Sertralina Krka: composition and pharmaceutical form
Sertralina Krka comes as film-coated tablets. One tablet contains 50 mg or 100 mg of sertraline in the form of the hydrochloride.
The medicine is taken once a day — in the morning or in the evening, with food or independently of it. The two strengths make it possible to raise the daily dose in steps of 50 mg, as the titration scheme requires.
How Sertralina Krka works
In in vitro studies sertraline proved to be a strong and specific inhibitor of the uptake of serotonin by nerve cells, and in animals it enhanced serotonergic transmission. On the reuptake of noradrenaline and dopamine it has only a very weak influence. At therapeutic doses sertraline blocks the uptake of serotonin by human platelets.
Sertraline has no affinity for the muscarinic, serotonin, dopamine, adrenergic, histamine, GABA or benzodiazepine receptors, and it does not increase catecholaminergic activity. In animal experiments it showed no stimulant, sedative, anticholinergic or cardiotoxic action, and in healthy volunteers it caused no sedation and did not impair psychomotor function. With prolonged administration to animals the number and sensitivity of the noradrenergic receptors of the brain decreased — an effect known for other antidepressants too.
Indications
The medicine is prescribed in episodes of major depression and to prevent their recurrence, in panic disorder — with or without agoraphobia — in social anxiety disorder and in post-traumatic stress disorder.
Besides that, sertraline is used in obsessive-compulsive disorder in adults and in children and adolescents aged 6 to 17. This is the only indication for which the medicine is prescribed under the age of 18: its efficacy in childhood depression has not been proved, and there are no data at all on its use in children under 6.
Method of use and dosage
In depression and obsessive-compulsive disorder the starting dose is 50 mg a day. In panic disorder, post-traumatic stress disorder and social anxiety one begins with 25 mg a day and moves to 50 mg after a week: this scheme reduces the frequency of the undesirable reactions typical of the start of treatment of anxiety disorders. If there is no response to 50 mg, the dose is increased by 50 mg no more often than once a week — the half-life of sertraline is about 24 hours, and faster changes make no sense. The maximum is 200 mg a day. The first signs of action are noticeable after about 7 days, but the full effect usually takes longer, especially in obsessive-compulsive disorder.
| Group of patients | Particulars of dosing |
|---|---|
| Children aged 6–12 with OCD | Start with 25 mg a day, 50 mg after a week; then an increase if needed, maximum 200 mg |
| Adolescents aged 13–17 with OCD | Start with 50 mg a day, then as required, maximum 200 mg |
| Elderly patients | Caution because of the increased risk of hyponatraemia |
| Liver disease | Smaller doses or less frequent dosing; in severe hepatic failure the medicine is not used |
| Impaired kidney function | No dose adjustment is required |
The length of treatment and withdrawal
In long-term maintenance therapy the dose is held at the lowest level at which the effect is retained. Depression is treated for at least 6 months after the symptoms have gone, and to prevent repeat episodes the dose that helped in the current one is usually kept. In panic disorder and OCD the need to continue therapy is reviewed regularly: the ability of the medicine to prevent relapses in these diagnoses has not been proved. Abrupt withdrawal is unacceptable — the dose is reduced gradually over at least one or two weeks, and if withdrawal symptoms appear the doctor returns to the previous dose and reduces it more slowly.
Contraindications
Sertraline is not prescribed in hypersensitivity to it or to any excipient of the medicine, nor together with irreversible MAO inhibitors — because of the risk of serotonin syndrome, which shows itself as agitation, tremor and hyperthermia.
Sertraline may be started no earlier than 14 days after the end of treatment with an irreversible MAO inhibitor, and before such therapy begins sertraline is withdrawn at least 7 days in advance. Concomitant use of pimozide is contraindicated.
Special warnings and precautions
Depression itself is linked to an increased risk of suicidal thoughts, self-harm and suicide, and the risk remains until there is significant improvement. That may come only after several weeks, so until then the patient is watched especially closely; clinical experience shows that the danger also grows in the early stage of recovery. A meta-analysis of placebo-controlled studies showed an increased risk of suicidal behaviour in patients under 25. Monitoring is intensified at the start of treatment and after every change of dose, and the patient and those close to them are warned: if the symptoms worsen, if suicidal thoughts or unusual changes of behaviour appear, they must contact a doctor immediately. In children and adolescents on antidepressants suicidal behaviour and hostility were noted more often, and long-term safety with regard to growth, sexual maturation and cognitive development has not been studied — during long treatment the doctor monitors the child's development.
- switching to sertraline from other SSRIs and antidepressants calls for caution, especially if the previous medicine is long-acting, for example fluoxetine;
- combination with tryptophan, fenfluramine, 5-HT receptor agonists and St John's wort is avoided where possible because of the pharmacodynamic interaction;
- with a history of mania or hypomania caution is needed, and if a manic phase sets in the medicine is withdrawn; in schizophrenia an intensification of psychotic symptoms is possible;
- in unstable epilepsy sertraline is not used; in controlled epilepsy close monitoring is maintained and the medicine is withdrawn if seizures appear;
- skin haemorrhages are possible — petechiae and purpura — and also gastrointestinal and gynaecological bleeding; caution is needed with anticoagulants, antipsychotics and phenothiazines, tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs;
- hyponatraemia is possible, often as a consequence of the syndrome of inappropriate antidiuretic hormone secretion; falls in sodium below 110 mmol/l have been described, and the risk group includes older people and those taking diuretics; the symptoms include headache, difficulty with concentration and memory, confusion, weakness and loss of balance, and in severe cases hallucinations, fainting, seizures and coma;
- akathisia — a distressing inner restlessness with the inability to sit or stand still — arises more often in the first weeks; increasing the dose is harmful in that case;
- in diabetes mellitus glycaemic control may change, so the glucose level is checked regularly and the doses of insulin or of oral medicines are reviewed if necessary.
