- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Concentrate for solution for infusion containing 200mg zidovudine in 20ml solution (10mg/ml zidovudine).
Short term management of serious manifestations of Human Immunodeficiency Virus (HIV) infection in patients with Acquired Immune Deficiency Syndrome (AIDS) who are unable to take oral formulations. Preferably, zidovudine should not be used as monotherapy.
Monotherapy for HIV-positive pregnant women (over 14 weeks of gestation) and their new-born infants for primary prophylaxis of maternal-foetal HIV transmission when oral treatment is not possible.
Treatment should be initiated by a specialist experienced in the management of HIV infection.
It is recommended treatment should not exceed a duration of 2 weeks.
Zidovudine infusion should only be administered until oral therapy can be received.
Treatment of HIV
0.8mg/kg to 2mg/kg bodyweight every 4 hours in combination with other antiretroviral agents.
Monotherapy for the prevention of maternal-foetal transmission during labour and delivery
2mg/kg bodyweight, followed by a continuous infusion at 1mg/kg/h, until the umbilical cord is clamped.
In the case of a planned caesarean, infusion should start 4 hours prior the operation.
In the event of a false labour, infusion should be stopped and oral formulations should be administered.
There is currently no data available in patients over 65 years of age.
Children aged 12 to 18 years
0.8mg/kg to 1mg/kg every 4 hours.
Children aged 3 months to 12 years
60mg per square metre to 80mg per square metre every 6 hours.
Monotherapy for the prevention of maternal-foetal transmission
Children from Birth to 6 weeks old
1.5mg/kg bodyweight, every 6 hours, infused over a duration of 30 minutes.
Patients with Renal Impairment
Severe renal impairment
1mg/kg to be intravenously infused 3 to 4 times a day, in combination with other antiretroviral agents.
Dose may be adjusted based on individual patient response.
The Renal Drug Handbook recommends to following doses:
Glomerular filtration rate 20ml/minute to 50ml/minute: 100% of normal dose to be administered every 8 hours.
Glomerular filtration rate 10ml/minute to 20ml/minute: 100% of normal dose to be administered every 8 hours.
Glomerular filtration rate less than 10ml/minute: Reduce dose by 50%, to be administered every 8 hours.
Haemodialysis and peritoneal dialysis
100mg administered every 6 to 8 hours.
The diluted solution is administered by slow intravenous infusion over a one hour period.
Zidovudine concentrate for solution for infusion must be diluted prior to administration - see Reconstitution.
Zidovudine infusion must be diluted under full aseptic conditions, preferably immediately before administration.
The required dose should be diluted with glucose intravenous infusion 5% w/v to give a final zidovudine concentration of either 2mg/ml or 4mg/ml. These dilutions are physically and chemically stable at both 5 degrees C and 25 degrees C for up to 48 hours.
Discard any unused portion of the vial.
Discard preparation if turbidity appears either before or after dilution or during infusion.
Abnormally low neutrophil count (less than 0.75 x 10 to the power of 9/L) or abnormally low haemoglobin levels (less than 7.5g/decilitre or 4.65 mmol/litre)
Neonates with hyperbilirubinaemia requiring treatment other than phototherapy, or with raised transaminase levels of over five times the upper limit of normal.
Breastfeeding - see "Lactation" section
Porphyria - see "Porphyria" section
Precautions and Warnings
Treatment should be initiated by a physician experienced in the management of HIV infection.
Zidovudine is not a cure for HIV infection and patients still remain at risk of developing illnesses associated with immune suppression, including opportunistic infections and neoplasms.
Treatment does not prevent risk of HIV transmission through sexual contact or blood contamination. Appropriate precautions should continue to be taken.
Pregnancy of less than 14 weeks gestation - see Pregnancy section.
Elderly - see Dosage section; Elderly.
Severe renal impairment - see Dosage section; Renal Impairment.
Hepatic impairment - see Dosage section; Hepatic Impairment.
Patients should be warned about concurrent use of self-administered medication.
Anaemia, neutropenia and leucopenia can be expected to occur in patients receiving zidovudine. These occurred more frequently at higher doses (1200 to 1500mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV. The incidence of neutropenia is increased in those with low neutrophil counts, low haemoglobin levels and low serum vitamin B12 levels at the start of treatment.
