Download Citalopram Dosage and Precautions: New Zealand Data Sheet and more Lecture notes Marketing in PDF only on Docsity!
1. PRODUCT NAME
Citalopram, tablets, film-coated, 20 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Name and strength of the active substance
Each film-coated tablet contains 24.99 mg citalopram hydrobromide Ph. Eur corresponding to 20 mg of citalopram base.
Citalopram hydrobromide is a fine white to off-white, crystalline material. Sparingly soluble in water, soluble in ethanol (96%), freely soluble in chloroform and very slightly soluble in diethyl ether. No polymorphic forms have been detected.
Excipient(s) with known effect For the full list of excipients, see section 6.1.
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not receive this medicine (also refer Section 4.4 Special warnings and precautions ).
3. PHARMACEUTICAL FORM
Oral, film-coated tablets
Presentation White to off-white, oval, biconvex, film-coated tablets with break-line on one side & ‘20’ embossed on the other side.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications Adults Treatment of depressive illness in the initial phase and as maintenance against potential relapse or recurrence.
4.2 Dose and method of administration
The dose may be taken in the morning or evening without regard for food. As the treatment result in general can be evaluated only after 2-3 weeks' treatment, a possible dose increase in increments of 10mg should take place with intervals of 2-3 weeks.
Adults Should be administered as a single oral dose of 20mg daily. Dependent on individual patient response and severity of depression the dose may be increased to a maximumof 40mg daily.
The maximum daily dose of citalopram should not exceed 40mg/day as doses above 40mg/day are associated with an increased risk of QT prolongation.
A maximum dose of 20mg/day is recommended for patients known to be CYP2C19 poor metabolisers or in patients taking cimetidine or other CYP2C19 inhibitors.
A dose of 20mg/day is recommended for patients with hepatic impairment and patients aged >60 years. A dose of 40mg/day should be only used for non-respondingpatients.
Poor metabolisers of CYP2C An initial dose of 10mg daily during the first two weeks of treatment is recommended for patients who are known to be poor metabolisers with respect to CYP2C19. A maximum dose of 20mg/day is recommended for patients known to be CYP2C19 poor metabolisers depending on individual patient response. For patients taking CYP2C inhibitors eg. cimetidine and omeprazole, the citalopram dose should not exceed the maximum dose of 20mg/day.
Elderly patients The starting dose is 10mg/day. The dose can be increased by 10mg to a maximum of 20mg/day.
Use in children and adolescents (under 18 years of age) Safety and efficacy have not been established in this population. Consequently, citalopram should not be used in children and adolescents under 18 years of age ( referSection 4.4 Special warnings and precautions for use ).
Reduced hepatic function A dose of 20mg/day is recommended for patients with hepatic impairment and patients aged
60 years. A dose of 40mg/day should only be used for non-responding patients.
Reduced renal function Dosage adjustment is not necessary in patients with mild or moderate renal impairment. No information is available on treatment of patients with severely reduced renal function (creatinine clearance < 20 mL/min.).
Duration of treatment The anti-depressive effect usually sets in after 2 to 4 weeks. A treatment period of at least six months is usually necessary to provide adequate maintenance against the
potential for relapse.
4.4 Special warnings and precautions for use
Warnings
Children and adolescents (under 18 years of age) In clinical trials, adverse events related to suicidality (suicidal thoughts and suicidal behaviours) and hostility (predominantly aggression, oppositional behaviour and anger)were more frequently observed in children and adolescents treated with SSRIs (and venlafaxine) compared to those treated with placebo. Consequently, citalopram shouldnot be used in children and adolescents less than 18 years of age.
Clinical worsening and suicide risk Patients of any age with major depressive disorder may experience worsening of their depression and/or emergence of suicidal ideation and behaviours (suicidality), whetheror not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
There has been a long-standing concern that some antidepressants may have a role in the emergence of suicidality in some patients. The possible risk of increased suicidality inpatients applies to all classes of antidepressant medicines, as available data are not adequate to exclude this risk for any antidepressant. Therefore, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patients presenting symptoms. Generally, when stopping an antidepressant, doses should be tapered rather than stopped abruptly.
