Prevention of severe tissue damage with intravenous promethazine (Phenergan) (2023)

PProblem: Promethazine (Phenergan, Wyeth) is a commonly used injectable product with antihistaminic, sedative, anti-disease, and antiemetic effects. The drug is also a well-known blistering agent that is highly corrosive to the intima of blood vessels and surrounding tissues. Formulated with phenol, promethazine has a pH between 4 and 5.5. Although deep intramuscular (IM) injection into a large muscle is the preferred route of parenteral administration, the product label indicates that the drug can be administered by slow intravenous injection, the method normally used in most hospitals. However, due to the frequency of serious and tragic local injuries following accidental intra-arterial infiltration or injection, the FDA's Institute for Safe Medication Practices (ISMP) recommends re-examining product labeling and considering eliminating intravenous (IV) administration. Administration.

Severe tissue damage can occur regardless of the parenteral route of administration, although accidental intravenous and intra-arterial or subcutaneous (SQ) administration leads to more serious complications, including burning, erythema, pain, swelling, severe vascular spasm, thrombophlebitis, venous thrombosis, phlebitis, nerve damage, paralysis, abscess, tissue necrosis and gangrene. Surgical intervention is sometimes required, such as fasciotomy, skin grafting, and even amputation.

The true extent of the problem may not be known, but it appears that patients are harmed more often than is commonly believed. Dozens of reports have been filed with the ISMP, the US Pharmacopoeia and the Pennsylvania Patient Safety Reporting System. articles in specialist literature; news of lawsuits in the media; and postings on various internet lists and message boards (ISMP, National Patient Safety Foundation,, and others) were also widely used.

The following scenarios have been brought to our attention in ISMP:

  • A 19-year-old woman presented to the emergency department (ED) with flu-like symptoms. She received IV promethazine.1During the injection, she cried out in pain and was tempted to pull out the IV tube. Afterward, she told the nurse that her arm was still sore and she felt "something was wrong." The nurse calmed the patient down and left the room. The patient's arm and fingers became purple and blotchy. The patient remained hospitalized for 30 days, during which time she observed her previously healthy fingers turning black and withering (Fig(Figure 1).1). His thumb, index finger and the tip of his middle finger had to be amputated.

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    illustration 1

    The fingers of a patient given promethazine shrank and turned black. The patient's thumb, index finger and tip of the middle finger had to be amputated.

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  • One patient received 12.5 mg of promethazine at an IV site in the hand. The patient complained of a strong burning sensation during the injection, but the nurse continued to administer the drug. An area of ​​necrosis developed on the patient's hand, and skin grafts and physical rehabilitation were eventually required.

  • Vermont professional guitarist Diana Levine was awarded $2.4 million in past and future medical expenses and $5 million in pain and suffering after suffering two amputations following accidental arterial administration of the brand-name drug Phenergan.2Because of a migraine, the patient went to the emergency room, where she was given Phenergan intended for IV administration. She had circulatory problems and then progressive gangrene that led to the gradual amputation of her arm. His case eventually reached the Supreme Court.

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SsecurePpracticeRRecommendation: The Phenergan package insert states, "Proper IV administration of this product is well tolerated, but use by this route carries some risks." To reduce the risk of these dangers, the manufacturer recommends using the drug in concentrations of no more than 25 mg/ml and no more than 25 mg/minute. The drug should be injected through the tubing of an infusion set that is working and functioning satisfactorily, and the injection should be stopped immediately if the patient reports burning in order to assess possible arterial placement or a perivascular leak. However, the ISMP believes that healthcare providers, the FDA, and the manufacturers of promethazine must take additional steps to avoid these long-standing risks.

Along with the manufacturer's recommendations, the following strategies should be considered to prevent or minimize tissue damage when patients are receiving intravenous promethazine:

  1. limit concentration.Because 25 mg/mL is the highest dose of promethazine that can be administered intravenously, only this concentration (not 50 mg/mL) should be stored.

