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Chlorfenvinphos (BAN) is also known as Clofenvinfos (Rec.INN)
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Glossary
| BAN | British Approved Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Claricin may be available in the countries listed below.
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Class: Anorexigenic Agents and Respiratory and Cerebral Stimulants, Miscellaneous
VA Class: RE900
CAS Number: 7081-53-0
Brands: Dopram
CNS stimulant; a monohydrated pyrrolidinone derivative.128 a
Treatment of drug-induced postanesthetic respiratory depression or apnea not caused by skeletal muscle relaxants.127 a
Other supportive therapy preferred due to questionable benefit and high potential for toxicity with doxapram.a Limited role due to availability of safer and shorter-acting anesthetic agents.128
Has been used in conjunction with supportive measures to stimulate respiration and hasten arousal in patients with respiratory and CNS depression secondary to drug overdose (e.g., barbiturates, opiate analgesics, general anesthetics).127 a
However, use as an analeptic is strongly discouraged by most clinicians;a analeptic therapy largely abandoned in favor of intensive supportive care (e.g., mechanical ventilation, oxygenation, cardiovascular support) and specific antidotes (e.g., pure opiate antagonists).135 a
Short-term use in patients with acute respiratory insufficiency associated with COPD.127 a
Role in such patients is limited; other supportive therapy (i.e., noninvasive ventilation using either negative- or positive-pressure device) is preferred.132 133 134 a
Has been used for the treatment of neonatal apnea†,100 101 102 103 104 105 106 107 108 120 121 123 124 125 principally in combination with theophylline104 105 106 120 or caffeine.107
Limited support for this use; no apparent advantage over methylxanthines and risk of substantial adverse effects with doxapram therapy.128 130 131 The commercially available injection contains benzyl alcohol; use of this preparation in neonates is not recommended.110 117 118 120 127 136 (See Pediatric Use under Cautions.)
Should not be used in conjunction with mechanical ventilation.127
Establish adequate airway and oxygenation prior to administration; take measures to prevent vomiting and aspiration.127 a
Use minimum effective dosage to avoid adverse effects.127 a
Monitor BP, heart rate, and deep tendon reflexes; adjust dosage or rate of infusion accordingly.127 Monitor for recurrence of unconsciousness or development of respiratory depression; provide supportive care as required.127
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV injection or IV infusion.127 a
Predictable blood gas patterns in patients with COPD and acute hypercapnia are more readily established with IV infusion therapy.127
Avoid extravasation and repeated use of a single injection site to minimize local reactions and thrombophlebitis.127 a
Prepare 1-mg/mL solution by adding 250 mg of doxapram hydrochloride (12.5 mL) to 250 mL of 5% dextrose, 10% dextrose, or 0.9% sodium chloride injection.127
Prepare 2-mg/mL solution by adding 400 mg of doxapram hydrochloride (20 mL) to 180 mL of 5% dextrose, 10% dextrose, or 0.9% sodium chloride injection.127
Rapid infusion may result in hemolysis; infuse diluted solution at slow rate.127 a
Postanesthetic use: Initiate IV infusion with 1-mg/mL solution at a rate of approximately 5 mg/minute until desired response achieved; usual maintenance rate is 1–3 mg/minute.127
Acute hypercapnia associated with COPD: Initiate IV infusion with 2-mg/mL solution at a rate of 1–2 mg/minute; may increase to maximum rate of 3 mg/minute.127
Available as doxapram hydrochloride; dosage expressed in terms of the salt.127
Children ≥12 years of age: 0.5–1 mg/kg as a single injection; may repeat every 5 minutes to a maximum total dosage of 2 mg/kg.127
