Promethazine Hydrochloride

• Promethazine hydrochloride injection should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression.Postmarketing 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

  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. Postmarketing 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

• Severe chemical irritation and

  damage to tissues regardless of the route of parenteral administration

  has been reported in patients treated with promethazine hydrochloride injection including gangrene, tissue necrosis, and thrombophlebitis; and in some cases, surgical intervention including fasciotomy, skin graft, and/or amputation have been required (see

  Severe Tissue Injury, Including Gangrene

  • Promethazine hydrochloride injection has been reported to cause severe chemical irritation and d

    amage to tissues, including gangrene, regardless of the route of parenteral administration

    . Intra-arterial and subcutaneous administration have resulted in more significant complications. The use of promethazine hydrochloride injection by intravenous injection at concentrations greater than 1 mg/mL, intra- arterial injection, or subcutaneous injection is contraindicated (see CONTRAINDICATIONS).
  • Irritation and damage can result from perivascular extravasation, intra- arterial injection, and intraneuronal or perineuronal infiltration. Inadvertent intra-arterial injection can cause severe arteriospasm. Other reported adverse reactions included 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.
  • The preferred route of administration of promethazine hydrochloride injection is by deep intramuscular administration.
    Promethazine hydrochloride injection may be administered intravenously after dilution through an intravenous catheter inserted in a large vein. Preferably through a central venous catheter (see DOSAGE AND ADMINISTRATION).
  • If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion, evaluate for possible arterial injection or perivascular extravasation, and initiate appropriate medical management.

  .).
• The use of promethazine hydrochloride injection by the following routes of administration is CONTRAINDICATED:
  • Intravenous injection at concentrations greater than 1 mg/mL
  • Intra-arterial injection
  • Subcutaneous injection (see

    CONTRAINDICATIONS

    The use of promethazine hydrochloride injection is contraindicated:

    • In pediatric patients less than 2 years of age due to the risk of respiratory depression (see

    WARNINGS – Respiratory Depression

    ).

    • For use as an intravenous injection at concentrations greater than 1 mg/mL due to the risk of perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration (see

    WARNINGS - Severe Tissue Injury, Including Gangrene

    and

    DOSAGE AND ADMINISTRATION

    ).

    • For use as an intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see

    WARNINGS - Severe Tissue Injury, Including Gangrene

    ).

    • For use as a subcutaneous injection because chemical irritation and necrotic lesions have been reported (see

    WARNINGS - Severe Tissue Injury, Including Gangrene

    ).

    • In patients in a comatose state.

    •

    In patients who have demonstrated an idiosyncratic reaction or hypersensitivity to promethazine hydrochloride or other phenothiazines.

    ).
• The preferred route of administration is by deep intramuscular administration.
• Promethazine hydrochloride injection may be administered intravenously after dilution through an intravenous catheter inserted in a large vein. Preferably through a central venous catheter (see

  DOSAGE AND ADMINISTRATION

  Important Administration Information for Adult and
  Pediatric Patients 2 Years of Age and Older

  • The preferred route of administration of promethazine hydrochloride injection is by deep intramuscular administration (see
    WARNINGS - Severe Tissue Injury, Including Gangrene
    ).
  • Promethazine hydrochloride injection may be administered intravenously after dilution as recommended below
    (see Preparation and Administration).
    If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion, and evaluate for possible arterial injection or perivascular extravasation.

  Allergic Conditions

  The average adult dose is 25 mg. This dose may be repeated within two hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg.

  Sedation

  In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25 to 50 mg of promethazine hydrochloride injection.

  Nausea and Vomiting

  For control of nausea and vomiting, the usual adult dose is 12.5 to 25 mg, not to be repeated more frequently than every four hours. When used for control of postoperative nausea and vomiting, the dosage of analgesics and barbiturates should be reduced accordingly (see

  PRECAUTIONS - Drug Interactions

  ).

  Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see

  PRECAUTIONS - Pediatric Use

  ).

  Preoperative and Postoperative Use

  As an adjunct to preoperative or postoperative medication, 25 to 50 mg of promethazine hydrochloride injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly (see

  PRECAUTIONS - Drug Interactions

  ).

  Promethazine hydrochloride is contraindicated for use in pediatric patients less than two years of age.

