Lopralex Actions

• Actions of Lopralex in details
• Lopralex administration
• Lopralex pharmacology
• Lopralex reviews

Actions of Lopralex in details

A selective and potent serotonin re-uptake inhibitor (SSRI).

Pharmacology: Lopralex is a potent selective and inhibitor of serotonin uptake with antidepressant effect.

Lopralex has no or very low affinity for a series of receptors including muscarine cholinergic receptors, histamine receptors and adrenoceptors. This absence of effects on receptors could explain why Lopralex produces fewer of the traditional adverse effects of tricyclic antidepressants eg, dry mouth, blurred vision, sedation, cardiotoxicity and orthostatic hypotension. Unlike other available SSRIs, Lopralex is only a very weak inhibitor of the cytochrome P-450 II D6 metabolic pathway with a consequent reduction in potential for adverse events and interactions.

The antidepressant effect usually sets in after 2-4 weeks.

Lopralex does not affect the cardiac conduction system or blood pressure. This is particularly important for elderly patients. In addition, Lopralex does not affect the haematological, hepatic or renal systems. The low frequency of side effects and the minimal sedative properties of Lopralex make it especially useful in long-term treatment. Moreover, Lopralex neither causes weight gain nor potentiates the effect of alcohol.

Pharmacokinetics: The oral bioavailability of Lopralex is about 80%. Maximum Lopralex plasma levels are reached 2-4 hrs after dosing. The protein-binding is <80%. Metabolism proceeds by demethylation, deamination and oxidation. Unchanged Lopralex is the predominant compound in plasma. The kinetics is linear. Steady-state conditions are achieved in 1-2 weeks. The biological half-life is about 1½ days. Excretion is via urine and faeces.

How should I take Lopralex?

Take Lopralex only as directed by your doctor, to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Lopralex should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Lopralex may be taken with or without food. If your doctor tells you to take it at a specific time, follow your doctor's instructions.

If you are using the oral liquid, shake the bottle well before measuring each dose. Use a marked measuring spoon, oral syringe or medicine cup to measure each dose. The average household teaspoon may not hold the right amount of liquid.

You may have to take Lopralex for a month or longer before you begin to feel better.

Dosing

The dose of Lopralex will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Lopralex. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (solution or tablets):
  • For depression:
    • Adults—At first, 20 milligrams (mg) once a day, taken either in the morning or evening. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
    • Older adults—20 mg once a day, taken either in the morning or evening.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of Lopralex, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Lopralex administration

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Measure liquid medicine with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

It may take 4 weeks or longer before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment.

Do not stop using Lopralex suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using Lopralex.

Store at room temperature away from moisture and heat.

Lopralex pharmacology

Pharmacodynamics

The mechanism of action of Lopralex HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). In vitro and in vivo studies in animals suggest that Lopralex is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. Tolerance to the inhibition of 5-HT uptake is not induced by long-term (14-day) treatment of rats with Lopralex. Lopralex is a racemic mixture (50/50), and the inhibition of 5-HT reuptake by Lopralex is primarily due to the (S)-enantiomer.

Lopralex has no or very low affinity for 5-HT1A, 5-HT2A, dopamine D1 and D2, α1-, α2-, and β-adrenergic, histamine H1, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of other psychotropic drugs.

Pharmacokinetics

The single- and multiple-dose pharmacokinetics of Lopralex are linear and dose-proportional in a dose range of 10-60 mg/day. Biotransformation of Lopralex is mainly hepatic, with a mean terminal half-life of about 35 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of Lopralex in plasma, based on the half-life, is expected to be 2.5 times the plasma concentrations observed after a single dose.

Absorption and Distribution

Following a single oral dose (40 mg tablet) of Lopralex, peak blood levels occur at about 4 hours. The absolute bioavailability of Lopralex was about 80% relative to an intravenous dose, and absorption is not affected by food. The volume of distribution of Lopralex is about 12 L/kg and the binding of Lopralex (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma proteins is about 80%.

Metabolism and Elimination

Following intravenous administrations of Lopralex, the fraction of drug recovered in the urine as Lopralex and DCT was about 10% and 5%, respectively. The systemic clearance of Lopralex was 330 mL/min, with approximately 20% of that due to renal clearance.

Lopralex is metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), Lopralex-N-oxide, and a deaminated propionic acid derivative. In humans, unchanged Lopralex is the predominant compound in plasma. At steady state, the concentrations of Lopralex's metabolites, DCT and DDCT, in plasma are approximately one-half and one-tenth, respectively, that of the parent drug. In vitro studies show that Lopralex is at least 8 times more potent than its metabolites in the inhibition of serotonin reuptake, suggesting that the metabolites evaluated do not likely contribute significantly to the antidepressant actions of Lopralex.

In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of Lopralex.

Population Subgroups

Age - Lopralex pharmacokinetics in subjects ≥ 60 years of age were compared to younger subjects in two normal volunteer studies. In a single-dose study, Lopralex AUC and half-life were increased in the subjects ≥ 60 years old by 30% and 50%, respectively, whereas in a multiple-dose study they were increased by 23% and 30%, respectively. 20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age, due to the risk of QT prolongation.

