23 Mar 2020 [Special Edition: March 2020] Pill splitting: Making the most of meds in a time of need
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click on the image to view pill splitting video
Clinical vignette
A 54 year-old mechanic with type 2 diabetes and hypertension had a myocardial infarction in 2015.
He currently takes ASA 81mg/d (over the counter) plus 6 generic prescription drugs dispensed monthly:
- atorvastatin 40mg/d
- ramipril 5mg/d
- empagliflozin 25mg/d
- escitalopram 10mg/d
- sildenafil 50mg 4 times/month
- duloxetine 90mg/d (60 mg + 30 mg)
He has been stable and working full-time but is concerned about potential drug shortages and costs, as he was just laid off. Hearing that splitting pills could save money, he bought a $3 pill-splitter. During a Telehealth appointment (or call to your pharmacy) you realize that some of his pills could be prescribed at twice the dose per pill, but then split. This could save your patient unnecessary trips to the pharmacy, and precious dollars during the COVID-19 pandemic. A pharmacist can also recommend this. In the EMPA-REG trial, empagliflozin 10mg/d performed similarly to 25mg/d.1 Dividing the 25mg pill to 12.5mg/d could halve the cost and extend supply. Duloxetine can’t be split. But since it didn’t help his back pain, you deprescribe by tapering his remaining supply.
Could tablet splitting help maintain drug supply during the pandemic?
The COVID-19 pandemic could affect pharmaceutical supplies, which were already subject to many shortages in Canada. Prudent prescribers, pharmacists and patients can help everyone get what they really need. This Letter covers basic information that may assist health professionals and the public to conserve medications wisely.
Twenty-five years ago, Therapeutics Letter #10 pointed out that we often prescribe larger doses than necessary to achieve intended pharmacological effects. We noted that larger ‘recipe’ doses increase the chance of adverse effects as well as cost.2 A 2018 study found that BC had Canada’s highest rates of cost-related nonadherence due to prescription drug costs3, a national problem that greater affordability could address.
The Cochrane Hypertension Group has shown that much of the blood pressure lowering effect of antihypertensive drugs occurs at the lower end of the approved dose ranges.4,5 This applies to most if not all drugs used for high blood pressure. Statins also achieve most of their cholesterol lowering effect at the bottom end of their dose ranges. This is also generally true for analgesics, including acetaminophen, NSAIDs, opioids, gabapentin/pregabalin, duloxetine and tricyclics.6 Studies of antidepressants, antipsychotics, anxiolytics, sedatives, and many inhalers (including corticosteroids) show similar patterns.7,8 Official product monographs available by internet search often confirm that high doses are not superior to “low” doses.
For most preventive drugs we have no evidence about dose-response. Therapeutics Letter #87 concluded in 2013 that high dose statins are not clinically superior to lower doses.9 This has also been shown often for ASA (aspirin).
Pill splitting is one way to stretch prescriptions. This approach has been used to adjust doses for children, elderly or people with low body weight, and recommended previously both for safety and cost savings.10 Even rich societies with little previous incentive for cost containment may soon find this strategy appealing, if not compelling. People who check their own blood pressure or capillary glucose may be able to adjust some drugs to the intended targets (surrogate outcomes).
Dividing capsules is much harder. While many can be subdivided by a careful patient, this is not discussed here.
Advantages of pill splitting
- reduce shortages by extending patients’ medication supply;
- minimize trips to the pharmacy for refills, facilitating social distancing;
- save money for patients and payers;
- improve medication adherence for people with financial barriers.
When not to split pills
- narrow therapeutic index, e.g. warfarin;
- full dose essential, e.g. anticoagulants, chemotherapy drugs, birth control pills, anti-seizure medications for epilepsy, corticosteroids for adrenal insufficiency or steroid-dependent patients;
- antibiotics and antivirals, unless advised by a professional;
- biologicals, for which we have little dose-response evidence;
- fragile pills that crumble easily.
When in doubt, patients should consult the prescriber or pharmacist.
Modified release tablets
Manufacturers and pharmacists typically warn against splitting enteric-coated or timed-release drugs (ER/CR/CD/SR/LA, etc). This may be overly conservative. For example, the TI has found no scientific reason why splitting a proton pump inhibitor (PPI) will prevent it from suppressing stomach acid. Swallowing a fragment with a full glass of water assists absorption. Timed-release drugs often have a relatively wide intrinsic range of peak concentration (Cmax) and time to peak (Tmax). If a sudden peak could cause profound sedation, low blood pressure, or respiratory depression, splitting the dose may not be safe. Drugs intended for delivery to the large bowel such as 5’ASA (Asacol) or controlled release l-DOPA (Sinemet CR) typically should not be split.