  Obstetrics

  Promethazine hydrochloride injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25 to 75 mg (average dose, 50 mg) promethazine hydrochloride injection may be given with an appropriately reduced dose of any desired narcotic (see

  PRECAUTIONS - Drug Interactions

  ). If necessary, promethazine hydrochloride injection with a reduced dose of analgesic may be repeated once or twice at four-hour intervals in the course of a normal labor. A maximum total dose of 100 mg of promethazine hydrochloride injection may be administered during a 24-hour period to patients in labor.

  Pediatric Patients

  Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than 2 years of age (see

  WARNINGS - Respiratory Depression

  ). Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age or older. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided (see

  WARNINGS - Respiratory Depression

  ).

  In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 1.1 mg per kg of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug (see

  PRECAUTIONS - Drug Interactions

  ). Antiemetics should not be used in vomiting of unknown etiology in pediatric patients.

  Preparation and
  Administration Instructions for Diluted Intravenous Infusion in Adults

  Inspect the solution for particulate matter and discoloration, before dilution, after dilution, and before administration

  .

  Discard the vial, ampule, or bag if particulates and/or discoloration are observed.

  1. Determine the recommended dose of promethazine hydrochloride injection.

  2. Aseptically withdraw the required volume from the vial or ampule and transfer it into an infusion bag.

  • Use a filter needle when withdrawing promethazine hydrochloride injection from the ampule.

  3. Dilute with the recommended volume of 0.9% Sodium Chloride Injection, see Table 1. Avoid mixing and/or diluting with any other drugs or solutions other than 0.9% Sodium Chloride Injection.

  4. Gently invert the infusion bag.

  5. Check patency of the access site before administration.

  6. Administer the diluted solution through an intravenous catheter, inserted in a large vein (preferably through a central venous catheter), over 20 to 40 minutes; for maximum infusion rates, see Table 1.

  • Do
    NOT
    administer via an intravenous catheter in the hand or wrist.

  7. If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion and evaluate for possible arterial injection or perivascular extravasation.

  Table 1. Preparation and Infusion Information by Adult Dose of Promethazine Hydrochloride Injection

  Dose of Promethazine Hydrochloride Injection	Volume of 0.9% Sodium Chloride Injection for Dilution	Maximum Concentration of the Diluted Promethazine Hydrochloride Injection Solution	Maximum Rate of Infusion
  12.5 mg	50 mL	1 mg/mL	2.5 mL/minute
  25 mg	50 mL		2.5 mL/minute
  50 mg	50 mL		2.5 mL/minute
  75 mg	100 mL		5 mL/minute

  
  
  

  Preparation
  and Administration Instructions for Diluted Intravenous Infusion to Pediatric
  Patients 2 Years of Age and Older.

  Inspect the solution for particulate matter and discoloration, before dilution, after dilution, and before administration. Discard the vial, ampule, syringe or bag if particulates and/or discoloration are observed.

  1. Determine the recommended dose of promethazine hydrochloride injection for pediatric patients 2 years of age and older.

  2. Aseptically withdraw the required volume from the vial or ampule and transfer it into an appropriately sized syringe or bag for use with an infusion pump.

  • Use a filter needle when withdrawing promethazine hydrochloride injection from the ampule.

  3. Dilute with the recommended volume of 0.9% Sodium Chloride Injection, see Table 2. Avoid mixing and/or diluting with any other drugs or solutions other than 0.9% Sodium Chloride Injection.

  4. Gently invert the syringe or bag.

  5. Check patency of the access site before administration.

  6. Administer the diluted solution through an intravenous catheter, inserted in a large vein (preferably through a central venous catheter) with a maximum infusion rate of 1.25 mL/minute.

  • Do
    NOT
    administer via an intravenous catheter in the hand or wrist.

  7. If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion and evaluate for possible arterial injection or perivascular extravasation.

  Table 2. Preparation and Infusion Information by Pediatric Dose of Promethazine Hydrochloride Injection

  Dose of Promethazine Hydrochloride Injection	Volume of 0.9% Sodium Chloride Injection for Dilution	Maximum Concentration of the Diluted Promethazine Hydrochloride Injection Solution	Maximum Rate of Infusion
  Up to 25 mg	25 mL	1 mg/mL	1.25 mL/minute
  25 mg to 50 mg	50 mL

  *Avoid mixing and/or diluting with any other drugs or solutions besides 0.9% Sodium Chloride Injection

  
  
  

  Storage of Diluted
  Promethazine Hydrochloride Injection

  Diluted solution may be stored up to 4 hours at room temperature, 20°C to 25°C (68°F to 77°F), or refrigerated at 2°C to 8°C (36° to 46°F), up to 24 hours.

