Fentanyl vs. morphine: Differences, similarities & side effects

In this article:

• Key differences
• Conditions treated
• Is fentanyl stronger than morphine?
• Coverage and cost comparison
• Side effects
• Drug interactions and warnings

In this article

• Key differences
• Conditions treated
• Is fentanyl stronger than morphine?
• Coverage and cost comparison
• Side effects
• Drug interactions and warnings

Fentanyl and morphine are both generic prescription drugs used to treat severe pain. They are potent pain relievers that belong to a class of medications called opioids, or opioid analgesics. Opioids work by activating brain receptors that block pain signals. Although fentanyl and morphine have similar mechanisms of action, they also have key differences, such as fentanyl acting more quickly and being around 100 times stronger than morphine.

Fentanyl vs. morphine: Key differences

“Morphine and fentanyl are both used to treat pain, but they are definitely not identical,” says Blair Gingerich, Pharm.D., an ambulatory care pharmacist in northern Indiana and a member of the SingleCare Medical Board.

“Fentanyl comes in more options for routes of administration,” adds Inna Melamed, Pharm.D., a functional medicine practitioner and author of Digestive Reset. “[Fentanyl] comes in patches, whereas morphine does not. Fentanyl also comes intranasally, and morphine does not have that delivery system.” Finally, Dr. Melamed says that while fentanyl is a much more potent pain reliever, it comes with a higher risk of addiction and also does not last as long. Given these features, fentanyl tends to be used in more acute settings, such as for breakthrough pain during cancer treatment or immediately after surgery. 

Compare fentanyl vs. morphine key differences
	Fentanyl	Morphine
Drug class	Opioid	Opioid
Brand/generic status	Generic	Generic
What is the brand name?	Actiq, Fentora, Abstral, Subsys, Lazanda, Duragesic	Duramorph, Infumorph, Mitigo, MS Contin
What form(s) does the drug come in?	Oral transmucosal lozenges (referred to as “lollipops”), effervescent oral tablets, sublingual tablets, sublingual sprays, nasal sprays, transdermal patches, injection	Tablet, extended-release tablet, extended-release capsule, liquid oral solution, suppository, injection
What is the standard dosage?	Dosage varies by form. The usual dosage for skin patches to treat severe and persistent pain is one patch delivering 12 to 100 micrograms per hour, applied for 72 hours.	Dosage varies by form. For regular tablets, the usual starting dose is 15 to 30 mg every four hours. For extended-release tablets, the typical starting dose is 15 mg every eight to twelve hours.
How long is the typical treatment?	As needed for moderate to severe pain that is acute or chronic	As needed for moderate to severe pain that is acute or chronic
Who typically uses the medication?	Depends on the dosage form. Some forms are approved for adults and children 2 years and older.	Depends on the dosage form. Some forms are approved for adults and children 2 years and older.

 

Fentanyl vs. morphine: Conditions treated

Fentanyl and morphine are both used to treat moderate to severe pain that is acute or chronic. Because it is more potent, fentanyl is typically used to manage severe pain in patients who are already on another opioid for pain relief or for patients who are experiencing acute, short-term pain related to surgery. 

Off-label uses for morphine include “almost any condition that causes pain.” This may include intravenous morphine for severe chest pain in an emergency department setting or severe migraines that have not responded to first-line treatments. Dr. Gingerich says off-label uses may even include dyspnea (breathlessness) in critically ill patients. However, she cautions that the evidence for these off-label uses is “very poor.”

Fentanyl’s uses are similar to morphine’s, although fentanyl is more potent. Fentanyl is also approved for use as a pre-operative pain reliever, adjunctive therapy to anesthesia, and anesthesia during surgery. It is also sometimes used for postoperative pain.

Compare fentanyl vs. morphine conditions treated
Condition	Fentanyl	Morphine
Acute and chronic pain management	Yes	Yes
Procedural sedation	Yes	Yes
Anesthesia	Yes	Yes
Postoperative pain	Yes	Yes
Dyspnea	Off-label	Off-label

 

Is fentanyl stronger than morphine?

Yes, fentanyl is around 100 times stronger than morphine. In other words, 100 micrograms (mcg) of fentanyl can offer the same pain relief as 10 mg of morphine. Still, Dr. Melamed emphasizes that, although fentanyl is more potent and fast-acting, its effects do not last as long as morphine. However, the duration of effect can vary based on the dosage form and how a person processes the drug. 

In one randomized controlled trial comparing transdermal fentanyl and oral morphine, the fentanyl group reported higher quality of life and lower pain scores than the morphine group for chronic non-cancer pain. A different clinical trial found that morphine gave better pain relief after surgery than fentanyl but caused more nausea and vomiting after leaving the hospital (59% versus 24%). There were no significant differences in recovery times, but more people on fentanyl needed extra pain medicine (69% versus 17%).

As a potent synthetic opioid, fentanyl may present a more serious risk of opioid overdose, which can be fatal if not immediately treated with naloxone, an opioid antagonist. The best opioid or non-opioid analgesic should only be determined by a healthcare provider who knows the person’s medical history, including other medical conditions and prescription or over-the-counter medications being taken. 

Fentanyl vs. morphine: Insurance coverage and cost comparison

Many commercial health insurance plans and Medicare prescription drug plans cover fentanyl or morphine when prescribed for severe or chronic pain. For example, morphine is commonly prescribed and covered for cancer pain. However, some plans may require prior authorization, a process between insurance companies and healthcare providers documenting that the treatment is medically necessary. 