Pill splitting is not for everyone
Pill-splitting may be inappropriate for people with unstable, complicated or dangerous conditions. The most responsible prescriber(s) should determine safety of any possible changes. For people with serious psychiatric conditions, a prescriber who knows the patient should be consulted.
What is the evidence on the benefits and safety of pill splitting?
BC’s modest pill splitting record could easily be improved. In 2006, splitting only 2.6% of statin prescriptions saved an estimated $2.3 million. People with low incomes and women tended to take advantage of this strategy.11
A 2012 review of tablet splitting studies (statins, antihypertensives and one antipsychotic) suggested that cost savings can be achieved without adverse clinical outcomes.12
A 2015 CADTH review assessed clinical and cost effectiveness and found one guideline, from the Liverpool Children’s Hospital.13 For hospitalized patients, this recommended using a pill-splitter along the tablet scoreline, and not < ¼ segments.
Can a “drug holiday” or deprescribing be considered?
At any careful medication review, it is worth considering a “drug holiday” (temporary deprescribing) or permanent deprescribing.
Writing the prescription
Communicate clearly and unambiguously. Partial example for case vignette:
- Atorvastatin 80mg tablets. Dispense 45 to last 90d. Take ½ = 40mg daily for secondary prevention of IHD.
- Empagliflozin 25mg tablets. Dispense 45 to last 90d. Take ½ = 12.5mg daily to prevent complications of type 2 diabetes.
- Escitalopram 20mg tablets. Dispense 45 to last 90d. Take ½ = 10mg daily for depression.
- STOP duloxetine (patient will taper his remaining supply).
Conclusions
- Consider deprescribing. Does this patient really need this medication? Could one try stopping it?
- Consider pill splitting to stretch prescriptions and save money. This may assist social distancing or quarantine, and extend drug supplies. Halving the dose can work well for many indications. Splitting a larger pill can maintain dose at lower cost.
- Some drugs, e.g. anticoagulants (“blood thinners”) should not be split.
- Patients considering this strategy should talk with their prescriber or dispensing pharmacist, if possible.
Table: Potential savings from Rx pill splitting (vignette)
Some branded drugs cost much more (e.g. Lipitor, Altace, Cipralex)
BC prices based on BC PharmaCare Low Cost Alternative Program, 1 March 2020
Total possible savings from splitting five pills and deprescribing one drug: ≈ $1300
(Substituting generic for brand name drugs could save more)
** maximum reimbursed by BC PharmaCare; pharmacies may charge more.
References
- Therapeutics Initiative. EMPA-REG OUTCOME Trial: What does it mean? Therapeutics Letter. July-August 2017. 107:1-2. https://ti.ubc.ca/letter107
- Therapeutics Initiative. Dose titration: Minimize to maximise. Therapeutics Letter. October 1995. 10:1-2. https://ti.ubc.ca/letter10
- Law MR, Cheng L, Kolhatkar A, et al. The consequences of patient charges for prescription drigs in Canada: a cross-sectional survey. CMAJ Open. 2018. 6(1):E63-E70. DOI: 10.9778/cmajo.20180008
- Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database of Systematic Reviews. 2014. Issue 5. Art. No.: CD003824. DOI: 10.1002/14651858.CD003824.pub2
- Heran BS, Wong MMY, Hera IK, Wright JM. Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database of Systematic Reviews. 2008. Issue 4. Art. No.: CD003823. DOI: 10.1002/14651858.CD003823.pub2
- Therapeutics Initiative. Gabapentin and pregabalin: Are high doses justified? Therapeutics Letter. January 2019. 117:1-2. https://ti.ubc.ca/letter117
- Adams NP, Bestall JC, Jones P, et al. Fluticasone at different doses for chronic asthma in adults and children. Cochrane Database of Systematic Reviews. 2008. Issue 4. Art. No.: CD003534. DOI: 10.1002/14651858.CD003534.pub3
- Li C, Xia J, Wang J. Risperidone dose for schizophrenia. Cochrane Database of Systematic Reviews. 2009. Issue 4. Art. No.: CD007474. DOI: 10.1002/14651858.CD007474.pub2
