Summary of Product Characteristics Updated 23-Jul-2016 | Panpharma UK Ltd
Prevention and treatment of post-operative nausea and vomiting (PONV).Adults: 0.625 mg to 1.25 mg (0.25 to 0.5 ml).Elderly (over 65 years): 0.625 mg (0.25 ml)Renal/hepatic impairment: 0.625 mg (0.25 ml)Pediatric populationChildren (2 to 11 years) and adolescents (12 to 18 years): 10 to 50 microgram/kg (up to a maximum of 1.25 mg).Children (below the age of 2 years): not recommended.Administration of droperidol is recommended 30 minutes before the anticipated end of surgery. Repeat doses may be given every 6 hours as required.The dosage should be adapted to each individual case. The factors to be considered here include age body weight, use of other medicinal products, type of anaesthesia and surgical procedure.
Prevention of nausea and vomiting induced by morphine derivatives during post-operative patient controlled analgesia (PCA).Adults: 15 to 50 micrograms droperidol per mg of morphine, up to a maximum daily dose of 5 mg droperidol.Elderly (over 65 years), renal and hepatic impairment: no data in PCA available. Pediatric populationChildren (2 to 11 years) and adolescents (12 to 18 years): not indicated in PCA.Continuous pulse oximetry should be performed in patients with identified or suspected risk of ventricular arrhythmia and should continue for 30 minutes following single i.v. administration.For instructions on dilution of the product before administration, see section 6.6. See also sections 4.3, 4.4 and 5.1.
Central Nervous SystemDroperidol may enhance CNS depression produced by other CNS-depressant drugs. Any patient subjected to anaesthesia and receiving potent CNS depressant medicinal products or showing symptoms of CNS depression should be monitored closely.Concomitant use of metoclopramide and other neuroleptics may lead to an increase in extrapyramidal symptoms and should be avoided (see section 4.5).Use with caution in patients with epilepsy (or a history of epilepsy) and conditions predisposing to epilepsy or convulsions.
CardiovascularMild to moderate hypotension and occasionally (reflex) tachycardia have been observed following the administration of droperidol. This reaction usually subsides spontaneously. However, should hypotension persist, the possibility of hypovolaemia should be considered and appropriate fluid replacement administered.Patients with, or suspected of having, the following risk factors for cardiac arrhythmia should be carefully evaluated prior to administration of droperidol:- a history of significant cardiac disease including serious ventricular arrhythmia, second or third- degree atrio-ventricular block, sinus node dysfunction, congestive heart failure, ischemic heart disease and left ventricular hypertrophy;- family history of sudden death;- renal failure (particularly when on chronic dialysis); - significant chronic obstructive pulmonary disease and respiratory failure;- risk factors for electrolyte disturbances, as seen in patients taking laxatives, glucocorticoids, potassium-wasting diuretics, in association with the administration of insulin in acute settings, or in patients with prolonged vomiting and/or diarrhoea.Patients at risk for cardiac arrhythmia should have serum electrolytes and creatinine levels assessed and the presence of QT prolongation excluded prior to administration of droperidol.Continuous pulse oximetry should be performed in patients with identified or suspected risk of ventricular arrhythmia and should continue for 30 minutes following single i.v. administration.
GeneralTo prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance (hypokalaemia and/or hypomagnesaemia) e.g. potassium-wasting diuretics, laxatives and glucocorticoidsSubstances inhibiting the activity of cytochrome P450 iso-enzymes (CYP) CYP1A2, CYP3A4 or both could decrease the rate at which droperidol is metabolised and prolong its pharmacological action. Hence, caution is advised if droperidol is given concomitantly with strong CYP 1A2 and CYP3A4 inhibitors (see section 4.5).Patients who have, or are suspected of having, a history of alcohol abuse or recent high intakes, should be thoroughly assessed before droperidol is administered.In case of unexplained hyperthermia, it is essential to discontinue treatment, since this sign may be one of the elements of malignant syndrome reported with neuroleptics.Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with droperidol and preventive measures undertaken.The dose should be reduced in the elderly and those with impaired renal and hepatic function (see section 4.2).This medicinal product contains less than 1 mmol sodium (23 mg) per 1 ml, i.e. essentially 'sodium-free'.
