Raltegravir

Registered South African indications:

• HIV infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Severe hepatic impairment
• Elderly
• History of depression or psychiatric illness
• Previous history or risk factors for myopathy or rhabdomyolysis
• Risk factors for osteonecrosis
• Alcohol consumption
• Severe immunosuppression
• Higher body mass index patients
• Diabetes mellitus
• Phenylketonuria (chu)
• Galactose intolerance (chu and tab)
• Galactosaemia (chu and tab)
• Lapp lactase deficiency (chu and tab)
• Glucose-galactose malabsorption (chu and tab)
• Fructose intolerance (chu)
• Sorbitol/mannitol intolerance (chu)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

HIV infection

• Oral (tab): 400mg, 12hrly

Do not chew, crush or divide tablets

Paed. forms avail. in SA and covered in this monograph: tab, chu

HIV-1 infection

Oral (tab)

• >25kg: See adult dosage

Oral (chu)
- Weight-based dosing recommendation based on approx 6mg/kg/dose, 12hrly; Max: 600mg/24hrs

• 7-<10kg: 50mg, 12hrly

• 10-<14kg: 75mg, 12hrly

• 14-<20kg: 100mg, 12hrly

• 20-<28kg: 150mg, 12hrly

• 28-<40kg: 200mg, 12hrly

• >40kg: 300mg, 12hrly

Chewable tab can be chewed, swallowed whole and divided if needed

Do not substitute chewable tablets for 400mg tablet

Max dose for chewable tab is 300mg, 12hrly

Raltegravir dosage should be adjusted as the child grows

Safety and efficacy in preterm (<37 weeks gestation) and low birth weight (<2000g) newborns have not been established

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy

• Caution
• There are no data for the use of raltegravir chewable tablets in pregnant women. A moderate amount of data on pregnant women (between 300 - 1,000 pregnancy outcomes from first trimester exposure) indicate no malformative or feto/neonatal toxicity of raltegravir 400 mg film-coated tablets twice daily. Animal studies have shown reproductive toxicity. Raltegravir should be used during pregnancy only if the expected benefit justifies the potential risk to the foetus
• Limited data on the use of raltegravir at recommended doses, covering the perioconception period, first trimester and other trimesters of pregnancy did not result in an increase of neural tube defects or other congenital malformations. In vivo human studies confirmed that raltegravir readily crosses the human placenta
• After due consideration of treatment options in pregnancy, the use of raltegravir can be considered if an integrase strand transfer inhibitor is deemed indicated to be a component of antiretroviral therapy in pregnancy. Mother and embryo/foetal wellbeing should be frequently monitored/assessed by appropriate methods
• As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account in order to characterise the safety for the foetus

Breastfeeding

• Caution; not recommended
• It is unknown whether raltegravir/metabolites are excreted in human milk. Available pharmacodynamics/ toxicological data in animals have shown excretion of raltegravir/metabolites in milk. A risk to the newborns/ infants cannot be excluded. Raltegravir should not be used during breastfeeding

Fertility

• No effect on fertility was seen in male and female rats at doses up to 600mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose

Renal Impairment

• No dose adjustment recommended
  ESRD on intermittent hemodialysis patients should be dosed after dialysis on dialysis days

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Abnormal dreams
• Insomnia
• Nightmare
• Abnormal behaviour
• Depression
• Mental disorder
• Suicide attempt
• Anxiety
• Confusional state
• Depressed mood
• Major depression
• Mood altered
• Panic attack
• Sleep disorder
• Suicidal ideation
• Suicidal behaviour
• Dizziness
• Headache
• Psychomotor hyperactivity
• Amnesia
• Carpal tunnel syndrome
• Cognitive disorder
• Disturbance in attention
• Postural dizziness
• Hypersomnia
• Hypoaesthesia
• Lethargy
• Memory impairment
• Migraine
• Peripheral neuropathy
• Paraesthesia
• Tension headache
• Tremor
• Asthenia
• Fatigue

Cardiovascular Disorders

• Palpitations
• Sinus bradycardia
• Ventricular extrasystoles
• Hot flush
• Hypertension

Respiratory Disorders

• Dysphonia
• Epistaxis
• Nasal congestion
• Nasopharyngitis
• Upper respiratory tract infection

Gastrointestinal Disorders

• Abdominal distention
• Abdominal pain
• Diarrhoea
• Flatulence
• Nausea and vomiting
• Dyspepsia
• Gastritis
• Abdominal discomfort
• Abdominal tenderness
• Anorectal discomfort
• Constipation
• Dry mouth
• Erosive duodenitis
• Eructation
• Gastroesophageal reflux disease
• Gingivitis
• Glossitis
• Odynophagia
• Acute pancreatitis
• Peptic ulcer
• Rectal haemorrhage
• Gastroenteritis