- Therapeutics Initiative. High dose versus standard dose statins in stable coronary heart disease. Therapeutics Letter. July-August 2012. 87:1-2. https://ti.ubc.ca/letter87
- McCormack JP, Allan GM, Virani AS. Is bigger better? An argument for very low starting doses. CMAJ. Jan 2011. 183(1):65-69. DOI: 10.1503/cmaj.091481
- Dormuth CR, Schneeweiss S, Brookhart AM, et al. Frequency and predictors of tablet splitting in statin prescriptions: a population-based analysis. Open Med. 2008. 2(3):e74–e82. https://www.ncbi.nlm.nih.gov/pubmed/21602952
- Freeman MK, White W, Iranikhan M. Tablet splitting: a review of the clinical and economic outcomes and patient acceptance. Consult Pharm. 2012. 27:239-53. DOI: 10.4140/TCP.n.2012.421
- Canadian Agency for Drugs and Technologies in Health. Pill splitting: A review of clinical effectiveness, cost-effectiveness, and guidelines. Rapid Response Report. June 2015. https://cadth.ca/sites/default/files/pdf/htis/june-2015/RC0663%20Pill%20Splitting%20Final.pdf
ET
Posted at 11:53h, 24 MarchPill splitting is routine in the US Veterans Affairs system. If I start a patient on sertraline 25mg, the computer will force a Rx for ½ of a 50mg tablet. If, after 2 weeks, I want to change the order to 50mg/day, the computer changes it to ½ of a 100mg tablet.
Academic psychiatrist, US Veterans Affairs system, USA
(no conflict of interest)
Cristi Froyman
Posted at 13:41h, 27 MarchThank you to the TI for a very practical post! One note to readers, in the table, ramipril 10 mg is used as an example. In Canada, it is only available as a capsule, so more difficult to split. Most Pharmacies do sell capsules, so a person could split the powder into 2 I suppose and put it in an empty capsule…but then you have to add the cost of the capsules to that.
Tom Perry
Posted at 16:44h, 27 MarchThank you for your comment.
A similar comment received today from Nancy Dyck (also a BC Provincial Academic Detailing pharmacist) pointed out that ramipril is not available in Canada as tablets. Tablets are licensed and the product monographs are available online. We apologize for this error. Apparently suppliers do not make it available to pharmacies.
Ramipril is commonly dispensed in Canada as a capsule, which is relatively difficult to split. In the case vignette, the cost saving would be insignificant. In case of a drug shortage, ACE-inhibitors are generally interchangeable, and many available in tablet form can easily be split. The video demonstration uses perindopril 8 mg as an example.
Dr. Thomas L Perry jr MD, FRCPC
Chair, Education Working Group
Editor in Chief, Therapeutics Letter
UBC Therapeutics Initiative
Dr. A.K. Tandon
Posted at 15:24h, 04 AprilIdea is good but just as a curiosity will the half dose by splitting the pill (reduced dose of medicine) be effective and keep the disease under control? Particularly hypertension and diabetes?
Dr. A.K. Tandon
General Physician, Apollo Hospitals, Delhi
[no conflict of interest]
Tom Perry
Posted at 15:29h, 04 AprilThank you very much for your inquiry. Often, with the exception of certain drugs exemplified in this Special Edition Therapeutics Letter, it probably makes relatively little difference most of the time. If shortages arise now or in future, and we have only enough antihypertensive drugs to treat half of people with high BP, it would make much more sense to share the resource. We know from dose finding studies that the average difference in achieved blood pressure from any one antihypertensive drug is usually quite modest (e.g. 4-10mm Hg systolic blood pressure reduction). In some conditions like malignant hypertension or hyperaldosteronism, or serious kidney disease, drug effects may be much more obvious, but we know little about dose-response from experiments.
Similarly, in Type 2 diabetes the hypoglycemic effects of standard drugs like metformin are not proportionate to dose (and the desired clinical effects remain controversial). With some drugs, such as SGLT-2 inhibitors, large clinical trials like EMPA-REG outcome showed little difference between the lower and the higher drug doses.
