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Doxapram hydrochloride parenteral

Presentation

Intravenous infusion and intravenous injection of doxapram hydrochloride

Drugs List

  • doxapram 100mg/5ml injection
  • doxapram 1g/500ml intravenous infusion
  • Therapeutic Indications

    Uses

    Postoperative respiratory depression
    Respiratory failure - acute

    Dosage

    Adults

    Acute Respiratory Failure
    1.5 mg to 4 mg per minute by intravenous infusion, administered concurrently with oxygen. Whenever possible, perform frequent measurement of blood gas tension and adjust dose according to patient's condition and response.

    The following dosage regime have been shown to result in rapid production of steady state plasma concentration of doxapram:
    0 to 15 minutes: 4 mg/min
    15 to 30 minutes: 3 mg/min
    30 to 60 minutes: 2 mg/min
    60 minutes onwards: 1.5 mg/min

    Post Operative Respiratory Depression
    1 mg to 1.5 mg/kg by intravenous injection over at least 30 seconds, repeated if necessary after intervals of 1 hour.

    2 mg to 3 mg per minute by intravenous infusion, adjusted according to response of the patient.

    Delay doxapram therapy for at least 10 minutes following discontinuance of anaesthesia with agents known to sensitise the myocardium to catecholamines, e.g. halothan, cyclopropane and enflurane.

    Elderly

    See Dosage; Adult

    Contraindications

    Children under 18 years
    Cerebral oedema
    Cerebrovascular accident
    Coronary arteriosclerosis
    Head trauma
    Hyperthyroidism
    Physical obstruction of respiratory tract
    Pulmonary embolism
    Seizures
    Severe hypertension
    Status asthmaticus
    Thyrotoxicosis

    Precautions and Warnings

    Breastfeeding
    Bronchospasm
    Hepatic impairment
    Mild hypertension
    Phaeochromocytoma
    Poor cardiac reserve
    Pregnancy

    Use with beta-adrenergic bronchodilator in bronchoconstriction
    Administer concurrent oxygen in severe irreversible airway obstruction
    Administer concurrent oxygen in severely decreased lung compliance
    Not all presentations are licensed for all indications
    Delay therapy for 10mins after anaesthetics known to sensitise the heart
    Following anaesthesia, monitor patient until fully alert for 1/2 to 1 hour
    May stimulate vomiting - consider airway protection
    Monitor blood pressure
    Monitor deep tendon reflexes
    Stimulant effect may not outlast effects of respiratory depressant drugs
    Discontinue if sudden hypotension or dyspnoea develops
    Maintain treatment at the lowest effective dose

    Doxapram should not be used in conjunction with mechanical ventilation.

    The administration of this agent does not diminish the need for continuous monitoring of all aspects of patient response, including frequent analysis of arterial-blood gases.

    Pregnancy and Lactation

    Pregnancy

    Use doxapram hydrochloride with caution in pregnancy.

    No reports describing the use of doxapram in human pregnancy have been located. The animal data is limited but does not suggest a major risk for the embryo and/or foetus. Moreover, although the elimination half-life of the drug is unknown, the duration of effect is very short and the agent is extensively metabolised. Thus, the embryo and/or foetal exposure are probably limited except when continuous infusions are administered.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Lactation

    Use doxapram hydrochloride with caution in breastfeeding.

    No reports describing the use of doxapram during human lactation have been located. In addition, the indications for the drug suggest that such reports will be rare. However, doxapram has been given to newborns at risk for respiratory depression when narcotic analgesics or general anaesthetics were used during delivery. No adverse effects attributable to doxapram were observed. The molecular weight of the free base (about 379) suggests that the drug will be excreted into breast milk. The maternal plasma elimination half-life is unknown, but the relatively short duration of effect combined with the extensive hepatic metabolism, probably indicates a short half-life, at least for the parent compound. Of note, though, doxapram is a basic drug and accumulation in the relatively acidic breast milk by ion trapping is a potential concern, especially if continuous infusions are used.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

    Side Effects

    Arrhythmias
    Bilateral Babinski
    Bradycardia
    Bronchospasm
    Chest pain
    Chest tightness
    Clonus
    Confusion
    Convulsions
    Cough
    Dizziness
    Dyspnoea
    Extrasystoles
    Flushing
    Hallucinations
    Headache
    Hyperactive deep tendon reflexes
    Hyperactivity
    Increased blood pressure
    Increased heart rate
    Laryngospasm
    Muscle contraction
    Muscle spasticity
    Nausea
    Perineal warmth
    Pyrexia
    Salivation
    Sinus tachycardia
    Sweating
    Urinary incontinence
    Urinary retention
    Vomiting

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: May 2015

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 13 May 2015.

    Summary of Product Characteristics: Doxapram Hydrochloride BP 20mg/ml Solution for Injection. MercuryPharm Ltd. Revised September 2012.

    Summary of Product Characteristics: Doxapram Hydrochloride 20mg/ml Solution for Infusion. MercuryPharm Ltd. Revised September 2012.

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    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

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