Hepatobiliary Disorders

• Hepatitis
• Hepatic steatosis
• Alcoholic hepatitis
• Hepatic failure
• Increased alanine aminotransferase
• Increased aspartate aminotransferase
• Increased blood bilirubin

Genitourinary Disorders

• Renal failure
• Nephritis
• Nephrolithiasis
• Nocturia
• Renal cyst
• Renal impairment
• Tubulointerstitial nephritis
• Erectile dysfunction
• Gynaecomastia
• Menopausal symptoms
• Urine glucose present
• Red blood cells urine positive

Endocrine and Metabolic Disorders

• Decreased appetite
• Increased appetite
• Cachexia
• Diabetes mellitus
• Dyslipidaemia
• Hypercholesterolaemia
• Hyperglycaemia
• Hyperlipidaemia
• Hyperphagia
• Polydipsia
• Body fat disorder
• Increased blood triglycerides
• Increased lipase
• Increased blood pancreatic lipase  
• Increased alkaline phosphatase
• Increased blood amylase
• Increased blood cholesterol
• Increased blood creatinine
• Increased blood glucose
• Increased blood urea nitrogen
• Increased creatinine phosphokinase
• Increased fasting blood glucose
• Increased high density lipoprotein
• Increased low density lipoprotein
• Increased waist circumference

Musculoskeletal Disorders

• Arthralgia
• Arthritis
• Back pain
• Flank pain
• Musculoskeletal pain
• Myalgia
• Neck pain
• Osteopenia
• Pain in extremity
• Tendonitis
• Rhabdomyolysis
• Osteonecrosis

Skin and Subcutaneous Tissue Disorders

• Rash
• Acne
• Alopecia
• Dermatitis acneiforme
• Dry skin
• Erythema
• Facial wasting
• Hyperhidrosis
• Lipoatrophy
• Acquired lipodystrophy
• Lipohypertrophy
• Night sweats
• Prurigo
• Pruritus
• Maculo-papular rash
• Skin lesion
• Urticaria
• Xeroderma
• Stevens Johnson syndrome
• Drug rash with eosinophilia and systemic symptoms (DRESS)
• Folliculitis
• Molluscum contagiosum
• Skin papilloma

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Iron deficiency anaemia
• Lymph node pain
• Lymphadenopathy
• Neutropenia
• Thrombocytopenia
• Immune reconstitution syndrome
• Drug hypersensitivity
• Hypersensitivity
• Herpes simplex
• Herpes virus infection
• Herpes zoster
• Genital herpes
• Influenza
• Lymph node abscess
• Fever
• Face oedema
• Atypical lymphocytes
• Decreased absolute neutrophil count
• Decreased blood albumin
• Increased international normalised ratio
• Decreased platelet count
• Decreased white blood cell count

Sensory Disorders

• Visual impairment
• Vertigo
• Tinnitus
• Dysgeusia

Others

• Chest discomfort
• Chills
• Increased fat tissue
• Submandibular mass

• UGT1A1 inducers
• Rifampicin
• UGT1A1 inhibitors
• Atazanavir
• Indinavir
• Saquinavir
• Aluminium and/or magnesium containing antacids

None routine. Specific cases may require

• Hepatic function
• Mental status
• Viral load
• CD4 count

Tablet 400mg - EML (Tertiary)

Tablet chewable 25mg, Tablet chewable 100mg - Non-EML

Chewable tablet

• The 100 mg chewable tablet can be divided into equal 50 mg doses. However, breaking the tablets should be avoided whenever possible

Immune and reconstitution syndrome

• During the initial phase of treatment, patients responding to antiretroviral therapy such as raltegravir may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jirovecii pneumonia, and tuberculosis, or reactivation of varicella zoster virus), which may necessitate further evaluation and treatment
• Autoimmune disorders (such as Graves' disease, Guillain-Barré syndrome and polymiositis) have also been reported to occur in the setting of immune reconstitution, however reported time to onset is more variable and these events can occur many months after initiation of treatment

Raltegravir is an integrase strand transfer inhibitor active against the human immunodeficiency virus. It inhibits the catalytic activity of integrase, an HIV-encoded enzyme that is required for viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of the HIV genome into the host cell genome. HIV genomes that fail to integrate cannot direct the production of new infectious viral particles, so inhibiting integration prevents propagation of the viral infection.

Tablet chewable 25mg

• Isentress (MSD) originator

Tablet chewable 100mg

• Isentress (MSD) originator

Tablet 400mg

• Isentress (MSD) originator