This is clearly true of statins dose and LDL-C reduction, something proven over and over for each licensed statin drug. This is easy to confirm. For example, the Canadian product monograph for rosuvastatin, the most potent statin, shows that the large majority of the effect is attained at 1/8 of the maximum approved dose (5mg/d vs. 40mg/d). (reference: https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/crestor-product-monograph-en.pdf at p. 29-30/47). Muscle toxicity (myopathy) is relatively clearly dose-related. Comparative studies of dose-response for clinically important outcomes such as death, stroke, or ischemic heart disease have not shown convincingly that higher doses achieve better results.
Literally billions of dollars could be saved by pill splitting strategies when appropriate, and it looks as if one gets the most of the effect out of lower doses of drugs like SGLT-2 inhibitors.
Dr. Thomas L Perry jr MD, FRCPC
Chair, Education Working Group
Editor in Chief, Therapeutics Letter
UBC Therapeutics Initiative
Giorgio Karam
Posted at 18:27h, 05 AprilThis is a timely article that hopefully will help the many Canadians struggling with medication costs right now. Some comments:
(1) “the TI has found no scientific reason why splitting a proton pump inhibitor (PPI) will prevent it from suppressing stomach acid.” The rationale for the enteric coating on PPIs is that PPIs are activated by acid. Normally, they are absorbed into the bloodstream and from there return to the canaliculus of the parietal cell. In this highly acidic environment, they are activated and form a disulfide bond with the proton pump, inhibiting it. If they were to be activated upon ingestion, they might form irreversible disulfide bonds indiscriminately with cysteine residues on proteins throughout the stomach (Roche VF. The chemically elegant proton pump inhibitors. Am J Pharm Educ. 2006 Oct 15;70(5):101.).
(2) One must be careful of avoiding type II error when claiming that there are no differences between lower and higher doses of medications. The difference in magnitude of effect will be smaller when comparing low and high doses, so most studies will be underpowered (they would probably require at least double the sample size as studies comparing drug vs. placebo). To illustrate, the cited Therapeutics Letter on statins claims there is no mortality benefit of high dose statins because the RR = 0.99 (0.93 to 1.06). However, given that the RR of mortality with statin vs. no statin is 0.90, this confidence interval is consistent with the expected smaller but still real mortality benefit of high-dose vs. low-dose statins. And there is every reason to believe higher doses of statins decrease mortality, albeit to a small degree, since doubling statin dose decreases LDL concentrations by an additional 6 percentage points and LDL concentration is causal in atherosclerotic events.
Tom Perry
Posted at 20:26h, 13 April(1) Thank you for this very interesting comment and reference. Like most other drugs, proton pump inhibitors are absorbed primarily from the small intestine. At intestinal pH, they are not ionized, but absorbed and transported to parietal cells through the systemic circulation. Studies conducted by AstraZeneca on pharmacokinetics of omeprazole and esomeprazole administered the drugs by mouth as aqueous solution, as granules, and as whole coated tablets. In at least some studies (possibly all), dissolved omeprazole/esomeprazole was preceded and followed by bicarbonate solution as a buffer to protect the drug from acid hydrolysis. No measurements of stomach pH were undertaken in these studies to demonstrate to what extent bicarbonate raised stomach pH. (Andersson T et al. Pharmacokinetic Studies with Esomeprazole, the (S)-Isomer of Omeprazole. Clin Pharmacokinet 2001; 40: 411-26; Andersson T et al. Pharmacokinetics of Orally Administered Omeprazole in Children. Am J Gastroenterology 2000; 95: 3101-6). TI could not determine whether AstraZeneca established whether an aqueous solution of PPI is absorbed adequately even if unaccompanied by buffer. A laboratory capable of measuring PPIs in plasma could clarify this issue definitively by administering an aqueous solution with or without buffer, or tablets split and intact. In regular practice, ingesting an intact dose of PPI (or intact granules, of which such tablets are composed), powerfully suppresses stomach acid secretion for as long as 24 hours. Thus, one could expect a large fraction of unprotected PPI to pass through the stomach of a person in whom acid secretion is already suppressed.
(2) It is possible that higher dose statins reduce total mortality compared with lower doses. If so, this is likely to be a very small absolute risk reduction, given that the absolute reduction for non-fatal myocardial infarction was about 1.2% over 4.8-6.7 years in secondary prevention of ischemic heart disease. The Cholesterol Treatment Trialists meta-analysis of individual patient data did not claim a difference in total mortality between high and low dose statin groups in RCTs. (Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet 2010; DOI:10.1016/S0140-6736(10)61350-5).
