Toxicity
Comprehensive clinical data on citalopram overdose are limited and many cases involve concomitant overdoses of other drugs/alcohol. Fatal cases of citalopram overdose have been reported with citalopram alone; however, the majority of fatal cases have involved overdose with concomitant medications.
Fatal dose is not known. Patients have survived ingestion of more than 2 g citalopram.
The effects may be potentiated by alcohol taken at the same time.
Potential interaction with TCAs, MAOIs and other SSRIs.
Symptoms
The following symptoms have been seen in reported overdose of citalopram: convulsion, tachycardia, somnolence, QT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, mydriasis, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, hyperpyrexia, and atrial and ventricular arrhythmia.
ECG changes including nodal rhythm, prolonged QT intervals and wide QRS complexes may occur. Fatalities have been reported.
Prolonged bradycardia with severe hypotension and syncope has also been reported.
Rarely, features of the "serotonin syndrome" may occur in severe poisoning. This includes alteration of mental status, neuromuscular hyperactivity and autonomic instability. There may be hyperpyrexia and elevation of serum creatine kinase. Rhabdomyolysis is rare.
Treatment
There is no known specific antidote to citalopram.
Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of ECG and vital signs until stable. ECG monitoring is advisable in case of overdose in patients with congestive heart failure/bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment.
Consider oral activated charcoal in adults and children who have ingested more than 5 mg/kg body weight within 1 hour. Activated charcoal given ½ hour after ingestion of citalopram has been shown to reduce absorption by 50%.
Osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered.
If consciousness is impaired the patient should be intubated.
Control convulsions with intravenous diazepam if they are frequent or prolonged.
5 years
Not applicable
Tablet core:
Maize starch
Lactose
Microcystalline-cellulose
Copolyvidone
Glycerol
Croscarmellose Sodium Type A
Magnesium stearate
Coating:
Methylhydroxypropyl-cellulose
Macrogol
Titanium dioxide.
Acute toxicity
Citalopram has low acute toxicity.
Chronic toxicity
In chronic toxicity studies there were no findings of concern for the therapeutic use of citalopram.
Reproduction studies
Based on data from reproduction toxicity studies (segment I, II and III) there is no reason to have special concern for the use of citalopram in women of child-bearing potential.
Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in the implantation number and abnormal sperm at exposure well in excess of human exposure.
Mutagenic and carcinogenic potential
Citalopram has no mutagenic or carcinogenic potential.
Pharmacotherapeutic group: antidepressants, selective serotonin reuptake inhibitors
ATC-code: N 06 AB 04
Mechanism of action
Biochemical and behavioural studies have shown that citalopram is a potent inhibitor of the serotonin (5-HT)-uptake.4, 4.5, 4.8 and 4.9).
Absorption
Absorption is almost complete and independent of food intake (T maxaverage/mean 3.8 hours). Oral bioavailability is about 80%.
Distribution
The apparent volume of distribution (Vd)β is about 12.3 L/kg. The plasma protein binding is below 80% for citalopram and its main metabolites.
Biotransformation
Citalopram is metabolized to the active demethylcitalopram, didemethylcitalopram, citalopram-N-oxide and an inactive deaminated propionic acid derivative. All the active metabolites are also SSRIs, although weaker than the parent compound. Unchanged citalopram is the predominant compound in plasma.
Elimination
The elimination half-life (T½β) is about 1.5 days and the systemic citalopram plasma clearance (Cls) is about 0.33 L/min, and oral plasma clearance (Cl oral) is about 0.41 L/min.
Citalopram is excreted mainly via the liver (85%) and the remainder (15%) via the kidneys. About 12% of the daily dose is excreted in urine as unchanged citalopram. Hepatic (residual) clearance is about 0.35 L/min and renal clearance about 0.068 L/min.
The kinetics are linear. Steady state plasma levels are achieved in 1-2 weeks. Average concentrations of 250 nmol/L (100-500 nmol/L) are achieved at a daily dose of 40 mg. There is no clear relationship between citalopram plasma levels and therapeutic response or side effects.
Elderly patients (> 65 years)
Longer half-lives and decreased clearance values due to a reduced rate of metabolism have been demonstrated in elderly patients.
Reduced hepatic function
Citalopram is eliminated more slowly in patients with reduced hepatic function. The half-life of citalopram is about twice as long and steady state citalopram concentrations at a given dose will be about twice as high as in patients with normal liver function.Reduced renal function
Citalopram is eliminated more slowly in patients with mild to moderate reduction of renal function, without any major impact on the pharmacokinetics of citalopram. At present no information is available for treatment of patients with severely reduced renal function (creatinine clearance <20 mL/min).December 2016
Lundbeck Limited
2nd floor
Building 3, Abbey View
Everard Close
St Albans
Hertfordshire
AL1 2PS
United Kingdom
Do not store above 25°C
Press through packs (UPVC/PVdC with aluminium closure) 28 tablets.
| Cipramil 10 mg film-coated tablets Citalopram 10 mg film-coated tablets | PL 0458/0057 |
| Cipramil 20 mg film-coated tablets Citalopram 20 mg film-coated tablets | PL 0458/0058 |
| Cipramil 40mg film-coated tablets Citalopram 40 mg film-coated tablets | PL 0458/0059 |
None
First authorisation : 17 March 1995
Renewal of authorisation: 16 March 2010
