Dosing & Uses
Dosage Forms & Strengths
lamivudine/zidovudine
tablet
- 150mg/300mg
HIV Infection
150 mg/300 mg (1 tablet) PO q12hr
Monitor amylase q4-8wk
Because of fixed dose, avoid administering to patients < 30 kg, patients with CrCl < 50 mL/min, or in hepatic impairment
Dosage Forms & Strengths
lamivudine/zidovudine
tablet
- 150mg/300mg
HIV Infection
<12 years: Not recommended; fixed-dose combination cannot be adjusted for children
> 12 years and < 30 kg: Not recommended
>12 years and >30 kg: As adults; 150 mg/300 mg (1 tablet) PO q12hr
Monitor amylase q4-8wk
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (2)
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
zidovudine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.
lamivudine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals. - emtricitabine
emtricitabine and lamivudine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.
emtricitabine, lamivudine. Other (see comment). Contraindicated. Comment: Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.
Serious - Use Alternative (16)
- betibeglogene autotemcel
zidovudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
lamivudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells. - cabotegravir
zidovudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended. - cidofovir
cidofovir, zidovudine. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: When cidofovir is administered concurrently with probenecid, zidovudine clearance may be decreased. Reduce dose of zidovudine by 50% on days of cidofovir/probenecid administration. .
- elivaldogene autotemcel
elivaldogene autotemcel, lamivudine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
- clozapine
clozapine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of myelosuppression.
- deferiprone
deferiprone, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- elivaldogene autotemcel
elivaldogene autotemcel, zidovudine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
- ganciclovir
ganciclovir increases toxicity of zidovudine by pharmacodynamic synergism. Contraindicated.
- pretomanid
pretomanid will increase the level or effect of zidovudine by Other (see comment). Avoid or Use Alternate Drug. In vitro studies demonstrated that pretomanid significantly inhibits OAT3; monitor for increased adverse effects and consider dosage reduction for OAT3 substrates.
- ribavirin
ribavirin decreases effects of zidovudine by Other (see comment). Avoid or Use Alternate Drug. Comment: Mechanism: Competition for thymidine kinase for conversion to active form.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, zidovudine. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- sorbitol
sorbitol will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Sorbitol-containing solution decreased systemic exposure of lamivudine oral solution in a pediatric study (ARROW trial). Results showed lower rates of virologic suppression, lower plasma lamivudine exposure, and development of viral resistance more frequently than children receiving lamivudine tablets.
- stavudine
zidovudine decreases effects of stavudine by Other (see comment). Contraindicated. Comment: Mechanism: Competition for thymidine kinase for conversion to active form.
- tafenoquine
tafenoquine will increase the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.
- trilaciclib
trilaciclib will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.
- valganciclovir
valganciclovir increases toxicity of zidovudine by pharmacodynamic synergism. Contraindicated.
Monitor Closely (66)
- abacavir
abacavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
abacavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - acalabrutinib
acalabrutinib, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- atazanavir
atazanavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- atazanavir
atazanavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- azathioprine
azathioprine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- cabozantinib
lamivudine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- carboplatin
carboplatin, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- cidofovir
cidofovir, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- cisplatin
cisplatin, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- clarithromycin
clarithromycin increases toxicity of zidovudine by unknown mechanism. Use Caution/Monitor. Increased risk of myelosuppression.
clarithromycin, zidovudine. Mechanism: unknown. Use Caution/Monitor. Clarithromycin may increase or decrease levels of zidovudine. Literature describes conflicting reports. Separate administration by minimum 2 to 4 hours. . - clofarabine
clofarabine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- conivaptan
conivaptan increases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dasatinib
dasatinib, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- dexrazoxane
dexrazoxane, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- doxorubicin
zidovudine increases toxicity of doxorubicin by pharmacodynamic synergism. Use Caution/Monitor. Inreased risk of myelosuppression.
doxorubicin decreases effects of zidovudine by Other (see comment). Use Caution/Monitor. - doxorubicin liposomal
zidovudine increases toxicity of doxorubicin liposomal by pharmacodynamic synergism. Use Caution/Monitor. Inreased risk of myelosuppression.
doxorubicin liposomal decreases effects of zidovudine by Other (see comment). Use Caution/Monitor. Comment: Concomitant administration of zidovudine and doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro. - efavirenz
efavirenz and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
efavirenz and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - emtricitabine
emtricitabine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- enfuvirtide
enfuvirtide and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- enfuvirtide
enfuvirtide and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- erdafitinib
lamivudine increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.
- fosamprenavir
fosamprenavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
fosamprenavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - ganciclovir
ganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increased risk of hematologic toxicity.
- hydroxyurea
hydroxyurea, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
zidovudine, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression. - ibritumomab tiuxetan
ibritumomab tiuxetan, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- ifosfamide
ifosfamide, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Ifosfamide may enhance the toxicities of myelosuppressive agents. Monitor for increased risk of myelosuppression.