We welcome additional comments from readers with knowledge of any effects of tablet splitting on PPI absorption and efficacy/effectiveness, especially if referenced.
Dr. Thomas L Perry jr MD, FRCPC
Chair, Education Working Group
Editor in Chief, Therapeutics Letter
UBC Therapeutics Initiative
Carl Stovel
Posted at 11:11h, 06 AprilI am a retired psychiatrist in Victoria, BC. During my thoroughly enjoyable career from 1974-2012, I had the privilege to participate in the lives of >8000 mentally ill (depression and bipolar illness) patients and their families. Most of these folks did well on various antidepressants, mainly sertraline (Zoloft) and venlafaxine (Effexor-XR) or mood stabilizers such as lithium, valproate (Epival), carbamazepine (Tegretol) and lamotrigine (Lamictal), and NEVER on the dangerous atypical antipsychotics.
I would estimate that half of the patients who were prescribed venlafaxine (Effexor) were capable of stopping their medication precipitously/cold turkey. Of course, I always recommended a gradual reduction in any medication while monitoring return of illness symptoms and withdrawal symptoms. There was always a small cohort of patients who had extreme withdrawal effects. They were all successfully weaned of venlafaxine (Effexor) either by tapering more slowly by opening the 37.5 mg capsules and tapering the individual pellets, or adding long acting fluoxetine (Prozac) as the lower doses of venlafaxine (Effexor) 37.5-75 mg are reached. The fluoxetine (Prozac) essentially tapers itself.
On a side note, I never ever prescribed paroxetine (Paxil) for a variety of compelling reasons.
Carl Stovel MD, FRCPC
Retired Psychiatrist
Victoria, BC, Canada
[No conflict of interest]
Steve Larigakis
Posted at 23:31h, 13 AprilHow do I write a prescription so that my patient has a chance to receive a larger number of doses, if the patient is willing to split tablets? If my prescription is intended as a longer duration, I don’t want the dispensing pharmacist to adjust it by reducing the number of pills to split.
Steve Larigakis MD, Surrey, BC
[No conflict of interest]
Tom Perry
Posted at 23:35h, 13 AprilHere is how I might write a prescription for atorvastatin 40mg/d, intended to last for 3 months or 100 days, which is typically the longest dispensing for which PharmaCare will reimburse. I also try to practice “indication-based prescribing”, showing the purpose as part of the label.
Patient name, Date
We will consider posting other responses, especially from dispensing pharmacists or prescribers who have sorted out how to write pill-splitting prescriptions using an EMR.
Dr. Thomas L Perry jr MD, FRCPC
Chair, Education Working Group
Editor in Chief, Therapeutics Letter
UBC Therapeutics Initiative
Gloria Chu
Posted at 10:26h, 14 AprilAdding the words “Patient will split at home, take 1/2 tablet = 40mg daily. To last 90 days” is really helpful to clearly indicate to a dispensing pharmacy that higher strength tablets are requested and will be split by the patient. This can save time and confusion in case of a language barrier or if someone else drops off the Rx who is not aware of the conversation between patient and prescriber.
If an Rx is faxed in as “atorvastatin 80mg 0.5 tab po od for 3 months” but the patient’s profile shows previous dispensing has always been for atorvastatin 40mg once daily, the pharmacy may default automatically to exactly what was dispensed previously. The dispensing pharmacist may assume patient preference not to split. Therefore, specifying the need “to split tablets” would be a great way to prevent lapses in communication.
As for the 30-day supply, there is a Canadian Pharmacists Association recommendation for such a limit during the Covid-19 pandemic to mitigate impact of actual or potential drug shortages (https://www.pharmacists.ca/news-events/news/covid-19-and-the-responsible-allocation-of-medications-to-patients/). Most pharmacies have adopted this practice, but it is only a recommendation, not a rule. The recommendation and states “unless clinically justified” so pharmacies and pharmacists can make decisions to dispense longer – up to 100 days’ supply in BC as per PharmaCare reimbursement policy.
If a patient lives far away, is high risk and should stay home as much as possible, or has low income so more frequent dispensing fees could cause significantly more burden, the pharmacist has discretion to accommodate.
Note that some drugs were already shorted before the pandemic (which can depend on the individual pharmacy’s prescription volume and wholesale suppliers as shortages do vary).
