Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals
Prevention of maternal-foetal HIV transmission

Treatment of Human Immunodeficiency Virus (HIV) infection in combination with other anti-retroviral agents.

Preventing maternal-foetal HIV transmission, in HIV positive pregnant women who are over 14 weeks gestation.

Primary prophylaxis of HIV infection in newborn infants.

Contraindications

Haemoglobin concentration below 7.5g / dL
Neutrophil count below 0.75 x 10 to the power of 9 / L
Breastfeeding
Hepatic impairment - Child-Pugh score greater than 7
Neonatal hyperbilirubinaemia
Neonates with raised transaminases
Porphyria

Precautions and Warnings

Children weighing less than 4kg
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Predisposition to hepatic disorder
Predisposition to hepatic steatosis
First trimester of pregnancy
Haemodialysis
Hepatic impairment
Hepatic steatosis
Hepatitis
Hepatitis C treated with alpha interferon and ribavirin
Hepatomegaly
Hereditary fructose intolerance
Renal impairment - creatinine clearance below 10ml/minute
Vitamin B12 deficiency

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
May contain sodium benzoate: may increase risk of jaundice in neonates
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Monitor blood counts regularly
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor haematological parameters regularly throughout treatment
Monitor patients at risk of hepatic disease
Monitor patients with hepatic impairment
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Discontinue if raised LFTs/hepatomegaly/lactic acidosis occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue or interrupt dose if anaemia, neutropenia or leucopenia occur

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.

In patients with significant anaemia, dosage adjustments do not necessarily eliminate the need for transfusions. For patients with advanced symptomatic HIV disease it is generally recommended that blood tests are performed every two weeks for the first three months of therapy and at least monthly thereafter. For those with early HIV disease (with good bone marrow reserves) or those whose condition is less serious blood monitoring may be carried out less frequently, for example every 1 to 3 months.

Caution should be exercised and close monitoring is advisable when administering nucleoside analogues to at risk patients (particularly obese women) with hepatomegaly, hepatitis, or any known risk factors for hepatic disease and hepatic steatosis. Patients co-infected with hepatitis C being treated with alpha interferon and ribavirin may constitute a special risk.

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.

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 those with a longer treatment duration and associated metabolic disturbances. Clinical examinations should include looking for physical signs of fat redistribution, and lipid disorders should be managed appropriately.

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. Late onset neurological disorders (hypertonia, convulsions, abnormal behaviour) have been reported, the duration of these effects are unknown. Any child exposed in utero (including HIV-negative infants) should be fully investigated for mitochondrial impairment if any relevant signs or symptoms develop.

Cases of osteonecrosis have been reported, especially in patients with long term exposure to combination anti-retroviral therapy and/or advanced HIV-disease. The aetiology is considered multifactorial including; corticosteroid use, higher body mass index (BMI), severe immunosuppression and alcohol consumption. Advise patients to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Use zidovudine with caution during first trimester of pregnancy.

The manufacturer recommends that zidovudine can be used during pregnancy (over 14 weeks gestation) if required to reduce the vertical transmission of HIV from the mother to infant.

Zidovudine has been shown to cross the placenta, and 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 (Briggs, 2015).

Animal studies have shown reproductive toxicity, and that zidovudine may inhibit cellular DNA replication, and was found to be a transplacental carcinogen.

Lactation

Zidovudine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of zidovudine during breastfeeding.

Zidovudine is excreted into breast milk.

In order to avoid transmission of HIV to the infant it is recommended that HIV infected women do not breastfeed their infants under any circumstances.

Side Effects

Abdominal pain
Anaemia
Anorexia
Anxiety
Aplastic anaemia
Asthenia
Autoimmune hepatitis
Bone marrow hypoplasia
Cardiomyopathy
Chest pain
Chills
Convulsions
Cough
Depression
Diarrhoea
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Fever
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatic disorders
Hepatic steatosis
Hepatomegaly
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increases in hepatic enzymes
Influenza-like syndrome
Insomnia
Insulin resistance
Lactic acidosis
Leucopenia
Lipodystrophy
Loss of mental acuity
Malaise
Metabolic disorders
Myalgia
Myopathy
Nausea
Neuropathy
Neutropenia
Osteonecrosis
Pain - generalised
Pancreatitis
Pancytopenia
Paraesthesia
Pigmentation of nails, skin and oral mucosa
Pruritus
Rash
Red cell aplasia
Serum bilirubin increased
Somnolence
Sweating
Taste disturbances
Thrombocytopenia
Urinary frequency
Urticaria
Vomiting

Presentation

Oral formulations of zidovudine.

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals
Prevention of maternal-foetal HIV transmission

Treatment of Human Immunodeficiency Virus (HIV) infection in combination with other anti-retroviral agents.

Preventing maternal-foetal HIV transmission, in HIV positive pregnant women who are over 14 weeks gestation.

Primary prophylaxis of HIV infection in newborn infants.

Dosage

Treatment should be initiated by a specialist experienced in the management of HIV infection.

