25 mg, 100 mg & 200 mg tabletsPRESCRIBING INFORMATION
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
The INTELENCE® SmPCs are available at:
Therapy should be initiated by a physician experienced in the management of HIV infection. Used in combination with a boosted protease inhibitor and other antiretroviral medicines for treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients and in antiretroviral treatment-experienced paediatric patients from 6 years of age.
DOSAGE & ADMINISTRATION:
Tablets to be swallowed whole with liquid following a meal. If unable to swallow, can be dispersed in cold liquid and drunk immediately.
Adults: 200 mg twice daily.
Children over 6 years of age and weighing at least 16 kg:
Dosage based on body weight:
16 kg to less than 20 kg - 100 mg twice daily;
20 kg to less than 25 kg - 125 mg twice daily;
25 kg to less than 30 kg - 150 mg twice daily;
greater than 30 kg - 200 mg twice daily.
Children less than 6 years of age or weighing less than 16 kg:
Safety/efficacy not established. No data available.
Elderly: Limited information.
Hepatic impairment: See “Precautions” below.
Renal impairment: No dose adjustment.
Pregnancy and postpartum: No dose adjustment required.
Hypersensitivity to active substance or any excipients. Co-administration with elbasvir/grazoprevir.
SPECIAL WARNINGS & PRECAUTIONS:
Advise patients that current antiretroviral therapy does not cure HIV and to take precautions to avoid transmission.
Cutaneous reactions: Severe cutaneous adverse drug reactions reported, including erythema multiforme and Stevens-Johnson Syndrome (<0.1%). Discontinue treatment if these occur. Caution in patients with history of NNRTI-associated cutaneous reactions. Cases reported of severe hypersensitivity syndromes, including DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) and TEN (toxic epidermal necrolysis), sometimes fatal. Time to onset usually 3-6 weeks. Outcome in most cases favourable upon discontinuation and initiation of corticosteroid therapy. Seek medical advice if severe rash or hypersensitivity reactions occur. Patients with hypersensitivity reaction whilst on therapy must discontinue INTELENCE® immediately; delay in stopping may result in life-threatening reaction. Do not re-start therapy with INTELENCE® where treatment stopped due to hypersensitivity reactions.
Rash: Usually mild to moderate and occurring in the second week of therapy, self-limiting and generally resolved within 1 to 2 weeks of therapy. Incidence of rash higher in females.
Liver disease: Not recommended in patients with severe liver impairment (no data). Caution in patients with moderate hepatic impairment. Caution in patients co-infected with hepatitis B or C virus (limited data).
Immune reconstitution syndrome (IRS): Inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions or aggravation of symptoms in patients with severe immune deficiency at start of combination antiretroviral therapy (CART). Autoimmune disorders have been reported to occur in the setting of IRS.
Increase in weight, levels of blood lipids and glucose may occur, may partly be linked to disease control and life style. Monitor blood lipids and glucose; refer to HIV treatment guidelines; manage as appropriate.
Osteonecrosis: Patients with advanced HIV disease and/or long-term exposure to CART may develop osteonecrosis. Seek medical advice if joint or movement problems occur.
Lactose intolerance and lactase deficiency: 25mg and 100mg tablets contain lactose. These strengths should not be taken by patients with galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 200mg tablets do not contain lactose.
Pregnancy: Increased etravirine exposure during pregnancy; caution with concomitant medications or comorbidities that may further increase etravirine exposure.
Very common: Rash (most frequently mild to moderate)
Common: Myocardial infarction, thrombocytopenia, anaemia, peripheral neuropathy, headache, gastro-oesophageal reflux disease, diarrhoea, vomiting, nausea, abdominal pain, flatulence, gastritis, renal failure, night sweats, diabetes mellitus, hyperglycaemia, hypercholesterolaemia, hypertriglyceridaemia, hyperlipidaemia, hypertension, fatigue, anxiety and insomnia.