Children ≥12 years of age: 0.5–1 mg/kg, up to a maximum dosage of 4 mg/kg.127
Children ≥12 years of age: Initiate at a rate of 1–2 mg/minute; increase to a maximum rate of 3 mg/minute if indicated.127 Continuation beyond a single 2-hour infusion not recommended.127 a
0.5–1 mg/kg as a single injection; may repeat every 5 minutes to a maximum total dosage of 2 mg/kg.127
0.5–1 mg/kg, up to a maximum dosage of 4 mg/kg.127
Initiate at a rate of 1–2 mg/minute; increase to a maximum rate of 3 mg/minute if indicated.127 Continuation beyond a single 2-hour infusion not recommended.127 a
Children ≥12 years of age: Maximum 1.5 mg/kg for a single injection, 2-mg/kg total dosage for repeat injections; do not exceed 3 g daily.127
Children ≥12 years of age: Maximum 4 mg/kg; do not exceed 3 g daily.127
Children ≥12 years of age: Maximum 3 mg/minute.127 Limit use to a single 2-hour infusion.127
Maximum 1.5 mg/kg for a single injection, 2-mg/kg total dosage for repeat injections; do not exceed 3 g daily.127
Maximum 4 mg/kg; do not exceed 3 g daily.127
Maximum 3 mg/minute.127 Limit use to a single 2-hour infusion.127
No special population dosage recommendations at this time.127
Known hypersensitivity to doxapram or any ingredient in the formulation.127 a
Seizure disorders.127 a
Suspected or confirmed pulmonary embolism.127 a
Mechanical disorders of ventilation (e.g., mechanical obstruction, muscle paresis, flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis or other restrictive lung diseases).127 a
Head injury, cerebrovascular accident, or cerebral edema.127 a
Substantial cardiovascular impairment (i.e., uncompensated heart failure, severe CAD).127 a
Severe hypertension including that associated with hyperthyroidism or pheochromocytoma.127 a (See Postanesthetic Use under Cautions.)
Doxapram hydrochloride injection contains benzyl alcohol as a preservative, which has been associated with toxicity (including deaths) in neonates.109 110 111 112 113 114 115 116 117 122 127 Use of this preparation in neonates is not recommended.110 117 118 120 127 (See Pediatric Use under Cautions.)
Do not use doxapram in conjunction with mechanical ventilation.127 a
Doxapram is not an antagonist to muscle relaxants nor a specific opiate antagonist.127 Assess adequacy of ventilation with specific tests (e.g., peripheral nerve stimulation, airway pressures, head lift, pulse oximetry, end-tidal carbon dioxide) prior to use.127
Narcosis may recur; observe patient closely until fully alert for 0.5–1 hour.127
Concomitant use with a volatile general anesthetic may increase potential for arrhythmias.127 (See Specific Drugs under Interactions.)
Use with caution in patients with hypermetabolic states (e.g., hyperthyroidism, pheochromocytoma).127
May not be effective in patients with severe CNS or respiratory depression; manufacturers state that doxapram may be used adjunctively with established supportive and resuscitative measures.127
If no response, perform neurologic evaluation to identify other potential causes of sustained coma.127
Do not increase rate of infusion to lower carbon dioxide tension.127
Arrhythmias have been reported in patients with acute respiratory failure secondary to COPD.127 a Use with caution in these patients.127
To prevent respiratory acidosis in patients with COPD, monitor arterial blood gases at baseline and every 30 minutes. 127 Discontinue drug and initiate mechanical ventilation if arterial blood gases deteriorate.127
Use does not reduce need for supplemental oxygen.127
Possible changes in heart rate, lowered T-waves, and dysrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, QT interval prolongation).127 128 a Use with caution and monitor cardiac rhythm.127 a
Increases in BP usually are modest, but substantial increases reported.127 Avoid use in patients with severe hypertension.127 (See Contraindications under Cautions.)