Adults

Children

Patients with Renal Impairment

Contraindications

Haemoglobin concentration below 7.5g / dL
Neutrophil count below 0.75 x 10 to the power of 9 / L
Breastfeeding
Hepatic impairment - Child-Pugh score greater than 7
Neonatal hyperbilirubinaemia
Neonates with raised transaminases
Porphyria

Precautions and Warnings

Children weighing less than 4kg
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Predisposition to hepatic disorder
Predisposition to hepatic steatosis
First trimester of pregnancy
Haemodialysis
Hepatic impairment
Hepatic steatosis
Hepatitis
Hepatitis C treated with alpha interferon and ribavirin
Hepatomegaly
Hereditary fructose intolerance
Renal impairment - creatinine clearance below 10ml/minute
Vitamin B12 deficiency

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
May contain sodium benzoate: may increase risk of jaundice in neonates
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Monitor blood counts regularly
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor haematological parameters regularly throughout treatment
Monitor patients at risk of hepatic disease
Monitor patients with hepatic impairment
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Discontinue if raised LFTs/hepatomegaly/lactic acidosis occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue or interrupt dose if anaemia, neutropenia or leucopenia occur

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.

In patients with significant anaemia, dosage adjustments do not necessarily eliminate the need for transfusions. For patients with advanced symptomatic HIV disease it is generally recommended that blood tests are performed every two weeks for the first three months of therapy and at least monthly thereafter. For those with early HIV disease (with good bone marrow reserves) or those whose condition is less serious blood monitoring may be carried out less frequently, for example every 1 to 3 months.

Caution should be exercised and close monitoring is advisable when administering nucleoside analogues to at risk patients (particularly obese women) with hepatomegaly, hepatitis, or any known risk factors for hepatic disease and hepatic steatosis. Patients co-infected with hepatitis C being treated with alpha interferon and ribavirin may constitute a special risk.

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.

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 those with a longer treatment duration and associated metabolic disturbances. Clinical examinations should include looking for physical signs of fat redistribution, and lipid disorders should be managed appropriately.

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. Late onset neurological disorders (hypertonia, convulsions, abnormal behaviour) have been reported, the duration of these effects are unknown. Any child exposed in utero (including HIV-negative infants) should be fully investigated for mitochondrial impairment if any relevant signs or symptoms develop.

Cases of osteonecrosis have been reported, especially in patients with long term exposure to combination anti-retroviral therapy and/or advanced HIV-disease. The aetiology is considered multifactorial including; corticosteroid use, higher body mass index (BMI), severe immunosuppression and alcohol consumption. Advise patients to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Use zidovudine with caution during first trimester of pregnancy.

The manufacturer recommends that zidovudine can be used during pregnancy (over 14 weeks gestation) if required to reduce the vertical transmission of HIV from the mother to infant.

Zidovudine has been shown to cross the placenta, and 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 (Briggs, 2015).

Animal studies have shown reproductive toxicity, and that zidovudine may inhibit cellular DNA replication, and was found to be a transplacental carcinogen.

Lactation

Zidovudine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of zidovudine during breastfeeding.

Zidovudine is excreted into breast milk.

In order to avoid transmission of HIV to the infant it is recommended that HIV infected women do not breastfeed their infants under any circumstances.

Side Effects

Abdominal pain
Anaemia
Anorexia
Anxiety
Aplastic anaemia
Asthenia
Autoimmune hepatitis
Bone marrow hypoplasia
Cardiomyopathy
Chest pain
Chills
Convulsions
Cough
Depression
Diarrhoea
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Fever
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatic disorders
Hepatic steatosis
Hepatomegaly
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increases in hepatic enzymes
Influenza-like syndrome
Insomnia
Insulin resistance
Lactic acidosis
Leucopenia
Lipodystrophy
Loss of mental acuity
Malaise
Metabolic disorders
Myalgia
Myopathy
Nausea
Neuropathy
Neutropenia
Osteonecrosis
Pain - generalised
Pancreatitis
Pancytopenia
Paraesthesia
Pigmentation of nails, skin and oral mucosa
Pruritus
Rash
Red cell aplasia
Serum bilirubin increased
Somnolence
Sweating
Taste disturbances
Thrombocytopenia
Urinary frequency
Urticaria
Vomiting

Overdosage

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 ).

Further Information

Last Full Review Date: January 2020

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Retrovir 100mg / 10ml, Oral Solution. ViiV Healthcare UK. Revised December 2018.
Summary of Product Characteristics: Retrovir 250mg Capsules. ViiV Healthcare UK. Revised December 2018.
Summary of Product Characteristics: Retrovir 100mg Capsules. ViiV Healthcare UK. Revised December 2018.

The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.

NAPOS, The Drug Database for Acute Porphyria.
Available at; https://www.drugs-porphyria.org/
Zidovudine Last revised: 14 December 2014
Last accessed: 27 January 2020

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: 31 October 2018
Last accessed: 27 January 2020