Contraindicated for concomitant useMedicinal products known to cause torsades de pointes through QT prolongation should not be concomitantly administered with droperidol. Examples include:- Class IA antiarrhythmics e.g. quinidine, disopyramide, procainamide- Class III antiarrhythmics e.g. amiodarone, sotalol- macrolide antibiotics e.g. erythromycin, clarithromycin- fluoroquinolone antibiotics e.g. sparfloxacin- antihistamines e.g. astemizole, terfenadine- certain antipsychotic medications e.g. chlorpromazine, haloperidol, pimozide, thioridazine- anti-malaria agents e.g. chloroquine, halofantrine- cisapride, domperidone, methadone, pentamidine.Concomitant use of medicinal products that induce extrapyramidal symptoms, e.g. metoclopramide and other neuroleptics, may lead to an increased incidence of these symptoms and should therefore be avoided.Consumption of alcoholic beverages and medicines should be avoided.
Caution is advised for concomitant use.Caution is advised when droperidol is used with any other medication known to prolong the QT interval.To reduce the risk of QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance (hypokalaemia and/or hypomagnesaemia) e.g. potassium-wasting diuretics, laxatives and glucocorticoids.Droperidol may potentiate the action of sedatives (barbiturates, benzodiazepines, morphine derivatives). The same applies to antihypertensive agents, so that orthostatic hypotension may ensue. Like other sedatives, droperidol may potentiate respiratory depression caused by opioids.Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.Substances inhibiting the activity of cytochrome P450 iso-enzymes (CYP) CYP1A2, CYP3A4 or both could decrease the rate at which droperidol is metabolised and prolong its pharmacological action. Hence, caution is advised if droperidol is given concomitantly with CYP1A2 inhibitors (e.g. ciprofloxacin, ticlopidine), CYP3A4 inhibitors (e.g. diltiazem, erythromycin, fluconazole, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, verapamil) or both (e.g. cimetidine, mibefradil).
PregnancyA limited amount of clinical data have shown no increase of malformative risk.Droperidol has not been shown to be teratogenic in rats. Animal studies are insufficient with respect to the effects on pregnancy and embryonal/foetal, parturition and postnatal development.In newborn babies from mothers under long-term treatment and high doses of neuroleptics, temporary neurological disturbances of extrapyramidal nature have been described. In practice, as a precautionary measure, it is preferable not to administer droperidol during pregnancy. In late pregnancy, if its administration is necessary, monitoring of the newborn's neurological functions is recommended.
BreastfeedingNeuroleptics of the butyrophenone type are known to be excreted in breast milk; treatment with droperidol should be limited to a single administration. Repeat administration is not recommended.
FertilityFor droperidol, there were no effects on fertility in studies conducted in male and female rats (see section 5.3). The clinical effect of droperidol on fertility has not been established
|System Organ Class||Common ≥1/100 to < 1/10||Uncommon ≥1/1,000 to < 1/100||Rare ≥1/10,000 to < 1/1,000||Very Rare < 1/10,000||Not known (cannot be estimated from the available data)|
|Blood and lymphatic systems disorders||Blood dyscrasias|
|Immune system disorders||Anaphylactic reaction; Angioneurotic oedema; Hyper-sensitivity|
|Metabolism and nutrition disorders||Inappropriate anti-diuretic hormone secretion|
|Psychiatric disorders||Anxiety; Restlessness/ Akathisia;||Confusional states; Agitation||Dysphoria||Hallucinations|
|Nervous system disorders||Drowsiness||Dystonia; Oculogyration||Extra- pyramidal disorder; Convulsions; Tremor||Epileptic fits; Parkinson's disease; Psychomotor hyperactivity; Coma|
|Cardiac disorders||Tachycardia; Dizziness||Cardiac arrhythmias, including ventricular arrhythmias||Cardiac arrest Torsade de pointes; Electrogram QT prolonged|
|Respiratory, thoracic and mediastinal disorders||Broncho- spasm; Laryngospasm|
|Skin and subcutaneous system disorders||Rash|
|General disorders and administration site conditions||Neuroleptic malignant syndrome (NMS)||Sudden death|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
SymptomsThe manifestations of droperidol overdose are an extension of its pharmacologic actions. Symptoms of accidental overdose are psychic indifference with a transition to sleep, sometimes in association with lowered blood pressure.At higher doses or in sensitive patients, extrapyramidal disorders may occur (salivation, abnormal movements, sometimes muscle rigidity). Convulsions may occur at toxic doses.Cases of QT-interval prolongation, ventricular arrhythmias and sudden death have been reported rarely.
TreatmentNo specific antidote is known. However, when extrapyramidal reactions occur, an anticholinergic should be administered.Patients with droperidol overdose should be closely monitored for signs of QT interval prolongation. Factors which predispose to torsades de pointes, e.g. electrolyte disturbances (especially hypokalaemia or hypomagnesaemia) and bradycardia should be taken into consideration.Pronounced hypotension should be treated by boosting circulation volume and taking other appropriate measures. Clear airways and adequate oxygenation should be maintained; an oropharyngeal airway or endotracheal tube might be indicated.If required, the patient should be observed carefully for 24 hours or longer; body warmth and adequate fluid intake should be maintained.
