Cyclizine (Systemic)


VA CLASSIFICATION
Primary: GA609

Commonly used brand name(s): Marezine; Marzine.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiemetic—

Indications

Accepted

Motion sickness (prophylaxis and treatment)—Oral cyclizine is indicated for the prophylaxis and treatment of nausea, vomiting, {08} {12} {15} and dizziness {19} associated with motion sickness. Parenteral cyclizine is indicated for the treatment of nausea and vomiting of motion sickness when the oral route cannot be used. {04}

Nausea and vomiting, postoperative (prophylaxis and treatment)—Parenteral cyclizine is used to prevent or relieve postoperative nausea and vomiting. {02} {07} {12}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Cyclizine hydrochloride: 302.85 {14}
    Cyclizine lactate: 356.46 {14}


pH
    Cyclizine lactate: 3.2 to 4.7 {13}

pKa—
    7.7 {05}

Mechanism of action/Effect:

Antiemetic—The mechanism by which cyclizine exerts its antiemetic and antimotion sickness effects is not precisely known but may be related to its central anticholinergic actions. It diminishes vestibular stimulation and depresses labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. {04} {05} {12}


Other actions/effects:

Cyclizine also has antihistaminic, anticholinergic, antivertigo, {05} {12} central nervous system (CNS) depressant, and local anesthetic effects. {05}

Duration of action:

4 to 6 hours.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Problems in humans have not been documented.

Cyclizine has been shown to be teratogenic in rats {05} at doses above the human therapeutic range.

Breast-feeding

It is not known whether cyclizine is distributed into breast milk. {12} However, problems in humans have not been documented.

Because of its anticholinergic actions, cyclizine may inhibit lactation. {06}

Pediatrics

Appropriate studies on the relationship of age to the effects of cyclizine have not been performed in the pediatric population. {17} However, it is known that pediatric patients exhibit increased sensitivity to anticholinergics, which are related pharmacologically to cyclizine.


Geriatrics


No information is available on the relationship of age to the effects of cyclizine in geriatric patients. However, it is known that geriatric patients exhibit increased sensitivity to anticholinergics, {06} which are related pharmacologically to cyclizine. Therefore, constipation, dryness of mouth, and urinary retention (especially in males) are more likely to occur in the elderly.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use may potentiate the CNS depressant effects of either these medications or cyclizine {02} {04} {12} {15})


Anticholinergics or other medications with anticholinergic activity (See Appendix II ){11}    (concurrent use with cyclizine may potentiate anticholinergic effects)


Apomorphine    (prior administration of cyclizine may decrease the emetic response to apomorphine {04} {12})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Skin tests using allergen extracts    (may inhibit the cutaneous histamine response, thus producing false-negative results; it is recommended that cyclizine be discontinued at least 72 hours before testing begins {05})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Bladder neck obstruction or
Prostatic hyperplasia, symptomatic{02}{12}{15}    (anticholinergic effects of cyclizine may precipitate urinary retention {04})


Cardiac failure, severe    (cyclizine may decrease cardiac output and increase heart rate, pulmonary wedge pressure, and mean arterial pressure in patients with cardiac failure {04})


Gastroduodenal obstruction    (decrease in motility and tone may occur, aggravating obstruction and gastric retention {04})


Glaucoma, angle-closure, or predisposition to    (increased intraocular pressure may precipitate an attack of angle-closure glaucoma {04})


Glaucoma, open-angle    (mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted with continued use of cyclizine {04})


Pulmonary disease, chronic obstructive{15}    (reduction in bronchial secretion may cause inspissation and formation of bronchial plugs {18})


Sensitivity to cyclizine{04}{12}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness{04}{05}{12}{15}

Incidence less frequent or rare
    
Blurred{04} or double{12} vision
    
constipation{04}{12}
    
diarrhea{12}
    
difficult or painful urination{04}{12}
    
dizziness{04}
    
dryness of the mouth, nose, and throat{04}{12}
    
fast heartbeat{04}{12}
    
loss of appetite{04}{12}
    
nervousness, restlessness, or trouble in sleeping{04}{12}
    
skin rash{04}{12}
    
upset stomach{04}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Meclizine/Buclizine/Cyclizine (Systemic)

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to cyclizine

Pregnancy—Animal studies have shown cyclizine to be teratogenic at doses above human therapeutic range





Breast-feeding—May inhibit lactation due to anticholinergic effects





Use in children—Possible increased susceptibility to anticholinergic side effects






Use in the elderly—Possible increased susceptibility to anticholinergic side effects
Other medications, especially other CNS depressants

Proper use of this medication
Not taking more medication than the amount prescribed

» Proper dosing
Missed dose (if on a regular dosing schedule): Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Possible interference with skin tests using allergens; need to inform physician of use of this medication