Chest pain and tightness in chest also reported.127 a
Discontinue drug if sudden hypotension develops.127 a
Establish and protect airways.127
Discontinue drug if sudden dyspnea develops.127
Lowered carbon dioxide tension induced by hyperventilation may cause cerebral vasoconstriction and decreased cerebral circulation.127 a Pressor effect on pulmonary circulation may lead to decreased arterial oxygen tension.127 Monitor arterial blood gases.127
May cause seizures and other adverse effects due to general CNS stimulation.127 a Anticonvulsants, oxygen, and resuscitative equipment should be readily available; carefully observe patient and administer drug slowly if treatment continued.127
Potential for local reactions including thrombophlebitis; administer dilute solutions at a slow rate, prevent extravasation, and avoid repeated use of a single injection site.127 a
Rapid infusion may result in hemolysis.127 a (See Rate of Administration under Dosage and Administration.)
Category B.127 129
Not known whether doxapram is distributed into milk;127 however, molecular weight of free base suggests drug may be distributed into milk.129
Benzyl alcohol in commercial preparation is associated with toxicity in neonates; caution if used in nursing women.127 (See Pediatric Use under Cautions.)
Safety and efficacy not established in children <12 years of age.127 a
Each mL of doxapram hydrochloride injection contains 9 mg of benzyl alcohol;109 use of this preparation in neonates is not recommended.110 117 118 120 127 Although a causal relationship has not been established, large amounts of benzyl alcohol (100–400 mg/kg daily) have been associated with toxicity in neonates.109 110 111 112 113 114 115 116 117 122 127
Use with caution.127 Possible decrease in rate of metabolism or clearance in patients with substantial hepatic impairment.127
Use with caution.127 Possible decrease in rate of metabolism or clearance in patients with substantial renal impairment.127
Cough,127 128 dyspnea,127 128 tachypnea,127 128 headache,127 128 dizziness,127 128 apprehension,127 128 hypertension,127 128 flushing,127 128 sweating,127 128 nausea,127 128 vomiting,127 128 diarrhea,127 128 urinary retention,127 128 muscle spasticity.127 128
Drug | Interaction | Comments |
|---|---|---|
Anesthetics, inhalation (known to sensitize myocardium to catecholamines) | May increase potential for arrhythmias including ventricular tachycardia and ventricular fibrillation127 a Increased BUN and albuminuria observeda | Delay administration of doxapram until anesthetic excreted127 Importance of observed increase in BUN and albuminuria not establisheda |
CNS depressants | Increased BUN and albuminuria observeda | Importance not establisheda |
MAO inhibitors | Possible synergistic pressor effect127 a | Use with caution127 a |
Neuromuscular blocking agents | May temporarily mask residual effects of muscle relaxants127 | Use with cautiona |
Sympathomimetic agents | Possible synergistic pressor effect127 a | Use with caution127 a |
Theophyllines (e.g., aminophylline) | Possible increased skeletal muscle activity, agitation, and hyperactivity127 |
Following single IV injection, onset of respiratory stimulation occurs within 20–40 seconds and peaks at 1–2 minutes.127
Duration of respiratory stimulation may vary from 5–12 minutes following single IV injection.127
Doxapram and its metabolites are generally well distributed into tissues in animals.a
Rapidly metabolized following single IV dose.128 a Undergoes hydroxylation to ketodoxapram, an active metabolite.136
Excreted mainly in urine and feces as metabolites within 24–48 hours following administration;128 a following single IV dose, 40–50% of dose recovered in urine as metabolites;128 small amounts of metabolites may continue to be excreted for up to 120 hours.a
Elimination half-life approximately 6.6–9.9 hours in premature neonates receiving IV infusions of doxapram.124 125 126
20–25°C.127
For information on systemic interactions resulting from concomitant use, see Interactions.
