MHM Magazine

S5 CHAMPIX ® 41/34/0573/4. PHARMACOLOGICAL CLASSIFICATION: A 34 Other INDICATIONS: CHAMPIX is indicated as an aid to smoking cessation in determined. CONTRA-INDICATIONS: Hypersensitivity to varenicline or to any of the excipients. WARNINGS AND SPECIAL PRECAUTIONS: Physiological changes resulting from smoking cessation,with orwithout treatmentwithCHAMPIX,may alter the pharmacokinetics or pharmacodynamics of some medicines, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin). However, in post-marketing data there were cases of increased INR. INR should be monitored more frequently and the warfarin dose adjusted while using CHAMPIX, and after discontinuation of CHAMPIX. Neuropsychiatric symptoms and suicidality: Serious neuropsychiatric symptoms have been reported in patients being treated with CHAMPIX. These post-marketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, aswell as suicidal ideation, suicide attempt, and completed suicide.Some reported casesmay have been complicated by the symptoms ofnicotinewithdrawal inpatientswho stopped smoking.Depressedmoodmaybe a symptomofnicotinewithdrawal.Depression, rarely including suicidal ideation, hasbeen reported in smokers undergoing a smoking cessation attemptwithoutmedication.However, someof these symptoms have occurred in patients taking CHAMPIX who continued to smoke. When symptoms were reported, most were during CHAMPIX treatment, but somewere following discontinuation ofCHAMPIX therapy. These events have occurred in patientswith andwithout pre-existing psychiatric disease; some patients have experiencedworsening of their psychiatric illnesses. All patients being treatedwithCHAMPIX should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Advise patients and caregivers that the patient should stop takingCHAMPIX andcontactahealth careprovider immediately ifagitation,depressedmood,changes inbehaviouror thinking that are not typical for thepatient areobserved,or if thepatientdevelops suicidal ideationor suicidalbehaviour. Inmanypost-marketing cases, resolution of symptoms after discontinuation of CHAMPIX was reported, although in some cases the symptoms persisted, therefore, ongoingmonitoring and supportive care should be provided until symptoms resolve. Angioedema and hypersensitivity reactions: There have been post-marketing reports of hypersensitivity reactions including angioedema in patients treated with CHAMPIX. Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). There were infrequent reports of life-threatening angioedema requiring urgent medical attention due to respiratory compromise. Patients should be instructed to discontinue CHAMPIX and immediately seekmedical care if they experience these symptoms. Serious skin reactions: There have been post-marketing reports of serious skin reactions, including Stevens-Johnson Syndrome and ErythemaMultiforme in patients usingCHAMPIX. As these skin reactions can be life- skin rashwithmucosal lesions or any other signs of hypersensitivity. Patients should be instructed to notify their health careprofessionalsofneworworseningcardiovascularsymptomsand toseek immediatemedicalattention if theyexperiencesignsandsymptoms ofmyocardial infarction or stroke. Patients should be advised to use caution driving or operating INTERACTIONS: Based on varenicline characteristics and S5 CHAMPIX ® 41/34/0573/4. PHARMACOLOGICAL CLASSIFICATION: A 34 Other INDICATIONS: CHAMPIX is indicated as an aid to smoking cessation in determined. CONTRA-INDICATIONS: Hypersensitivity to varenicline or to any of the excipients. WARNINGS AND SPECIAL PRECAUTIONS: Physiological changes resulting from smoking cessation,with orwithout treatmentwithCHAMPIX,may alter the pharmacokinetics or pharmacodynamics of some medicines, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin). However, in post-marketing data there were cases of increased INR. INR should be monitored more frequently and the warfarin dose adjusted while using CHAMPIX, and after discontinuation of CHAMPIX. Neuropsychiatric symptoms and suicidality: Serious neuropsychiatric symptoms have been reported in patients being treated with CHAMPIX. These post-marketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, aswell as suicidal ideation, suicide attempt, and completed suicide.Some reported casesmay have been complicated by the symptoms ofnicotinewithdrawal inpatientswho stopped smoking.Depressedmoodmaybe a