So to summarize:
(1) Include as much detail on Rx as possible, including the instruction “split tablets to = x mg” to indicate the need to split, and the desired tablet strength and quantity to be dispensed;
(2) Although a > 30-day supply cannot be guaranteed now, many pharmacies and pharmacists will still make the decision to dispense longer for patients who require this, depending on their inventory and supplier status.
Gloria Chu, dispensing pharmacist, BC
[No conflict of interest]
Wendy Jansen
Posted at 20:38h, 29 AprilGreat article on cost savings, however you totally missed the point on : “reduce shortages by extending patients’ medication supply; minimize trips to the pharmacy for refills, facilitating social distancing.” I agree that it *may* help reduce drug shortages overall in the population (as patients only need half of the quantity, hence the supply can be stretched further over more people), however pill splitting has absolutely nothing to do with extending patients medication supply or minimizing trips to the pharmacy for refills, …” The only way to extend medication supply is to encourage patients to take half of their dose (are we encouraging them to not follow their doctors orders), and absolutely nothing to do with minimizing trips to the pharmacy, as for example a 3 month supply is a three months supply, regardless if it’s 90 tabs of single dose tablets at one a day or 45 tabs of a double dosed medication at half a tablet a day.
Also it’s fine to state that “…much of the blood pressure lowering effect of antihypertensive drugs occurs at the lower end of the approved dose ranges.. … Statins also achieve most of their cholesterol lowering effect at the bottom end of their dose ranges. … generally true for analgesics, including acetaminophen, NSAIDs, opioids, gabapentin/pregabalin, duloxetine and tricyclics. … antidepressants, antipsychotics, anxiolytics, sedatives, and many inhalers (including corticosteroids) show similar patterns” however this is something that needs to be addressed at the prescribing level, and not by encouraging patients to just take half of their prescribed dose, which may be very detrimental to their health, as maybe they needed the additional benefit (even if it’s small) of the larger dose prescribed to them.
Pill splitting does not extend a patients supply or reduce the number of visits to the pharmacy. All prescriptions are written as dose, directions, and quantity, again unless you are suggesting patients take half of their dose there is no way to extend the supply because the pharmacist will cut the quantity in half, if they double the strength. For example: Rx is written for Atorvastatin 10mg OD x 90 days. Patient requests 20mg tablets, which is fine, but the pharmacist still needs to follow the prescription so it gets dispensed as Atorvastatin 20mg “Take 1/2 tablet (=10mg) once daily” and they only get 45 tablets now as that is a 90 day supply as prescribed … either way they must visit the pharmacy every 90 days!
In short, the only thing that pill splitting *may* accomplish is a more stable drug supply for the population as a whole (as less tablets are needed per person) and potential cost savings. Any attempt to say that by splitting medication you are extending patients supply and reducing the number of visits is totally incorrect, the only way to do that is by ignoring the prescriber’s orders and taking half of your prescribed dose, which is a totally different conversation.
Similar response crossed posed under the video, explaining how to split a pill as it also has the same incorrect information associated with it.
Alan Cassels @ TI
Posted at 16:12h, 07 AugustWendy: You may have, perhaps, misinterpreted our letter on pill splitting. You wrote: “Pill splitting does not extend a patients supply or reduce the number of visits to the pharmacy. All prescriptions are written as dose, directions, and quantity…”
Our letter is written with doctors and pharmacists in mind, and we are saying that any prescriber could provide a patient with a medication in double its dose size and then instruct them to split the pills taking half a pill per day. Clear instructions from the prescriber is obviously important if he/she wishes to reduce the number of trips the patient has to make to the pharmacy.
Adrian MacLaren
Posted at 11:15h, 02 FebruaryIn Jardiance’s product monograph it says that the pill should not be divided or cut. How did you come to the conclusion to recommend differently from the product monograph. Do you have any references?
Thanks,
Adrian MacLaren RPh (Victoria, BC)
Conflict of interest declaration: nothing to declare.
Cait O'Sullivan
Posted at 08:56h, 18 FebruaryYes in clinical practice we have always been comfortable tablet splitting when:
a) it is not a narrow therapeutic window drug,
b) splitting the tablet achieves an equally effective dose,
c) the tablet has no delayed/modified release characteristics,
d) tablet splitting results in a relevant and meaningful benefit for the patient (ie, large cost saving or achieves a lower dose that is as effective and better tolerated).
