Deprivox

Deprivox is an antidepressant. It belongs to the category of selective SSRIs of the neuronal type.

Indications Deprivoxa

It is used to treat depression as well as OCD.

Release form

Release in tablets - 10 pieces inside a blister. In a separate package - 2, 5 or 10 blister plates with tablets.

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Pharmacodynamics

End-on synthesis tests have demonstrated that fluvoxamine is a potent SSRI both in vitro and in vivo. It has minimal affinity for serotonin receptor subtypes.

The drug has a weak ability to synthesize with α- and ß-adrenergic receptors, as well as with muscarinic, histaminergic, acetylcholine or dopaminergic endings.

Pharmacokinetics

Fluvoxamine is fully absorbed after oral administration of the tablet. Peak plasma levels are observed approximately 3-8 hours after administration of the drug. Due to the fact that the drug is subject to the first-pass effect, the bioavailability level only reaches 53%. The pharmacokinetic parameters of the substance do not change when taken with food.

In vitro, fluvoxamine is 80% synthetized with plasma protein. The distribution volume is 25 l/kg.

The substance undergoes intensive hepatic metabolism. Although in vitro tests the main isoenzyme (participant in the processes of metabolism of the active component of the drug) is the CYP2D6 element, the plasma values in people with a reduced level of CYP2D6 element activity are only slightly higher than similar values in people with an intensive metabolic process.

The half-life from plasma is approximately 13-15 hours after a single use of the drug and is slightly extended (up to 17-22 hours) in the case of multiple use. At the same time, the substance reaches equilibrium plasma concentrations after multiple use over a period of 10-14 days.

Intensive transformation of the component is observed in the liver - mainly through the process of oxidative demethylation. In this case, at least 9 decay products are formed, excreted by the kidneys. 2 main decay products of the substance are inactive. Fluvoxamine is a strong inhibitor of the CYP1A2 element. In addition, it moderately slows down the action of CYP2C components with CYP3A4, and has only a marginal slowing effect on the CYP2D6 element.

The pharmacokinetics of the active component of Deprivox is linear (in the case of taking a single dose of the drug).

Steady-state plasma values are higher than those calculated from single-dose information and are also disproportionately higher when larger daily doses are used.

Dosing and administration

The medicine should be swallowed without chewing, washed down with water.

For depression (in adults).

The required initial dose is 50 or 100 mg per day. It should be taken once per day; preferably before bedtime. The dosage can be increased gradually as prescribed by a doctor, until a clinical result is achieved. The most effective daily dose is 100 mg. The daily dosage should be selected individually, taking into account the patient's response to the drug. No more than 300 mg is allowed per day. In case of dosages exceeding 150 mg, it is necessary to divide its use into several doses per day (2-3 times). According to WHO requirements, after the patient's signs of depression have disappeared, therapy should be continued for at least another 6 months.

To prevent relapse, it is necessary to take 100 mg of Deprivox per day.

For the treatment of OCD (in children from 8 years of age and adults).

The starting daily dose is 50 mg during the first 3-4 days of the course, and then it is gradually increased until the maximum possible effective dosage is reached (usually 100-300 mg per day). The maximum adult daily dose is 300 mg, and the child's dose (children over 8 years old) is 200 mg. Doses that do not exceed 150 mg are taken once a day (recommended before bedtime). If dosages greater than 150 mg are prescribed, the portion must be divided into 2-3 doses per day. After achieving the medicinal effect, the course should be continued further, in a dosage that is selected taking into account the therapeutic result. If there are no symptoms of improvement after 10 weeks of the course, it is necessary to reconsider the advisability of further administration of the drug.

Although there is no information on systematic testing to determine the limits of acceptable duration of drug use, since OCD is a chronic disease, it is considered appropriate to continue therapy for more than 10 weeks even in individuals who have achieved a therapeutic result. The dosage is selected for each patient individually, carefully - so that the person carries out maintenance treatment in the minimum effective doses. Periodically, it is necessary to review the need for continuing the course. People who have benefited from pharmacotherapy may also be prescribed behavioral psychotherapy as an adjunctive treatment.

The drug should be discontinued gradually, not abruptly. After the decision to discontinue the drug, the dosage should be gradually reduced over a period of 1-2 weeks to reduce the likelihood of withdrawal syndrome. If, as a result of reducing the dosage or after stopping the drug, the signs of the above syndrome still appear, it is necessary to return to the previous regimen. Then the dosage can be reduced further (under the supervision of a doctor), but even more gradually.

In case of kidney or liver failure, as well as cardiac pathologies.

