Rectal Drug Administration at End of Life - OnePoint Patient Care

Rectal Drug Administration at End of Life

The oral route is by far the most popular and convenient means of drug administration, even in the hospice setting. However, for various reasons (e.g., dysphagia, nausea / vomiting, bowel obstruction, obtundation) as many as 70% of hospice patients will need their medications to be administered by non-oral routes.a-c

Rectal drug administration is probably done more so in hospice than in any other setting. To ensure safe and effective symptom management with rectal administration, follow the five steps outlined below.

Step 1: Determine whether or not your patient is a candidate

Rectal drug administration is not recommended in patients with diarrhea, significant constipation, or anorectal disease.d Patients with neutropenia or thrombocytopenia are potentially at increased risk for infection or bleeding, respectively, with rectal drug administration, so some experts avoid it in these cases, though this is not necessarily an evidence-based practice.d Lastly, despite reported high tolerability, not all patients or caregivers will agree to it due to perceived invasiveness / awkwardness.d

Step 2: Review your patient’s list of medications and determine which ones are suitable

First things first, take this as another opportunity to deprescribe any unnecessary medications… just because you can continue medications by switching to rectal administration, doesn’t always mean you should. Loss of swallow is a very valid reason to consider deprescribing, especially when it’s expected to precede the active dying process.

Rectal absorption of drugs can be highly variable and is influenced by individual drug properties (e.g., lipophilicity, pH, pKa), excipient properties, dosage form (e.g., tablet, suppository, liquid), and individual patient characteristics (e.g., hydration status). Clinical evidence is sometimes available for individual medications to support or refute their suitability for rectal administration (see Table 1).

Some drugs have what’s called a narrow therapeutic index. For these drugs, even small changes in serum drug concentrations can often lead to serious treatment failure or drug toxicity. Due to the significant potential for altered levels when converting to rectal dosing, many of these drugs (e.g., lithium, warfarin) are probably poor candidates unless clinical studies exist to guide dosing.

Table 1: Summary of Literature on Rectal Drug Administration

Acetaminophen1-4Suppositories commercially available
Supp, susp: PR bioavailability similar to PO
Amitriptyline5Supp: case report of multi-symptom improvement
Aspirin1,2,6Suppositories commercially available
PR bioavailability of aqueous microenema > supp
PR bioavailability (relative to oral)
Supp (various bases used): 12-90% (mean 54%)
Baclofen7,8Susp: no drug detected
Tab: detectable serum levels, successful treatment reported in 1 of 2 patients
Bumetanide9Supp: observable diuretic effects
PR bioavailability (relative to oral)

