Leparox Sr

Uses

Leparox Sr is used for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Posttraumatic Stress Disorder.

Leparox Sr is also used to associated treatment for these conditions: Generalized Anxiety Disorder (GAD), Irritable Bowel Syndrome (IBS), Major Depressive Disorder (MDD), Obsessive Compulsive Disorder (OCD), Panic Disorder, Post Traumatic Stress Disorder (PTSD), Premature Ejaculation, Premenstrual Dysphoric Disorder, Social Anxiety Disorder (SAD), Vasomotor Symptoms Associated With Menopause

How Leparox Sr works

Leparox Sr enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor. This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including Citalopram, Fluoxetine, and Fluvoxamine. The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation.

Leparox Sr shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors. The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons. In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the 5-HT neurons and subsequent release of serotonin at the synaptic cleft.

Dosage

Leparox Sr dosage

Major Depressive Disorder:

• Usual Initial Dosage: Leparox Sr (Leparox Sr hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Systematic evaluation of the efficacy of Leparox Sr hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder (OCD):

• Usual Initial Dosage: Leparox Sr (Leparox Sr hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Leparox Sr in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder:

• Usual Initial Dosage: Leparox Sr should be administered as a single daily dose with or without food, usually in the morning. The target dose of Leparox Sr in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. The maximum dosage should not exceed 60 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder (SAD):

• Usual Initial Dosage: Leparox Sr should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder (GAD):

• Usual Initial Dosage: Leparox Sr should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Posttraumatic Stress Disorder (PTSD):

• Usual Initial Dosage: Leparox Sr should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Side Effects

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.

Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.

Panic disorder: Asthenia, sweating, decreased appetite, decreased libido , tremor, abnormal ejaculation, female genital disorders and impotence.

Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawn, abnormal ejaculation, female genital disorders and impotence.

Generalised anxiety disorder: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating and abnormalejaculation.

Post-traumatic stress disorder: Asthenia, sweating nausea, dry mouth, diarrhoea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders and impotence.

Toxicity

The acute LD50 in mice and rats is 350 mg/kg.

Overdose information

The lowest dose of paroxetine reported to lead to a fatal outcome is approximately 400 mg. The largest reported paroxetine overdose from which a patient has survived and recovered is a dose of 2000 mg. Common manifestations in a paroxetine overdose include fatigue, fever, insomnia hypertension, tachycardia, nausea, vomiting, somnolence, tremor, dizziness, agitation, confusion, anxious symptoms, headache, insomnia, hyperhidrosis, dilated pupils, seizures, paresthesia, serotonin syndrome, involuntary muscle contraction, and change in mental status. It should be noted that in some cases, patients may have consumed alcohol in addition to taking an overdose of paroxetine. Some of these symptoms may also be seen with clinical use. There is no specific antidote to an overdose of paroxetine.

Precaution

Cardiac conditions: Leparox Sr does not produce clinically significant changes in blood pressure, heart rate and ECG. Nevertheless, as with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.

Epilepsy: As with other antidepressants, Leparox Sr should be used with caution in-patients with epilepsy.

Seizures: Overall, the incidence of seizures is < 0.1% in patients treated with Leparox Sr. Leparox Sr should be discontinued in any patient who develops seizures.

ECT: There is little clinical experience of concurrent administration of Leparox Sr with ECT.

Ability to drive/use machines: Clinical experience has shown that therapy with Leparox Sr is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.

Discontinuation of Treatment with Leparox Sr: Recent clinical trials supporting the various approved indications of Leparox Sr employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped.

Interaction

Food/antacids: The absorption and pharmacokinetics of Leparox Sr are not affected by food or antacids.

Tryptophan: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Leparox Sr and Tryptophan may occur, resulting in a ‘serotonin syndrome’ suggested by a combination of agitation, restlessness and gastrointestinal symptoms including diarrhoea.