The following symptoms have been reported in adult and paediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania. Although a causal link between the emergenceof such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutics regimen, including possibly discontinuing the medication, in patients forwhom such symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Because of the possibility of co-morbidity between major depression disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders.
Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. In addition, there is a possibility of an increased risk of suicidal behaviour in young adults.
Patients (and caregivers of patients) should be alerted about the need to monitor or the emergence of such events and to seek medical advice immediately if these symptoms present.
Mania and bipolar disorder A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with any antidepressant alone may increase the likelihood of a mixed/manic episode in patients at risk of bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at riskfor bipolar disorder. It should be noted that esitalopram is not approved for use in treating bipolar disorder.
QT- Prolongation and Torsades de Pointes Clinical studies have shown that citalopram use is associated with dose-dependent QT prolongation. In addition, there have been post-marketing reports of QT prolongation and Torsades de Pointes in association with citalopram use.
Citalopram is contraindicated for use in combination with pimozide. Citalopram is not recommended for use in patients at high risk of developing prolongation of the QTc interval. This includes patients with congenital long QT syndrome; structural heart disease or left ventricular dysfunction, concomitant use of other QTc prolonging medicines, bradyarrhythmias, hypokalaemia or severe hypomagnesaemia (or a predisposition to hypokalaemia or hypomagnesaemia because of concomitant illness ormedicine use). However, if citalopram use is considered essential in these patients thencitalopram should be used at the lowest possible dose and ECG monitoring should be undertaken prior to starting treatment, at steady state, after dose increases or after starting any potentially interacting medicine. Hypokalaemia and hypomagnesaemia should be corrected prior to initiation of treatment and periodically monitored.
Patients should be informed of symptoms of arrhythmia (e.g. dizziness, palpitations, syncope or new onset seizures) and should be advised to seek medical assistance if theyoccur. An ECG should be performed in all patients experiencing symptoms that could be indicative of an arrhythmia. Citalopram should be used in caution in patients with other risk factors for QTc prolongation including age >65 years, female sex, high doses of citalopram and use of medicines that inhibit the metabolism of citalopram. ECG monitoring should beperformed in any patient considered at significant risk for QTc prolongation.
Citalopram should be stopped and specialist advice should be sought in patients who have persistent QTc prolongation >500ms or in whom the QTc interval has increased >60ms during treatment.
Withdrawal symptoms seen on discontinuation of SSRIs Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there havebeen very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though insome individuals they may be prolonged (2-3 months or more). It is therefore advised that citalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs.
Monoamine Oxidase Inhibitors Simultaneous administration of citalopram and a Monoamine Oxidase Inhibitor (MAOI) may cause serotonin syndrome, a serious, sometimes fatal, reaction in patients receivingan SSRI in combination with a MAOI and in patients treated with an SSRI and a MAOI in close proximity. Some cases presented with features resembling neuroleptic malignant syndrome. Symptoms and signs of serotonin syndrome include rapid onset, clonus, myoclonus, tremor, shivering, hyperreflexia, hyperthermia, rigidity, autonomic instability with possible rapid fluctuations of vital signs and mental status changes that include extreme agitation progressing to delirium and coma. Treatment with citalopram may be instituted 14 days after discontinuation of irreversible MAOIs and a minimum of one drug free day after discontinuation of moclobemide. Treatment with MAOIs may be introduced 14 days after discontinuation of citalopram.
Hyponatraemia
Hypronatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported as a rare adverse reaction with the use of SSRIs. Risk factors include old age and concomitant therapy with diuretics; most cases occur during the first 3weeks of therapy.
ECT (electroconvulsive therapy) There is little clinical experience of concurrent use of citalopram and ECT, therefore caution is advised.
Akathisia/psychomotor restlessness The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental and it may be necessary to review the use of SSRIs/SNRIs.
Seizures Although animal experiments have shown that citalopram has no epileptogenic potential it should, like other antidepressants, be used with caution in patients with ahistory of seizures.
Diabetes As described for other psychotropics, citalopram may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients; inaddition, the depressive illness itself may affect patients’ glucose balance.
