VoXRa Xl 150mg. 300mg Tablet

VOXRA XL is indicated for the treatment of depression as defined by DSM IV Criteria. Following a satisfactory response, continuation with VOXRA XL therapy is effective in preventing relapse and preventing recurrence of further depressive episodes.

Therapy should be initiated by medical practitioners experienced in the treatment of depression. Posology Initial treatment: The initial dose of VOXRA XL is 150 mg taken as a single daily dose in the morning. Patients who are not responding adequately to a dose of 150 mg/day may benefit from an increase to the usual adult target dose of 300 mg/day, given once daily. There should be an interval of at least 24 hours between successive doses. Insomnia is a very common adverse event which is often transient. Insomnia may be reduced by avoiding dosing at bedtime (provided there is at least 24 hours between doses) or, if clinically indicated, dose reduction. Switching Patients from sustained release tablets: When switching patients from sustained release tablets to extended-release tablets; give the same total daily dose when possible. Patients who are currently being treated with sustained release tablets at 300 mg/day (e.g.,150 mg twice daily) may be switched to extended-release tablets 300 mg once daily. Special Populations: Children and Adolescents: VOXRA XL is not indicated for use in children or adolescents aged less than 18 years (see section 4.3) Elderly: Greater sensitivity of some elderly individuals to VOXRA XL cannot be ruled out, hence a reduced frequency and/or dose may be required (see section 4.4). Renal Impairment: Treatment of patients with renal impairment should be initiated at a reduced frequency and/or dose, as bupropion and its metabolites may accumulate in such patients to a greater extent than usual (see section 4.4.). Liver Impairment: VOXRA XL should be used with caution in patients with mild liver impairment. Because of increased variability in VOXRA XLu2019s pharmacokinetics in patients with mild hepatic cirrhosis, a reduced frequency of dosing should be considered (see sections 4.8 and 4.4.). VOXRA XL is contra-indicated in patients with moderate to severe hepatic cirrhosis. Method of administration VOXRA XL tablets should be swallowed whole. The tablets should not be cut, crushed or chewed as this may lead to an increased risk of adverse effects including seizures.

• Hypersensitivity to bupropion hydrochloride or to any of the excipients of VOXRA XL listed in section 6.1.
• Patients under 18 years.
• VOXRA XL is contra-indicated in patients with a seizure disorder.
• VOXRA XL should not be administered to patients currently being treated with any other preparation containing bupropion, as the incidence of seizures is dose dependent and to avoid overdosage.
• Voxra XL is contraindicated in patients with a known central nervous system tumour.
• VOXRA XL is contra-indicated in patients undergoing abrupt discontinuation of alcohol or sedatives.
• VOXRA XL is contra-indicated in patients with a current or previous diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was seen in this patient population when bupropion was administered.
• Concomitant administration of VOXRA XL with monoamine oxidase inhibitors (MAOIs) is contra-indicated. At least 14 days should elapse between the discontinuation of MAOIs and initiation of treatment with VOXRA XL.
• VOXRA XL is contraindicated for use in patients with liver disease, Child-Pugh grades B and C, range 7-13.N
• Women of child-bearing potential not using contraception.

The recommended dose of VOXRA XL should not be exceeded, since bupropion is associated with a dose-related risk of seizure. VOXRA XL should be discontinued promptly if patients experience hypersensitivity reactions during treatment (see section 4.8). Clinicians should be aware that symptoms may persist beyond the discontinuation of VOXRA XL and clinical management should be provided accordingly. The overall incidence of seizure with VOXRA XL in clinical trials was approximately 0,1 %. There is an increased risk of seizures occurring with the use of VOXRA XL in the presence of predisposing risk factors, which lower the seizure threshold. Therefore, VOXRA XL should not be administered to patients with one or more conditions predisposing to a lowered seizure threshold, which include:

• history of head trauma
• central nervous system (CNS) tumour
• history of seizures
• concomitant administration of other medications known to lower the seizure threshold
• excessive use of alcohol or sedatives (see section 4.3)
• diabetes treated with hypoglycaemics or insulin
• use of stimulants or anorectic products.