- imatinib
imatinib, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- indinavir
indinavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
indinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - interferon alfa 2b
interferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.
interferon alfa 2b increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor. - interferon alfa n3
interferon alfa n3 increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor. Interferons may enhance potential for adverse effects. Patients should be monitored for signs and symptoms of increased myelosuppression and liver decompensation.
- nelfinavir
nelfinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- interferon beta 1a
interferon beta 1a increases levels of zidovudine by decreasing renal clearance. Use Caution/Monitor. Interferons may enhance potential for adverse effects. Patients should be monitored for signs and symptoms of increased myelosuppression and liver decompensation.
- interferon beta 1b
interferon beta 1b increases levels of zidovudine by decreasing renal clearance. Use Caution/Monitor. Interferons may enhance potential for adverse effects. Patients should be monitored for signs and symptoms of increased myelosuppression and liver decompensation.
- ketoconazole
ketoconazole increases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lamivudine
lamivudine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- lenalidomide
lenalidomide, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- levoketoconazole
levoketoconazole increases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- methotrexate
methotrexate, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- mitomycin
mitomycin, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- nelfinavir
nelfinavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- nevirapine
nevirapine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
lamivudine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - nirmatrelvir
nirmatrelvir will decrease the level or effect of zidovudine by unknown mechanism. Use Caution/Monitor.
- orlistat
orlistat will decrease the level or effect of lamivudine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will decrease the level or effect of zidovudine by unknown mechanism. Use Caution/Monitor.
- orlistat
orlistat will decrease the level or effect of zidovudine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
- oxaliplatin
oxaliplatin, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- peginterferon alfa 2a
peginterferon alfa 2a, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.
- peginterferon alfa 2b
peginterferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.
peginterferon alfa 2b will increase the level or effect of zidovudine by Other (see comment). Use Caution/Monitor. Interferons may enhance adverse effects of zidovudine including increased myelosuppression. - primaquine
primaquine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- ribavirin
ribavirin increases toxicity of lamivudine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.
- probenecid
probenecid increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor.
- rifabutin
rifabutin will decrease the level or effect of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin decreases levels of zidovudine by increasing metabolism. Use Caution/Monitor.
- ritonavir
ritonavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
ritonavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - saquinavir
saquinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
saquinavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - stavudine
lamivudine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
stavudine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - tenofovir DF
lamivudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
tenofovir DF and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor. - thiotepa
thiotepa, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.
- tipranavir
tipranavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
- tipranavir
tipranavir and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
tipranavir decreases levels of zidovudine by unspecified interaction mechanism. Use Caution/Monitor. - tobramycin inhaled
tobramycin inhaled and zidovudine both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity
- tocilizumab
tocilizumab decreases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Interaction applies to inflammatory conditions, such as rheumatoid arthritis, associated with increased levels of IL-6.
- trimethoprim
trimethoprim increases levels of zidovudine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .
trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity. - ublituximab
ublituximab decreases effects of zidovudine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.
ublituximab decreases effects of lamivudine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. - valganciclovir
valganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.
- valproic acid
valproic acid increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor. Potential for increased toxicity. .
Minor (17)
- amphotericin B deoxycholate
zidovudine increases toxicity of amphotericin B deoxycholate by pharmacodynamic synergism. Minor/Significance Unknown.
- black cohosh
black cohosh increases toxicity of zidovudine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hepatoxicity.
- cyanocobalamin
zidovudine decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown.
- dapsone
zidovudine, dapsone. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased bone marrow toxicity.
- didanosine
zidovudine increases levels of didanosine by decreasing renal clearance. Minor/Significance Unknown.
- fluconazole
fluconazole increases levels of zidovudine by decreasing metabolism. Minor/Significance Unknown.
- flucytosine
zidovudine increases toxicity of flucytosine by pharmacodynamic synergism. Minor/Significance Unknown.
- food
food decreases levels of zidovudine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- isavuconazonium sulfate
isavuconazonium sulfate will increase the level or effect of lamivudine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.
- kava
kava increases toxicity of zidovudine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hepatoxicity.
- lamivudine
lamivudine increases effects of zidovudine by pharmacodynamic synergism. Minor/Significance Unknown. Beneficial synergism.
- methadone
methadone increases levels of zidovudine by decreasing renal clearance. Minor/Significance Unknown.
- pentamidine
zidovudine increases toxicity of pentamidine by pharmacodynamic synergism. Minor/Significance Unknown.
- pyrimethamine
zidovudine, pyrimethamine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased bone marrow toxicity.
- sulfamethoxazole
sulfamethoxazole increases levels of zidovudine by decreasing renal clearance. Minor/Significance Unknown.
zidovudine increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.
sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown. - valacyclovir
valacyclovir increases effects of zidovudine by unknown mechanism. Minor/Significance Unknown. Monitor for lethargy and fatigue.
