Usual Adult Dose for HIV Infection

150 mg orally twice a day or 300 mg orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Usual Adult Dose for Chronic Hepatitis B

100 mg orally once a day

Comments:

• HIV counseling and testing should be offered to all patients before starting treatment with this product and periodically during therapy due to risk of resistant HIV-1 emerging and limited treatment options if this product is prescribed to treat chronic HBV infection in a patient who has unrecognized HIV-1 infection or acquires HIV-1 infection during therapy.
• The optimal duration of therapy is not known.

Use: For the treatment of chronic HBV infection associated with evidence of hepatitis B viral replication and active liver inflammation

Usual Adult Dose for Nonoccupational Exposure

US CDC Recommendations:

• Weight less than 50 kg: 4 mg/kg orally twice a day
• Maximum dose: 150 mg/dose
• Weight at least 50 kg: 150 mg orally twice a day OR 300 mg orally once a day

Duration of therapy: 28 days

Comments:

• This drug and zidovudine plus (raltegravir or dolutegravir) is recommended as the preferred regimen for nonoccupational postexposure prophylaxis of HIV infection in adults with CrCl less than 60 mL/min; this drug and zidovudine plus darunavir/ritonavir is recommended as an alternative regimen for such patients. Dose should be adjusted to degree of renal function.
• If other alternatives are considered, this drug is recommended as a component in various regimens.
• Prophylaxis should be started as soon as possible, within 72 hours of exposure.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure

US Public Health Service Working Group Recommendations:

• Preferred dose: 300 mg orally once a day
• Alternative dose: 150 mg orally twice a day

Duration of therapy: 28 days, if tolerated

Comments:

• Recommended as a component in alternative regimens for HIV postexposure prophylaxis
• Prophylaxis should be started as soon as possible, preferably within hours after exposure.
• The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection

3 months or older:
Oral solution: 5 mg/kg orally twice a day OR 10 mg/kg orally once a day

• Maximum dose: 300 mg/day

Tablets:

• Weight 14 to less than 20 kg: 75 mg orally twice a day OR 150 mg orally once a day
• Weight 20 to less than 25 kg: 75 mg orally in the morning and 150 mg in the evening OR 225 mg orally once a day
• Weight at least 25 kg: 150 mg orally twice a day OR 300 mg orally once a day

Comments:

• For patients starting therapy with the oral solution, HIV-1 viral load and CD4+ cell count/percentage should be considered when selecting dosing interval.
• The scored tablet is the preferred formulation for HIV-1-infected patients weighing at least 14 kg who can safely and reliably swallow tablets; ability to swallow tablets should be assessed before the scored tablets are prescribed.
• In a clinical trial, pediatric patients who received lamivudine oral solution (at doses about 8 mg/kg/day) with other antiretroviral oral solutions had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more often than those receiving lamivudine tablets.
• When possible, an all-tablet regimen should be used to avoid potential interaction with sorbitol.
• More frequent monitoring of HIV-1 viral load should be considered when treating with the oral solution.
• Tablets: Data regarding efficacy of once-daily dosing limited to patients who switched from twice-daily dosing to once-daily dosing after 36 weeks of therapy.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) Recommendations:
Oral Solution:

• Neonates (at least 32 weeks gestation at birth) and infants (birth to less than 4 weeks): 2 mg/kg orally twice a day
• Infants and children aged 4 weeks to less than 3 months: 4 mg/kg orally twice a day
• Infants and children aged 3 months to less than 3 years: 5 mg/kg orally twice a day
• Maximum dose: 150 mg/dose
• Children and adolescents aged 3 years or older: 5 mg/kg orally twice a day OR 10 mg/kg orally once a day
• Maximum dose: 300 mg/day

Tablets:

• Weight 14 to less than 20 kg: 75 mg orally twice a day OR 150 mg orally once a day
• Weight 20 to less than 25 kg: 75 mg orally in the morning and 150 mg in the evening OR 225 mg orally once a day
• Weight at least 25 kg: 150 mg orally twice a day OR 300 mg orally once a day

Comments:

• The Panel supports switching from twice-daily dosing to once-daily dosing of this drug in patients 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 T lymphocyte counts.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Chronic Hepatitis B

2 to 17 years: 3 mg/kg orally once a day
Maximum dose: 100 mg/day

Comments:

• HIV counseling and testing should be offered to all patients before starting treatment with this product and periodically during therapy due to risk of resistant HIV-1 emerging and limited treatment options if this product is prescribed to treat chronic HBV infection in a patient who has unrecognized HIV-1 infection or acquires HIV-1 infection during therapy.
• The optimal duration of therapy is not known.