symptomofnicotinewithdrawal.Depression, rarely including suicidal ideation, hasbeen reported in smokers undergoing a smoking cessation attemptwithoutmedication.However, someof these symptoms have occurred in patients taking CHAMPIX who continued to smoke. When symptoms were reported, most were during CHAMPIX treatment, but somewere following discontinuation ofCHAMPIX therapy. These events have occurred in patientswith andwithout pre-existing psychiatric disease; some patients have experiencedworsening of their psychiatric illnesses. All patients being treatedwithCHAMPIX should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Advise patients and caregivers that the patient should stop takingCHAMPIXand contact ahealth careprovider immediately ifagitation,depressedmood,changes inbehaviouror thinking that are not typical for thepatient areobserved,or if thepatientdevelops suicidal ideationor suicidalbehaviour. Inmanypost-marketing cases, resolution of symptoms after discontinuation of CHAMPIX was reported, although in some cases the symptoms persisted, therefore, ongoingmonitoring and supportive care should be provided until symptoms resolve. Angioedema and hypersensitivity reactions: There have been post-marketing reports of hypersensitivity reactions including angioedema in patients treated with CHAMPIX. Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). There were infrequent reports of life-threatening angioedema requiring urgent medical attention due to respiratory compromise. Patients should be instructed to discontinue CHAMPIX and immediately seekmedical care if they experience these symptoms. Serious skin reactions: There have been post-marketing reports of serious skin reactions, including Stevens-Johnson Syndrome and ErythemaMultiforme in patients usingCHAMPIX. As these skin reactions can be life- skin rashwithmucosal lesions or any other signs of hypersensitivity. Patients should be instructed to notify their health careprofessionalsofneworworseningcardiovascularsymptomsand toseek immediatemedicalattention if theyexperiencesignsandsymptoms ofmyocardial infarction or stroke. Patients should be advised to use caution driving or operating INTERACTIONS: Based on varenicline characteristics and clinicalexperience todate,CHAMPIXhasnoclinicallymeaningfuldrug interactions.NodosageadjustmentofCHAMPIXorco-administereddrugs listed below is recommended. In vitro studies demonstrate that CHAMPIX does not inhibit cytochrome P450 enzymes or induce the activity of cytochromeP450enzymes1A2and3A4. In vitro studiesdemonstrate thatCHAMPIXdoesnot inhibithuman renal transportproteinsat therapeutic In vitro studies demonstrate that active renal secretion of CHAMPIX is mediated by the human organic cation transporter, OCT2. Co-administration with inhibitors of OCT2 does not require a dose adjustment of CHAMPIX as the increase in systemic exposure to varenicline tartrate is not expected to be clinically meaningful. Furthermore since metabolism of CHAMPIX represents less than 10 % of its clearance, drugs known to not be required. Metformin: Cimetidine: Co-administration of an OCT2 inhibitor, cimetidine (300 mg four times daily), with CHAMPIX (2mg singledose) increased the systemic exposure ofCHAMPIXby 29%due to a reduction inCHAMPIX renal clearance.Nodosage adjustment is recommendedbasedon concomitant cimetidine administration. Digoxin: CHAMPIX (1mg twicedaily)didnot alter the steady-state pharmacokinetics of digoxin administered as a 0,25mg daily dose. Warfarin: CHAMPIX (1mg twice daily) did not alter the pharmacokinetics of warfarin pharmacokinetics. However, in post-marketing data there were cases of increased INR. INR should be monitored more frequently and the warfarin dose adjusted while using CHAMPIX, and after discontinuation of CHAMPIX. Use with other therapies for smoking cessation: PREGNANCYANDLACTATION: Pregnancy: ThesafetyofCHAMPIX inhumanpregnancyhasnotbeenestablished. Womenofchild-bearingpotential: Where therapy is initiated, treatment should be timed such that the course is completed before conception occurs. Lactation: The safety ofCHAMPIX during lactation has notbeen established. DOSAGEANDDIRECTIONSFORUSE: Patients shouldbe treatedwithCHAMPIX for 12weeks. The recommendeddoseofCHAMPIX is1mg twicedaily following a 1-week titration as follows: Days 1 – 3: 0,5mgoncedaily in the evening Days 4 – 7: 0,5mg twicedaily Day 8 –Endof treatment: 1mg twicedaily The patient should