  ).
• If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion and evaluate for possible arterial injection or perivascular extravasation, and initiate appropriate medical management.

Promethazine hydrochloride injection is indicated for the following conditions:

• Amelioration of allergic reactions to blood or plasma.
• In anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled.
• For other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.
• For sedation and relief of apprehension and to produce light sleep from which the patient can be easily aroused.
• Active treatment of motion sickness.
• Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.
• As an adjunct to analgesics for the control of postoperative pain.
• Preoperative, postoperative, and obstetric (during labor) sedation.
• 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.

• The preferred route of administration of promethazine hydrochloride injection is by deep intramuscular administration (see
  Severe Tissue Injury, Including Gangrene

  • Promethazine hydrochloride injection has been reported to cause severe chemical irritation and d

    amage to tissues, including gangrene, regardless of the route of parenteral administration

    . Intra-arterial and subcutaneous administration have resulted in more significant complications. The use of promethazine hydrochloride injection by intravenous injection at concentrations greater than 1 mg/mL, intra- arterial injection, or subcutaneous injection is contraindicated (see CONTRAINDICATIONS).
  • Irritation and damage can result from perivascular extravasation, intra- arterial injection, and intraneuronal or perineuronal infiltration. Inadvertent intra-arterial injection can cause severe arteriospasm. Other reported adverse reactions included 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.
  • The preferred route of administration of promethazine hydrochloride injection is by deep intramuscular administration.
    Promethazine hydrochloride injection may be administered intravenously after dilution through an intravenous catheter inserted in a large vein. Preferably through a central venous catheter (see DOSAGE AND ADMINISTRATION).
  • If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion, evaluate for possible arterial injection or perivascular extravasation, and initiate appropriate medical management.
  ).
• Promethazine hydrochloride injection may be administered intravenously after dilution as recommended below
  (see

  Preparation and
  Administration Instructions for Diluted Intravenous Infusion in Adults

  Inspect the solution for particulate matter and discoloration, before dilution, after dilution, and before administration

  .

  Discard the vial, ampule, or bag if particulates and/or discoloration are observed.

  1. Determine the recommended dose of promethazine hydrochloride injection.

  2. Aseptically withdraw the required volume from the vial or ampule and transfer it into an infusion bag.

  • Use a filter needle when withdrawing promethazine hydrochloride injection from the ampule.

  3. Dilute with the recommended volume of 0.9% Sodium Chloride Injection, see Table 1. Avoid mixing and/or diluting with any other drugs or solutions other than 0.9% Sodium Chloride Injection.

  4. Gently invert the infusion bag.

  5. Check patency of the access site before administration.

  6. Administer the diluted solution through an intravenous catheter, inserted in a large vein (preferably through a central venous catheter), over 20 to 40 minutes; for maximum infusion rates, see Table 1.

  • Do
    NOT
    administer via an intravenous catheter in the hand or wrist.

  7. If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion and evaluate for possible arterial injection or perivascular extravasation.

  Table 1. Preparation and Infusion Information by Adult Dose of Promethazine Hydrochloride Injection

  Dose of Promethazine Hydrochloride Injection	Volume of 0.9% Sodium Chloride Injection for Dilution	Maximum Concentration of the Diluted Promethazine Hydrochloride Injection Solution	Maximum Rate of Infusion
  12.5 mg	50 mL	1 mg/mL	2.5 mL/minute
  25 mg	50 mL		2.5 mL/minute
  50 mg	50 mL		2.5 mL/minute
  75 mg	100 mL		5 mL/minute

  
  
  

  ). 
  If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion, and evaluate for possible arterial injection or perivascular extravasation.

Promethazine hydrochloride injection is contraindicated in pediatric patients less than 2 years of age, because of the potential for fatal respiratory depression. Promethazine hydrochloride injection should be used with caution in pediatric patients 2 years of age and older (see

Promethazine hydrochloride injection may increase, prolong, or intensify the sedative action of central-nervous-system depressants, such as alcohol, sedative/hypnotics (including barbiturates), general anesthetics, narcotics, narcotic analgesics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine hydrochloride. When given concomitantly with promethazine hydrochloride injection, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine hydrochloride injection relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.