Supp: 10-62% (dependent on suppository base)
Carbamazepine1,10-13Susp: PR bioavailability similar to PO
Tab (crushed, in gelatin capsule): therapeutic levels achieved in 5 of 6 patients
Chlorpromazine1,14,15Commercially available suppositories discontinued, but not due to safety or efficacy concerns
Supp: effectively managed symptoms in patients @ EOL
Clonazepam1Therepeutic serum levels and effective seizure control reported
Codeine1OPPC does not recommend
Soln: PR absorption reported
Dependence on hepatic metabolism to active metabolite (morphine) likely a disadvantage; first-pass metabolism limited when given PR
Dexamethasone1Use is anecdotal
Diazepam1,2,16,17Gel, soln: PR bioavailability similar to PO
OPPC does not recommend using suppositories for acute seizure treatment due to erratic and low plasma concentrations
Diclofenac1,2,18Suppositories commercially available in Canada
PR bioavailability (relative to oral enteric-coated tablet)
Supp (as diclofenac sodium): 55%
Diphenhydramine1Use is anecdotal
Doxepin13Therapeutic serum levels achieved with capsules in 3 out of 4 patients
Eslicarbazepine19OPPC does not recommend
Poor PR absorption; possibly extrapolated from oxcarbazepine data since both drugs share the same active metabolite
Fluoxetine20,21OPPC does not recommend
Improved mood reported after PR administration, but therapeutic serum levels not attained
Cap: PR bioavailability significantly reduced
Furosemide22Supp: diuretic effects similar to those expected from tablets
Gabapentin23OPPC does not recommend
Soln: PR bioavailability significantly reduced
Haloperidol24Use is anecdotal
Hydromorphone1,2,25,26Suppositories comercially available
PO to PR conversion: increased PR doses and longer dosing intervals have been suggested
PR bioavailability (relative to oral)
Supp: reduced
Ibuprofen4,27Soln, supp: PR bioavailability similar to PO
Imipramine28Supp: serum levels similar to PO
Indomethacin1,2,29Suppositories commercially available
Soln, supp: PR bioavailability similar to PO
Ketamine2,30-32PR bioavailability (relative to oral)
Supp: ~100-150%; dose reduction may be necessary
Ketoprofen1,2,33Suppositories commercially available in Canada
Supp: PR bioavailability similar to PO
Lamotrigine1,34,35PR bioavailability (relative to oral)
Tab: 63% +/- 33%; ODT: 52% +/- 23%
Suggested PO:PR conversion ratio is 1:1-1.5
Levetiracetam36-39Supp: PR bioavailability similar to PO
Susp: PR plasma concentrations ~50% lower vs. PO
Tab: absorption confirmed in 4 patients
Suggested PO:PR conversion ratios are 1:1 (supp) and 1:2 (susp)
Levodopa40-42OPPC does not recommend
Minimal drug detected in serum; levodopa relies on amino transport system in small intestine for adequate absorption
Levothyroxine43-46Suggested PO:PR conversion ratio is 1:1.4-1.8
Lorazepam1,47-49PR bioavailability (relative to oral)
Soln: variable; ~50-120% (mean 86%)
Methadone1,50-52PR bioavailability (relative to oral)
Soln: similar (80-90%), Supp: 35-58%
Metoclopramide1,53-55Supp: PR bioavailability variable (30-105%), dose-dependent
Metronidazole1,56-58Supp, susp: PR bioavailability similar to PO
Midazolam1,2,59-61Soln: PR bioavailability similar to PO
Morphine1,2,62,63Suppositories commercially available
PR bioavailability generally accepted to be similar to oral
Dose reductions necessary in 11 of 39 of patients who receieved ER tablets PR
Naproxen1,64Soln, supp: PR bioavailability similar to PO; reduced if doses >500mg
Olanzapine65Supp: effective for treating delirium and nausea/vomiting in terminally ill patients
Ondansetron1,66,67Soln: PR bioavailability similar to PO
Supp: PR bioavailability ~50% lower than PO, but equivalent efficacy when dosed similar to PO
Oxcarbazepine19,68OPPC does not recommend
Susp: PR bioavailability significantly reduced
Oxybutynin1,2,69Supp: symptom improvement reported in 48% of patients
Reduced formation of active metabolite may result in less anticholinergic activity; first-pass metabolism limited when given PR
Oxycodone1,2,70,71Suppositories comercially available in Canada
Soln: effective for analgesia
Supp: PR bioavailability similar to PO
Do not administer ER tab PR; increased risk of adverse events due to higher PR absorption
Phenobarbital1,72-76Soln: PR bioavailability (90%) similar to PO
Supp: PR bioavailability reduced (40-74%)
Not recommended for acute seizure treatment due to slower absorption; more significant delay with suppository (vs. solution)
Suggested PO:PR conversion ratios are 1:1 (soln) and 1:2 (supp)
Phenytoin1,77,78OPPC does not recommend
Soln, supp: PR absorption is unreliable
Prednisone2,79OPPC does not recommend
Supp (prednisone): drug detected in urine; PR dose evaluated was significantly higher than typical therapeutic PO doses
Prednisone's dependence on hepatic metabolism to active form (prednisolone) likely a disadvantage; first-pass metabolism limited when given PR
Prochlorperazine1,2Suppositories commercially available; given at higher dose / longer dosing interval vs. PO forms
Dosing for nausea/vomiting
PO: 5-10mg Q6-8 hours; PR: 25mg Q12 hours
Promethazine1,2,80-83Suppositories commercially available
Soln, supp: PR bioavailability similar to PO
Propranolol84-85PR bioavailability at least 2x higher vs. PO after single doses due to first-pass metabolism avoidance; actual extent/significance of difference is unclear after multiple doses (increased bioavailability observed)
Quetiapine86PR bioavailability (relative to oral)
Supp: 189% (single-dose crossover study)
Topiramate87-89Susp: PR bioavailability similar to PO
Suggested PO:PR conversion ratio is 1:1
Tramadol1OPPC does not recommend
Supp: PR bioavailability similar to PO
Dependence on hepatic metabolism to active metabolite likely a disadvantage; first-pass metabolism limited when given PR
Trazodone90Supp: case report of effective antidepressant effects following switch from PO to PR
Valproic acid1,91-93Soln, supp: PR bioavailability similar to PO
Suggested PO:PR conversion ratio is 1:1