» Avoiding use of alcohol or other CNS depressants

» Caution if drowsiness occurs

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks


General Dosing Information
For prophylaxis against motion sickness, this medication should be taken at least 30 minutes before exposure to conditions that may precipitate motion sickness. {05}


Oral Dosage Forms

CYCLIZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Motion sickness (prophylaxis and treatment)
Oral, 50 mg thirty minutes before travel. Dose may be repeated every four to six hours as needed. {08} {09} {15}


Usual adult prescribing limits
Up to 200 mg daily. {08} {15}

Usual pediatric dose
Motion sickness (prophylaxis and treatment)


Children up to 6 years of age:
Use is not recommended unless directed by a physician. {15}



Children 6 to 12 years of age:
Oral, 25 mg thirty minutes before travel. Dose may be repeated every six to eight hours as needed; {03} {15} or

1 mg per kg of body weight or 33 mg per square meter of body surface area three times a day. {09}



Children 13 years of age or older:
See Usual adult and adolescent dose.{15}



Note: The total daily dose for pediatric patients should not exceed 75 mg. {01} {03} {15}


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


50 mg (OTC) [Marezine (scored)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. {13}

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

CYCLIZINE LACTATE INJECTION USP

Usual adult and adolescent dose
Motion sickness (prophylaxis and treatment)
Intramuscular, 50 mg every four to six hours as needed. {04} {09} {16}

Nausea and vomiting, postoperative (prophylaxis and treatment)
Intramuscular, 50 mg fifteen to thirty minutes before end of operation. Dose may be repeated three times a day during the first few postoperative days, if needed. {02}


Usual pediatric dose
Motion sickness (prophylaxis and treatment)
Intramuscular, 1 mg per kg of body weight {09} {16} or 33 mg per square meter of body surface area {16} three times a day as needed.

Nausea and vomiting, postoperative (prophylaxis and treatment)


Children up to 6 years of age:
Intramuscular, 12.5 mg fifteen to thirty minutes before end of operation. Dose may be repeated three times a day during the first few postoperative days, if needed. {12}



Children 6 to 12 years of age:
Intramuscular, 25 mg fifteen to thirty minutes before end of operation. Dose may be repeated three times a day during the first few postoperative days, if needed. {02}



Children 13 years of age or older:
See Usual adult and adolescent dose.



Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


50 mg per mL (Rx) [Marzine]

Packaging and storage:
Store between 5 and 10 °C (41 and 50 °F), {16} unless otherwise specified by manufacturer. Protect from light. {12} {13} Protect from freezing.

Preparation of dosage form:
Cyclizine may be given intravenously if it is diluted to at least 10 mL with sterile water for injection or 0.9% sodium chloride injection and administered slowly. {12}

Stability:
When stored at room temperature for several months, a slight yellowing of the solution may occur. This does not affect potency. {04} {16}

Incompatibilities:
Cyclizine lactate injection is incompatible with solutions having a pH greater than 6.8. {10} {16}



Revised: 06/18/2002



References
  1. Personal communication, USOC drug testing hotline, 8/24/92.
  1. Marzine (Burroughs Wellcome). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 27th ed. Ottawa: Canadian Pharmaceutical Association, 1992: 426.
  1. Fed Regist 1988 Sep; 53(179): 35809.
  1. Marezine injection package insert (Burroughs Wellcome—US), Rev 5/89, Rec 11/20/89.
  1. McEvoy GK, editor. AHFS Drug information 92. Bethesda, MD: American Society of Hospital Pharmacists, 1992: 1657-8.
  1. Knoben J, Anderson P. Handbook of clinical drug data. 6th ed, Hamilton, IL: Drug Intelligence Publications.
  1. Drug evaluations subscription. Chicago: American Medical Association, Spring 1992: 414-5.
  1. Marezine tablet package labeling (Burroughs Wellcome—US), Rev 1984, Rec 8/19/91.
  1. Benitz WE, Tatro DS. The pediatric drug handbook. 2nd ed. Chicago: Year Book Medical Publishers, Inc., 1988: 397.
  1. Trissel LA. Handbook on injectable drugs. 5th ed. Bethesda, MD: American Society of Hospital Pharmacists, 1988: 217.
  1. McInnes G, Brodie M. Drug interactions that matter. Drugs 1988; 36: 83-110.
  1. Marzine (Burroughs Wellcome). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 761.
  1. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 438.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1996. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1995: 192.
  1. Cyclizine tablets package label (Himmel—US), Rec 8/16/95.
  1. Trissel LA. Handbook on injectable drugs. 7th ed. Bethesda, MD: American Society of Hospital Pharmacists, 1992: 259-60.
  1. Panel comment, 10/95.
  1. Reviewers' consensus on monograph revision of 10/95.
  1. Manufacturer comment, 11/95.
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