People with such disorders should begin treatment with Deprivox at the lowest possible effective dose. The patient should be constantly monitored by the attending physician during therapy.

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Use Deprivoxa during pregnancy

Epidemiological data show that taking selective SSRIs (including fluvoxamine) during pregnancy, especially in the later stages, can increase the likelihood of developing pulmonary hypertension (persistent type) in newborns. Cases of such a disorder due to taking drugs were recorded in 5 per 1000 pregnancies. In general, 1-2 such cases per 1000 are noted.

It is prohibited to prescribe Deprivox to pregnant women. Such use can be justified only in situations where the patient's condition requires the use of this drug.

Isolated cases of withdrawal syndrome in neonates have been reported following use of SSRIs in late pregnancy. Breathing/swallowing problems, hypoglycemia, seizures, muscle tone disorders, cyanosis, and tremor have been reported in some neonates following use of SSRIs in the third trimester. Temperature instability, tremors, drowsiness, lethargy, irritability, persistent crying, sleep disturbances, and vomiting have also been reported. All of these manifestations may require prolonged hospitalization.

Small amounts of the drug pass into breast milk, which is why it is prohibited to prescribe it to nursing mothers.

Contraindications

Contraindications include: combined use with ramelteon, tizanidine or MAOIs. Therapy may be started at least 2 weeks after discontinuing irreversible MAOIs, as well as the day after discontinuing reversible MAOIs (such as linezolid or moclobemide). Any drug from the MAOI category may be started at least 1 week after discontinuing Deprivox.

It is also prohibited to prescribe to people with intolerance to the substance fluvoxamine maleate or other components of the drug.

Side effects Deprivoxa

Taking the pills may cause the following side effects:

• reactions of the systemic blood flow and lymph: bleeding occurs (this includes bleeding in the gastrointestinal tract, gynecological type, as well as purpura with ecchymosis);
• endocrine pathologies: inadequate ADH secretion rate and development of hyperprolactinemia;
• nutritional disorders and metabolic disorders: loss of appetite accompanied by anorexia, weight loss or gain, and the development of hyponatremia;
• mental illness: feeling of confusion, the emergence of suicidal thoughts, hallucinations, the development of mania or suicidal behavior;
• disorders in the functioning of the nervous system: the appearance of a feeling of nervousness, drowsiness, agitation, and anxiety. Tremor, insomnia, headache, ataxia, and also extrapyramidal disorders and dizziness may develop. Convulsions, symptoms similar to neuroleptic syndrome of a malignant nature, and in addition serotonin intoxication, dysgeusia and paresthesia with akathisia/psychomotor agitation are also observed;
• manifestations in the visual organs: development of mydriasis or glaucoma;
• cardiac dysfunction: tachycardia and increased heart rate;
• vascular disorders: orthostatic collapse;
• reactions from the gastrointestinal tract: development of constipation, nausea, abdominal pain, dyspeptic symptoms, vomiting, diarrhea and dry mouth;
• manifestations from the hepatobiliary system: disorders in liver function;
• dermatological disorders and reactions of the subcutaneous layer: the appearance of hyperhidrosis, signs of photosensitivity, as well as manifestations of allergies (such as itching, rashes and Quincke's edema);
• dysfunction of the musculoskeletal system, bone and connective tissues: development of myalgia or arthralgia, as well as bone fractures. Epidemiological tests, which were mainly conducted with patients over 50 years of age, demonstrated an increased likelihood of bone fractures in people taking tricyclics or SSRIs. It was not possible to determine the mechanism causing such a disorder;
• renal and urinary system dysfunction: problems with urination (this includes incontinence and urinary retention, as well as enuresis and nocturia with pollakiuria);
• manifestations from the mammary glands and reproductive organs: development of anorgasmia or galactorrhea, as well as delayed ejaculation and menstrual irregularities (including hypomenorrhea with amenorrhea, as well as uterine bleeding and hypermenorrhea);

Systemic disorders: development of asthenia or general malaise, as well as withdrawal syndrome.

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Overdose

Signs of overdose include vomiting, diarrhea, and nausea, as well as dizziness and drowsiness. In addition, there have been reports of renal dysfunction, bradycardia with tachycardia, and decreased blood pressure, as well as coma and convulsions.

Fluvoxamine has a wide safety spectrum in case of intoxication. There are isolated reports of fatalities due to fluvoxamine poisoning. The highest dosage recorded in case of overdose is 12 g. The patient who took this dose subsequently recovered completely. There have been cases of severe complications with intentional overdose of Deprivox in combination with other drugs.