Use in patients with cardiac disease Citalopram has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. However, the electrocardiograms of 1,116 patients who received citalopram in clinical trials were evaluated and the data indicate that citalopram is not associated with the developmentof clinically significant ECG abnormalities. Fatal arrhythmias with prolonged QTc intervalwere observed in preclinical (animal toxicology) studies ( refer Section 5.3 Preclinical safety data ). Like other SSRIs, citalopram causes a small decrease in heart rate. Consequently, caution should be observed when citalopram is initiated in patients with pre-existing slow heart rate. Due to the risk of QT prolongation, ECG monitoring is advised when using citalopram in patients with other risk factors of QT prolongation including structural heart disease/LV dysfunction, bradycardia, hypokalaemia or severe hypomagnesaemia, or who are taking other medicines that prolong QT interval. Caution is advised in treating patients with diseases, or who are taking medicines, that cause hypokalaemia or hypomagnesaemia ( refer Section 4.4 Special warnings and precautions for use ).
Haemorrhage Bleeding abnormalities of the skin and mucous membranes have been reported with the use of SSRIs (including purpura, ecchymosis haematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding). Citalopram should therefore be used with caution in patients concomitantly treated with oral anticoagulants, medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory medicinal products (NSAIDS), ticlopidine and dipyridamole) as well as in patients with a past history of abnormal bleeding or those with predisposing conditions.
Pharmacological gastroprotection should be considered for high risk patients.
Carcinogenicity/mutagenicity Citalopram has low acute toxicity. In chronic toxicity studies there were no findings of concern for the therapeutic use of citalopram. Based on data from reproduction toxicitystudies (segment I, II and III) there is no reason to have special concern for the use of citalopram in women of child-bearing potential. Citalopram has no mutagenic or carcinogenic potential.
However, co-administration of citalopram (40mg) and ketoconazole (200mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of citalopram suggesting that the co-administration with citalopram or a medicine that inhibits CYP2D6 is unlikely to have clinically significant effects on citalopram metabolism. Co-administration of citalopram (single dose) with omeprazole (a CYP2C19 inhibitor) increased the plasma levels of citalopram. Citalopram 20mg/day is themaximum recommended dose for patients taking concomitant CYP2C inhibitors (e.g. omeprazole) because of the risk of QT-prolongation ( refer Section 4.2 Dose and method of administration ).
CYP2D6 inhibitors Citalopram steady state levels were not significantly different in poor metabolisers and extensive -2D6 metabolisers after multiple dose administration of citalopram, suggesting that co- administration, with citalopram, of a drug that inhibits CYP2D6, is unlikely to haveclinically significant effects on citalopram metabolism.
Protein binding Protein binding is relatively low (< 80%). These properties give citalopram a lowpotential for clinically significant drug interactions.
Pimozide Co-administration of a single dose of pimozide 2mg to subjects treated with racemic citalopram 40 mg/day for 11 days caused an increase in AU and Cmax of pimozide, although not consistently throughout the study. The co-administration of pimozide andcitalopram resulted in a mean increase in the QTc interval of approximately 10 msec. Due to the interaction noted at a low dose of pimozole, concomitant administration ofcitalopram and pimozole is contraindicated ( refer Section 4.3 Contraindications ).
Lithium and tryptophan There is no pharmacokinetic interaction between lithium and citalopram. However, there have been reports of enhanced serotonergic effects when other SSRIs have been given with lithium and tryptophan and therefore the concomitant use of citalopram withthese drugs should be undertaken with caution. Increased monitoring of lithium levels isnot required.
Imipramine and other tricyclic antidepressants (TCAs) In a pharmacokinetic study, no effect was demonstrated on either citalopram or imipramine levels, although the level of desipramine, the primary metabolite of imipramine, was increased. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the co-administration of citalopram andtricyclic antidepressants.
Medicines affecting the central nervous system Given the primary CNS effects of citalopram, caution should be used when it is taken in combination with other centrally acting drugs.
Medicines lowering the seizure threshold SSRIs can lower the seizure threshold.
