PROMETHAZINE HYDROCHLORIDE

PROMETHAZINE HYDROCHLORIDE- promethazine hydrochloride injection, solution
XGen Pharmaceuticals DJB, Inc.

BOXED WARNING

RESPIRATORY DEPRESSION: Pediatrics

Promethazine hydrochloride injection should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression. Post-marketing cases of respiratory depression, including fatalities, have been reported with use of promethazine in pediatric patients less than 2 years of age. Caution should be exercised when administering promethazine hydrochloride injection to pediatric patients 2 years of age and older (see WARNINGS — Respiratory Depression).

Severe Tissue Injury, Including Gangrene

Promethazine hydrochloride injection can cause severe chemical irritation and damage to tissue regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, thrombophlebitis, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation have been required (see WARNINGS — Severe Tissue Injury, Including Gangrene).

Due to the risks of intravenous injection, the preferred route of administration of promethazine hydrochloride injection is deep intramuscular injection. Subcutaneous injection is contraindicated. See DOSAGE AND ADMINISTRATION for important notes on administration.

DESCRIPTION

Promethazine hydrochloride injection, USP is a sterile, pyrogen-free solution for deep intramuscular or intravenous administration. Promethazine hydrochloride (10H-Phenothiazine-10-ethanamine, N, N, α -trimethyl-, monohydrochloride, (±)-) is a racemic compound and has the following structural formula:

image
(click image for full-size original)

image

Each mL contains promethazine hydrochloride, either 25 mg or 50 mg, edetate disodium 0.1 mg, calcium chloride 0.04 mg, sodium metabisulfite 0.25 mg and phenol 5 mg in Water for Injection, USP. pH 4.0 to 5.5; buffered with acetic acidsodium acetate. Sealed under nitrogen.

Promethazine hydrochloride injection is a clear, colorless solution. The product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

CLINICAL PHARMACOLOGY

Promethazine hydrochloride is a phenothiazine derivative which possesses antihistaminic, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. Promethazine is a competitive H1 receptor antagonist, but does not block the release of histamine. Structural differences from the neuroleptic phenothiazines result in its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties. 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. Promethazine hydrochloride is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine. Following intravenous administration in healthy volunteers, the plasma half-life for promethazine has been reported to range from 9 to 16 hours. The mean plasma half-life for promethazine after intramuscular administration in healthy volunteers has been reported to be 9.8 ± 3.4 hours.

INDICATIONS AND USAGE

Promethazine hydrochloride injection is indicated for the following conditions:

1. Amelioration of allergic reactions to blood or plasma.

2. In anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled.

3. For other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.

4. For sedation and relief of apprehension and to produce light sleep from which the patient can be easily aroused.

5. Active treatment of motion sickness.

6. Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.

7. As an adjunct to analgesics for the control of postoperative pain.

8. Preoperative, postoperative, and obstetric (during labor) sedation.

9. Intravenously in special surgical situations, such as repeated bronchoscopy, ophthalmic surgery, and poor-risk patients, with reduced amounts of meperidine or other narcotic analgesic as an adjunct to anesthesia and analgesia.

CONTRAINDICATIONS

Children Less Than 2 Years of Age

Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than two years of age due to the risk of respiratory depression (see WARNINGS — Respiratory Depression).

Comatose State

Promethazine hydrochloride injection is contraindicated in comatose states.

Intra-Arterial Injection

Under no circumstances should promethazine hydrochloride injection be given by intra arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS — Severe Tissue Injury, Including Gangrene).

Subcutaneous Injection

Promethazine hydrochloride injection should not be given by the subcutaneous route because evidence of chemical irritation has been noted, and necrotic lesions have resulted following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.

Idiosyncratic Reaction or Hypersensitivity

Promethazine hydrochloride injection is contraindicated in patients who have demonstrated an idiosyncratic reaction or hypersensitivity to promethazine or other phenothiazines.

WARNINGS

Respiratory Depression

Pediatrics

Promethazine hydrochloride injection should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression. Post marketing cases of respiratory depression, including fatalities, have been reported with use of promethazine in pediatric patients less than 2 years of age. A wide range of weight-based doses of promethazine hydrochloride injection have resulted in respiratory depression in these patients.

Caution should be exercised when administering promethazine hydrochloride injection to pediatric patients 2 years of age and older. It is recommended that the lowest effective dose of promethazine hydrochloride injection be used in pediatric patients 2 years of age and older. Avoid concomitant administration of other drugs with respiratory depressant effects because of an association with respiratory depression, and sometimes death, in pediatric patients.

Other

Because of the risk of potentially fatal respiratory depression, use of promethazine hydrochloride injection in patients with compromised respiratory function or patients at risk for respiratory failure (e.g. COPD, sleep apnea) should be avoided.

Severe Tissue Injury, Including Gangrene

Promethazine hydrochloride injection can cause severe chemical irritation and damage to tissues, regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, erythema, swelling, sensory loss, palsies, paralysis, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, and gangrene. In some cases surgical intervention, including fasciotomy, skin graft, and/or amputation have been required.

Because of the risks of intravenous injection, the preferred route of administration of promethazine hydrochloride injection is deep intramuscular injection (see DOSAGE AND ADMINISTATION). Subcutaneous injection is contraindicated. Due to close proximity of arteries and veins in the areas most commonly used for intravenous injection, extreme care should be exercised to avoid perivascular extravasation or unintentional intra-arterial injection as pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation are likely under such circumstances. Aspiration of dark blood does not preclude intra-arterial needle placement because blood is discolored upon contact with promethazine hydrochloride injection. Use of syringes with rigid plungers or small-bore needles might obscure typical arterial backflow if this is relied upon alone.

In the event that a patient complains of pain during intravenous injection of promethazine hydrochloride injection, the injection should be stopped immediately to evaluate for possible arterial injection or perivascular extravasation.

There is no proven successful management of unintentional intra-arterial injection or perivascular extravasation after it occurs. Sympathetic block and heparinization have been employed during the acute management of unintentional intra-arterial injection, because of the results of animal experiments with other known arteriolar irritants.

Page 1 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.