Summary of the safety profile In randomised clinical trials raltegravir 400 mg twice daily was administered in combination with fixed or optimised background treatment regimens to treatment- naïve (N=547) and treatment-experienced (N=462) adults for up to 96 weeks.
A further 531 treatment-naïve adults have received raltegravir 1,200 mg once daily with emtricitabine and tenofovir disoproxil fumarate for up to 96 weeks. 1. The most frequently reported adverse reactions during treatment were headache, nausea and abdominal pain.
The most frequently reported serious adverse reactions were immune reconstitution syndrome and rash. The rates of discontinuation of raltegravir due to adverse reactions were 5% or less in clinical trials. Rhabdomyolysis was an uncommonly reported serious adverse reaction in post- marketing use of raltegravir 400 mg twice daily.
Tabulated summary of adverse reactions Adverse reactions considered by investigators to be causally related to raltegravir (alone or in combination with other ART), as well as adverse reactions established in post-marketing experience, are listed below by System Organ Class.
Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and not known (cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Infections and infestations Uncommon genital herpes, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon skin papilloma Blood and lymphatic system disorders Uncommon anaemia, iron deficiency anaemia, lymph node pain, lymphadenopathy, neutropenia, thrombocytopenia Immune system disorders Uncommon immune reconstitution syndrome, drug hypersensitivity, hypersensitivity Common decreased appetiteMetabolism and nutrition disorders Uncommon cachexia, diabetes mellitus, dyslipidaemia, hypercholesterolaemia, hyperglycaemia, hyperlipidaemia, hyperphagia, increased appetite, polydipsia, body fat disorder Common abnormal dreams, insomnia, nightmare, abnormal behaviour, depression Psychiatric disorders Uncommon mental disorder, suicide attempt, anxiety, confusional state, depressed mood, major depression, middle insomnia, mood altered, panic attack, sleep disorder, suicidal ideation, suicidal behaviour (particularly in patients with a pre-existing history of psychiatric illness) Common dizziness, headache, psychomotor hyperactivity Nervous system disorders Uncommon amnesia, carpal tunnel syndrome, cognitive disorder, disturbance in attention, dizziness postural, dysgeusia, hypersomnia, hypoaesthesia, lethargy, memory impairment, migraine, neuropathy peripheral, paraesthesia, somnolence, tension headache, tremor, poor quality sleep Eye disorders Uncommon visual impairment Common vertigoEar and labyrinth disorders Uncommon tinnitus Cardiac disorders Uncommon palpitations, sinus bradycardia, ventricular extrasystoles Vascular disorders Uncommon hot flush, hypertension Respiratory, thoracic and mediastinal disorders Uncommon dysphonia, epistaxis, nasal congestion Common abdominal distention, abdominal pain, diarrhoea, flatulence, nausea, vomiting, dyspepsia Gastrointestinal disorders Uncommon gastritis, abdominal discomfort, abdominal pain upper, abdominal tenderness, anorectal discomfort, constipation, dry mouth, epigastric discomfort, erosive duodenitis, eructation, gastroesophageal reflux disease, gingivitis, glossitis, odynophagia, pancreatitis acute, peptic ulcer, rectal haemorrhage Hepato-biliary disorders Uncommon hepatitis, hepatic steatosis, hepatitis alcoholic, hepatic failure Common rashSkin and subcutaneous tissue disorders Uncommon acne, alopecia, dermatitis acneiforme, dry skin, erythema, facial wasting, hyperhidrosis, lipoatrophy, lipodystrophy acquired, lipohypertrophy, night sweats, prurigo, pruritus, pruritus generalised, rash macular, rash maculo-papular, rash pruritic, skin lesion, urticaria, xeroderma, Stevens Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Uncommon arthralgia, arthritis, back pain, flank pain, musculoskeletal pain, myalgia, neck pain, osteopenia, pain in extremity, tendonitis, rhabdomyolysis Renal and urinary disorders Uncommon renal failure, nephritis, nephrolithiasis, nocturia, renal cyst, renal impairment, tubulointerstitial nephritis Reproductive system and breast disorders Uncommon erectile dysfunction, gynaecomastia, menopausal symptoms Common asthenia, fatigue, pyrexiaGeneral disorders and administration site conditions Uncommon chest discomfort, chills, face oedema, fat tissue increased, feeling jittery, malaise, submandibular mass, oedema peripheral, pain Common alanine aminotransferase increased, atypical lymphocytes, aspartate aminotransferase increased, blood triglycerides increased, lipase increased, blood pancreatic amylase increased Investigations Uncommon absolute neutrophil count decreased, alkaline phosphatase increased, blood albumin decreased, blood amylase increased, blood bilirubin increased, blood cholesterol increased, blood creatinine increased, blood glucose increased, blood urea nitrogen increased, creatine phosphokinase increased, fasting blood glucose increased, glucose urine present, high density lipoprotein increased, international normalised ratio increased, low density lipoprotein increased, platelet count decreased, red blood cells urine positive, waist circumference increased, weight increased, white blood cell count decreased Injury, poisoning and procedural complications Uncommon accidental overdose Description of selected adverse reactions In studies of raltegravir 400 mg twice daily, cancers were reported in treatment- experienced and treatment-naïve patients […]