ketorolac. The rationale isn't spelled out, but that has always been my understanding of it. If anyone else has more information about this, I'd certainly welcome it.

 

[farmadiazepine]

When I was in school I remember my med chem professor telling us ketorolac was so wonderful when it was first made because the analgesic effects were similar to that of morphine. It's a good drug.

 

[Promethean]

When I was in school I remember my med chem professor telling us ketorolac was so wonderful when it was first made because the analgesic effects were similar to that of morphine. It's a good drug.

It is a good analgesic. So is ibuprofen. There is a dose/route of most analgesics that can rival the analgesic effect of a given dose of morphine, so that isn't a really helpful statement. As always, dose and route help determine effect.

Any parenteral route is going to relieve pain faster than oral. Having a non-opiod parenteral analgesic to offer is indeed a wonderful thing! But that doesn't make it a better drug than ibuprofen. It is just that IV ibuprofen isn't a thing. Oral ketorolac is not a better analgesic than oral ibuprofen. They are very similar in onset and effect. Ketorolac just costs hundreds of times more per dose and has more adverse effects.

 

[Promethean]

There is IV ibuprofen. It exists.

Woah. Mind blown. Approved in 2009, I see, so my info is a touch out of date.

It sure wasn't available when I was a floor nurse, and we didn't have a lot of call to give it in the OR. Mea culpa.

Point still stands. Can anyone give a reason that oral ketorolac would be chosen over oral ibuprofen? With a cost of $3-5 per pill vs $0.03-0.05 per pill? The only reason I can see to choose it is if it has already been effective for pain and there were a desire to avoid switching to the cheaper agent. In actual clinical practice, I've never seen anyone continued on oral ketorolac. I've only seen it IV/IM while the patient is NPO, then when they can have oral, switch to ibuprofen.

 

[TheBlaah]

IV toradol is meant to act as a sort of loading dose. If not given the IV dose, the oral dosage alone may not control it as well which may lead to it being extended past 5 days, leading to adverse events.

 

[Promethean]

IV toradol is meant to act as a sort of loading dose. If not given the IV dose, the oral dosage alone may not control it as well which may lead to it being extended past 5 days, leading to adverse events.

Thank you for sharing this.

I notice that the reference for this explanation was "personal communication." I'm holding out hope that someone out there might have something more evidence based/official.

 

[zelman]

Thank you for sharing this.

I notice that the reference for this explanation was "personal communication." I'm holding out hope that someone out there might have something more evidence based/official.

Personal communication with the drug company is enough for me.

 

[rph3664]

When I was in school I remember my med chem professor telling us ketorolac was so wonderful when it was first made because the analgesic effects were similar to that of morphine. It's a good drug.

You are correct! Lots of people were taking it QID for chronic pain and didn't need opiates as a result.

Until they started developing gastritis and kidney failure; there was some talk about removing it from the market but that wasn't done when it was restricted to short-term use and those problems diminished. This was in the mid-1990s, shortly after I graduated.

 

[rph3664]

Woah. Mind blown. Approved in 2009, I see, so my info is a touch out of date.

It sure wasn't available when I was a floor nurse, and we didn't have a lot of call to give it in the OR. Mea culpa.

Point still stands. Can anyone give a reason that oral ketorolac would be chosen over oral ibuprofen? With a cost of $3-5 per pill vs $0.03-0.05 per pill? The only reason I can see to choose it is if it has already been effective for pain and there were a desire to avoid switching to the cheaper agent. In actual clinical practice, I've never seen anyone continued on oral ketorolac. I've only seen it IV/IM while the patient is NPO, then when they can have oral, switch to ibuprofen.

If ibuprofen isn't working and the doctor wants to avoid opiates, or minimize their use, and the patient hasn't passed that 5-day limit, they will sometimes order Toradol PO, and that includes outpatient use.

 

[njac]

When I was in school I remember my med chem professor telling us ketorolac was so wonderful when it was first made because the analgesic effects were similar to that of morphine. It's a good drug.

Slide from SMACC last year on pediatric pain

Sent from my iPhone using SDN mobile app

 

[peebinrx]

Thank you all for your replies! Using it as a loading dose to ensure shorter duration of therapy seems reasonable. However, it would be nice to see the trials it was studied in or a report from the group that decided to make this statement that is so pervasive. I have looked around a bit and have not seen much of anything. Also, the IM does not work any faster than the PO to control pain and their is only a slight increase in the concentrations so it doesn't seem much better than PO. Yet IM or IV can be given as the first dose.

 

[MatCauthon]

As an aside, I have seen patients that have prn 5-day oral courses of toradol for migraines, etc. I'm pretty sure they are not getting an injectable form before each of these courses.

 

[ancienbon]

I once received a script for toradol 10 po bid number 60 plus 5 refills for a patient.

 

[Promethean]

I once received a script for toradol 10 po bid number 60 plus 5 refills for a patient.

See? This (among so many other reasons) is why we need pharmacists. Thank you for not letting that patient be murdered by the prescriber.

