Opioid Conversion and Morphine Equivalents

1. The Oral Morphine Equivalent, and the Ratios This Tool Uses

Every conversion runs through oral morphine: each current opioid in, the results added, the total out to the target drug and route. Multiply the 24 hour dose by the factor, divide by it to go the other way. One common currency avoids a table of every drug pair and an answer that changes with the order you work in.

• The same metric does a second job. It is also an overdose-risk and regulatory score in chronic non-cancer pain, and the CDC states that its conversion factors are not to be used when switching one opioid for another. This tool does the switching job, for cancer and palliative pain.

Direction decides which disagreement hurts. Coming off hydromorphone, a factor of 4 against 7.5 is nearly double the morphine dose; going on to it, the same spread halves it. Where two conventions exist this tool prints both and uses the one an Indian guideline states.

2. Incomplete Cross-Tolerance, and the One Case Where You Do Not Reduce

Tolerance to one opioid is only partial to the next: receptor occupancy, metabolite profile and affinity all differ, so the calculated equianalgesic dose behaves as though it were larger. Take 25 to 50 per cent off and titrate up.

• The sources. ISSP 2020: 25 to 50 per cent. WHO 2018 reserves about 50 per cent for four circumstances. A total of 1 g of oral morphine equivalent or more in 24 hours. An elderly or frail patient. A switch made for intolerable effects such as delirium. A recent rapid escalation that may be opioid-induced hyperalgesia. The Faculty of Pain Medicine puts its high-dose threshold at 500 mg in 24 hours, and this tool uses the lower.
• No reduction when the molecule does not change. Oral to subcutaneous morphine is a bioavailability correction and the factor of 2 already contains it. The same holds for immediate release to sustained release.
• The counter-evidence. A 2018 systematic review of opioid rotation in cancer pain found that outside methadone the calculated dose of the second opioid had to be increased, not decreased. This tool reduces least where the switch is for uncontrolled pain.

3. The Breakthrough Dose, and What Six Rescues in a Day Is Telling You

The rescue dose is one sixth of the total daily dose, the same as one four-hourly dose, and ISSP states it in that form.

• Smaller fractions. ISSP allows one twelfth of the 24 hour dose in renal impairment, a modification found in no other guidance read for this tool. Scottish palliative guidance gives one sixth to one tenth.
• How often, disputed. ISSP allows a rescue as often as hourly; Northern Ireland guidance says two to four hourly. Time to peak effect is about an hour for oral immediate release and about twenty minutes for subcutaneous.
• More than six rescues in 24 hours is a background dose problem. Scottish guidance asks for review after six doses in a day, and urgent review if three doses in four hours have not helped. Count them, then add them into the new total.

4. Transdermal Fentanyl: The Lag, the Depot and Reading the Table Backwards

• The lag. Serum fentanyl levels off between 12 and 24 hours, so ISSP continues the four-hourly oral opioid for 12 hours after the patch goes on. Full equilibrium on a new strength takes up to six days: not the drug for a pain crisis.
• The depot. After removal, concentrations fall by about half in 17 hours by one section of the label and in 20 to 27 hours by another, with significant absorption for 24 hours or more. Removing the patch does not make a toxic patient safe.
• Reading the table backwards. The US label and the UK SmPC both restrict their tables to converting on to the patch, never off it, because they are deliberately conservative. That is written for chronic pain. In palliative practice a patch sometimes has to come off, so this tool does the arithmetic, adds no reduction beyond the ordinary cross-tolerance one, and gives an estimate to titrate against.
• Indian context. Strengths listed by an Indian manufacturer are 12.5, 25, 50, 75 and 100 mcg/h; National Cancer Grid guidance names the lowest as 12 mcg/h. Patches are changed every 72 hours. Heat raises absorption, so a fever, a hot water bottle or a heating pad over the patch is a real dose increase.

5. Buprenorphine: A Partial Agonist, Two Published Ratios and a Ceiling

A partial agonist at the mu receptor with very high affinity and slow dissociation, which buys a favourable respiratory profile and a long duration. A partial agonist with a ceiling effect does not sit on a full agonist's linear scale, which is why the CDC leaves it out of its morphine equivalent table.

• Two ratios for the patch. ISSP 75:1; WHO and the Faculty of Pain Medicine 100:1; neither the US label nor any UK patch SmPC read for this tool states a ratio at all. The sublingual figure of 75 is a different number for a different preparation.
• The ceiling that matters in India. Transdermal strengths confirmed on an Indian manufacturer's list are 5, 10 and 20 mcg/h, and at the ISSP ratio 20 mcg/h is about 36 mg of oral morphine a day. The US label caps treatment at one 20 mcg/h patch because of QT prolongation and says an alternative analgesic should be considered above 80 mg of oral morphine equivalent. The 35, 52.5 and 70 mcg/h strengths used elsewhere were not confirmed as marketed in India when this tool was written. It is a step 2 to early step 3 option here.
• Where it earns its place. ISSP places it fourth line for cancer pain. Its use is mainly in renal impairment, where it has no active metabolite that accumulates.

6. Methadone: Why There Is No Single Ratio

The elimination half-life is reported between 5 and 130 hours, averaging about 22, analgesia after repeated dosing lasts 8 to 12 hours, and steady state takes 5 to 14 days: the dose that looks correct on day two can be fatal on day seven. NMDA antagonism is why the ratio rises with the dose already being taken instead of staying fixed. The three ISSP 2020 bands below are the ones this tool uses.