Another common example is chlorthalidone which is commonly quartered to achieve 12.5 mg (almost no cost saving but it achieves an effective & better tolerated dose).
In the EMPA REG OUTCOME trial for empagliflozin, the HRs for the primary outcome (major adverse CV events) were similar between doses: 10mg/d: 0.85, 95%CI 0.72 to 1.02 and 25mg/d: 0.86, 95%CI 0.73 to 1.02.
Cait O’Sullivan, PharmD, member of the Education Working Group, UBC Therapeutics Initiative
Conflict of interest declaration: nothing to declare
Tom Perry
Posted at 09:10h, 18 FebruaryThe manufacturer may not be able to ensure that the drug is distributed equally within the tablet. However, because large RCTs have shown no clear difference between 10mg/d and 25mg/d for important outcomes, we think that small differences in the empagliflozin content of 1/2 tablet fragments should not be clinically important. Also, the mean elimination half-life of empagliflozin of about 12 h and its pharmacodynamics suggest that small variations in absorbed dose may not be clinically important. This would be less important, or course, than missing the occasional dose. With impaired kidney function, a longer elimination half-life may make this even less relevant. The potential savings to patient and society outweigh any minor differences in absorbed dose or plasma concentrations.
Tom Perry MD, FRCPC, Chair of the Education Working Group, UBC Therapeutics Initiative
Conflict of interest declaration: nothing to declare.
References:
Boehringer Ingelheim (Canada) Ltd. Product monograph: Jardiance (empagliflozin) tablets 10 mg and 25 mg, ATC Code: A10BK03, Sodium-glucose co-transporter 2 (SGLT2) inhibitors. April 15, 2020. https://www.boehringer-ingelheim.ca/sites/ca/files/documents/jardiancepmen.pdf
Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet 2014; 53:213-25. DOI: 10.1007/s40262-013-0126-x
Sasha Smith
Posted at 03:30h, 17 AugustIn the case of Jardiance (empagliflozin) the oval pills are not so easy to split with a standard pill cutter. You’ll rarely ever cut it exactly, unlike a round shape such as the 10 mg tablet. I spoke to my pharmacist, who tries to “best” align the blade when splitting pills. But oval pills will always split unequally. A few pill cutters available online have silicone moulds in the shape of various pill sizes and styles. Online reviews are mixed.
–
Sasha (a patient using empagliflozin in British Columbia who declares no conflict)
Tom Perry
Posted at 09:31h, 21 AugustThank you for this comment. Because the dose-response curve for empagliflozin and similar drugs is not very “steep,” it should make no clinical difference if the tablets are not split exactly in half. Also, a slightly lower dose one day will be balanced by a slightly higher dose the next day. The elimination half-life of empagliflozin averages about 12 hours, and urinary glucose excretion at 10mg/day was about 82% of that resulting from 25mg/day.(1) Clinical results were similar at either dose.
Dr. Thomas L Perry jr MD, FRCPC
Chair, Education Working Group
Editor in Chief, Therapeutics Letter
UBC Therapeutics Initiative
Reference:
1. Jardiance (empagliflozin) product monograph 2020. https://pdf.hres.ca/dpd_pm/00063412.PDF (accessed August 17, 2023).
Trudy Huyghebaert
Posted at 12:23h, 23 FebruaryThis is a great review of a number of cost-effective options to help patients manage their chronic conditions as well as great strategies to help mitigate the impacts drug shortages.
Tablet splitting may also have beneficial environmental impacts in terms of reducing the number of tablets as well as reducing wastage by utilizing current supply when decreasing doses (or increasing doses).
And lastly, I think there are many situations where patients may be over-treated for their chronic conditions and a dose reduction (reducing to 1/2 tablet or 1/2 dose) may result in reduced costs for the patient and healthcare system with minimal changes for their clinical outcomes. As mentioned in the article, we know the largest impact of the dosing range is at the first few dose increments.
We recently published a commentary on managing drug shortages in primary care that follows many of the principles listed in this article: CFP: How to navigate drug shortages with patients in primary care
Trudy Huyghebaert, PharmD ACPR CDE
Primary care pharmacist with the Department of Family Medicine at the University of Calgary in the Cumming School of Medicine and with Alberta Health Services in Calgary
—
No conflicts of interest to declare.