Fluvoxamine has no antidote. In case of poisoning with the drug, it is necessary to perform gastric lavage as quickly as possible, and then carry out procedures aimed at eliminating signs of disorders, as well as maintaining the condition of the victim. Along with this, it is necessary to take activated carbon, and, if necessary, an osmotic laxative. Hemodialysis or forced diuresis procedures will be ineffective.

Interactions with other drugs

It is prohibited to combine the drug with MAOIs (including linezolid), because there is a risk of developing serotonin intoxication.

The effect of fluvoxamine on the processes of oxidative metabolism of other drugs.

Fluvoxamine is able to inhibit the process of metabolism of those drugs that are metabolized by individual hemoprotein isoenzymes (CYP). In vitro and in vivo tests demonstrate a strong inhibitory effect of the drug on CYP1A2 with 2C19, but the inhibition of CYP2C9 with CYP2D6, as well as CYP3A4 is less noticeable. Drugs that are mainly metabolized with the participation of these isoenzymes are excreted more slowly and may have increased plasma values in case of combination with fluvoxamine.

Treatment with Deprivox in combination with similar drugs should be adjusted to the lowest and at the same time effective dosage. Plasma parameters, effects or side effects of concomitant drugs should be closely monitored with subsequent reduction of their dosages if necessary. This is especially important with drugs that have a narrow drug index.

The substance is ramelteon.

Administration of 100 mg fluvoxamine twice daily for 3 days, followed by a single dose of ramelteon (16 mg) plus fluvoxamine resulted in an approximately 190-fold increase in ramelteon AUC compared with monotherapy, and a 70-fold increase in peak drug levels.

Combinations with drugs that have a narrow drug index.

Careful monitoring of the condition of individuals taking fluvoxamine together with drugs from the above category (including theophylline with phenytoin, tacrine and cyclosporine with methadone and carbamazepine, and mexiletine) is required. Their metabolism is carried out exclusively by the CYP system or with the participation of CYP, which are slowed by fluvoxamine. If necessary, the dosage of this drug should be changed.

Neuroleptics and tricyclics.

There is information about the increase in plasma values of tricyclics (such as amitriptyline with clomipramine, as well as imipramine), as well as neuroleptics (including olanzapine with clozepine and quetiapine), which are mainly metabolized with the participation of hemoprotein P450 1A2 in combination with fluvoxamine. It is necessary to consider the option of reducing the dosage of these drugs in case of their combination with Deprivox.

Benzodiazepines.

In case of combination with Deprivox, an increase in plasma levels of benzodiazepines metabolized by oxidation (including midazolam with diazepam, as well as triazolam with alprazolam) may be observed. It is necessary to reduce the dosage of these drugs when combined with fluvoxamine.

Situations with increased indicators within the plasma.

As a result of simultaneous use with ropinirole, the plasma level of this drug may increase, which increases the likelihood of intoxication. Therefore, during therapy, it is necessary to monitor the patient's condition and reduce the dose of ropinirole if necessary (when used in combination with fluvoxamine, as well as after the latter is discontinued).

Since plasma levels of propranolol are increased when combined with Deprivox, a reduction in dosage can be expected.

Combination with warfarin leads to a significant increase in its plasma level, as well as an increase in PT indices.

Situations with an increased risk of developing side effects.

There are isolated data on the development of cardiotoxic effects in the case of a combination of the drug with thioridazine.

Plasma caffeine levels may increase when combined with fluvoxamine. Side effects of caffeine (such as increased heart rate, insomnia, tremors, nausea, and anxiety) may occur. Therefore, people who frequently consume caffeinated beverages should reduce their consumption while using fluvoxamine.

Drug interactions.

Potentiation of serotonergic effects is possible when the drug is combined with other serotonergic drugs (including St. John's wort, triptans, SSRIs, and tramadol).

Concomitant use of drugs with lithium (in patients suffering from severe forms of pathology) should be done with caution, because lithium (and, possibly, the substance tryptophan) is able to potentiate the serotonergic properties of fluvoxamine. Because of this, the combination of these drugs should be limited to use only in people with severe depression resistant to therapy.

Careful monitoring is required in people who combine Deprivox with oral anticoagulants, as this may increase the risk of bleeding.

It is necessary to refrain from drinking alcoholic beverages while using fluvoxamine.

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Storage conditions

Deprivox should be kept in a place inaccessible to small children. Temperature conditions – no more than 25°C.

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Shelf life

Deprivox can be used for a period of 3 years from the date of manufacture of the drug.