Caution is advised when concomitantly using othermedicinal products capable of lowering the seizure threshold (e.g. antidepressants (tricyclics, SSRIs) neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion and tramadol)
Digoxin In subjects who had received 21 days of 40 mg/day citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantlyaffect the pharmacokinetics of either citalopram or digoxin.
Medicines that interfere with haemostatis (NSAIDs, aspirin, warfarin, etc) Serotonin release by platelets plays an important role in haemostatis. There is an association between use of psychotropic drugs that interfere with serotonin re-uptakeand the occurrence of abnormal bleeding. Concurrent use of an NSAID, aspirin or warfarin potentiates this risk. Thus, patients should be cautioned about using such medicines concurrently with citalopram.
Carbamazepine
Combined administration of Citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of citalopram should be considered if thetwo drugs are co-administered.
Metoprolol A pharmacokinetic interaction between citalopram and metoprolol was observed, resulting in a twofold increase in metoprolol concentrations. The change in metabolismof metoprolol suggests an interaction between metoprolol and dimethyl citalopram related to the CYP2D6 isoenzyme. There was no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers by adding citalopram.
Cimetidine As a documented enzyme inhibitor, cimetidine caused a moderate increase in the average steady state levels of citalopram. Therefore, citalopram 20 mg/day is the maximum recommended dose for patients taking concomitant cimetidine because of the risk of QT prolongation ( refer Section 4.2 Dose and method of administration ).
Omeprazole Co-administration of citalopram (single dose) with omeprazole (a CYP2C19 inhibitor) increased the plasma levels of citalopram. Therefore, citalopram 20 mg/day is the maximum recommended dose for patients taking concomitant omeprazole because of the risk of QT prolongation ( refer Section 4.2 Dose and method of administration ). Caution should also be exercised when citalopram is used concomitantly with other CYP2C19 inhibitors (e.g. esomeprazole, lansoprazole).
Alcohol Neither pharmacodynamic nor pharmacokinetic interaction with alcohol has been shown. However, the combination of SSRIs and alcohol is not advisable.
There were no peri- or postnatal effects following the dosing of pregnant rats (conception through to weaning) where the systemic exposure levels (based on AUC)were approximately twice that of those expected clinically. However, the number of still births was increased and the size, weight and postnatal survival of offspring weredecreased when the systemic exposure level (AUC) was ~5-fold greater than the expected clinical level.
Animal data have shown that citalopram may affect sperm quality (see Further Information
- Preclinical Safety). Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observedso far.
New-born should be observed if maternal use of citalopram had continued into the later stages of pregnancy, particularly into the third trimester. If citalopram is used until or shortly before birth, discontinuation effects in the new-born are possible. Abrupt discontinuation should be avoided during pregnancy.
New-borns exposed to citalopram, other SSRIs, or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalisation, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In the majority of cases the complications begin immediately or soon (< 24 hours) after delivery. Epidemiological data suggests that the use of SSRIs and SNRIs in pregnancy mav be associated with a small but statistically significant increase in pre-term delivery.
Epidemiological data suggests that the use of SSRIs and SNRIs in pregnancy may be associated with a small but statistically significant increase in pre-term delivery. The use of SSRIs in pregnancy, particularly use in late pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the new-born (PPHN).
The absolute risk among those who used SSRIs late in pregnancy was estimated to be 4 to 5 times higher than the rate of 1 to 2 per 1,000 pregnancies observed in the general population.
Neonates exposed to citalopram, other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalisation, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinicalfindings have included respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRS or, possibly, a drug discontinuation syndrome. In the majority of cases the complications begin immediately or soon (<24 hours) after delivery.
Neonates should be observed if maternal use of citalopram had continued into the later stages of pregnancy, particularly into the third trimester. If citalopram is used until or shortly before the birth, discontinuation effects in the new-born are possible. Abrupt discontinuation should be avoided during pregnancy.
Use in Lactation Citalopram is excreted into human breast milk. Studies in nursing mothers have shown that the mean combined dose of citalopram and dimethyl citalopram transmitted to infants via breast milk (expressed as a percentage of the weight-adjusted maternal dose) is 4.4 - 5.1% (below the notional 10% level of concern). Plasma concentrations of thesedrugs in infants were very low or absent and there were no adverse effects. Whilst thecitalopram data supports the safety of use in breast-feeding women, the decision to breast-feed should always be made as an individual risk/benefit analysis.