For dosage adjustments in patients with haematological adverse effects see 'Dosage section; Additional dosage' .
In patients with significant anaemia, dosage adjustments do not necessarily eliminate the need for transfusions.
Haematological parameters should be closely monitored. Blood tests should be performed weekly in patients receiving intravenous zidovudine.
Lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, has been reported with the use of nucleoside analogues. This generally occurs after a few or several months of treatment.
Benign digestive symptoms (such as nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (such as rapid/deep breathing), or neurological symptoms (such as motor weakness) might be indicative of lactic acidosis development.
Lactic acidosis has a high mortality and may be associated with pancreatitis, hepatic failure or renal failure.
Treatment should be discontinued if the patients exhibits symptomatic hyperlactatemia, rapidly elevating aminotransferase levels, progressive hepatomegaly or metabolic/lactic acidosis.
Caution should be exercised and close monitoring is advisable when administering nucleoside analogues to at risk patients (particularly obese women) with hepatomegaly , hepatic enzyme abnormalities, hepatitis, or any known risk factors for hepatic disease and hepatic steatosis. Patients co-infected with hepatitis C and being treated with alpha interferon and ribavirin may constitute a special risk.
The safety and efficacy of zidovudine has not been established in patients with significant underlying hepatic disorders.
Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. If hepatic disease worsens in these patients, interruption or discontinuation of therapy should be considered.
Patients with pre-existing hepatic impairment, including chronic active hepatitis, have an increased risk of developing hepatic function abnormalities during therapy. These patients should be closely monitored and treatment should be interrupted or discontinued if hepatic disease worsens in these patients.
The redistribution of body fat (lipodystrophy) has occurred in HIV patients receiving combination antiretroviral therapy. The long term consequences and mechanisms of this effect are unknown, but a connection between lipoatrophy and nucleoside reverse transcriptase inhibitors has been suggested. There is believed to be an increased risk of lipodystrophy in older patients, and with a longer treatment duration and associated metabolic disturbances. Clinical examinations should include looking for physical signs of fat redistribution. Lipid disorders should be managed appropriately. Plasma lipids and blood glucose should be measured before starting antiretroviral therapy, after 3 to 6 months and then annually.
A variable degree of mitochondrial damage has been demonstrated during in vitro and in vivo studies with nucleoside and nucleotide analogues. There have also been reports of mitochondrial impairment in HIV-negative infants exposed in utero and/or postnatally to nucleoside analogues. Reported adverse effects include haematological (anaemia, neutropenia), metabolic (hyperlactatemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour). Any child exposed in utero (including HIV-negative infants) should be fully investigated for mitochondrial impairment if any symptoms develop.
When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or pneumocystis jiroveci ( previously pneumocystis carinii) pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.
The clinical status of the patient and the adverse events profile of zidovudine should be considered when assessing the patient's ability to drive.
Cases of osteonecrosis have been reported in patients with advanced HIV disease and/or long term exposure to combination antiretroviral therapy, although the aetiology of this condition is thought to multifactorial patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia for patients co-infected with hepatitis C virus.
Use in Porphyria
Zidovudine is considered to be probably porphyrinogenic by NAPOS (2004). Zidovudine may cause depression of the hepatic free haem pool and therefore increase the rate of haem synthesis.
Pregnancy and Lactation
When considering the treatment of a HIV infected women during pregnancy, the present and future health of the mother, the prevention of maternal to foetal transmission and the limitations from the drug toxicity to the HIV-exposed foetus should be considered. The optimal antiretroviral therapy regimen for each patient depends on their, HIV RNA levels, previous disease history, and obstetric history. Zidovudine is licensed for use in pregnancy after 14 weeks gestation for the prevention of maternal to foetal HIV transmission, and primary prophylaxis of HIV infection in newborn infants. Zidovudine crosses the placenta and foetal levels have been found to be similar to higher than the maternal levels. The use of zidovudine in pregnant women over 14 weeks of gestation, with subsequent treatment of their newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV significantly. Pregnant women should be advised that transmission may still occur in some cases despite therapy.