- zidovudine
lamivudine increases effects of zidovudine by pharmacodynamic synergism. Minor/Significance Unknown. Beneficial synergism.
Adverse Effects
>10%
Headache (35%)
Nausea (33%)
Malaise & fatigue (27%)
Cough (18%)
Diarrhea (18%)
Vomiting (13%)
Musculoskeletal pain (12%)
Neuropathy (12%)
Insomnia & other sleep disorders (11%)
1-10%
Anorexia &/or decreased appetite (10%)
Dizziness (10%)
Fever or chills (10%)
Abdominal pain (9%)
Depressive disorders (9%)
Skin rashes (9%)
Myalgia (8%)
Neutropenia (7.2% )
Abdominal cramps (6%)
Arthralgia (5%)
Dyspepsia (5%)
Anemia (2.9% )
Frequency Not Defined (serious)
Erythema multiforme
Stevens-Johnson syndrome
Lactic acidosis
Pancreatitis
Hepatomegaly (Severe)
Steatosis of liver (Severe)
Anaphylaxis
Immune hypersensitivity reaction
Rhabdomyolysis
Postmarketing reports
Immune reconstitution syndrome and fat redistribution
Warnings
Black Box Warnings
lamivudine
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues, including lamivudine and zidovudine (components of the combination product) alone or in combination with other antiretrovirals; discontinue therapy if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur alone or in combination with other antiretrovirals
- Not FDA approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of this drug have not been established in patients coinfected with HBV and HIV
- Tablets and oral solution formulations used to treat HIV infection contain a higher dose of lamivudine than formulations indicated for chronic hepatitis B infection; HIV patients should receive only formulation specific for HIV
- Exacerbations of hepatitis reported after discontinuation of lamivudine; monitor patients closely with both clinical and laboratory follow-up for at least several months after stopping treatment; if appropriate, initiate anti-hepatitis B therapy
zidovudine
- Neutropenia and severe anemia reported, particularly in patients with advanced HIV disease
- Myopathy associated with prolonged use
- Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) reported with nucleoside analogues alone or in combination
Contraindications
Hypersensitivity
Patients requiring separate lamivudine or zidovudine dose reduction
Cautions
Risk of immune reconstitution syndrome
Zidovudine use has been associated with hematologic toxicity including neutropenia and anemia, particularly in patients with advanced HIV-1 disease; use with caution in patients who have bone marrow compromise evidenced by granulocyte count < 1,000 cells per mm³ or hemoglobin < 9.5 g/dL; frequent blood counts strongly recommended in patients with advanced HIV-1 disease; periodic blood counts recommended for other HIV-1-infected patients; if anemia or neutropenia develops, dosage interruption may be needed
Myopathy and myositis, with pathological changes similar to that produced by HIV-1 disease associated with prolonged use of zidovudine
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use of nucleoside analogues, including lamivudine and zidovudine (components of the combination product) and other antiretrovirals reported; a majority of these cases have been in women; female sex and obesity may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues; suspend treatment in patients who develop clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)
Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine; monitor patients closely with both clinical and laboratory follow-up for at least several months after stopping treatment
Emergence of hepatitis B virus variants associated with resistance to lamivudine reported in HIV-1-infected subjects who received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus
Concomitant administration with other products containing lamivudine or zidovudine not recommended
Closely monitor patients receiving interferon alfa with or without ribavirin for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia; consider discontinuation of therapy as medically appropriate; dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6)
Use with caution in patients with a history of pancreatitis or other significant risk factors for the development of pancreatitis; treatment should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur Immune reconstitution syndrome reported
During initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have been reported to occur in setting of immune reconstitution; however, time to onset is more variable, and can occur many months after initiation of treatment
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy; mechanism and long-term consequences of these events are currently unknown; causal relationship not established
Treatment with zidovudine, a component of the combination product, has been associated with loss of subcutaneous fat; the incidence and severity of lipoatrophy are related to cumulative exposure; this fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to a non-zidovudine- containing regimen; patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine-containing products, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy
Not recommended for use in patients with hepatic or renal (CrCl< 50 mL/min) impairment
See also individual monographs
- lamivudine
- zidovudine
Pregnancy & Lactation
Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
Available data from APR show no difference in overall risk of birth defects for lamivudine or zidovudine compared with background rate for birth defects of 2.7% in Metropolitan Atlanta Congenital Defects Program (MACDP) reference population
Hyperlactatemia, which may be due to mitochondrial dysfunction, reported in infants with in utero exposure to zidovudine-containing products; causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum not established
Lactation
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection; lamivudine and zidovudine are present in human milk; there is no information on effects of lamivudine or zidovudine on breastfed infant or effects of drugs on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in breast infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog
Zidovudine: NRTI; interferes with HIV viral RNA-dependent DNA polymerase (inhibits viral replication); thymidine analog
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Formulary
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