  2. Dose limitation.Promethazine 6.25 to 12.5 mg should be considered as the initial IV dose, particularly in elderly patients. These smaller doses have proven very effective in hospitals.

  3. diluting the drug.Further dilution of the 25 mg/mL dosage is required to reduce blistering effects and allow for slow administration. For example, the drug can be diluted in 10 to 20 ml of normal saline when continuously administered intravenously. Alternatively, it can be prepared in mini-sachets with regular saline if the pharmacist has time to dispense as needed for individual patients. Extravasation is also detected more quickly when promethazine is diluted than when it is given in a smaller volume.

  4. With large patent veins.Promethazine should be given only through a large vein, preferably through a central venous line, not through veins in the hand or wrist. Access site clearance must be verified prior to administration. According to the package insert, aspiration of dark blood does not prevent intra-arterial placement of the needle because blood can become discolored upon contact with promethazine. The use of rigid-piston syringes or small-bore needles can mask typical arterial reflux when physicians rely on this method alone. The drug should be injected through a continuous IV line into the port furthest from the patient's vein.

    (Video) FDA IV Promethazine Warning

  5. Administer the medicine slowly.IV promethazine can be administered over 10 to 15 minutes.

  6. Check order forms.Pre-printed order forms should be checked to ensure that Promethazine orders reflect the security measures listed above.

  7. educate patients.Before administration, patients should be instructed to inform their doctor immediately if burning or pain occurs during or after the injection.

  8. Create notifications.A warning should appear on computer-generated medication administration records (MARs), electronic ARMs, and automated dispensing cabinet screens for caregivers to see each time they access and administer a dose of promethazine. This approach can be an effective reminder that the medication is effervescent and must be diluted and administered slowly through a continuous IV line.

  9. Treat that patient.The manufacturer cautions that no method has proven successful in treating an accidental intra-arterial injection or perivascular leak. However, sympathetic blockade and heparinization have been used during the acute treatment of promethazine extravasations.

  10. Try alternative therapies.Physicians may consider safer alternatives for several conditions commonly associated with IV be treated with promethazine. For example, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists can be used both for prophylaxis and as rescue antiemetics in postoperative nausea or vomiting (PONV). The package insert for ondansetron (Zofran, GlaxoSmith-Kline) states that patients not receiving prophylactic ondansetron and who have PONV can receive this agent to prevent further episodes. Eligible surgical patients should receive 5-HT3for PONV, and patients should be well hydrated to reduce the risk of PONV and reduce the need for emergency antiemetics.

    (Video) #46: promethazine (Phenergan) | Motion Sickness, Allergic Conditions, & Sedation | Drug Cards Daily

  11. Removal of promethazine from the mold.Some hospitals, which continued to experience adverse results despite safety measures, have eliminated promethazine from their prescription or banned its intravenous use.


The reports described in this column were obtained through the ISMP Medication Errors Reporting Program (MERP). Errors, call closures, or dangerous conditions can be reported on the ISMP website ( or communicated directly to ISMP by calling 1-800-FAILSAFE or emailinggro.pmsi@ofnipmsi


1.Friedrich SMisconduct allegations highlight anti-nausea drugthe everyday world; Aberdeen, WA: December 72005. Available March 3, 2009.[Google Scholar]

2.Patrick J..Marshfield Woman Wins $7.4M Jury Prize After Losing Her ArmThe Barre Montpelier Times Argus; Barre, VT: March 19, 2004.[Google Scholar]

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What action is needed to prevent serious tissue injury with IV promethazine? ›

Use large patent veins.

Give the medication only through a large-bore vein (preferably via a central venous access site, but absolutely no hand or wrist veins). Check patency of the access site before administration.

What precautions should be taken when administering promethazine intravenously? ›

Along with the manufacturer's recommendations, the following strategies should be considered to prevent or minimize tissue damage when patients receive IV promethazine:
  • Limiting the concentration. ...
  • Limiting the dose. ...
  • Diluting the drug. ...
  • Using large patent veins. ...
  • Administering the drug slowly. ...
  • Revising order forms.