Step 3: Determine which dosage form(s) are most suitable

Suppositories aren’t required for rectal drug absorption – they merely help with retention. The rectal administration of liquids allows for faster absorption, but volumes should be limited to 10-25ml to prevent discomfort and/or spontaneous expulsion. One instance where this is of clinical importance is with rectal diazepam for seizures. Compounded diazepam suppositories are inappropriate to use for treating status epilepticus because effective serum concentrations are reached too slowly.e  Instead, the solution for injection can be administered rectally as an alternative to commercially available diazepam rectal gel.We’ve previously posted about the rectal administration of anticonvulsants. Click here to revisit that post.

Solid oral dosage forms like tablets and capsules can be administered rectally as well.c  The Macy Catheter is a medical device that’s designed to facilitate rectal drug administration in a simplified and dignified manner. Included with the catheter is an apparatus designed to crush pills and dissolve them into aqueous solution.

Step 4: Determine the most appropriate dose(s)

For some drugs, oral to rectal conversion ratios have been approximated based on available bioavailability data and are described in Table 1. In the absence of this information, it’s reasonable to start with the same dose that was given orally, then adjusting as needed.

Step 5: Monitor for efficacy, adverse effects, toxicity

The final step of this process is to monitor how things are going post-conversion, primarily that the drugs remain effective, since rectal absorption is often less complete than oral absorption. Laboratory monitoring of serum drug concentrations is often avoided in the hospice setting to minimize patient exposure to needle sticks. However, if the drug has a narrow therapeutic index or symptom control is noted to be diminished following the conversion then it may make sense.

Discomfort, local irritation, and urge to defecate are potential adverse effects, though rectal drug administration is generally well-tolerated. Drug toxicity is uncommon, because, as mentioned above, rectal absorption is generally less than or equal to oral absorption, but typically not more.


Rectal administration of medications is almost never anyone’s first choice, but it can be necessary, particularly for terminally ill patients. Following the steps above will help maximize your chances for successful symptom control.

Written by: OnePoint Patient Care Clinical Team

Article References

a) Kestenbaum M, Vilches A, Messersmith S, et al. Alternate Routes to Oral Opioid Administration in Palliative Care: A Review and Clinical Summary. Pain Medicine. 2014;15:1129-1153. doi:10.1111/pme.12464

b) Mercadante S. When oral morphine fails in cancer pain: The role of the alternative routes. American Journal of Hospice and Palliative Care. 1998;15(6):333-342. doi:10.1177/104990919801500607

c) Samal R. Davis M. Fast Facts and Concepts #257 Palliative Care Per Rectum. Palliative Care Network of Wisconsin. May 2012. Updated June 2021. Accessed September 28, 2023.

d) Davis MP, et al. Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions. Support Care Cancer. 2002;10(2):117-138. doi:10.1007/s00520-001-0311-6.

e) Moolenaar F, et al. Biopharmaceutics of rectal administration of drugs in man IX. Comparative biopharmaceutics of diazepam after single rectal, oral, intramuscular and intravenous administration in man. Int J Pharm. 1980;5(2):127-137. doi:10.1016/0378-5173(80)90017-4.

Table References

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