Incompatible with strongly alkaline drugs or solutions.127 a
Compatible |
|---|
Dextrose 5 or 10% in water |
Sodium chloride 0.9% |
Incompatible |
|---|
Aminophylline |
Furosemide |
Sodium bicarbonate |
Thiopental sodium |
Ticarcillin |
Compatible |
|---|
Ampicillin sodium |
Caffeine citrate |
Calcium chloride |
Calcium gluconate |
Cefazolin sodium |
Ceftazidime |
Erythromycin lactobionate |
Fentanyl citrate |
Gentamicin sulfate |
Heparin sodium |
Metoclopramide HCl |
Metronidazole |
Oxacillin sodium |
Phenobarbital sodium |
Ranitidine HCl |
Vancomycin HCl |
Incompatible |
Clindamycin phosphate |
Compatible |
|---|
Amikacin sulfate |
Bumetanide |
Chlorpromazine HCl |
Cimetidine HCl |
Cisplatin |
Cyclophosphamide |
Dopamine HCl |
Doxycycline hyclate |
Epinephrine HCl |
Hydroxyzine HCl |
Isoniazid |
Lincomycin HCl |
Methotrexate sodium |
Phytonadione |
Pyridoxine HCl |
Terbutaline sulfate |
Thiamine HCl |
Tobramycin sulfate |
Vincristine sulfate |
Incompatible |
Aminophylline |
Ascorbic acid injection |
Cefotaxime |
Cefuroxime sodium |
Dexamethasone sodium phosphate |
Diazepam |
Digoxin |
Dobutamine HCl |
Folic acid |
Furosemide |
Hydrocortisone sodium phosphate |
Hydrocortisone sodium succinate |
Ketamine HCl |
Methylprednisolone sodium succinate |
Thiopental sodium |
Stimulates peripheral carotid and aortic chemoreceptors and central respiratory centers in a dose-related manner.127 128 a May cause tonic-clonic seizures with excessive CNS stimulation. a
Transiently increases tidal volume with slight increase in respiratory rate.127 a
May elicit a pressor response due to improved cardiac output and increased release of catecholamines.127 No direct effect on peripheral blood vessels.a
Does not antagonize the analgesic effects of opiates.127
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, seizure disorders).127
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.127
Importance of informing patients of other important precautionary information.127 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 20 mg/mL* | Dopram (with benzyl alcohol 0.9%) | Baxter |
Doxapram Hydrochloride Injection (with benzyl alcohol 0.9%) | Bedford |
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
100. Burnard ED, Moore RG, Nichol H. A trial of doxapram in the recurrent apnea of prematurity. In: Stern L, Oh W, Friis-Hansen B, eds. Intensive care in the newborn. Vol. II. New York: Masson; 1978:143-8.
101. Alpan G, Eyal F, Sagi E et al. Doxapram in the treatment of idiopathic apnea of prematurity unresponsive to aminophylline. J Pediatr. 1984; 104:634-7. [IDIS 183784] [PubMed 6707826]
102. Hayakawa F, Hakamada S, Kuno K et al. Doxapram in the treatment of idiopathic apnea of prematurity: desirable dosage and serum concentrations. J Pediatr. 1986; 109:138-40. [IDIS 218527] [PubMed 3723234]
103. Barrington K, Torok-Both G, Finer N et al. Dose-response relationship of doxapram in refractory idiopathic apnea of prematurity. Am Rev Respir Dis. 1986; 133(Suppl):A105. [IDIS 213882] [PubMed 3963628]
104. Eyal F, Alpan G, Sagi E et al. Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study. Pediatrics. 1985; 75:709-13. [IDIS 198191] [PubMed 3982903]
105. Sagi E, Eyal F, Alpan G et al. Idiopathic apnoea of prematurity treated with doxapram and aminophylline. Arch Dis Child. 1984; 59:281-3. [IDIS 184062] [PubMed 6424586]
106. Barrington KJ, Finer NN, Peters KL et al. Physiologic effects of doxapram in idiopathic apnea of prematurity. J Pediatr. 1986; 108:125-9.
107. Bairam A, Vert P. Low-dose doxapram for apnoea of prematurity. Lancet. 1986; 1:793-4. [IDIS 213923] [PubMed 2870280]
108. Martin RJ, Miller MJ, Carlo WA. Pathogenesis of apnea in preterm infants. J Pediatr. 1986; 109:733-41. [PubMed 3095518]
109. AH Robins Company. Dopram (doxapram hydrochloride) injection prescribing information. In: Huff BB, ed. Physicians’ desk reference. 43rd ed. Medical Economics Company Inc: Oradell, NJ; 1989:1693-5.