 

[Eichhoernchen]

I once received a script for toradol 10 po bid number 60 plus 5 refills for a patient.

I had similar script, called to verify, turns out they meant to write Tramadol..

 

[radio frequency]

I had similar script, called to verify, turns out they meant to write Tramadol..

I got one for ketorolac alongside meloxicam from the same podiatrist. Called and it turned out he meant to write for Keflex...

 

[BidingMyTime]

I got one for ketorolac alongside meloxicam from the same podiatrist. Called and it turned out he meant to write for Keflex...

That is one scary error. Thank God for double checks.

 

[skeptic1]

Ketorolac and ibuprofen are not pharmacologic equivalent (dose for dose it is different) and therapeutically ketorolac is more potent. With the widespread narcotic abuse epidemic in the U.S.A., this drug should not have been limited by big pharma and insurance companies to IV or IM first dose. It is a very orally well absorb and effective medicine for moderate to severe pain that could have prevented a lot of clinicians from issuing narcotic analgesics. The problem is when it came out, clinicians did not study the medicine's profile and know the drug well before prescribing it. It was rx'ed wantonly and the effect of wanton prescription writing by clinicians who does not know the drug well led to adverse effects that the FDA and pharma indicated it for IM/IV use only for first dose in the hopes that clinicians will opt for the pricier IM/IV form (do you know why healthcare cost is skyrocketing) and not use the cheaper oral form first. If you study the drug's profile, it does not make sense. The problem is when a warning comes out, pharmacists get scared to in filling the prescription without even knowing its safety profile and the reason it got a warning. In the hands of a skilled and well-studied and diligent clinician, this is heaven-sent in preventing the narcotic abuse epidemic problem that is going on. This is also an argument for a good clinician-pharmacist relationship so that the pharmacist can be confident about the physician who is prescribing it and not worry that it will be abused. I have used it to treat refractory migraine when they do not respond to sumatriptan alone, chronic intermittent slip disc pain, trigeminal nerve zoster pain, etc...… Again, knowledgeable skilled clinicians know how to use the oral form, its nuances and can communicate well to patients on how to use it only on prn basis and not continuous >5-7 day RTC dosing (patient profile considered also in using this medication). In today's managed care setting with 5 minute visits, some clinicians may not be well served using this medicine but thoughtful good clinicians can!

For more info: see decisional summary on ketorolac by the FDA.

 

[CetiAlphaFive]

Ketorolac and ibuprofen are not pharmacologic equivalent (dose for dose it is different) and therapeutically ketorolac is more potent. With the widespread narcotic abuse epidemic in the U.S.A., this drug should not have been limited by big pharma and insurance companies to IV or IM first dose. It is a very orally well absorb and effective medicine for moderate to severe pain that could have prevented a lot of clinicians from issuing narcotic analgesics. The problem is when it came out, clinicians did not study the medicine's profile and know the drug well before prescribing it. It was rx'ed wantonly and the effect of wanton prescription writing by clinicians who does not know the drug well led to adverse effects that the FDA and pharma indicated it for IM/IV use only for first dose in the hopes that clinicians will opt for the pricier IM/IV form (do you know why healthcare cost is skyrocketing) and not use the cheaper oral form first. If you study the drug's profile, it does not make sense. The problem is when a warning comes out, pharmacists get scared to in filling the prescription without even knowing its safety profile and the reason it got a warning. In the hands of a skilled and well-studied and diligent clinician, this is heaven-sent in preventing the narcotic abuse epidemic problem that is going on. This is also an argument for a good clinician-pharmacist relationship so that the pharmacist can be confident about the physician who is prescribing it and not worry that it will be abused. I have used it to treat refractory migraine when they do not respond to sumatriptan alone, chronic intermittent slip disc pain, trigeminal nerve zoster pain, etc...… Again, knowledgeable skilled clinicians know how to use the oral form, its nuances and can communicate well to patients on how to use it only on prn basis and not continuous >5-7 day RTC dosing (patient profile considered also in using this medication). In today's managed care setting with 5 minute visits, some clinicians may not be well served using this medicine but thoughtful good clinicians can!

For more info: see decisional summary on ketorolac by the FDA.

Do FDA directives apply in your country?

 

[Aznfarmerboi]

Ketorolac is a good option to have especially for people who experience puritis or other intolerable effects of opioids.

I don't see any problems with it because it's side effects are easily limited with day limits and proper counseling.

Of course if it was used more, we will see more serious side effects of it... but opioids epidemic anyone?

 

[BidingMyTime]

There is a reason why ketorolac was taken off the market in many countries. Yes, there is a use for it, but it's rare and should be used sparingly due to its risk factors.

 

[sosoo]

why is ketorolac opth often prescribed for long term use with multiple refills when the manufacturer indicate it for 2 weeks?

 

[Dred Pirate]

There is IV ibuprofen. It exists.

but if I remember right it is a tiny dosage form used for PFO closure