How withdrawal of the medicine goes
Withdrawal symptoms are common, especially with abrupt discontinuation: in clinical studies they were reported by 23% of the patients who were withdrawing sertraline, against 12% of those who continued treatment. Most often they are dizziness, disturbances of sensation including paraesthesia, sleep disorders with insomnia and vivid dreams, agitation or anxiety, nausea and vomiting, muscle tremor and headache. They are usually mild or moderate and pass on their own within two weeks, but in some patients they drag on for two or three months and longer. That is why the dose is reduced gradually — over several weeks or months, depending on the situation. Sertraline is metabolised in the liver to a considerable extent: in mild compensated cirrhosis the half-life was prolonged and the AUC and the maximum concentration rose about threefold, so in liver disease the medicine is used with caution and in smaller doses.
Drug interactions
The main restriction is irreversible MAO inhibitors and pimozide: these combinations are contraindicated. Caution is required with all agents that enhance serotonergic transmission: tryptophan, fenfluramine, 5-HT receptor agonists and St John's wort preparations. When switching from a long-acting antidepressant the doctor takes the time of its elimination into account.
Separate attention is due to medicines that affect platelet function and clotting: anticoagulants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs, phenothiazines, atypical antipsychotics and tricyclic antidepressants — together with sertraline they raise the risk of bleeding. Diuretics and other agents that reduce fluid volume increase the likelihood of hyponatraemia. No clinical studies of the combined use of sertraline and electroconvulsive therapy have been carried out, so such a combination requires medical assessment.
Pregnancy and breastfeeding
There are no controlled studies in pregnant women. In experimental work no congenital malformations caused by sertraline were observed; however, in some newborns whose mothers took the medicine during pregnancy symptoms consistent with a withdrawal syndrome were noted, and the same has been described for other SSRIs. The medicine is used in pregnancy only if the woman's condition justifies treatment and the expected benefit outweighs the possible risk.
If it is still being taken in the late stages, especially in the third trimester, the newborn is monitored: breathing disorders, cyanosis, apnoea, seizures, fluctuations of body temperature, feeding difficulties, vomiting, hypoglycaemia, changes in muscle tone, hyperreflexia, tremor, irritability, constant crying and sleep disturbances are possible, usually within the first 24 hours after birth. Epidemiological data point to a possible increase in the risk of persistent pulmonary hypertension of the newborn. Sertraline and its metabolite pass into breast milk in small amounts, and in breastfed children their serum concentration is, as a rule, very low or undetectable.
Adverse effects
The most frequent undesirable reaction is nausea. Sexual disturbances depend on the dose and often lessen as treatment continues.
- very common — nausea, diarrhoea, dry mouth, insomnia;
- common — headache, drowsiness, dizziness, tremor, anxiety, agitation, nervousness, nightmares, reduced libido, disturbances of ejaculation;
- common — abdominal pain, vomiting, constipation, dyspepsia, reduced or increased appetite, increased sweating;
- common — palpitations, flushes, yawning, tinnitus, visual disturbances, pharyngitis, tiredness;
- uncommon — disturbances of taste and concentration, increased muscle tone, involuntary movements, fainting, migraine, dilated pupils, tachycardia, raised blood pressure, bronchospasm, nosebleed, oedema;
- rare — coma, dyskinesia, glaucoma, double vision, bradycardia, allergic and anaphylactic reactions, hypothyroidism, hyperglycaemia, hyperprolactinaemia;
- frequency not known — hyponatraemia and disturbed antidiuretic hormone secretion, leucopenia and thrombocytopenia, suicidal thoughts and behaviour, seizures, akathisia, extrapyramidal disorders, prolongation of the QTc interval and ventricular tachycardia of the torsade de pointes type, bleeding including gastrointestinal;
- separately — signs of serotonin syndrome or neuroleptic malignant syndrome: agitation, confusion, sweating, diarrhoea, fever, raised blood pressure, muscle rigidity, tachycardia.
Overdose
The margin of safety depends on the patient's condition and on which other medicines have been taken. After an overdose of sertraline — both on its own and in combination with other medicines or with alcohol — fatal outcomes have been recorded, so intensive care is required in any case. The symptoms are linked to an excess of serotonin: drowsiness, digestive disturbances with nausea and vomiting, tachycardia, muscle tremor, agitation and dizziness; less often a coma develops. Prolongation of the QTc interval and ventricular tachycardia of the torsade de pointes type have also been described, so monitoring of the electrocardiogram is needed.
There is no specific antidote. A clear airway, adequate ventilation and oxygen therapy are ensured, the work of the cardiovascular system and the vital signs are monitored, and symptomatic and supportive treatment is given. Activated charcoal, including together with a laxative, is no less effective than gastric lavage; inducing vomiting is not recommended. Because of the large volume of distribution of sertraline, forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit.
How to get a prescription for Sertralina Krka online
Sertraline is dispensed on prescription: the doctor chooses the starting dose for the particular diagnosis and assesses concomitant illnesses and the risk of interactions.
During the online consultation the doctor will discuss with you the symptoms, the scheme for raising the dose and the rules of withdrawal and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
