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IV Dilution & Medication Referencev7.4
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Promethazine

Limited reviewed summaryFull monograph review pending

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Review note before using historical content

Promethazine historical concentration and infusion advice is superseded

The restored article already warns against IV push, but other concentration and infusion-time examples conflict with the later FDA labeling update. Deep intramuscular administration is preferred; if IV administration is necessary, follow the updated exact-product dilution and infusion instructions. Do not use the old maximum-IV-concentration sentence or infusion examples as current instructions.

Safety sources and review scope
  • FDA class-wide promethazine labeling safety update (opens in a new tab)Source URL: https://www.fda.gov/drugs/drug-alerts-and-statements/fda-requires-updates-labeling-promethazine-hydrochloride-injection-products

    Exact location: 2023-12-27 notice: administration recommendation paragraph; If intramuscular injection is not possible bullets; adult and pediatric dilution/infusion tables

    Source family: FDA class-wide promethazine labeling safety update

    Scope: Official route/concentration/administration update; not a complete individual product monograph.

  • Promethazine U.S. prescribing information implementing FDA update (opens in a new tab)Source URL: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1d02d52b-84bb-4e81-b352-125029eb39f6

    Exact location: CONTRAINDICATIONS UUID0e9dd230-b07d-cda7-e063-6394a90ae084; DOSAGE AND ADMINISTRATION UUID0eade268-8023-e418-e063-6294a90a6ff9, Important Administration Information and Preparation/Administration for Diluted IV Infusion, Tables1/2

    Source family: Promethazine U.S. prescribing information implementing FDA update

    Scope: Example updated SPL version8 effective2024-01-05. It confirms the label change; stocked manufacturer/package and latest marketing status remain unreconciled.

Historical source in disagreement: Archived GlobalRPh article (opens in a new tab)Historical source URL: https://globalrph.com/dilution/promethazine/

Historical location: Drug Dilution:15–30 minute examples; Stability/Miscellaneous: Limit concentration paragraph and historical ISMP strategies

Review-note ID: H62-SAFETY-PROMETHAZINE-ADMINISTRATION. The historical source remains preserved; this note does not qualify its complete monograph.

Historical dilution reference. Verify the preparation against the label for the product in hand.

Original GlobalRPh article: Promethazine (opens in a new tab)Original source URL: https://globalrph.com/dilution/promethazine/ Retrieved 2026-11-04

Historical source details

Original publication date: unavailable in the retrieved article.

Source location and file checksums
Original source URL
https://globalrph.com/dilution/promethazine/ (opens in a new tab)
Source date
Not established in the retrieved source
Retrieved
2026-11-04T19:47:24.201827+00:00
Source location
div.post-content
Packaged content SHA-256
2dd4f01d4b5b9cebbd4a0fc3532d9ab8b2a155ba12f47798a9daf216ea448069
Original response SHA-256
8356be5791a8cf5f99a89fc495f637c3dd450f1a5d5c268ed747f78741912194
Source body SHA-256
c675d139591292ad2d9f3b480197f6042ee80945fbf2ea8ee47cfdacaa9fec3f

Promethazine

The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

NS, D5W

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

Promethazine historical concentration and infusion advice is superseded

The restored article already warns against IV push, but other concentration and infusion-time examples conflict with the later FDA labeling update. Deep intramuscular administration is preferred; if IV administration is necessary, follow the updated exact-product dilution and infusion instructions. Do not use the old maximum-IV-concentration sentence or infusion examples as current instructions.

Current-source reference: 2023-12-27 notice: administration recommendation paragraph; If intramuscular injection is not possible bullets; adult and pediatric dilution/infusion tables

Current-source reference: CONTRAINDICATIONS UUID0e9dd230-b07d-cda7-e063-6394a90ae084; DOSAGE AND ADMINISTRATION UUID0eade268-8023-e418-e063-6294a90a6ff9, Important Administration Information and Preparation/Administration for Diluted IV Infusion, Tables1/2

Follow your local protocol....
Detroit VAMC Dilution:
[0 - 25 mg] [ 50 -100 ml] [ 15 - 30 min]

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

Promethazine historical concentration and infusion advice is superseded

The restored article already warns against IV push, but other concentration and infusion-time examples conflict with the later FDA labeling update. Deep intramuscular administration is preferred; if IV administration is necessary, follow the updated exact-product dilution and infusion instructions. Do not use the old maximum-IV-concentration sentence or infusion examples as current instructions.

