IV Dilution &
Medication Reference

Promethazine

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Concentration studied in Trissel: (0.1 mg/ml)
[12.5 mg] [ 125 ml] [ 15 to 30 min]
[25 mg] [ 250 ml] [ 15 to 30 min]

If a patient complains of pain during intended intravenous injection, stop the injection immediately; suspect inadvertent intra-arterial injection.

Stability / Miscellaneous

Dilution opinion (D. McAuley):
A 10-fold dilution will result in a negligible change in the pH ( ~+ 0.3). NaCl is the salt of a strong acid and strong base and has a neutral pH. Promethazine is considered a weak acid and is only partially dissociated in solution. The degree of dissociation is proportional to its Ka (dissociation constant). Larger Ka --> stronger acid (greater dissociation). What does all this mean?? 1) The pH of promethazine after a 10-fold dilution (or greater) is still quite low. 2) The primary purpose of the dilution is to facilitate a slower administration rate and to reduce the amount of drug present per unit of volume.

Dosing (Adults): (Preferred routes: oral or IM). If administered IV, dilute drug and administer slowly as indicated above.
Allergic conditions (including allergic reactions to blood or plasma): Oral, rectal: 25 mg at bedtime or 12.5 mg before meals and at bedtime (range: 6.25 to 12.5 mg 3 times/day). I.M., I.V.: 25 mg, may repeat in 2 hours when necessary; switch to oral route as soon as feasible.

Antiemetic: Oral, I.M., I.V., rectal: 12.5 to 25 mg every 4 to 6 hours as needed.
Sedation: Oral, I.M., I.V., rectal: 12.5 to 50 mg/dose.

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Background information:

Title: Action needed to prevent serious tissue injury with IV promethazine.

"ISMP believes these long-standing hazards require further action on the part of healthcare providers, FDA, and promethazine manufacturers. In the 1970s, after numerous reports of infiltration and inadvertent intraarterial injection of hydroxyzine, FDA asked the manufacturer to revise the label and remove IV as an approved route. Today the drug is only indicated for IM or oral administration. Similarly, FDA should carefully investigate adverse events with this drug to determine if labeling changes are warranted, including removal of approval for IV administration."

Safe Practice Recommendations: ... [See ISMP for further info ] Limited direct quotes from this source.

Along with the manufacturer recommendations, the following strategies should be considered to prevent or minimize tissue damage when giving IV promethazine.... [See ISMP for further info ]

Limit concentration. Since 25 mg/mL is the highest concentration of promethazine that can be given IV, stock only this concentration (not the 50 mg/mL concentration). Limit the dose. Consider 6.25 to 12.5 mg of promethazine as the starting IV dose, especially for elderly patients. Hospitals have reported that these smaller doses have proven quite effective. Dilute the drug. Require further dilution of the 25 mg/mL strength to reduce vesicant effects and enable slow administration. For example, dilute the drug in 10 to 20 mL of normal saline if it will be administered via a running IV, or prepare the medication in minibags containing normal saline if there is time for pharmacy to dispense them as needed for individual patients. Extravasation can also be recognized more quickly when promethazine is diluted than if the drug is given in a smaller volume. 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... [See ISMP for further info ] Inject into the furthest port. Administer IV promethazine through a running IV line at the port furthest from the patient's vein. Educate patients. Before administration of the drug, tell patients to let you know immediately if burning or pain occurs during or after the injection. Use alternatives. Consider safer alternatives that can be used for the various conditions treated with IV promethazine. For example, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists may be used for both prophylaxis and as a rescue antiemetic. ... [See ISMP for further info ] Remove from formulary. Some hospitals that have continued to experience adverse outcomes despite safety measures have removed promethazine from their formulary or banned its IV use.The above message comes from "ISMP", who is solely responsible for its content.

Nursing forum responses (Various sources - original sources unknown)
"At my hospital the doc's usually write for 6.25mg-12.5mg at a time. We give the full 25mg very rarely. I dilute it in 10cc NS and if fluids are running I hang it as a secondary over 10-20 minutes depending on the pt's vein status. I've pushed it diluted over 5 minutes before and it caused chemical phlebitis."

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"Mosby's drug guide for nurses states to dilute with 9ml NaCl and administer over 2 minutes. Always dilute phenergan when giving it IV. My DH was in ER a while ago for what turned out to be food poisoning, they gave him undiluted phenergan and his vein sclerosed from wrist to bicep (no I'm NOT exaggerating)"

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"As a nurse, I have had many patients complain aobut how much Phenergan burns. I would always just politely tell them them that it would burn and then push it slow diluted in 10 cc's of NS but then it was my turn. I was hospitalized and was given IV Phenergan and it not only burned like heck but I swear I felt like I was having a full blown MI. My entire arm was numb not to mention the IV site had to be changed and I developed phlebitis all around the site. I don't give Phenergan anymore without diluting it in 50 cc's of NS. I learned my lesson."