Use: For the treatment of chronic HBV infection associated with evidence of hepatitis B viral replication and active liver inflammation

Renal Dose Adjustments

HBV INFECTION:
Adults:

• CrCl 30 to 49 mL/min: 100 mg orally as first dose, then 50 mg orally once a day
• CrCl 15 to 29 mL/min: 100 mg orally as first dose, then 25 mg orally once a day
• CrCl 5 to 14 mL/min: 35 mg orally as first dose, then 15 mg orally once a day
• CrCl less than 5 mL/min: 35 mg orally as first dose, then 10 mg orally once a day

Pediatric Patients:

• Renal dysfunction: Insufficient data to recommend a specific dosage

HIV-1 INFECTION:
Adults and Adolescents (at least 25 kg):

• CrCl 30 to 49 mL/min: 150 mg orally once a day
• CrCl 15 to 29 mL/min: 150 mg orally as first dose, then 100 mg orally once a day
• CrCl 5 to 14 mL/min: 150 mg orally as first dose, then 50 mg orally once a day
• CrCl less than 5 mL/min: 50 mg orally as first dose, then 25 mg orally once a day

Pediatric Patients:

• Renal dysfunction: Insufficient data to recommend a specific dose adjustment; reduction in dose and/or increase in dosing interval should be considered.

Comments:

• HBV Infection: The 5 mg/mL oral solution should be used for doses below 100 mg.

Liver Dose Adjustments

Liver dysfunction: No adjustment recommended.

Comments:

• Safety and efficacy have not been established in patients with decompensated liver disease.

Precautions

US BOXED WARNINGS:

• EXACERBATIONS OF HEPATITIS B: Severe acute exacerbations of hepatitis B reported in patients with HBV (including those coinfected with HIV-1) after stopping this drug. Hepatic function of HBV-infected patients should be closely monitored with clinical and laboratory follow-up for at least several months after stopping this drug. If appropriate, initiation/resumption of antihepatitis B therapy may be necessary.
• IMPORTANT DIFFERENCES AMONG LAMIVUDINE-CONTAINING PRODUCTS: Epivir tablets and oral solution (used to treat HIV-1 infection) contain a higher dose of lamivudine than Epivir-HBV tablets and oral solution (used to treat chronic HBV infection). Only products appropriate for treatment of HIV-1 should be used in HIV-1-infected patients.
• RISK OF HIV-1 RESISTANCE WITH EPIVIR-HBV USE IN UNRECOGNIZED/UNTREATED HIV-1 INFECTION: Epivir-HBV is not approved for treatment of HIV-1 infection as the lamivudine dosage is subtherapeutic and monotherapy is inappropriate. HIV-1 resistance may develop in chronic HBV-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before starting Epivir-HBV and periodically during therapy.

CONTRAINDICATIONS:
Previous hypersensitivity reaction to the active component or any of the ingredients

Safety and efficacy of Epivir and Epivir-HBV have not been established in patients younger than 3 months and 2 years, respectively.

Consult WARNINGS section for additional precautions.

Dialysis

Conventional 4-hour hemodialysis and peritoneal dialysis: No additional dose adjustments needed after adjustment for renal dysfunction (based on CrCl); no supplemental dose needed after dialysis.
Prolonged or continuous hemodialysis: Data not available

Other Comments

Administration advice:

• Administer with or without food.
• If patient is unable to swallow a tablet safely and reliably, use the oral solution.
• Only use products appropriate for treatment of HIV-1 in patients with HIV-1 infection; use in combination with other antiretroviral agents.
• Use the formulation and dose recommended for HIV-1 therapy (as part of an appropriate combination regimen) in patients coinfected with HIV-1 and HBV.
• Consult the manufacturer product information regarding missed doses.

Storage requirements:

• Oral solutions: Store in tightly closed bottles at 20C to 25C (68F to 77F).
• Tablets: Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).

General:

• Limitations of Use (Epivir): The dosage of this product is for HIV-1 and not HBV.
• The following should be considered when starting therapy with Epivir-HBV:
• Due to high rates of resistance development in treated patients, starting Epivir-HBV should only be considered when use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate.
• Epivir-HBV has not been evaluated in patients coinfected with HIV, HCV, or hepatitis delta virus.
• Epivir-HBV has not been evaluated in liver transplant recipients or in patients with chronic HBV infection with decompensated liver disease.
• During HBV therapy, combinations of events (e.g., persistently elevated ALT recurring, HBV DNA levels increasing over time after initial decline below assay limit, clinical signs/symptoms of hepatic disease progression, and/or hepatic necroinflammatory findings worsen) may indicate loss of therapeutic response; such events should be considered when deciding whether to continue this drug.
• The durability of hepatitis B e antigen (HBeAg) seroconversions occurring during HBV therapy and the relationship between treatment response and long-term outcomes (e.g., hepatocellular carcinoma, decompensated cirrhosis) have not been established.
• The oral solutions contain sucrose; Epivir contains 3 g sucrose per 15-mL dose and Epivir-HBV contains 4 g sucrose per 20-mL dose.

Monitoring:

• Gastrointestinal: For signs/symptoms of pancreatitis in pediatric patients
• General: HIV testing (before starting and periodically during HBV therapy)
• Hepatic: ALT and HBV DNA levels (during HBV therapy); hepatic function of HBV-infected patients with clinical and laboratory follow-up (for at least several months after stopping therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Stop this drug if clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity develop.
• HBV INFECTION:
• Do not discontinue this product without first informing health care provider.
• Report any new/worsening symptoms to physician without delay.
• HIV-1 INFECTION:
• Discuss any changes in regimen with health care provider.
• Monitor pediatric patients for signs/symptoms of pancreatitis.
• Notify health care provider at once of any signs/symptoms of infection.

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