3TC Special Precautions

Lamivudine is not recommended for use as monotherapy.
Patients should be advised that current antiretroviral therapy, including lamivudine, has not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue to be employed.
Patients receiving 3TC or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore they should remain under close clinical observation by physicians experienced in the treatment of patients with associated HIV diseases
Renal Impairment: Lamivudine plasma concentrations (AUC) are increased in patients with moderate to severe renal impairment due to decreased clearance. The dose should therefore be adjusted (see Dosage & Administration).
Pancreatitis: Pancreatitis has been observed in some patients receiving lamivudine. However it is unclear whether this was due to treatment with the medicinal product or to the underlying HIV disease. Pancreatitis must be considered whenever a patient develops abdominal pain, nausea, vomiting or elevated biochemical markers.
Discontinue use of lamivudine until diagnosis of pancreatitis is excluded.
Lactic Acidosis/Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues either alone or in combination, including lamivudine. A majority of these cases have been in women.
Clinical features which may be indicative of the development of lactic acidosis include generalized weakness, anorexia, and sudden unexplained weight loss, gastrointestinal symptoms and respiratory symptoms (dyspnea and tachypnea).
Caution should be exercised when administering lamivudine to any patient and particularly to those with known risk factors for liver disease. Treatment with lamivudine should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Fat Redistribution: Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, elevated serum lipid and blood glucose levels have been observed either separately or together in some patients receiving combination antiretroviral therapy (see Adverse Reactions).
Whilst all members of the PI and NRTI classes of medicinal products have been associated with one or more of these specific adverse events, linked to a general syndrome commonly referred to as lipodystrophy, data indicate that there are differences in the risk between individual members of the respective therapeutic classes.
In addition, the lipodystrophy syndrome has a multifactorial etiology; with for example HIV disease status, older age and duration of antiretroviral treatment all playing important, possibly synergistic roles.
The long-term consequences of these events are currently unknown.
Clinical examination should include evaluation for physical signs of fat redistribution. Consideration should be given to the measurement of serum lipids and blood glucose. Lipid disorders should be managed as clinically appropriate.
Immune Reconstitution Syndrome: In HIV-infected patients with severe immune deficiency at the time of initiation of antiretroviral therapy (ART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of ART. Relevant examples are cytomegalovirus retinitis, generalized and/or focal mycobacterial infections and Pneumocystis jiroveci (P. carinii) pneumonia. Any inflammatory symptoms must be evaluated without delay and treatment initiated when necessary.
Patients Co-Infected with Hepatitis B Virus: Clinical trial and marketed use of lamivudine, have shown that some patients with chronic hepatitis B virus (HBV) disease may experience clinical or laboratory evidence of recurrent hepatitis upon discontinuation of lamivudine, which may have more severe consequences in patients with decompensated liver disease. If lamivudine is discontinued in a patient with HIV and HBV co-infection, periodic monitoring of both liver function tests and markers of HBV replication should be considered.
Oral Solution: Diabetic patients should be advised that an adult dose contains sucrose 3 g.
Effects on the Ability to Drive or Operate Machinery: There have been no studies to investigate the effect of 3TC on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of lamivudine. Nevertheless, the clinical status of the patient and the adverse event profile of 3TC should be borne in mind when considering the patient's ability to drive or operate machinery.
Use in pregnancy & lactation: There are limited data available on the safety of 3TC in human pregnancy. Studies in humans have confirmed that lamivudine crosses the placenta. Use in pregnancy should be considered only if the benefit outweighs the risk. Although the results of animal studies (see Toxicology under Actions) are not always predictive of human response, the findings in the rabbit suggest a potential risk of early embryonic loss.
There have been reports of mild, transient elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical relevance of transient elevations in serum lactate is unknown. There have also been very rare reports of developmental delay, seizures and other neurological disease. However, a causal relationship between these events and NRTI exposure in utero or peri-partum has not been established. These findings do not affect current recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Health experts recommend that where possible, women infected with HIV do not breastfeed their infants in order to avoid the transmission of HIV. Following oral administration, lamivudine was excreted in human breast milk at similar concentrations to those found in serum (1-8 mcg/mL). Since lamivudine and the virus pass into breast milk, it is recommended that mothers taking lamivudine do not breastfeed their infants.