110. Food and Drug Administration. Parenteral drug products containing benzyl alcohol or other preservatives; intent and request for information. Notice of intent. [21 CFR Ch 1, Subchapter C; Docket No. 85N-0043] Fed Regist. 1985; 50:20233-5.
111. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]
112. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10-1.
113. Anon. Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]
114. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]
115. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]
116. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]
117. Jordan GD, Themelis NJ, Messerly SO et al. Doxapram and potential benzyl alcohol toxicity: a moratorium on clinical investigation? Pediatrics. 1986; 78:540-1. Letter. (IDIS 220422)
118. Jackson D. Doxapram and potential benzyl alcohol toxicity: a moratorium on clinical investigation? Pediatrics. 1986; 78:541. Reply. (IDIS 220423)
119. Cater G. Doxapram for apnea of prematurity. J Pediatr. 1987; 109:563.
120. Barrington KJ, Finer NN, Torok-Both G et al. Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity. Pediatrics. 1987; 80:22-7. [IDIS 231947] [PubMed 3110729]
121. Barrington KJ, Finer NN. Doxapram for apnea of prematurity. J Pediatr. 1987; 109:563.
122. Hiller JL, Benda GI, Rahatzad M et al. Benzyl alcohol toxicity: impact on mortality and intraventricular hemorrhage among very low birth weight infants. Pediatrics. 1986; 77:500-6. [IDIS 215931] [PubMed 3515306]
123. Peliowski A, Finer NN. A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity. J Pediatr. 1990; 116:648-53. [IDIS 265255] [PubMed 2181103]
124. Barrington KJ, Finer NN, Torok-Both G et al. Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity. Pediatrics.
125. Jamali F, Barrington KJ, Finer NN et al. Doxapram dosage regimen in apnea of prematurity based on pharmacokinetic data. Dev Pharmacol Ther. 1988; 11:253-7. [PubMed 3191816]
126. Beaudry MA, Bradley JM, Gramlich LM et al. Pharmacokinetics of doxapram in idiopathic apnea of prematurity. Dev Pharmacol Ther. 1988; 11:65-72. [PubMed 3371147]
127. Bedford Laboratories. Doxapram hydrochloride injection prescribing information. Bedford, OH; 2005 Jan.
128. Yost CS. A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006; 12:236-49. [PubMed 17227289]
129. Doxapram. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:511-12.
130. Henderson-Smart DJ, Steer P. Doxapram versus methylxanthines for apnea in preterm infants (review). Cochrane Database of Systematic Reviews. 2000, Issue 4. Article No: CD000075. DOI: 10.1002/14651858.CD000075.
131. Henderson-Smart DJ, Steer P. Doxapram treatment for apnea in preterm infants (review). Cochrane Database of Systematic Reviews. 2004, Issue 4. Article No: CD000074. DOI: 10.1002/14651858.CD000074.pub2.
132. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (brief summary). Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2006. Available at: . Accessed 2007 Jun 29.
133. National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care (brief summary). London, UK: National Institute for Clinical Excellence; 2004. Available at: . Accessed 2007 Jun 29.
134. Greenstone M, Lasserson TJ. Doxapram for ventilatory failure due to exacerbations of chronic obstructive pulmonary disease (review). Cochrane Database of Systematic Reviews. 2002, Issue 3. Article No: CD000223. DOI: 10.1002/14651858.CD000223.
135. Wax PM. Antiquated antidotes. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank's toxicologic emergencies. 7th ed. New York: McGraw-Hill; 2002: 18-22.
136. Baxter Healthcare Corp. Dopram (doxapram) hydrochloride injection prescribing information. Deerfield, IL; 2006 May.
137. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:574-76.
a. AHFS drug information 2007. McEvoy GK, ed. Doxapram hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2484-5.
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