Out-of-pocket costs for fentanyl versus morphine vary depending on a patient’s insurance plan, the drug form, and whether the form used is generic or brand-name. Generic drugs are generally less expensive than brand-name drugs. For an accurate price estimate on fentanyl or morphine, contact your health insurance company.

For people paying out-of-pocket, the average retail price for a one-month supply of fentanyl is around $178. That price is for two boxes of five 72-hour transdermal patches (10 patches total). A SingleCare coupon can lower the cost to $39 for the same one-month supply. On the other hand, the out-of-pocket price for 60 morphine ER tablets with a strength of 15 mg is around $93, with a SingleCare coupon reducing that price to around $25. 

Compare fentanyl vs. morphine cost & coverage
	Fentanyl	Morphine
Typically covered by insurance?	Sometimes	Sometimes
Typically covered by Medicare Part D?	Usually	Usually
Quantity	2 boxes of 5, 72-hour transdermal patches	60 tablets
SingleCare cost	$39	$25

 

Fentanyl vs. morphine side effects

Fentanyl and morphine commonly cause central nervous system (CNS) depressant effects, such as drowsiness, sedation, and confusion. These opioids can also lead to gastrointestinal problems like nausea, vomiting, and constipation.

Serious adverse reactions to opiates include breathing problems like respiratory depression (slowed breathing), cardiac arrest (when the heart suddenly stops beating), and bradycardia (slow heart rate). However, serious side effects are typically related to an overdose of these medications.  

Although opioids can help with analgesia, they are also linked to a long list of serious adverse effects. Consult a healthcare professional for a complete list of these side effects and potential adverse reactions.

Compare fentanyl vs. morphine side effects
	Fentanyl transdermal skin patch	Morphine sulfate extended-release capsule
Side effect	Applicable?	Applicable?
Nausea	Yes	Yes
Vomiting	Yes	Yes
Drowsiness	Yes	Yes
Dizziness	Yes	Yes
Headache	Yes	Yes
Constipation	Yes	Yes
Anxiety	No	Yes
Confusion	No	Yes

Source: DailyMed (morphine sulphate capsule and fentanyl transdermal patch)

Fentanyl and morphine drug interactions

It’s important to tell your prescribing healthcare provider about all the medications you take, including over-the-counter drugs, vitamins, and supplements, before taking fentanyl or morphine. 

Fentanyl and morphine should be used with caution when taking certain medicines that affect how drugs are broken down by the body. These include some antibiotics like macrolides, antifungal medicines like azoles, and medicines used to treat HIV called protease inhibitors. Taking these together can increase the amount of fentanyl or morphine in your body to dangerous levels. Other medications, like certain anticonvulsants, can lower fentanyl or morphine levels and reduce their effect.

The use of fentanyl or morphine should be avoided while taking a monoamine oxidase inhibitor (MAOI) or for at least 14 days after stopping an MAOI. Combining these opioids with an MAOI can increase the risk of serious side effects, including serotonin syndrome or opioid toxicity.

Opioids should not be taken with other drugs that slow down the CNS, such as benzodiazepines and muscle relaxants. Combining these can increase the risk of dangerous side effects, including trouble breathing, extreme drowsiness, and even death. Avoid using opioids with these or similar medications.

The table below provides an overview of drugs that interact with fentanyl or morphine, but it is not a complete list. Consult a healthcare provider for medical advice on drug interactions before taking fentanyl or morphine.

Compare fentanyl vs. morphine drug interactions
Drug	Drug class	Fentanyl	Morphine
Nardil (phenelzine) Parnate (tranylcypromine) Marplan (isocarboxazid)	MAOI	Yes	Yes
Erythrocin (erythromycin) Biaxin (clarithromycin) Zithromax (azithromycin)	Macrolide antibiotic	Yes	Yes
Nizoral (ketoconazole) Sporanox (itraconazole) Diflucan (fluconazole)	Azole antifungal	Yes	Yes
Prezista (darunavir) Norvir (ritonavir) Kaletra (lopinavir / ritonavir)	Protease inhibitor	Yes	Yes
Xanax (alprazolam) Klonopin (clonazepam)	Benzodiazepine	Yes	Yes
Flexeril (cyclobenzaprine) Robaxin (methocarbamol) Soma (carisoprodol) Zanaflex (tizanidine)	Muscle relaxant	Yes	Yes
Tegretol (carbamazepine) Dilantin (phenytoin)	Anticonvulsant	Yes	Yes
Prozac (fluoxetine) Lexapro (escitalopram) Effexor (venlafaxine) Elavil (amitriptyline)	Antidepressant	Yes	Yes

 

Fentanyl and morphine drug warnings

Fentanyl and morphine have boxed warnings, also called black box warnings, which are indications that a medication carries a serious risk of severe or life-threatening complications. 

For example, both have a boxed warning about the potential for addiction, abuse, and misuse. Fentanyl and morphine are extremely habit-forming, especially in people with a history of substance use disorder. “Fentanyl works faster than morphine, which makes it easier to get addicted to,” Dr. Melamed says. 

Fentanyl and morphine also have the potential to cause life-threatening respiratory depression. In some cases, these opioids can cause dangerous drops in blood pressure (hypotension) and hormone problems (adrenal insufficiency) that may need treatment and stopping the drug. The use of these drugs is especially risky for people with head injuries or brain problems and should not be used in someone who is unconscious.

Before taking morphine or fentanyl, it is important to tell your healthcare provider if you are pregnant, plan to become pregnant, or are breastfeeding. It’s important to share all past and current medical conditions and medications. With this information, your healthcare provider can determine the best drug for your condition.