Other side effects include: Atrial fibrillation, angina pectoris, convulsion, bronchospasm, pancreatitis, haematemesis, stomatitis, immune reconstitution syndrome, drug hypersensitivity, hepatitis (including cytolytic), hepatomegaly, angioneurotic oedema, erythema multiforme, haemorrhagic stroke. Stevens-Johnson Syndrome (rare), toxic epidermal necrolysis (very rare). Hypersensitivity reactions, including DRESS, characterised by rash, fever and sometimes organ involvement (see Special Warnings & Precautions section above).
Refer to SmPC for other side effects.
Clinical data very limited, animal data suggests malformative risk unlikely in humans.
HIV infected women should not breast-feed their infants.
Refer to SmPC before initiating therapy with etravirine. Interaction studies have only been performed in adults. Co administration with elbasvir/grazoprevir contraindicated.
Medicinal products that affect etravirine:
INTELENCE® must not be co-administered with medicinal products that inhibit CYP3A4, CYP2C9 or CYP2C19 which may decrease clearance of etravirine. Medicinal products that induce CYP3A4, CYP2C9 or CYP2C19 may result in lowered plasma concentrations of etravirine.
Medicinal products affected by etravirine:
NRTIs - No interactions expected.
NNRTIs - Co-administration with efavirenz, nevirapine and rilpivirine not recommended.
PIs Unboosted (i.e. without co administration of low dose ritonavir) - Co-administration not recommended.
PIs Boosted (with low dose ritonavir) - Co-administration with tipranavir not recommended. Amprenavir and fosamprenavir may require dose reduction when co-administered with etravirine. Darunavir, atazanavir, lopinavir and saquinavir can be used without dose adjustment.
PIs Boosted (with cobicistat) - Co-administration with atazanavir/cobicistat or darunavir/cobicistat not recommended.
CCR5 Antagonists - Recommended dose for maraviroc when combined with etravirine in presence of potent CYP3A4 inhibitors is 150 mg b.i.d. except for fosamprenavir/ritonavir (maraviroc dose 300 mg b.i.d.). No dose adjustment necessary for etravirine.
Fusion Inhibitors - No interaction expected.
Integrase Strand Transfer Inhibitors - No dose adjustments with raltegravir, should only be used with dolutegravir when co-administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. These combinations can be used without dose adjustment.
Non-antiretroviral products - Oestrogen and/or progesterone-based contraceptives, digoxin, ribavirin, telaprevir, paroxetine (SSRIs), methadone, azithromycin, fluconazole, itraconazole, ketoconazole, posaconazole,voriconazole, H2-receptor antagonists (ranitidine) and proton pump inhibitors (omeprazole) can be used without dose adjustments. Caution and concentration monitoring recommended with amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone and quinidine. Consider alternatives to clarithromycin for Mycobacterium avium complex (MAC). Monitor INR with warfarin. Carbamazepine, phenobarbital and phenytoin combination not recommended. Direct acting HCV antivirals daclatasvir and simeprevir not recommended.
Caution with: rifabutin. Consider alternatives to diazepam.
Caution with: systemic dexamethasone or consider alternatives, particularly for chronic use. Increased clinical and laboratory monitoring for HIV and HCV suppression is recommended with boceprevir. St John’s Wort, rifampicin and rifapentine not recommended. Atorvastatin can be given without dose adjustments, however, dose of atorvastatin may need to be altered based on clinical response. Fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin (HMG Co A reductase inhibitors) may require dose adjustments.
Caution with: systemic immunosuppressants; cyclosporin, sirolimus and tacrolimus as plasma concentrations of these may be affected. Concomitant use of PDE 5 inhibitors may require dose adjustment. Concomitant use of clopidogrel discouraged. Closely monitor antimalarial response when given with artemether/lumefantrine.
Refer to SmPC for full details of interactions.
LEGAL CATEGORY: POM.
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|MARKETING AUTHORISATION NUMBER(S)||BASIC NHS COST(S)|
|25 mg tablets||120||EU/1/08/468/003||£75.32|
|100 mg tablets||120||EU/1/08/468/001||£301.27|
|200 mg tablets||60||EU/1/08/468/002||£301.27|
MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
FURTHER INFORMATION AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK
Prescribing information last revised: July 2017