Company: GlaxoSmithKline (Ireland) Ltd.
Legal category: Prescription. Hospital only. Sport permitted.
Active ingredients: Dolutegravir (as sodium)/abacavir (as sulfate)/lamivudine 50/600/300mg.
Description: Purple, biconvex, oval, film-coated tablets marked 572 Trı.
Presentation: 30, €1294.00.
Indication: Treatment of Human Immunodeficiency Virus (HIV).
Pharmacology: Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration which is essential for the HIV replication cycle. Abacavir and lamivudine are potent selective inhibitors of HIV-1 and HIV-2. Lamivudine-TP (an analogue for cytidine) and carbovir-TP (the active triphosphate form of abacavir, an analogue for guanosine) are substrates for and competitive inhibitors of HIV reverse transcriptase (RT). However, their main antiviral activity is through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination.
Dosage: Adult: One tablet once daily. Elderly: 65 years and over (caution), limited data. Children: Over 12 years (at least 40kg bodyweight), as per adults. Under 12 years, safety and efficacy not established.
Contraindications: Hypersensitivity to the active ingredients or to any of the excipients. Lactation.
Special precautions: Not for use in patients carrying the HLA-B*5701 allele. Screen for HLA-B*5701 allele before initiation in any patient, irrespective of racial origin. Do not use in patients under 40kg or those requiring dose adjustments. Not recommended: Moderate to severe hepatic impairment, creatinine clearance (cc) <50 ml/min, integrase inhibitor resistance. Caution: Hepatomegaly (especially obese women), hepatitis or other risk factors for liver disease and hepatic steatosis (including certain drugs and alcohol). Monitor liver aminotransferases and bilirubin. Lactic acidosis (sometimes fatal; usually associated with hepatomegaly and hepatic steatosis) reported with nucleoside analogues. Discontinue if hyperlactatemia and metabolic/lactic acidosis, progressive hepatomegaly or rapidly elevating aminotransferase levels occur. Hypersensitivity reactions may occur; permanently discontinue if suspected (if suspended for other reasons (see SPC) restart where medical assistance is available). Evaluate for lipodystrophy; consider measuring fasting serum lipids and blood glucose. Pre-existing liver dysfunction (including chronic active hepatitis); consider interruption or discontinuation if liver disease worsens. Hepatitis B or C co-infection (monitor liver chemistries). Chronic hepatitis B or C (increased risk of severe and potentially fatal hepatic adverse reactions). Hepatitis B co-infected patients; withdrawal may acutely exacerbate hepatitis B (periodically monitor liver function tests and markers of HBV replication if discontinue); may require an additional antiviral. Evaluate any inflammatory symptoms; autoimmune disorders (such as Graves’ disease) reported in the setting of immune reactivation (can occur months after initiation). Minimize modifiable risk factors for myocardial infarction (e.g. smoking, hypertension, hyperlipidaemia). Osteonecrosis reported (especially with advanced HIV-disease or long-term exposure); advise patients to seek medical advice if joint aches and pain, joint stiffness or difficulty in movement occur. Opportunistic infections and other complications of HIV may occur. Transmission. Pregnancy (only if benefit justifies risk). Driving/using machines (dizziness).
Drug interactions: Contraindicated: Dofetilide. Do not use polyvalent cation-containing antacids (during 6 hours before or 2 hours after) or other drugs containing dolutegravir, abacavir, lamivudine or emtricitabine. Avoid: St. John’s wort, phenobarbital, phenytoin, oxcarbazepine, carbamazepine. Not recommended: Etravirine (unless also receiving atazanavir/ritonavir, lopinavir/ritonavir or darunavir/ritonavir); efavirenz, nevirapine, rifampicin, tipranavir/ritonavir, cladribine. Caution: Alpha interferon and ribavirin (hepatitis C co-infection), ribavirin. Magnesium/ aluminium-containing antacids or calcium/iron (during 6 hours before or at least 2 hours after), metformin, inhibitors or inducers of CYP3A4 or P-gp, certain anti-acid agents, inducers or inhibitors of UGT enzymes, compounds eliminated through alcohol dehydrogenase, drugs where excretion is OCT2 or MATE-1- dependent, trimethoprim/sulfamethoxazole (renal impairment), methadone (some patients). P-pg and BCRP, drugs where excretion is OCT1/OCT2 or OAT3-dependent.
Adverse drug reactions: Gastrointestinal disorders, insomnia, dizziness, headache, hypersensitivity, anorexia, abnormal dreams, depression, nightmare, sleep disorder, somnolence, lethargy, cough, nasal symptoms, rash, pruritus, alopecia, arthralgia, muscle disorders, fatigue, fever, malaise, creatine phosphokinase elevations, ALT/AST elevations.
Full prescribing information and references available from GlaxoSmithKline (Ireland) Ltd. (01) 4955000. Fax: (01) 4955105.