Fertility Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in number in implantation and abnormal sperm at exposure well in excess of human exposure. Animal data have shown that citalopram may affect the sperm quality. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impacton human fertility has not been observed so far.
4.7 Effects on ability to drive and use machines
Citalopram does not impair intellectual function and psychomotor performance. However, patients who are prescribed psychotropic medication may be expected to have some impairment of general attention and concentration and should be cautioned about their ability to drive a car and operate machinery.
4.8 Undesirable effects
Adverse effects observed with citalopram are in general mild and transient. They aremost frequent during the first one or two weeks of treatment and usually attenuate subsequently. The most commonly observed adverse events associated with the use of citalopram in double-blind, placebo-controlled trials and not seen at an equal incidence among placebo-treated patients were nausea, somnolence, dry mouth, increased sweating, tremor, diarrhoea and ejaculation disorder. The incidence of each in excess over placebo is low. In comparative double-blind clinical trials with tri and tetracyclic antidepressants (TTCAs), the incidence of 10 adverse events was statistically significantly higher on TTCAs (dry mouth, increased sweating, constipation, tremor, dizziness, somnolence, abnormal accommodation, postural hypotension, palpitation, perverted taste) compared to citalopram. For two events (nausea, ejaculation disorder) the incidencewas statistically higher on citalopram compared to TTCAs.
(600) GASTRO-INTESTINAL SYSTEM
DISORDERS
Abdominal pain Constipation Diarrhoea Dyspepsia Flatulence Mouth dry Nausea Vomiting
(800) METABOLIC AND NUTRITIONAL
DISORDERS
Weight decrease 1.5 0. (1030) HEART RATE AND RHYTHM DISORDERS Palpitation 7.1 7. (1100) RESPIRATORY SYSTEM DISORDERS Coughing Pharyngitis Rhinitis Sinusitis Upper respiratory tract infection
(1300) URINARY SYSTEM DISORDERS
Micturition disorders 2.3 1. (1410) REPRODUCTIVE DISORDERS, MALE Ejaculation disorders Impotence
(1420) REPRODUCTIVE DISORDERS,
FEMALE
Menstrual disorders (CT ≤ 50 years: N = 447; PL ≤ 50 years: N =180)
(1810) BODY AS A WHOLE
Asthenia Back pain Chest pain Fatigue Fever Influenza-like symptoms Pain
- Statistically significant adverse events between groups, with a frequency of greater than 5% ( P < 0.05).
Including: dyskinesia, dystonia, hyperkinesia, hypertonia, hypokinesia.
Dose dependency of adverse events The potential relationship between the dose of citalopram administered and the incidence of adverse events was examined in a fixed dose study in depressed patients receiving placebo or citalopram 10, 20, 40, and 60 mg. Jonckheere's trend test revealeda positive dose response (p < 0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning.
Male and female sexual dysfunction with SSRIs While sexual dysfunction is often part of depression and other psychiatric disorders, there is increasing evidence that treatment with selective serotonin reuptake inhibitors (SSRIs) may induce sexual side effects. This is a difficult area to study because patients may not spontaneously report symptoms of this nature, and therefore, it is thought thatsexual side effects with the SSRIs may be underestimated. In placebo-controlled clinical trials (table), the reported incidence of decreased libido for the whole population was 2.5%; ejaculation disorder (primarily ejaculatory delay), and impotence in male depressed patients receiving citalopram (N=423) was 5.9%, and 2.8%, respectively. In female depressed patients receiving citalopram (N=660), the reported incidence of anorgasmia was 0.5%. The reported incidence of decreased libido was 0.4% among depressed patients receiving placebo, whilst sex specific adverse events were not reported among male and female depressed patients receiving placebo.
While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.
Vital sign changes Citalopram and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with citalopram treatment. In addition, a comparison of supine and standing vital sign measures for citalopram and placebo treatments indicated that citalopram treatment is not associated with orthostatic changes.
