Fluoxetine Aurovitas: composition and dosage form
One hard capsule contains 22.357 mg of fluoxetine hydrochloride, equivalent to 20 mg of fluoxetine. There is only one strength, and every regimen — from 20 mg a day in depression to 60 mg in bulimia — is built out of whole capsules.
It is taken by mouth, all at once or with the daily dose split, with food or between meals. The capsule is bioequivalent to the oral solution, which matters for children's regimens: a child's starting dose is measured out with the solution, because a 10 mg capsule cannot be divided.
How Fluoxetine Aurovitas works
Fluoxetine is a selective serotonin reuptake inhibitor, and that appears to be where its mechanism rests. It shows virtually no affinity for other receptors: not for α1, α2 and β adrenergic ones, nor for dopaminergic, histaminergic H1, muscarinic or GABA receptors. Hence the profile: the dry mouth, sedation and tachycardia typical of older antidepressants, which come from blocking those receptors, are not to be expected here.
The second feature is an unusually long stay in the body. The half-life of fluoxetine itself is 4 to 6 days, and that of its active metabolite norfluoxetine 4 to 16 days. After the medicine is stopped the substances remain in the body for several more weeks, and this has to be kept in mind both when starting treatment and when ending it: every change of dose plays out over weeks rather than over a day.
Indications
In adults the medicine is prescribed for episodes of major depression, for obsessive-compulsive disorder and for bulimia. In the last case it is not a treatment in its own right but an addition to psychotherapy: to reduce the urge to binge and purging behaviour.
In children and adolescents from the age of 8 there is a single indication: a moderate to severe episode of major depression, and only where it has not responded to psychological therapy after 4–6 sessions. At that age the antidepressant is given together with psychological therapy, not instead of it.
How to take it and dosage
In depression adults and older people are advised 20 mg a day. At 3–4 weeks the dose is reviewed and adjusted if needed, and after that the clinical picture guides it. If the response to 20 mg is insufficient the dose is raised gradually as far as 60 mg, bearing in mind that the likelihood of adverse reactions rises with it. Treatment of depression is continued for at least six months. In obsessive-compulsive disorder the start is the same — 20 mg with a possible rise to 60 mg; if there is no improvement within 10 weeks the case for treatment is reconsidered, and with a good response it goes on beyond 10 weeks because the disorder is chronic, although efficacy beyond 24 weeks has not been shown. In bulimia the dose is 60 mg a day from the outset, and efficacy beyond three months has not been shown. Doses above 80 mg have not been systematically evaluated.
In children from 8 years treatment is started and supervised by a specialist. The starting dose is 10 mg a day as 2.5 ml of oral solution, and after one or two weeks it can be raised to 20 mg. Experience with doses above 20 mg in children is minimal, and in a child of low body weight the effect is reached with smaller doses because the plasma concentration is higher. If there is no clinical benefit within 9 weeks the treatment is reconsidered, and in those who respond its continuation is discussed after six months. In older people the dose is raised cautiously, usually no higher than 40 mg a day with a maximum of 60 mg. With impaired liver function and with medicines that may interact, the dose is reduced or spaced out, for example 20 mg every other day. Stopping abruptly is not allowed: the dose is lowered gradually over at least one to two weeks, and if symptoms appear after a reduction the previous dose is resumed and lowered more slowly.
Contraindications
There are few contraindications and all three are firm. The first is hypersensitivity to the active substance or to any excipient. The second is the combination with irreversible non-selective monoamine oxidase inhibitors, for instance iproniazid: such combinations have produced severe and sometimes fatal reactions.
The third is narrow and easy to miss: metoprolol prescribed for heart failure. Fluoxetine strongly inhibits CYP2D6, which breaks metoprolol down, its concentration rises, and in heart failure excessive bradycardia is particularly dangerous.