Bupropion is metabolised to its major active metabolite hydroxybupropion primarily by the cytochrome P450 IIB6 (CYP2B6) (see section 5.2). Care should therefore be exercised when VOXRA XL is co-administered with medicines known to affect the CYP2B6 isoenzyme (e.g., orphenadrine, cyclophosphamide, ifosfamide, ticlopidine, clopidogrel). Although bupropion is not metabolised by the CYP2D6 isoenzyme, in vitro human P450 studies have shown that bupropion and hydroxybupropion are inhibitors of the CYP2D6 pathway. In a human pharmacokinetic study, administration of bupropion increased plasma levels of desipramine. This effect was present for at least 7 days after the last dose of bupropion. Concomitant therapy with medicines predominantly metabolised by this isoenzyme (such as certain beta-blockers, anti-dysrrhythmics, selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics) should be initiated at the lower end of the dose range of the concomitant medication. If VOXRA XL is added to the treatment regimen of a patient already receiving a medication metabolised by CYP2D6, the need to decrease the dose of the original medication should be considered, particularly for those concomitant medications with a narrow therapeutic index (see section 5.2). Medicines which require metabolic activation by CYP2D6 in order to be effective (e.g., tamoxifen), may have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Although citalopram is not primarily metabolised by CYP2D6, in one study, bupropion increased the C max and AUC of citalopram by 30 % and 40 %, respectively. Since bupropion is extensively metabolised, the co-administration of medicines known to induce metabolism (e.g., carbamazepine, phenobarbitone, phenytoin, ritonavir, efavirenz) or inhibit metabolism may affect its clinical activity. In a series of studies in healthy volunteers, ritonavir (100 mg twice daily or 600 mg twice daily) or ritonavir 100 mg plus lopinavir 400 mg twice daily reduced the exposure of bupropion and its major metabolites in a dose dependent manner by approximately 20 % up to 80 % (See section 4.3.). Similarly, efavirenz 600 mg once daily for two weeks reduced the exposure of bupropion by approximately 55 %. This effect of Ritonavir and Efavirenz is thought to be due to the induction of bupropion metabolism. Patients receiving Efavirenz with VOXRA XL may need increased doses of VOXRA XL but the maximum recommended dose of VOXRA XL should not be exceeded. There have been reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients drinking alcohol during VOXRA XL treatment. The consumption of alcohol during VOXRA XL treatment should be avoided. There have been post-marketing reports of serotonin syndrome, a potentially life-threatening condition, when WELLBUTRIN XR is co-administered with a serotonergic agent, such as Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs) (see section 4.4). Clinical data suggest a higher incidence of adverse events in patients receiving concurrent administration of bupropion and levodopa. Administration of VOXRA XL to patients receiving either levodopa or amantadine concurrently should be undertaken with caution. Concomitant use of VOXRA XL and a nicotine transdermal system (NTS) may result in elevations of blood pressure. Co-administration of digoxin with VOXRA XL may decrease digoxin levels. Clinicians should be aware that digoxin levels may rise on discontinuation of VOXRA XL, and the patient should be monitored for possible digoxin toxicity. Interactions involving laboratory tests: VOXRA XL interferes with the assay used in some rapid urine drug screens, which can result in false positive readings, particularly for amphetamines. A more specific alternative chemical method should be considered to confirm a positive result.

Pregnancy: Safety in pregnancy and lactation has not been established. VOXRA XL should not be used during pregnancy unless the clinical condition of the woman requires treatment with bupropion and alternative treatments are not an option. Women of childbearing potential must use reliable contraception. Studies of pregnancy outcomes following maternal exposure to bupropion in pregnancy have reported an increased risk of congenital cardiovascular malformations including ventricular septal defects and left outflow tract defects. Breastfeeding: Safety in lactation has not been established. As bupropion and its metabolites are excreted in human breast milk, mothers should be advised not to breastfeed while taking VOXRA XL. Fertility: There are no data on the effect of bupropion on human fertility. A reproductive study in rats revealed no evidence of impaired fertility.

Patients should exercise caution before driving or use of machinery until they are reasonably certain VOXRA XL tablets do not adversely affect their performance.

The list below provides information on the undesirable effects identified from clinical experience, categorised by system organ class and frequency. Frequencies are defined as : very common ( u2265 1/10), common ( u2265 1/100 to, < 1/10), uncommon ( u2265 1/1, 000, to < 1/100), rare ( u2265 1/10, 000, to < 1/1, 000), very rare ( u2265 1/10, 000). Immune system disorders*

• Common: Hypersensitivity reactions such as urticaria
• Very rare: More severe hypersensitivity reactions including angioedema, dyspnoea/bronchospasm and anaphylactic shock. Arthralgia, myalgia and fever have also been reported in association with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness.

• Common: Anorexia
• Uncommon: Weight loss
• Very rare: Blood glucose disturbances
• Not known: Hyponatremia

• Very common: Insomnia
• Common: Agitation, anxiety
• Uncommon: Confusion, depression
• Very rare: Aggression, hostility, irritability, restlessness, hallucinations, abnormal dreams, depersonalisation, delusions, paranoid ideation.
• Not known: Suicidal ideation, suicidal behaviour, psychosis, dysphemia, panic attack.

• Very common: Headache
• Common: Tremor, dizziness, taste disorders
• Uncommon: Concentration disturbance
• Rare: Seizures (see section 4.4.)
• Very rare: Dystonia, ataxia, parkinsonism, incoordination, memory impairment, paraesthesia, syncope.

• Common: Visual disturbance

• Common: Tinnitus

• Uncommon: Tachycardia
• Very rare: Palpitations

• Common: Increased blood pressure (sometimes severe), flushing
• Very rare: Vasodilation, postural hypotension

• Very common: Dry mouth, gastrointestinal disturbance including nausea and vomiting
• Common: Abdominal pain, constipation

• Rare: Elevated liver enzymes, jaundice, hepatitis

• Common: Rash, pruritus, sweating
• Very rare: Errythema multiforme and Stevens-Johnson syndrome, systemic lupus erythematosus syndrome aggravated, cutaneous lupus erythematosus, acute generalised exanthematous pustulosis, exacerbation of psoriasis.

• Very rare: Twitching

• Very rare: Urinary frequency and/or retention, urinary incontinence

• Common: Fever, asthenia, chest pain

In addition to those events reported under Side effects, overdose has resulted in symptoms including drowsiness, loss of consciousness and ECG changes such as conduction disturbances (including QRS prolongation) or dysrhythmias - cases of fatal outcome have been reported. Serotonin syndrome has also been reported. Acute ingestion of doses in excess of 10 times the maximum therapeutic dose has been reported. Treatment: In the event of overdose, hospitalisation is advised. ECG and vital signs should be monitored. Ensure an adequate airway, oxygenation and ventilation. The use of activated charcoal is recommended. No specific antidote for bupropion is known. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.