Wellbutrin Xl 150mg & 300mg ER Tablets

WELLBUTRIN XL is indicated for the treatment of depression as defined by DSM IV Criteria. Following a satisfactory response, continuation with WELLBUTRIN 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 WELLBUTRIN 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: WELLBUTRIN 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 WELLBUTRIN 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: WELLBUTRIN XL should be used with caution in patients with mild liver impairment. Because of increased variability in WELLBUTRIN XLu2019s pharmacokinetics in patients with mild hepatic cirrhosis, a reduced frequency of dosing should be considered (see sections 4.8 and 4.4). WELLBUTRIN XL is contraindicated in patients with moderate to severe hepatic cirrhosis. Method of administration: WELLBUTRIN 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 components of WELLBUTRIN XL listed in section 6.1.
• Patients under 18 years.
• WELLBUTRIN XL is contraindicated in patients with a seizure disorder.
• WELLBUTRIN XL should not be administered to patients currently being treated with any other preparation containing bupropion, as the incidence of seizures is dose dependent.
• WELLBUTRIN XL is contraindicated in patients with a known central nervous system tumour.
• WELLBUTRIN XL is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives.
• WELLBUTRIN XL is contraindicated 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 WELLBUTRIN XL with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 14 days should elapse between the discontinuation of MAOIs and initiation of treatment with WELLBUTRIN XL.
• WELLBUTRIN XL is contraindicated for use in patients with liver disease, Child-Pugh grades B and C, range 7-13.
• Women of child-bearing potential not using contraception.

The recommended dose of WELLBUTRIN XL should not be exceeded, since bupropion is associated with a dose-related risk of seizure. WELLBUTRIN XL should be discontinued promptly if patients experience hypersensitivity reactions during treatment (see SIDE EFFECTS). Clinicians should be aware that symptoms may persist beyond the discontinuation of WELLBUTRIN XL and clinical management should be provided accordingly. The overall incidence of seizure with WELLBUTRIN XL in clinical trials was approximately 0.1%.

There is an increased risk of seizures occurring with the use of WELLBUTRIN XL in the presence of predisposing risk factors, which lower the seizure threshold. Therefore, WELLBUTRIN 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.

WELLBUTRIN XL should be discontinued and is not recommenced in patients who experience a seizure while on treatment. Clinical worsening and suicide risk in adults associated with psychiatric disorders: Patients with major depressive disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking antidepressant medications. This risk may persist until significant remission occurs. A causal role, however, for antidepressant medicines in inducing such behaviour has not been established. As improvement may not occur during the first few weeks or more of treatment, patients being treated with WELLBUTRIN XL should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of therapy, or at the time of dose changes, either increases or decreases. Patients with a history of suicidal behaviour or thoughts, young adults and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.

Bupropion is metabolised to its major active metabolite hydroxybupropion primarily by the cytochrome P450 IIB6 (CYP2B6) (see Pharmacokinetic properties). Care should therefore be exercised when WELLBUTRIN 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 WELLBUTRIN 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 Cmax 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%. 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 WELLBUTRIN XL may need increased doses of WELLBUTRIN XL, but the maximum recommended dose of WELLBUTRIN XL should not be exceeded. There have been reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients drinking alcohol during WELLBUTRIN XL treatment. The consumption of alcohol during WELLBUTRIN 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 WELLBUTRIN XL to patients receiving either levodopa or amantadine concurrently should be undertaken with caution.

Pregnancy: Safety in pregnancy and lactation has not been established. WELLBUTRIN 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 WELLBUTRIN 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 WELLBUTRIN 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.

* See also u2018Skin and subcutaneous tissue disorders.u2019

Metabolism and nutritional disorders

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

Psychiatric disorders

• 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

Nervous system disorders

• 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.

Eye disorders

• Common: Visual disturbance

Ear and labyrinth disorders

• Common: Tinnitus

Cardiac disorders

• Uncommon: Tachycardia
• Very rare: Palpitations

Vascular disorders

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

Gastrointestinal disorders

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

Hepatobiliary disorders

• Rare: Elevated liver enzymes, jaundice, hepatitis

Skin and subcutaneous tissue disorders*

• 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.

* See also u2018Immune system disorders.

Musculoskeletal and connective tissue disorders

• Very rare: Twitching

Renal and urinary disorders

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

General disorders and administration site conditions

• Common: Fever, asthenia, chest pain

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of WELLBUTRIN XL is important. It allows continued monitoring of the benefit/risk balance of WELLBUTRIN XL. Health care providers are asked to report any suspected adverse reactions to: SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

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 dysrrhythmias u2013 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.