set the date to stop smoking. CHAMPIX dosing should start 1 – 2 weeks before this date. Patients who do not succeed in stopping smokingduring 12weeksof initial therapy,orwho relapse after treatment, shouldbe encouraged tomake another attemptonce factors S5 CHAMPIX ® 41/34/0573/4. PHARMACOLOGICAL CLASSIFICATION: A 34 Other INDICATIONS: CHAMPIX is indicated as an aid to smoking cessation in determined. CONTRA-INDICATIONS: Hypersensitivity to varenicline or to any of the excipients. WARNINGS AND SPECIAL PRECAUTIONS: Physiological changes resulting from smoking cessation,with orwithout treatmentwithCHAMPIX,may alter the pharmacokinetics or pharmacodynamics of some medicines, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin). However, in post-marketing data there were cases of increased INR. INR should be monitored more frequently and the warfarin dose adjusted while using CHAMPIX, and after discontinuation of CHAMPIX. Neuropsychiatric symptoms and suicidality: Serious neuropsychiatric symptoms have been reported in patients being treated with CHAMPIX. These post-marketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, aswell as suicidal ideation, suicide attempt, and completed suicide.Some reported casesmay have been complicated by the symptoms ofnicotinewithdrawal inpatientswho stopped smoking.Depressedmoodmaybe a symptomofnicotinewithdrawal.Depression, rarely including suicidal ideation, hasbeen reported in smokers undergoing a smoking cessation attemptwithoutmedication.However, someof these symptoms have occurred in patients taking CHAMPIX who continued to smoke. When symptoms were reported, most were during CHAMPIX treatment, but somewere following discontinuation ofCHAMPIX therapy. These events have occurred in patientswith andwithout pre-existing psychiatric disease; some patients have experiencedworsening of their psychiatric illnesses. All patients being treatedwithCHAMPIX should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Advise patients and caregivers that the patient should stop takingCHAMPIX andcontactahealth careprovider immediately ifagitation,depressedmood,changes inbehaviouror thinking that are not typical for thepatient areobserved,or if thepatientdevelops suicidal ideationor suicidalbehaviour. Inmanypost-marketing cases, resolution of symptoms after discontinuation of CHAMPIX was reported, although in some cases the symptoms persisted, therefore, ongoingmonitoring and supportive care should be provided until symptoms resolve. Angioedema and hypersensitivity reactions: There have been post-marketing reports of hypersensitivity reactions including angioedema in patients treated with CHAMPIX. Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). There were infrequent reports of life-threatening angioedema requiring urgent medical attention due to respiratory compromise. Patients should be instructed to discontinue CHAMPIX and immediately seekmedical care if they experience these symptoms. Serious skin reactions: There have been post-marketing reports of serious skin reactions, including Stevens-Johnson Syndrome and ErythemaMultiforme in patients usingCHAMPIX. As these skin reactions can be life- skin rashwithmucosal lesions or any other signs of hypersensitivity. Patients should be instructed to notify their health careprofessionalsofneworworseningcardiovascularsymptomsand toseek immediatemedicalattention if theyexperiencesignsandsymptoms ofmyocardial infarction or stroke. Patients should be advised to use caution driving or operating INTERACTIONS: Based on varenicline characteristics and clinicalexperience todate,CHAMPIXhasnoclinicallymeaningfuldrug interactions.NodosageadjustmentofCHAMPIXorco-administereddrugs listed below is recommended. In vitro studies demonstrate that CHAMPIX does not inhibit cytochrome P450 enzymes or induce the activity of cytochromeP450enzymes1A2and3A4. In vitro studiesdemonstrate thatCHAMPIXdoesnot inhibithuman renal transportproteinsat therapeutic In vitro studies demonstrate that active renal secretion of CHAMPIX is mediated by the human organic cation transporter, OCT2. Co-administration with inhibitors of OCT2 does not require a dose adjustment of CHAMPIX as the increase in systemic exposure to varenicline tartrate is not expected to be clinically meaningful. Furthermore since metabolism of CHAMPIX represents less than 10 % of its clearance, drugs known to not be required. Metformin: Cimetidine: