NEODOSE

INDICATIONS

• HIV-1 infection
  • Younger than 15 days: Data are insufficient to make a general recommendation for complete combination antiretroviral therapy (cART) in preterm or term infants younger than 15 days (until 42 weeks’ postmenstrual age). Consult a pediatric HIV expert if considering a 3-drug antiretroviral (ARV) regimen in infants younger than 2 weeks or premature infants. The preferred initial regimen is 2 NRTIs (zidovudine plus either (lamiVUDine or emtricitabine)) plus nevirapine. There are no data demonstrating improved outcomes when starting treatment within the first 14 days of age compared with after 14 days of age.
  • 14 days or older and 42 weeks’ post-gestational age: The preferred initial regimen is 2 NRTIs (zidovudine plus (lamiVUDine or emtricitabine)) plus lopinavir/ritonavir-boosted. If the infant is on nevirapine considering changing to lopinavir/ritonavir-boosted.

FDA APPROVED INDICATION

Treatment of HIV-1 infection, in combination with other antiretroviral agents, in children 2 weeks or older

CONTRAINDICATIONS

• Contraindicated with the coadministration of allopurinol, ribavirin, or stavudine.

PRECAUTIONS

• Concomitant Use:
  • Avoid use with hydroxyurea (with or without stavudine).
• Endocrine & Metabolic:
  • Lipoatrophy has been reported predominately in the face, limbs, and buttocks; severity related to cumulative exposure and is often not reversible. Monitoring recommended and consider alternative regimen if there is a suspicion of lipoatrophy.
• Hepatic:
  • Severe hepatomegaly with steatosis, including fatalities, have been reported with nucleoside analogs; increased risk in obesity, female gender, prolonged nucleoside exposure, or known risk factors for liver disease; suspend treatment if signs or symptoms occur.
  • Patients with preexisting liver dysfunction, including chronic active hepatitis, have increased risk of severe and potentially fatal hepatic adverse events; monitoring recommended and interruption or discontinuation of therapy may be necessary.
  • Non-cirrhotic portal hypertension has been reported, including fatalities or cases requiring liver transplantation; onset occurred months to years after start of therapy; discontinue use if suspected.
• Immunologic:
  • Autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) have been reported; onset variable, may occur many months after treatment initiation.
  • Immune reconstitution syndrome has been reported including inflammatory response to indolent or residual opportunistic infections; occurs during initial treatment phase.
• Neurologic:
  • Peripheral neuropathy has been reported; increased risk in patients with advanced HIV disease, history of neuropathy, or concurrent neurotoxic drug therapy; discontinuation may be necessary.
• Ophthalmic:
  • Retinal changes and optic neuritis have been reported; monitoring recommended.

ADVERSE EFFECTS

Pancreatitis occurred in 3% (2 out of 60) of pediatric patients during a clinical trial at doses below 300 mg/m(2)/day. Common adverse events include diarrhea, abdominal pain, vomiting, rash, and increased liver enzymes. Peripheral neuropathy, non-cirrhotic portal hypertension, retinal changes, optic neuritis, and insulin resistance/diabetes mellitus have also been reported in pediatric patients.

BLACK BOX WARNING

Warning: Pancreatitis, Lactic Acidosis and Hepatomegaly with Steatosis.

• Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Didanosine should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis..
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of didanosine and stavudine is contraindicated because of increased risk of serious and/or life-threatening events. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occurs.

ADMINISTRATION

Preferably, administer on an empty stomach (30 minutes before or 2 hours after a feeding). Shake well before measuring dose.

MONITORING

Monitor for early signs and symptoms of portal hypertension (eg, thrombocytopenia and splenomegaly). Perform retinal examinations periodically to screen for retinal changes and optic neuritis.