Special warnings and precautions
The main warning concerns suicide risk. Depression itself raises the likelihood of suicidal thoughts, self-harm and suicide, and the risk persists until meaningful remission; improvement may not come in the first weeks, so the patient needs watching until it does, and in the early stage of recovery the risk can even grow. A meta-analysis of placebo-controlled trials showed an increased risk of suicidal behaviour in patients under 25, and in children and adolescents suicidal thoughts and attempts and hostility were recorded more often. The patient and those close to them are warned: a worsening of the illness, suicidal thoughts or an unusual change of behaviour is a reason to see a doctor at once.
- Children and adolescents: in a 19-week study their gain in height and weight slowed, so height, weight and Tanner stage are monitored during treatment and afterwards; delayed puberty is also possible.
- Heart: QT prolongation and ventricular arrhythmias including torsade de pointes have been described. Caution is needed with congenital long QT syndrome, a family history, hypokalaemia, hypomagnesaemia, bradycardia, recent myocardial infarction and decompensated heart failure. With stable heart disease an ECG before starting is worthwhile, and if an arrhythmia appears during treatment the medicine is stopped.
- Seizures: the medicine is avoided in unstable seizure disorders and epilepsy, watched in controlled epilepsy, and withdrawn if seizures appear or become more frequent. Mania and hypomania are likewise grounds for immediate withdrawal, and in children they were recorded often.
- Bleeding: petechiae and purpura have been described, and less often genital and gastrointestinal bleeding; caution is needed with anticoagulants and with a history of clotting disorders.
- Akathisia: an exhausting restlessness with an urge to move, most often in the first weeks; raising the dose then does harm.
As for the rest. Serotonin syndrome and neuroleptic malignant syndrome are rare but possible, particularly alongside other serotonergic medicines and neuroleptics, and call for immediate withdrawal. Treatment can alter glycaemic control: hypoglycaemia was seen on the medicine and hyperglycaemia after stopping it, so insulin doses sometimes have to be reworked. Rash, anaphylaxis and progressive systemic features involving the skin, kidneys, liver or lungs call for the medicine to be stopped, and where there is a risk of narrow-angle glaucoma caution is needed because of pupil dilatation.
Drug interactions
The long half-life turns some interactions into a matter of the calendar rather than the dose. Irreversible non-selective monoamine oxidase inhibitors are contraindicated, and the intervals are not symmetrical: fluoxetine is started only 2 weeks after such an inhibitor is withdrawn, and the inhibitor after fluoxetine no sooner than 5 weeks. The signs of a dangerous combination are hyperthermia, muscle rigidity, myoclonus, autonomic instability, confusion and extreme agitation progressing to delirium and coma; cyproheptadine or dantrolene may help.
- Tamoxifen: CYP2D6 inhibitors lower the concentration of endoxifen, one of its most active forms, by 65–75%, and in some studies tamoxifen was less effective. The combination is avoided where possible.
- Metoprolol: inhibited metabolism raises the risk of adverse reactions, above all excessive bradycardia.
- QT-prolonging medicines: class IA and III antiarrhythmics, phenothiazines, pimozide, haloperidol, tricyclic antidepressants, sparfloxacin, moxifloxacin, intravenous erythromycin, halofantrine. The interaction has not been studied and an additive effect cannot be ruled out.
- Oral anticoagulants: the bleeding risk rises and the INR needs checking more often, both during treatment and after withdrawal.
- Diuretics, desmopressin, carbamazepine and oxcarbazepine cause hyponatraemia, which fluoxetine itself can also produce.
Fluoxetine does not potentiate alcohol or raise its blood level, but mixing drink with medicines of this group is still not advised. And the main point: when switching to another antidepressant that same long trail works against the patient, because the new medicine overlaps the old one that has not yet cleared.
Pregnancy and breastfeeding
Some epidemiological studies point to an increased risk of cardiovascular malformations in the fetus with use in the first trimester; the mechanism is unknown. In figures: about 2 cases per 100 against roughly 1 per 100 in the general population. There are also data on persistent pulmonary hypertension of the newborn with use late in pregnancy — about 5 cases per 1,000 pregnancies against the usual 1–2.