Does Phenergan cause tissue damage? ›

Promethazine injection is highly caustic to the intima of blood vessels and surrounding tissues. Reports from the United States describe serious tissue reactions including thrombosis, nerve damage, tissue necrosis and gangrene in patients who have received intravenous promethazine.

Why does promethazine cause tissue damage? ›

Because it possesses antihistamine, sedative, anti-motion sickness, and anti-emetic effects, it is often used for nausea and vomiting. Physicians may not be fully aware that it is also toxic to the intima of blood vessels and surrounding connective tissue; this can result in severe tissue damage and necrosis.

What are the nursing interventions for promethazine? ›

Monitor and report signs of neuroleptic malignant syndrome, including hyperthermia, diaphoresis, generalized muscle rigidity, altered mental status, tachycardia, changes in blood pressure (BP), and incontinence.

What considerations needs to have when taking promethazine? ›

Promethazine may cause breathing to slow or stop, and may cause death in children. Promethazine should not be given to babies or children who are younger than 2 years old and should be given with caution to children who are 2 years of age or older.

What are the requirements for Phenergan IV? ›

When administered intravenously, Phenergan Injection should be given in a concentration no greater than 25 mg per mL and at a rate not to exceed 25 mg per minute. It is preferable to inject through the tubing of an intravenous infusion set that is known to be functioning satisfactorily.

What are the problems with Phenergan IV? ›

severe pain, swelling, numbness, cold feeling, or discoloration in your fingers or toes; weak or shallow breathing; hallucinations; uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);

Which patients would a nurse determine cannot safely receive therapy with promethazine? ›

Promethazine hydrochloride (promethazine hydrochloride injection) is contraindicated in comatose states and in patients who have demonstrated an idiosyncrasy or hypersensitivity to promethazine or other phenothiazines.

Why can't you give promethazine IV? ›

The location of the I.V. catheter – veins of the hand, wrist, and antecubital fossa should NEVER be used for promethazine. There is a greater risk of nerve injury in these locations.

What is the risk of Phenergan? ›

The most common side effects include sedation, confusion, and disorientation, which may impair physical and mental abilities. However, in some cases, promethazine may paradoxically cause excitability, restlessness, or rare seizures.

Which problem can be avoided by administering promethazine IV? ›

Histamine can cause itching, sneezing, runny nose, and watery eyes. It can sometimes close up the bronchial tubes (air passages of the lungs) and make breathing difficult. Promethazine is also used to prevent and control motion sickness, nausea, vomiting, and dizziness.

Can promethazine cause permanent damage? ›

Promethazine is also associated with rare long-term side effects, including heart arrhythmias, low blood pressure, liver damage, bone marrow suppression and trouble regulating body temperature. It can also cause skin hyperpigmentation after long-term use, especially on body parts that are exposed to the sun.

Why was Phenergan discontinued? ›

The discontinuation of this product is due to the popularity of its recreational use.

What to avoid when taking promethazine? ›

Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can interact with promethazine and cause medical problems or increase side effects. Tell your doctor if you regularly use any of these medicines.

What do you monitor with promethazine? ›

Check with your doctor right away and stop taking your medicine (if directed by your doctor) if you have muscle stiffness, fever, difficult or fast breathing, seizures, fast heartbeat, increased sweating, loss of bladder control, unusually pale skin, or tiredness or weakness.

What is promethazine IV treatment? ›

Promethazine injection is used to relieve or prevent some types of allergy or allergic reactions. It works by preventing the effects of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, and watery eyes.

What are the 3 nursing interventions? ›

There are typically three different categories for nursing interventions: independent, dependent and interdependent.

