Venlafaxine Bluefish XL: composition and pharmaceutical form
Venlafaxine Bluefish XL comes as prolonged-release capsules containing 75 mg or 150 mg of venlafaxine as the hydrochloride.
Inside the capsule are granules from which the active substance is released slowly in the digestive tract. The insoluble part of those granules is passed out and may be visible in the stool — this is normal and does not mean the medicine has not worked.
How Venlafaxine Bluefish XL works
The antidepressant action of venlafaxine in humans is thought to be linked to increased neurotransmitter activity in the central nervous system. Preclinical studies showed that both venlafaxine itself and its active metabolite O-desmethylvenlafaxine inhibit the reuptake of serotonin and noradrenaline, while venlafaxine inhibits dopamine reuptake only weakly.
In addition, venlafaxine and its metabolite weaken the beta-adrenergic response, both after a single dose and with long-term treatment. In terms of their overall influence on neurotransmitter reuptake and on receptor binding the two substances behave very similarly, so the effect of the medicine is made up of the action of both.
Indications
The medicine is used to treat severe depressive episodes and to prevent their recurrence, and also in generalised anxiety disorder, social phobia and panic disorder with or without agoraphobia.
In children and adolescents under 18 the medicine is not recommended: controlled studies in major depressive episodes in that group showed no efficacy, and for the other indications efficacy and safety in minors have not been established.
Method of use and dosage
The capsules are taken daily with food, at roughly the same time, and swallowed whole with liquid. They must not be split, crushed, chewed or dissolved — otherwise the whole point of the prolonged-release form is lost.
| Indication | Dose |
|---|---|
| Severe depressive episode | start with 75 mg once a day; if there is no response an increase up to a maximum of 375 mg a day is possible |
| Generalised anxiety disorder | start with 75 mg a day, a maximum of 225 mg |
| Social phobia | 75 mg a day; there are no data on the benefit of higher doses, but if there is no response an increase to 225 mg is considered |
| Step of dose increase | with an interval of about 2 weeks or more; where clinically necessary, no shorter than 4 days |
| Switching from the immediate-release form | an equivalent dose is chosen: for example, 37.5 mg twice a day corresponds to 75 mg of the prolonged-release form once a day |
| Duration | usually several months or longer; after remission is reached treatment continues for at least 6 months |
The general rule is the lowest effective dose, and raising it is only appropriate after a clinical assessment: some of the adverse reactions depend directly on the size of the dose. The course of treatment is reviewed regularly, with an individual approach to every patient. In preventing repeat depressive episodes the dose is in most cases the same as in treating the current one.
Contraindications
There are few contraindications and all of them relate to the risk of serotonin syndrome.
- hypersensitivity to venlafaxine or to any excipient;
- concomitant use of irreversible MAO inhibitors — the combination threatens serotonin syndrome with agitation, tremor and hyperthermia;
- treatment with venlafaxine may be started no earlier than 14 days after an irreversible MAO inhibitor is withdrawn;
- venlafaxine is withdrawn at least 7 days before treatment with an irreversible MAO inhibitor begins.
Special warnings and precautions
Depression carries an increased risk of suicidal thoughts, self-harm and suicide, and that risk persists until full remission. Improvement may not come in the first weeks of treatment or later, so until it appears the patient is watched especially carefully; clinical experience shows the risk can rise in the early phase of recovery. A meta-analysis of placebo-controlled trials showed an increased risk of suicidal behaviour in patients under 25. The patient and those close to them are warned: if symptoms worsen, suicidal thoughts appear or behaviour changes unusually, a doctor must be contacted immediately.
Children and adolescents
The medicine is not used in patients under 18. In clinical trials suicidal behaviour — attempts and thoughts — and hostility, mainly aggression, oppositional behaviour and anger, occurred in children and adolescents on antidepressants more often than on placebo. If a decision to treat is nevertheless taken on clinical grounds, the patient is watched closely for suicidal manifestations. Moreover, there are no long-term data on the medicine's influence on growth, sexual maturation and cognitive and behavioural development.
Serotonin syndrome
Like other serotonergic agents, venlafaxine may cause serotonin syndrome, a potentially life-threatening condition. The risk rises with the concomitant use of agents that affect serotonin transmission: triptans, other antidepressants of this and related groups, lithium, sibutramine, St John's wort, fentanyl and its analogues, tramadol, dextromethorphan, tapentadol, pethidine, methadone and pentazocine, as well as medicines that slow serotonin metabolism, serotonin precursors such as tryptophan supplements, and antipsychotics and other dopamine antagonists. If the combination is clinically justified, the patient is watched especially closely at the start of treatment and when the dose is raised.
Drug interactions
Venlafaxine is not combined with irreversible MAO inhibitors: at least 14 days are left between their withdrawal and the start of the medicine and, after venlafaxine itself is withdrawn, an MAO inhibitor may be started no earlier than 7 days later. Reversible selective MAO-A inhibitors, for example moclobemide, are contraindicated because of the risk of serotonin syndrome; after their withdrawal the break may be shorter than 14 days, but a reversible MAO inhibitor is started no earlier than 7 days after venlafaxine. Linezolid — a weak reversible non-selective MAO inhibitor — is not prescribed to patients on venlafaxine.