Gender - In three pharmacokinetic studies (total N=32), Lopralex AUC in women was one and a half to two times that in men. This difference was not observed in five other pharmacokinetic studies (total N=114). In clinical studies, no differences in steady state serum Lopralex levels were seen between men (N=237) and women (N=388). There were no gender differences in the pharmacokinetics of DCT and DDCT. No adjustment of dosage on the basis of gender is recommended.

Reduced hepatic function - Lopralex oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function compared to normal subjects. 20 mg/day is the maximum recommended dose for hepatically impaired patients, due to the risk of QT prolongation.

CYP2C19 poor metabolizers -– In CYP2C19 poor metabolizers, Lopralex steady state Cmax and AUC was increased by 68% and 107%, respectively. Lopralex 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation.

CYP2D6 poor metabolizers - Lopralex steady state levels were not significantly different in poor metabolizers and extensive metabolizers of CYP2D6.

Reduced renal function - In patients with mild to moderate renal function impairment, oral clearance of Lopralex was reduced by 17% compared to normal subjects. No adjustment of dosage for such patients is recommended. No information is available about the pharmacokinetics of Lopralex in patients with severely reduced renal function (creatinine clearance < 20 mL/min).

Drug-Drug Interactions

In vitro enzyme inhibition data did not reveal an inhibitory effect of Lopralex on CYP3A4, -2C9, or -2E1, but did suggest that it is a weak inhibitor of CYP1A2, -2D6, and -2C19. Lopralex would be expected to have little inhibitory effect on in vivo metabolism mediated by these enzymes. However, in vivo data to address this question are limited.

CYP3A4 and CYP 2C19 inhibitors: Since CYP3A4 and CYP 2C19 are the primary enzymes involved in the metabolism of Lopralex, it is expected that potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of CYP2C19 (e.g., omeprazole) might decrease the clearance of Lopralex. However, coadministration of Lopralex and the potent CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of Lopralex. Lopralex 20 mg/day is the maximum recommended dose in patients taking concomitant cimetidine or another CYP2C19 inhibitor, because of the risk of QT prolongation.

CYP2D6 Inhibitors: Coadministration of a drug that inhibits CYP2D6 with Lopralex is unlikely to have clinically significant effects on Lopralex metabolism, based on the study results in CYP2D6 poor metabolizers.

Clinical Efficacy Trials

The efficacy of Lopralex as a treatment for depression was established in two placebo-controlled studies (of 4 to 6 weeks in duration) in adult outpatients (ages 18-66) meeting DSM-III or DSM-III-R criteria for major depression. Study 1, a 6-week trial in which patients received fixed Lopralex doses of 10, 20, 40, and 60 mg/day, showed that Lopralex at doses of 40 and 60 mg/day was effective as measured by the Hamilton Depression Rating Scale (HAMD) total score, the HAMD depressed mood item (Item 1), the Montgomery Asberg Depression Rating Scale, and the Clinical Global Impression (CGI) Severity scale. This study showed no clear effect of the 10 and 20 mg/day doses, and the 60 mg/day dose was not more effective than the 40 mg/day dose. In study 2, a 4-week, placebo-controlled trial in depressed patients, of whom 85% met criteria for melancholia, the initial dose was 20 mg/day, followed by titration to the maximum tolerated dose or a maximum dose of 80 mg/day. Patients treated with Lopralex showed significantly greater improvement than placebo patients on the HAMD total score, HAMD item 1, and the CGI Severity score. In three additional placebo-controlled depression trials, the difference in response to treatment between patients receiving Lopralex and patients receiving placebo was not statistically significant, possibly due to high spontaneous response rate, smaller sample size, or, in the case of one study, too low a dose.

In two long-term studies, depressed patients who had responded to Lopralex during an initial 6 or 8 weeks of acute treatment (fixed doses of 20 or 40 mg/day in one study and flexible doses of 20-60 mg/day in the second study) were randomized to continuation of Lopralex or to placebo. In both studies, patients receiving continued Lopralex treatment experienced significantly lower relapse rates over the subsequent 6 months compared to those receiving placebo. In the fixed-dose study, the decreased rate of depression relapse was similar in patients receiving 20 or 40 mg/day of Lopralex.

Analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics.

Comparison of Clinical Trial Results

Highly variable results have been seen in the clinical development of all antidepressant drugs. Furthermore, in those circumstances when the drugs have not been studied in the same controlled clinical trial(s), comparisons among the results of studies evaluating the effectiveness of different antidepressant drug products are inherently unreliable. Because conditions of testing (e.g., patient samples, investigators, doses of the treatments administered and compared, outcome measures, etc.) vary among trials, it is virtually impossible to distinguish a difference in drug effect from a difference due to one of the confounding factors just enumerated.

References

1. EPA DSStox. "Citalopram: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Lopralex are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Lopralex. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

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Information checked by Dr. Sachin Kumar, MD Pharmacology