Drug metabolizing enzyme inducers /inhibitors: The metabolism and pharmacokinetics of Leparox Sr may be affected by drugs, which induce or inhibit hepatic drug metabolizing enzymes. When Leparox Sr is to be coadministered with a known drug metabolizing inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Leparox Sr is considered necessary when it is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerabilityand efficacy).

Alcohol: Although Leparox Sr does not increase the impairment of mental and motor skill caused by alcohol, the concomitant use of Leparox Sr and alcohol in depressed patients is not advised.

Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Leparox Sr did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.

MAOls: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Leparox Sr and monoamine oxidase (MAO) inhibitors may occur.

Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of Leparox Sr and lithium should be undertaken with caution.

Lithium levels should be monitored. Phenytoin / anticonvulsants: Co-administration of Leparox Sr and phenytoin is associated with decreased plasma concentrations of Leparox Sr and increased adverse experiences. Co-administration of Leparox Sr with other anticonvulsants may also be associated with an increased incidence of adverse experiences.

Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction between Leparox Sr and warfarin, which may result in increased bleeding in the presence of unaltered prothrombin times. Leparox Sr should therefore be administered with great caution to patients receiving oral anticoagulants.

Food Interaction

• Avoid alcohol.
• Take with or without food. Food does not significantly affect absorption.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Leparox Sr Drug Interaction

Moderate: aspirin, aspirin, pregabalin, metoprolol, metoprolol, acetaminophen / hydrocodone, quetiapine, alprazolam, cetirizineUnknown: fluticasone / salmeterol, omega-3 polyunsaturated fatty acids, atorvastatin, esomeprazole, albuterol, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

Leparox Sr Disease Interaction

Major: depressionModerate: bone fractures, renal dysfunction, hyponatremia, glaucoma, liver disease, mania, platelet function, seizure disorders, SIADHMinor: weight loss

Volume of Distribution

Leparox Sr has a large volume of distribution and is found throughout the body, including in the central nervous system. Only 1% of the drug is found in the plasma. Leparox Sr is found in the breast milk at concentrations similar to the concentrations found in plasma.

Elimination Route

Leparox Sr is readily absorbed from the gastrointestinal tract. Due to the first-pass metabolism, the bioavailability ranges from 30-60%. Cmax is attained 2 to 8 hours after an oral dose. Mean Tmax is 4.3 hours in healthy patients. The steady-state concentration of paroxetine is achieved within 7 to 14 days of oral therapy. In a pharmacokinetic study, AUC in healthy patients was 574 ng·h/mL and 1053 ng·h/mL in those with moderate renal impairment.

Half Life

The mean elimination half-life of paroxetine is about 21 hours. In healthy young subjects, mean elimination half-life was found to be 17.3 hours.

Clearance

The apparent oral clearance of paroxetine is 167 L/h. The clearance of paroxetine in patients with renal failure is significantly lower and dose adjustment may be required, despite the fact that it is mainly cleared by the liver. Dose adjustments may be required in hepatic impairment.

Elimination Route

About 2/3 of a single paroxetine dose is found to be excreted in the urine and the remainder is found to be excreted in feces. Almost all of the dose is eliminated as metabolites; 3% is found to be excreted as unchanged paroxetine. About 64% of a 30 mg oral dose was found excreted in the urine, with 2% as the parent drug and 62% appearing as metabolites. Approximately 36% of the dose was found to be eliminated in the feces primarily as metabolites and less than 1% as the parent compound.

Pregnancy & Breastfeeding use

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of Leparox Sr on labor and delivery in humans is unknown.

Nursing Mothers: Like many other drugs, Leparox Sr is secreted in human milk, and caution should be exercised when Leparox Sr hydrochloride is administered to a nursing woman.

Contraindication

Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. This is contraindicated in patients with a hypersensitivity to Leparox Sr.

Special Warning

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Storage Condition

Keep out of the reach of children. Store at a cool and dry place. Protect from light and moisture.

Innovators Monograph

You find simplified version here Leparox Sr