• Other published sets. They run from 3:1 to 20:1 across six bands. A widely reproduced Australian table reaches 12:1 only in the 601 to 800 mg band and 20:1 only above 1000 mg a day. A separate family of tables, from chronic non-cancer pain practice, reaches 12:1 at 60 mg a day. Never use those for a cancer pain patient. Above roughly 1000 to 1200 mg of oral morphine equivalent the tables have no useful empirical support, and the published alternative is a fixed ceiling of about 30 mg of methadone a day.
• The QT interval. The S-enantiomer binds the hERG channel. Two thresholds are quoted in the Indian methadone literature, both from the 2014 American Pain Society safety guideline. A QTc above 450 ms is a signal to reconsider. A QTc of 500 ms, or a rise of more than 60 ms from the patient's own baseline, is a reason to withhold or discontinue. An ECG within the last three months with a QTc under 450 ms can serve as the baseline. At the end of life the same guidance permits an informed conversation with the patient and family and continuing methadone without further investigation.
• Who starts it. Every source read for this tool says methadone is started by somebody experienced with it, and one declines to publish any ratio at all on the grounds that a number invites a calculation where a judgement is required. Have a colleague repeat the arithmetic before the first dose.

7. The Kidney and the Liver

Morphine is glucuronidated to morphine-6-glucuronide, an analgesic many times more potent than morphine, and morphine-3-glucuronide, which is not analgesic and is neurotoxic. About 90 per cent of the conjugates leave by the kidney, and in renal failure their half-life has been reported to rise from about 4 hours to between 14 and 119. The patient becomes drowsy, myoclonic and confused on a dose that was correct last week.

• What to use instead, and how firm that is. Fentanyl, buprenorphine and methadone have no renally cleared active metabolite and are the ones recommended as the eGFR falls. A 2017 systematic review concluded that the preference rests on pharmacokinetics and clinical experience rather than trials, and that no recommendation on a preferred opioid could be formulated from the evidence.
• Where the sources differ. Codeine and hydromorphone are avoided in stage 4 and 5 chronic kidney disease in Scottish guidance, while a 2024 American source considers hydromorphone preferable to morphine. UK guidance names alfentanil for a syringe pump at a very low eGFR, its own threshold having moved from below 30 in the 2019 document to 20 or less in the current one. This tool does not convert to alfentanil: it is not a notified Essential Narcotic Drug and no Indian guideline read for this tool names it.
• The liver. Codeine, tramadol and tapentadol are prodrugs or depend on hepatic activation, so they accumulate and stop being reliable analgesics at the same time. Pethidine is avoided outright, because seizures from normeperidine occur even at reduced doses. In severe impairment oxycodone starts at 30 to 50 per cent of the usual dose and hydromorphone at 50 per cent, while morphine is used at lower doses but normal intervals early and at longer intervals as the disease advances. Fentanyl is described by some as preferred here, on empirical grounds.

8. Prescribing Opioids in India: The NDPS Amendment of 2014

The Narcotic Drugs and Psychotropic Substances Act 1985 was amended in 2014 to create the Essential Narcotic Drug, defined in section 2 as a narcotic drug notified by the Central Government for medical and scientific use. It replaced a patchwork of state licences with one central rule set, and it is the single most important change to opioid access in Indian palliative care.

• The notified list carries morphine, codeine and ethyl morphine, fentanyl, oxycodone, methadone and hydrocodone. The Ministry of Health and Family Welfare operational guidelines of 2017 list five and omit methadone, which was approved for sale for pain management in India in 2016; the discrepancy is recorded rather than papered over. ISSP reported in 2020 that oxycodone and hydromorphone were not marketed in India.
• The institution, not the doctor, holds the licence. A government, municipal or Zilla Parishad hospital or dispensary with at least one registered medical practitioner trained in pain relief and palliative care is a deemed Recognised Medical Institution under Rule 52N. A private institution applies to the State Drug Controller on Form 3F, is inspected and expects a decision within 60 days; recognition runs in renewable three year periods and the certificate is Form 3G. The prerequisites are a trained doctor in charge, double locked storage and a consumption register.
• What the prescription must carry. Rule 52G requires it in writing, dated and signed, with the prescriber's full name, address and registration number, the name and address of the patient, and the total quantity together with the daily dose and the period of consumption. A prescription giving a dose but no total quantity does not meet the rule.
• When a patient cannot get morphine, the obstacle is almost never the law as it now stands. It is that the institution never applied, or that the register and the double lock were never set up.

9. What This Tool Does Not Cover

• The opioid-naive patient. This tool converts an existing regimen, it does not set a first dose. The ISSP starting point is oral immediate release morphine four hourly: 5 mg in a naive adult, 10 mg in a patient already on step 2, and 2.5 mg four to six hourly in the elderly, titrated in increments of 5 to 10 mg.
• Children. Every ratio here is adult. Paediatric palliative dosing is a separate discipline and a separate set of documents.
• Pethidine. Deliberately not converted: normeperidine accumulates and causes seizures, the duration is too short for chronic pain, and no dependable equianalgesic ratio for palliative use was found in the sources read. It stays in the drug list so the tool can say so rather than stay silent.
• Diamorphine. In every UK syringe pump table and absent from Indian practice, so the divide by three line those tables carry does not apply. Morphine is the syringe pump opioid in India, and subcutaneous tissue absorbs about 3 mL an hour, which is the practical constraint at high doses.
• Alfentanil, sufentanil and remifentanil. Not converted, for the reason given in pearl 7.
• Intrathecal and epidural routes. A different order of ratio entirely and a specialist decision.
• Opioid use disorder. Buprenorphine and methadone in substitution therapy are a different indication, with different doses and a different legal route.
• Whether an opioid is the right answer. Neuropathic pain, bone pain, bowel colic and total pain each need something added rather than a larger opioid dose.