Breaching these intervals has led to severe reactions: muscle tremor, myoclonic convulsions, profuse sweating, nausea and vomiting, sudden flushing of the face, dizziness and hyperthermia with features of neuroleptic malignant syndrome, seizures and death. Concomitant use with serotonin precursors, including tryptophan supplements, is not recommended. Caution is also needed with any agents acting on the central nervous system.
Pregnancy and breastfeeding
There are no sufficient data on use in pregnant women; animal studies showed a harmful effect on reproduction, and the risk to humans is unknown. The medicine is used in pregnancy only if the expected benefit outweighs the possible risk. Taking it during pregnancy or shortly before delivery may cause withdrawal symptoms in the newborn. In some children exposed to venlafaxine at the end of the third trimester, complications arose that required respiratory support, tube feeding or prolonged hospitalisation, and that right after birth.
Epidemiological data for medicines with a similar mechanism point to a possible increase in the risk of persistent pulmonary hypertension of the newborn; for venlafaxine that risk cannot be ruled out. With use late in pregnancy, irritability, tremor, reduced muscle tone, continuous crying and difficulty sucking and sleeping are possible in the newborn — usually in the first day after delivery. Venlafaxine and its active metabolite pass into breast milk; in breastfed children crying, irritability and disturbances of the sleep rhythm have been described and, after breastfeeding stopped, symptoms consistent with withdrawal of the medicine. The decision whether to continue breastfeeding or treatment is taken by weighing the benefit for the child against that for the mother.
Adverse effects
The most frequent — in more than one in ten patients — are nausea, dry mouth, headache and sweating, including at night.
- very common: dizziness, headache;
- common: drowsiness, tremor, paraesthesia, increased muscle tone, visual disturbances with pupil dilation and impaired accommodation, tinnitus, palpitations, reduced appetite;
- common in the psychic sphere: confusion, depersonalisation, absence of orgasm, reduced libido, nervousness, insomnia, unusual dreams;
- uncommon: akathisia and psychomotor restlessness, fainting, myoclonic convulsions, disturbances of coordination and balance, altered taste, tachycardia;
- uncommon in the psychic sphere: hallucinations, a sense of unreality, agitation, apathy, hypomania, bruxism;
- rare: seizures, mania;
- frequency not known: suicidal thoughts and behaviour during treatment or right after stopping it, delusions, aggression, neuroleptic malignant syndrome, serotonin syndrome, extrapyramidal disturbances, tardive dyskinesia;
- frequency not known: hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion, thrombocytopenia and other blood disorders up to agranulocytosis, aplastic anaemia and pancytopenia, anaphylactic reactions, closed-angle glaucoma, ventricular tachycardia and ventricular fibrillation.
In children and adolescents the profile is broadly the same, but in addition reduced appetite and weight, raised blood pressure and cholesterol, and suicidal thoughts, hostility and self-harm were recorded; abdominal pain, agitation, dyspepsia, petechiae, nosebleeds and muscle pain occurred more often.
Overdose
Cases of overdose after the medicine reached the market were recorded mainly in combination with alcohol or other medicines. The most frequent symptoms are tachycardia, disturbances of consciousness from drowsiness to coma, pupil dilation, seizures and vomiting. Changes on the ECG were also noted: prolongation of the QT interval, bundle branch block, widening of the QRS complex and, besides that, ventricular tachycardia, bradycardia, a fall in blood pressure, dizziness and fatal outcomes.
Retrospective studies indicate that an overdose of venlafaxine may carry a greater risk of death than an overdose of SSRI antidepressants, but a lower one than of tricyclics. At the same time, patients on venlafaxine start out with more suicide risk factors, so it is unclear what share of the risk belongs to the toxicity of the medicine itself. Hence the practical rule: prescribe the smallest quantity consistent with the prescribed regimen. Treatment is general supportive and symptomatic, with monitoring of heart rhythm and vital signs; where there is a risk of aspiration vomiting is not induced, gastric lavage is justified soon after intake or with clinical symptoms, and activated charcoal may reduce absorption. Forced diuresis, dialysis, haemoperfusion and exchange transfusion are probably ineffective. There is no specific antidote.
How to get a prescription for Venlafaxine Bluefish XL online
Venlafaxine Bluefish XL is a prescription-only medicine: the doctor chooses the starting dose by diagnosis, sets the pace of increase and the length of the course, and checks compatibility with other medicines — above all with serotonergic agents and MAO inhibitors.
During the online consultation the doctor will clarify the symptoms, go through the medicines you take and assess contraindications. If the medicine is suitable, they will issue an electronic prescription and explain what to expect in the first weeks and how to finish treatment properly so as to avoid withdrawal symptoms.