Current-source reference: 2023-12-27 notice: administration recommendation paragraph; If intramuscular injection is not possible bullets; adult and pediatric dilution/infusion tables

Current-source reference: CONTRAINDICATIONS UUID0e9dd230-b07d-cda7-e063-6394a90ae084; DOSAGE AND ADMINISTRATION UUID0eade268-8023-e418-e063-6294a90a6ff9, Important Administration Information and Preparation/Administration for Diluted IV Infusion, Tables1/2

EXP: 1 DAY (RT)
Label: Do not Refrigerate. Protect from light.
If a patient complains of pain during intended intravenous injection, stop the injection immediately. DO NOT GIVE IV PUSH - MUST DILUTE FIRST AND ADMINISTER BY SLOW IV INFUSION- SEE BELOW. PREFERRED ROUTES: IM OR ORAL.

Subcutaneous or intra-arterial injection is contraindicated as these routes of administration may cause tissue necrosis and gangrene of the affected extremity, respectively (Prod Info Phenergan(R),).

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."

Open this historical article on its own

Reviewed product information

Applies to

Phenergan promethazine hydrochloride injection, Hikma 25 mg/mL, 1 mL vial. Adult IV guidance only when deep IM administration is not possible. Excludes the 50 mg/mL presentation.

The FDA safety communication and corresponding U.S. label address severe tissue injury. Use the adult table for the ordered dose. Keep the earlier safety notice above the historical article.

Preparation sources checked 2026-11-13.

Route Safety

Deep IM administration is preferred. If IV use is necessary, dilute for infusion and use a catheter in a large vein, preferably central. Avoid hand and wrist veins.

Sources and exact locations

Claim ID: IVR-70-PROMETHAZINE-001

Review basis: FDA postmarketing safety assessment

  1. Source 1

    PHENERGAN U.S. prescribing information (opens in a new tab)

    Exact location: Important Administration Information for Adult and Pediatric Patients 2 Years of Age and Older (SPL section 417cce0e-dd9f-4739-ae0f-18a6398c7bee); Preparation and Administration Instructions for Diluted Intravenous Infusion in Adults (SPL section 1cfdf8d9-79d5-4584-8733-f87251357977)

    Publisher: DailyMed / Hikma Pharmaceuticals USA Inc.

    Source family: U.S. product prescribing information

    Retrieved: 2026-11-13T14:23:07.348573+00:00

  2. Source 2

    FDA promethazine injection safety communication (opens in a new tab)

    Exact location: If intramuscular injection is not possible, first bullet

    Publisher: U.S. Food and Drug Administration

    Source family: U.S. Food and Drug Administration

    Retrieved: 2026-11-13T14:23:07.428917+00:00

    FDA safety communication underpinning the label update. These documents are related evidence.

Dilution

Use only 0.9% sodium chloride for dilution. IV concentrations above 1 mg/mL are contraindicated. Use the dose-specific adult dilution table.

Sources and exact locations

Claim ID: IVR-70-PROMETHAZINE-002

Review basis: FDA postmarketing safety assessment

  1. Source 1

    PHENERGAN U.S. prescribing information (opens in a new tab)

    Exact location: WARNING: RESPIRATORY DEPRESSION IN PEDIATRICS AND SEVERE TISSUE INJURY, INCLUDING GANGRENE (SPL section 1f481ae1-6ac8-4575-97dc-de183cc2f310); Preparation and Administration Instructions for Diluted Intravenous Infusion in Adults (SPL section 1cfdf8d9-79d5-4584-8733-f87251357977)

    Publisher: DailyMed / Hikma Pharmaceuticals USA Inc.

    Source family: U.S. product prescribing information

    Retrieved: 2026-11-13T14:23:07.348573+00:00

  2. Source 2

    FDA promethazine injection safety communication (opens in a new tab)

    Exact location: Diluent and concentration bullets; adult Table 1

    Publisher: U.S. Food and Drug Administration

    Source family: U.S. Food and Drug Administration

    Retrieved: 2026-11-13T14:23:07.428917+00:00

    FDA safety communication underpinning the label update. These documents are related evidence.