How fast does IV promethazine work? ›

It normally takes about 30 minutes to work. To prevent motion sickness, take promethazine the night before a long journey or 1 to 2 hours before a short journey. Common side effects of promethazine include drowsiness, headaches, nightmares and feeling dizzy, restless or confused.

How long does IV promethazine last? ›

Promethazine can last in your system for between two and four days. Every 10 to 19 hours the level of promethazine in the blood drops by 50 percent.

What are contraindications for Phenergan? ›

Phenergan Tablets and Suppositories are contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma.

Does promethazine cause heart problems? ›

You should not take it if you have bone marrow disease or you take other drugs that affect the ability of your bone marrow to make blood cells. For people with heart disease: If you have heart disease, taking this drug may make it worse. This drug can cause the rhythm of your heart to be abnormal.

What is the FDA warning for Phenergan? ›

Injectable promethazine hydrochloride (former brand name, Phenergan) should carry a boxed warning to emphasize the risk for severe tissue injury when the drug is given incorrectly, the FDA announced on Wednesday. (Promethazine is used as a sedative and to treat nausea and vomiting.)

Is promethazine injection safe? ›

To reduce the risk of these hazards, manufacturer labeling recommends the following: Give the drug in concentrations no greater than 25 mg/mL. Administer the drug at a rate no greater than 25 mg/minute. Inject the drug through the tubing of an infusion set that is running and known to be functioning satisfactorily.

What is promethazine therapeutic action? ›

Promethazine is a medication used to manage and treat allergic conditions, nausea and vomiting, motion sickness, and sedation. It also has off-label uses for nausea and vomiting in pregnancy. Promethazine is a phenothiazine derivative with antidopaminergic, antihistamine, and anticholinergic properties.

What is the action of promethazine injection? ›

Promethazine injection is used to relieve or prevent some types of allergy or allergic reactions. It works by preventing the effects of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, and watery eyes.

What mechanism of action or pharmacological action is best associated with promethazine? ›

Promethazine is a an antagonist of histamine H1, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. The antihistamine action is used to treat allergic reactions. Antagonism of muscarinic and NMDA receptors contribute to its use as a sleep aid, as well as for anxiety and tension.

What is promethazine expected action? ›

Promethazine antagonizes the central and peripheral effects of histamine mediated by histamine H1 receptors. The effects include bronchoconstriction, vasodilation and spasmodic contractions of gastrointestinal smooth muscle.

What is the therapeutic effect of Phenergan? ›

Promethazine is used to prevent and treat nausea and vomiting related to certain conditions (such as before/after surgery, motion sickness). It is also used to treat allergy symptoms such as rash, itching, and runny nose.

What is the onset of action of promethazine IV? ›

Clinical effects are generally apparent within 5 minutes of an intravenous injection and within 20 minutes of an intramuscular injection. Duration of action is four to six hours, although effects may persist up to 12 hours.

Is promethazine injection painful? ›

This medication has caused serious side effects in some patients after it was injected into a vein. Watch closely for any signs or symptoms of a local reaction like burning, pain, redness, swelling, and blistering and tell your care team immediately if any occur.

What organ does promethazine effect? ›

This can cause symptoms such as a runny nose or skin rashes. Promethazine blocks the effects of histamine in your brain and this reduces symptoms. It enters the brain in large quantities and this can make you feel drowsy.

Does promethazine reduce inflammation? ›

Descriptions. Promethazine is used to relieve or prevent the symptoms of hay fever, allergic conjunctivitis (inflammation of the eye), and other types of allergy or allergic reactions.

Does promethazine affect the brain? ›

Promethazine medications are a type of sedative, in the class of antihistamine drugs. One widely known commercial promethazine is Phenergan. They work on the central nervous system, resulting in a decrease in brain cell activity.

What drugs should not be taken with promethazine? ›

Promethazine interacts with other medications or substances that cause drowsiness. These include opioids, benzodiazepines, and alcohol. It also interacts with anticholinergic medications and monoamine oxidase inhibitors (MAOIs).


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