Co-administration of an OCT2 inhibitor, cimetidine (300 mg four times daily), with CHAMPIX (2mg singledose) increased the systemic exposure ofCHAMPIXby 29%due to a reduction inCHAMPIX renal clearance.Nodosage adjustment is recommendedbasedon concomitant cimetidine administration. Digoxin: CHAMPIX (1mg twicedaily)didnot alter the steady-state pharmacokinetics of digoxin administered as a 0,25mg daily dose. Warfarin: CHAMPIX (1mg twice daily) did not alter the pharmacokinetics of warfarin pharmacokinetics. However, in post-marketing data there were cases of increased INR. INR should be monitored more frequently and the warfarin dose adjusted while using CHAMPIX, and after discontinuation of CHAMPIX. Use with other therapies for smoking cessation: PREGNANCYANDLACTATION: Pregnancy: ThesafetyofCHAMPIX inhumanpregnancyhasnotbeenestablished. Womenofchild-bearingpotential: Where therapy is initiated, treatment should be timed such that the course is completed before conception occurs. Lactation: The safety ofCHAMPIX during lactation has notbeen established. DOSAGEANDDIRECTIONSFORUSE: Patients shouldbe treatedwithCHAMPIX for12weeks. The recommendeddoseofCHAMPIX is 1mg twicedaily following a1-week titration as follows: Days1 – 3: 0,5mgoncedaily in the evening Days4 – 7: 0,5mg twicedaily Day8 –Endof treatment: 1mg twicedaily The patient should set the date to stop smoking. CHAMPIX dosing should start 1 – 2 weeks before this date. Patients who do not succeed in stopping smokingduring 12weeksof initial therapy,orwho relapse after treatment, shouldbe encouraged tomake another attemptonce factors Patients No dosage adjustment is necessary for patientswithmild tomoderate renal impairment. For patientswith severe renal to 1mg once daily. Patientswith hepatic impairment: No dosage adjustment is necessary for patientswith hepatic impairment. Use in elderly patients: No dosage adjustment is necessary for elderly patients. Because elderly patients are more likely to have decreased renal function, doctorsshouldconsider the renalstatusofanelderlypatient. Use inchildren: beenestablished; therefore,CHAMPIX isnot recommended foruse inpatientsunder18 yearsofage. SIDEEFFECTS:Metabolismandnutrition disorders: Common: Increased appetite. Psychiatric disorders: Very common: Abnormal dreams, insomnia. Nervous system disorders: Very common: Headache. Common: Somnolence, dizziness, dysgeusia. Gastrointestinal disorders: Very common: Nausea. Common: Vomiting, Generaldisordersandadministrationsite conditions: Common: Fatigue. Post-MarketingExperience: There havebeen reports ofdepression,mania,psychosis, hallucinations,paranoia, delusions, homicidal ideation, aggression, hostility, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide in patients attempting to quit smokingwhile takingCHAMPIX. Smoking cessationwith orwithout treatment is associatedwith nicotinewithdrawal symptoms and the exacerbation of underlying psychiatric illness. Not all patients had known pre-existing psychiatric illness and not all had discontinued smoking. There have been reports of hypersensitivity reactions, including angioedema.Clinical signs included swelling of the face, mouth (tongue, lips,andgums),extremities,andneck (throatand larynx).Therehavealsobeen reportsof serious skin reactions, includingStevens Johnson Syndrome and Erythema Multiforme in patients taking CHAMPIX. There have been reports of seizures, feeling abnormal and crying. KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: No cases of overdose were reported in pre-marketing clinical trials. In case of overdose, standard supportivemeasures should be instituted as required.CHAMPIX has been shown to be dialyzed in patientswith end stage renaldisease,however, there isno experience indialysis followingoverdose. NAMEANDBUSINESSADDRESSOFTHE HOLDEROFTHECERTIFICATEOFREGISTRATION: SouthAfrica.TelNo.:0860PFIZER (734937).PIRef.:23/03/2015.Please refer todetailedpackage insert forcompleteprescribing information. 29101Pfizer_Champix_AbbrP.I. Layout_20180612_13.42.indd 1 2018/06/12 1: The Smoking cessation treatment specifically designed to target the neurobiological mechanism of nicotine dependenc (2) A dual mechanism of action (1, 3) PP-CHM-ZAF-0121 To report an adverse event, please contact ZAF.AEReporting@pfizer.com. If you wish to contact Pfizer for any other pur s , plea e use contact details below. +2711 320 6000 or 0860 734 937 (SA Only). Monday-Friday 09h00-17h00.