Adult Preparation Example

For a prescribed 25 mg adult dose, use 50 mL of 0.9% sodium chloride for dilution. Infuse over 20 to 40 minutes and do not exceed 2.5 mL/min.

Sources and exact locations

Claim ID: IVR-70-PROMETHAZINE-003

Review basis: FDA postmarketing safety assessment

  1. Source 1

    PHENERGAN U.S. prescribing information (opens in a new tab)

    Exact location: Preparation and Administration Instructions for Diluted Intravenous Infusion in Adults (SPL section 1cfdf8d9-79d5-4584-8733-f87251357977)

    Publisher: DailyMed / Hikma Pharmaceuticals USA Inc.

    Source family: U.S. product prescribing information

    Retrieved: 2026-11-13T14:23:07.348573+00:00

  2. Source 2

    FDA promethazine injection safety communication (opens in a new tab)

    Exact location: Adult Table 1, 25 mg row and preceding infusion-time paragraph

    Publisher: U.S. Food and Drug Administration

    Source family: U.S. Food and Drug Administration

    Retrieved: 2026-11-13T14:23:07.428917+00:00

    FDA safety communication underpinning the label update. These documents are related evidence.

Safety resources for this medication (1)

Read the linked communication and current prescribing information before use. Resource dates and affected product scopes differ; a listed resource is not a full monograph or a lot-specific clearance.

Product identifiers and clinical review status

Selected prescribing information available. Full monograph review pending.

Selected product identity

Matched to U.S. product NDC 0641-6084 for the preparation statements shown.

View product identifiers and primary-label provenance
Selected product scope
Phenergan promethazine hydrochloride injection, Hikma 25 mg/mL, 1 mL vial. Adult IV guidance only when deep IM administration is not possible. Excludes the 50 mg/mL presentation.
Field ID: IVR-70-PROMETHAZINE-META-PRODUCT_SCOPE

Primary source (opens in a new tab) | Product data elements and the claim-specific formulation described in the cited preparation sections

Complete product reconciliation: pending.

Labeler
Hikma Pharmaceuticals USA Inc.
Field ID: IVR-70-PROMETHAZINE-META-LABELER

Primary source (opens in a new tab) | SPL author/assignedEntity/representedOrganization/name

Complete product reconciliation: pending.

Application number(s)
ANDA083312
Field ID: IVR-70-PROMETHAZINE-META-APPLICATION_NUMBERS

Primary source (opens in a new tab) | SPL subjectOf/approval/id/@extension

Complete product reconciliation: pending.

NDC(s)
0641-6084-01; 0641-6084-25
Field ID: IVR-70-PROMETHAZINE-META-NDCS

Primary source (opens in a new tab) | SPL manufacturedProduct/asContent/containerPackagedProduct/code/@code and How Supplied

Complete product reconciliation: pending.

DailyMed Set ID
481866da-a712-48a5-853f-8e84aacaab6d
Field ID: IVR-70-PROMETHAZINE-META-SETID

Primary source (opens in a new tab) | SPL document/setId/@root

Complete product reconciliation: pending.

SPL version
8
Field ID: IVR-70-PROMETHAZINE-META-SPL_VERSION

Primary source (opens in a new tab) | SPL document/versionNumber/@value

Complete product reconciliation: pending.

Label printed revision date
Not established
SPL effective date
2024-05-20
Field ID: IVR-70-PROMETHAZINE-META-REVISION_DATE

Primary source (opens in a new tab) | SPL document/effectiveTime/@value

Complete product reconciliation: pending.

Retrieved
2026-11-13T14:23:07.348573+00:00
Field ID: IVR-70-PROMETHAZINE-META-RETRIEVED_AT

Primary source (opens in a new tab) | Timestamp recorded when source bytes were retrieved

Complete product reconciliation: pending.

Downloaded XML SHA-256
dacccf6673cf58652022b1b926dd4d4cb4cfb1f4feed74e19fcdd83ed9e82b9d
Field ID: IVR-70-PROMETHAZINE-META-XML_SHA256

Primary source (opens in a new tab) | SHA-256 computed over the exact downloaded XML bytes

Complete product reconciliation: pending.

What remains to be completed
  • Extract and verify presentation-specific IV preparation.
  • Complete indication- and age-specific dosing, incompatibility, monitoring and stability review.
  • Assess any proposed compounding BUD for the exact formulation, concentration, container and conditions.