Patients should be cautioned about the concomitant use of self-administered medications (see Interactions).
Patients should be advised that therapy has not been proven to prevent the transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue to be taken.
RETROVIR is not a cure for HIV infection and patients remain at risk of developing illnesses which are associated with immune suppression, including opportunistic infections and neoplasms. Whilst it has been shown to reduce the risks of opportunistic infections, data on the development of neoplasms, including lymphomas, are limited. The available data on patients treated for advanced HIV disease indicate that the risk of lymphoma development is consistent with that observed in untreated patients. In patients with early HIV disease on long-term treatment the risk of lymphoma development is unknown.
Pregnant women considering the use of RETROVIR during pregnancy for prevention of HIV transmission to their infants should be advised that transmission may still occur in some cases despite therapy.
Haematological adverse reactions: Anaemia (usually not observed before 6 weeks of RETROVIR therapy but occasionally occurring earlier), neutropenia (usually not observed before 4 weeks' therapy but sometimes occurring earlier) and leucopenia (usually secondary to neutropenia) can be expected to occur in patients with advanced symptomatic HIV disease receiving RETROVIR. These occurred more frequently at higher dosages (1200-1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease.
Haematological parameters should be carefully monitored.
Syrup: For patients with advanced symptomatic HIV disease it is generally recommended that blood tests are performed at least every 2 weeks for the first 3 months of therapy and at least monthly thereafter. In patients with early HIV disease (where bone marrow reserve is generally good), haematological adverse reactions are infrequent. Depending on the overall condition of the patient, blood tests may be performed less often, for example every 1 to 3 months.
IV infusion: It is generally recommended that blood tests are performed at least weekly in patients receiving RETROVIR I.V. for Infusion.
If the haemoglobin level falls to between 7.5 g/dl (4.65 mmol/l) and 9 g/dl (5.59 mmol/l) or the neutrophil count falls to between 0.75 x 109/l and 1.0 x 109/l, the daily dosage may be reduced until there is evidence of marrow recovery; alternatively, recovery may be enhanced by brief (2-4 weeks) interruption of RETROVIR therapy. Marrow recovery is usually observed within 2 weeks after which time RETROVIR therapy at a reduced dosage may be reinstituted. In patients with significant anaemia, dosage adjustments do not necessarily eliminate the need for transfusions (see Contraindications).
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 zidovudine. A majority of these cases have been in women.
Clinical features which may be indicative of the development of lactic acidosis include generalised weakness, anorexia and sudden unexplained weight loss, gastrointestinal symptoms and respiratory symptoms (dyspnoea and tachypnoea).
Caution should be exercised when administering RETROVIR, particularly to those with known risk factors for liver disease. Treatment with RETROVIR should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis with or without hepatitis (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Lipoatrophy: Treatment with zidovudine 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 several months when switching to a zidovudine-free regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with RETROVIR and other zidovudine containing products (Combivir), and if feasible therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy development.
Serum lipids and blood glucose: Serum lipid and blood glucose levels may increase during antiretroviral therapy. Disease control and life style changes may also be contributing factors. Consideration should be given to the measurement of serum lipids and blood glucose. Lipid disorders should be managed as clinically appropriate.
Immune Reconstitution Syndrome (IRIS): In HIV-infected patients with severe immune deficiency at the time of initiation of anti-retroviral 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, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci (P. carinii) pneumonia. Any inflammatory symptoms must be evaluated without delay and treatment initiated when necessary. Autoimmune disorders (such as Graves' disease, polymyositis and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment and sometimes can be an atypical presentation.
Patients co-infected with hepatitis C virus: Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated. Therefore, the co-administration of ribavirin and zidovudine is not advised and consideration should be given to replacing zidovudine in a combination ART regimen if this is already established. This is particularly important in patients with a known history of zidovudine induced anaemia.
Latex allergy: IV infusion: The rubber stopper of the RETROVIR I.V. for infusion vials contains dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.
Effects on Ability to Drive and Use Machines: Syrup: There have been no studies to investigate the effect of RETROVIR on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance. Nevertheless, the clinical status of the patient and the adverse event profile of RETROVIR should be borne in mind when considering the patient's ability to drive or operate machinery.
IV infusion: RETROVIR I.V. for Infusion is generally used in an in-patient hospital population and information on ability to drive and use machinery is not usually relevant. There have been no studies to investigate the effect of RETROVIR on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance. Nevertheless, the clinical status of the patient and the adverse event profile of RETROVIR should be borne in mind when considering the patient's ability to drive or operate machinery.