PONVIn a systematic review of 222 studies on prevention of PONV, the risk of PONV was decreased compared to placebo by RR (95% confidence interval) 0.65 (0.60-0.71) for nausea, 0.65 (0.61-0.70) for vomiting and by 0.62 (0.58-0.67) for nausea and vomiting combined.In a combined analysis of 2061 high risk PONV patients, 1.25mg droperidol was more effective than 4 mg ondansetron or 0.625 mg droperidol in preventing nausea (p<0.05; absence of nausea 43%, 29%, 29% respectively), in preventing vomiting (complete response 0-24h 56%, 53%, 48%) and in reducing the need for rescue medication (26%, 34%, 32%).
MonotherapyA meta-analysis study examined data from 74 clinical trials involving 5351 patients who received 24 different regimens of droperidol and 3372 patients who received placebo or no treatment. The incidence of early (0-6 hours) and late PONV (0-24 hours) in adults and children was analysed (see table).Early and late outcomes after droperidol compared to placebo or no treatment. Percentages shown refer to incidence of nausea or vomiting.
|Parameter||Droperidol Average (range) in %||Placebo/no treatment Average (range) in %|
|Early outcome (0-6 hours)||Nausea||16 (3-41)||33 (15-80)|
|Vomiting||14 (0-56)||29 (6-86)|
|Late outcome (0-24 hours)||Nausea||45 (1-86)||58 (1196)|
|Vomiting||28 (4-83)||46 (12-97)|
Combination therapyA randomised study in 4123 patients assessed the effectiveness of single and combined antiemetic interventions in patients at high risk of PONV. Treatment included 1.25 mg of droperidol or no droperidol; 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone. The addition of further antiemetics reduced the incidence of PONV, corresponding to an approximate 26% reduction in relative risk of nausea and vomiting for each additional antiemetic. All antiemetics tested were equally effective.
PCAA systematic review of 14 studies involving 1117 patients receiving PCA was performed. Droperidol was used in 6 with a dose range of 0.017-0.17 mg/mg of morphine; 0.017-0.33 mg/bolus. The incidence of any emetic event in patients receiving placebo was 66% compared to 30% for patients receiving droperidol.
QTcIn a placebo-controlled study, treatment with droperidol identified a QT interval prolongation at 3-6 min after administration of 0.625 and 1.25 mg droperidol (respectively 15 ± 40 and 22 ± 41 ms), but these changes did not differ significantly from that seen with placebo (12 ± 35 ms). There were no statistically significant differences compared to placebo in the number of patients with greater than 10% QTc prolongation. A second study with 0.75 mg intravenous droperidol and 4 mg ondansetron identified significant QTc interval prolongation (17 ± 9 ms droperidol, 20 ± 13ms ondansetron), with the QTc interval significantly lower after the 90th minute.A study looking at the combination of ondansetron (4 mg) and droperidol (1 mg) showed that both drugs increased QTc interval separately (17 ± 10 ms ondansetron, 25 ± 8 ms droperidol) but there was no additive effect when given together (28 ± 10 ms).
DistributionFollowing intravenous administration, plasma concentrations fall rapidly during the first 15 minutes; this is metabolism independent, redistribution of the drug. Plasma protein binding amounts to 85 90 %. The distribution volume is approximately 1.5 l/kg.
MetabolismDroperidol is extensively metabolised in the liver, and undergoes oxidation, dealkylation, demethylation and hydroxylation by cytochrome P450 isoenzymes 1A2 and 3A4, and to a lesser extent by 2C 19. The metabolites are devoid of neuroleptic activity.
EliminationElimination occurs mainly through metabolism; 75% is excreted via the kidneys. Only 1% of the active substance is excreted unchanged with urine, and 11% with faeces. Plasma clearance is 0.8 (0.4 - 1.8) l/min. The elimination half-life (t1/2ß) is 134 ± 13 min.
Drug InteractionsA study combining ondansetron (4 mg) and droperidol (1 mg) showed that when administered together there was no pharmacokinetic interaction between the two drugs.
Paediatric PopulationIn a study of 12 children (age 3.5 to 12 years), the values for distribution volume and clearance reported were lower than those found in the adult population (0.58 ± 0.29 l/kg and 4.66 2.28 ml/kg*min respectively) and decrease in parallel. The elimination half-life (101.5 ± 26.4 min) was similar to that found in adults.
Environmental Risk Assessment (ERA)This product is unlikely to represent a risk to the environment following its prescribed use in patients.
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