Fluoxetine is therefore not used in pregnancy unless the woman's condition requires precisely this medicine and justifies the possible risk to the fetus. Nor may treatment be broken off abruptly. Late in pregnancy and shortly before delivery particular caution is needed: irritability, tremor, muscle hypotonia, incessant crying and difficulty feeding and sleeping have been described in newborns — this may be either a serotonergic effect or a withdrawal syndrome, and the timing is tied to that same slow elimination. Fluoxetine and norfluoxetine pass into breast milk and adverse events were observed in breastfed infants, so giving up feeding is considered and, if it continues, the lowest effective dose is prescribed.
Adverse reactions
The commonest reports are headache, nausea, insomnia, tiredness and diarrhoea. The frequency and severity of reactions usually fall over time and as a rule do not lead to treatment being stopped. What follows is a selection of the commonest and the most dangerous, not a full list.
- Very common: insomnia, headache, diarrhoea, nausea, tiredness.
- Common: reduced appetite and weight, anxiety, nervousness, lowered libido, sleep disturbance and nightmares, dizziness, drowsiness, tremor, blurred vision, palpitations and a prolonged QT on the ECG, vomiting, dyspepsia, dry mouth, rash, itching, sweating, joint pain, disturbed erection and ejaculation.
- Rare: thrombocytopenia, neutropenia, leucopenia, anaphylaxis, hyponatraemia and inappropriate antidiuretic hormone secretion, hypomania and mania, hallucinations, aggression, seizures, akathisia, serotonin syndrome, ventricular arrhythmia and torsade de pointes, vasculitis, pulmonary processes with inflammation or fibrosis, idiosyncratic hepatitis, angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis, urinary retention, hyperprolactinaemia.
Two observations stand apart. The first: epidemiological studies, mainly in people over 50, show an increased risk of bone fractures with medicines of this group, and the mechanism is unknown. The second concerns the withdrawal syndrome, and the numbers there are sobering: adverse events after stopping treatment occurred in about 60% of patients both on fluoxetine and on placebo, and were severe in 17% and 12%. Dizziness, sensory disturbance, sleep disturbance, weakness, anxiety, nausea, tremor and headache usually appear in the first days and most often pass within two weeks, though in some people they last two or three months.
Overdose
An overdose of fluoxetine alone usually runs a mild course and fatal outcomes are exceedingly rare. Nausea, vomiting, seizures and cardiac disturbances are possible — from asymptomatic arrhythmias and QT prolongation on the ECG to cardiac arrest, with very rare cases of torsade de pointes — as well as breathing problems and states ranging from agitation to coma.
There is no specific antidote: cardiac activity and vital signs are monitored and treatment is symptomatic. Forced diuresis, dialysis, haemoperfusion and exchange transfusion are usually of no use, while activated charcoal, including with sorbitol, may be no worse than gastric lavage. The possibility that several medicines were taken at once is also considered: if the person was also taking a tricyclic antidepressant, observation is extended, because fluoxetine slows its elimination.
How to get a prescription for Fluoxetine Aurovitas online
Fluoxetine leaves the longest trail among the usual antidepressants, and that is why a doctor needs to know not only the current prescription but also what came before and what is planned afterwards: 2 weeks after a monoamine oxidase inhibitor, 5 weeks before starting one, the overlap with a previous antidepressant when switching. These are calendar limits that cannot be reconstructed from a single pack in the hand.
An online consultation is above all suited to continuing a regimen that has already been worked out. The questionnaire covers the diagnosis, how long the medicine has been taken and the current dose, age, previous and planned antidepressants, episodes of mania, seizures in the history, heart disease and QT prolongation, use of anticoagulants, diabetes, liver disease, pregnancy or plans for one, and also tamoxifen and metoprolol. The doctor studies the answers and, where there are sufficient grounds, issues an electronic prescription that arrives as a code for a Polish pharmacy.