Zidovudine is not teratogenic in animals except at very high doses, and the experience in humans shows no pattern of birth defects (Briggs, Freeman & Yaffe, 2011). Zidovudine is known to cause neonatal anaemia. Mitochondrial dysfunction in neonates following in utero zidovudine exposure has also been reported. It is unknown whether there are any long term consequences of in utero and infant exposure to zidovudine.
Animal studies on rats showed that zidovudine is toxic to rodent embryos, by preventing blastocyst development, if given before implantation occurs. Briggs, Freeman & Yaffe (2011) report that there is some experience that zidovudine may affect human trophoblast cell growth and function in a dose related manner. Therefore, zidovudine should only be used in pregnancy prior to the 14th week of gestation if the potential benefit to the mother outweighs the risk to the foetus.
The efficacy of zidovudine to reduce the maternal foetal transmission in women with previously prolonged treatment with zidovudine or other antiretroviral agents or women infected with HIV strains with reduced sensitivity to zidovudine is unknown.
Based on the animal carcinogenicity/mutagenicity findings a carcinogenic risk to humans cannot be excluded. The relevance of these findings to both infected and uninfected infants exposed to zidovudine is unknown. Pregnant women should be made aware of these findings when considering zidovudine treatment.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Licensed in pregnancy? - Yes, only after 14 weeks gestation
Known human teratogen? - No
Animal data - Animal data did not reveal any teratogenicity, however zidovudine was toxic to rodent embryos.
Crosses placenta? - Yes
Effects on foetus - Zidovudine is known to cause anaemia, and may cause mitochondrial dysfunction.
Zidovudine is contraindicated while breastfeeding. Zidovudine is excreted into breast milk. HIV can be transmitted from mother to child through breast milk. Therefore it is recommended that HIV-infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Drug excreted in breast milk? - Yes
Considered suitable or recommended by manufacturer? - No. Note that all authorities in the UK recommend that HIV positive mothers should not breastfeed to reduce maternal transmission of HIV in milk.
Drug substance licensed in infants? - Yes.
Effects on Ability to Drive and Operate Machinery
Zidovudine infusion is generally used in an in-patient hospital population and so information on the ability to drive and use machinery is not usually relevant.
The effect of zidovudine on driving performance or the ability to operate machinery has not been studied.
The clinical status of the patient and the adverse events profile of zidovudine should be considered when assessing the patient's ability to drive.
Advise patients to check with their doctor or pharmacist before self-administering medications because of the risk of zidovudine toxicity.
Patients should be informed that zidovudine is not a cure for HIV infection and that they may continue to acquire illnesses associated with HIV infection, including opportunistic infections.
Advise patients that current antiretroviral therapy has not been shown to prevent the risk of transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue to be used.
Patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.
Advise pregnant women that a carcinogenic risk to the foetus cannot be excluded.
Bone marrow hypoplasia
Red cell aplasia
Increases in hepatic enzymes
Serum bilirubin increased
Pigmentation of nails, skin and oral mucosa
Loss of mental acuity
Pain - generalised
Injection site reactions
Immune Reactivation Syndrome
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Shelf Life and Storage
Do not store above 30 degrees C.
Store in the original outer carton.
Storage after reconstitution
The diluted solutions are chemically and physically stable for up to 48 hours at both 5 degrees C and 25 degrees C. Should any visible turbidity appear in the product either before or after dilution or during infusion, the preparation should be discarded.
Last Full Review Date: September 2009
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Retrovir 10mg/ml IV for Infusion. ViiV Healthcare UK Ltd. Revised December 2018.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
British HIV Association. Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child=transmission of HIV.
Available at: https://www.bhiva.org/files/file1030325.pdf
Dated 31st March 2005.
Last accessed: September 7, 2009
NAPOS, The Drug Database for Acute Porphyria.
Available at; https://www.drugs-porphyria.org/
Zidovudine last revised October 1, 2004.
Last accessed: November 27, 2012.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Zidovudine Last revised: August 31, 2012.
Last accessed: November 27 2012.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 August 2017
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