Weight changes Patients treated with citalopram in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients.
Laboratory changes Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, haematology, and urinalysis variables and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with citalopram treatment.
Skin and Appendages Disorders Uncommon : photosensitivity reaction, urticaria, acne, eczema, skin discoloration,alopecia, dermatitis, skin dry, psoriasis, rash. Rare: hypertrichosis, decreased sweating, melanosis, keratitis, pruritus ani. Unknown: ecchymosis angioedema.
Musculoskeletal System Disorders Uncommon : arthritis, muscle weakness, skeletal pain. Rare: bursitis, osteoporosis.
Central and Peripheral Nervous System Disorders Common: migraine. Uncommon: vertigo, leg cramps, involuntary muscle contractions, speech disorder, abnormal gait, hypoaesthesia, neuralgia, ataxia, convulsions. Rare: abnormal coordination, hyperesthesia, ptosis, stupor.
Vision Disorders Common : abnormal accommodation. Uncommon: conjunctivitis, eye pain. Rare: mydriasis, photophobia, abnormal lacrimation, cataract, diplopia. Unknown: visual disturbance.
Special senses other, Disorders Common: taste perversion. Rare: taste loss.
Psychiatric Disorders Common: amnesia, apathy, depression, increased appetite, aggravated depression. Uncommon: aggressive reaction, increased libido, paroniria, drug dependence, depersonalisation, hallucination, euphoria, psychotic depression, delusion, paranoidreaction, emotional lability, panic reaction, psychosis. Rare: catatonic reaction, melancholia, suicide-related events. Unknown: bruxism, restlessness.
Gastro-intestinal System Disorders Common: saliva increased. Uncommon: gastritis, gastroenteritis, eructation, haemorrhoids, dysphagia, gingivitis, stomatitis, teeth grinding, oesophagitis. Rare: colitis, gastric ulcer, duodenal ulcer, gastroesophageal reflux, diverticulitis, glossitis, hiccups, rectal haemorrhage. Unknown: gastrointestinal haemorrhage.
Immune System Disorder Unknown: anaphylactic reaction, hypersensitivity NOS.
Liver and Biliary System Disorders Uncommon: ALT increased, gamma-GT increased, ALP increased, AST. Rare: cholecystitis, cholelithiasis, bilirubinaemia, jaundice, hepatitis. Unknown: liver function test abnormal.
Metabolic and Nutritional Disorders Common: increased weight. Uncommon: thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance. Rare: hypokalaemia, obesity, hypoglycaemia, dehydration.
Endocrine Disorders Rare: hypothyroidism, goitre, gynaecomastia.
Cardiovascular Disorders, General Common: postural hypotension, hypotension. Uncommon: hypertension, oedema (extremities), cardiac failure, bradycardia,tachycardia. Unknown: orthostatic hypotension.
Myo-, Endo-, Pericardial & Valve Disorders Uncommon: angina pectoris, myocardial infarction, myocardial ischaemia.
Heart Rate and Rhythm Disorders Common: tachycardia. Uncommon: bradycardia, extrasystoles. atrial fibrillation. Uncommon: bradycardia, extrasystoles. atrial fibrillation. Rare: bundle branch block, cardiac arrest, QT Prolongation, torsades de pointes. Vascular (Extracardiac) Disorders Uncommon: cerebrovascular accident, flushing, transient ischemic attack. Rare: phlebitis.
Respiratory System Disorders Uncommon: bronchitis, dyspnoea, pneumonia. Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased.
Red Blood Cell Disorders Uncommon: anaemia. Rare: hypochromic anaemia. White Cell and Reticuloendothelial System Disorders Uncommon: leucopenia, leukocytosis, lymphadenopathy. Rare: granulocytopenia, lymphocytosis, lymphopenia.
Platelet, Bleeding & Clotting Disorders Uncommon : abnormal bleeding, predominantly ofthe skin and mucous membranes, including purpura, epistaxis, haematomas, vaginal bleeding and gastrointestinal bleeding. Rare: pulmonary embolism, coagulation disorder, gingival bleeding. Unknown: thrombocytopenia.
