Drugs List

Therapeutic Indications

Uses

Chronic hepatitis B
HIV infection-combined with other antiretrovirals

HIV-1 infection in combination with other antiretroviral agents in adults and children aged 2 years and older.

Chronic hepatitis B in adults with compensated liver disease, with evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis.

Chronic hepatitis B in adults with evidence of lamivudine-resistant hepatitis B virus.

Chronic hepatitis B in adults with decompensated liver disease.

Chronic hepatitis B in children aged 2 years to 18 years with compensated liver disease and evidence of immune active disease including active viral replication and persistently elevated serum ALT levels, or histological evidence of moderate to severe inflammation and/or fibrosis.

Contraindications

Children under 2 years
Breastfeeding
Renal impairment - creatinine clearance below 10ml/minute
Renal impairment in children under 18 years

Precautions and Warnings

Children aged 2 to 18 years
Patients over 65 years
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Monitor HBV levels during and after treatment in patients with co-infection
Reduce dose in patients with creatinine clearance below 50ml/min
Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of Hepatitis B
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
HIV therapy: Must be used in combination with other antiretrovirals
If unknown HIV status,antibody testing should be offered prior to treatment
Not all available products are licensed for all age groups
Not all formulations are suitable for use in children under 12 years
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced with HIV/HBV management
Some formulations contain lactose
Monitor renal function prior to initiating treatment
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Hepatitis B:Monitor liver function for at least 6months after discontinuing
Monitor children exposed in utero for mitochondrial impairment
Monitor patients with renal impairment for toxic effects
Monitor renal function after 2-4 weeks, 3 months and 3-6 monthly thereafter
Monitor renal function in patients with renal impairment
Monitor renal function in patients with risk factors for renal impairment
Monitor serum phosphate levels
On discontinuation, may cause recurrence of hepatitis B
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
May cause weight gain
Risk of developing opportunistic infections
Raised ALTs may be due to HBV clearance
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Interrupt treatment if serum phosphate decreases to below 1 mg/dL
Suspend therapy if renal function deteriorates; reinstitute when normal
Advise patient not to take NSAIDs unless advised by clinician
Take another dose if vomiting occurs within one hour

If serum phosphate levels fall to less than 1.5mg/dl (0.48mmol/l) or creatinine clearance is decreased to less than 50ml/minute, renal function should be re-evaluated within 1 week (including measurements of blood glucose, blood potassium and urine glucose concentrations). If serum phosphate levels decrease to 1.0mg/dl (0.32mmol/l) or creatinine clearance is decreased to less than 50ml/minute an interruption of treatment may be considered necessary. Interrupting treatment should also be considered in case of progressive decline of renal function when no other cause has been identified.

Pregnancy and Lactation

Pregnancy

Use tenofovir disoproxil with caution during pregnancy.

The manufacturer permits the use of tenofovir disoproxil in pregnancy if it is considered clinically necessary, and states that no malformations or foetal/neonatal toxicity was found in human data, and no reproductive toxicity was evidenced in animal studies.

Briggs states that, although animal studies suggest there could be a risk of decreased growth, the risk to the foetus is low.

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 to 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 ).

Lactation

Tenofovir disoproxil is contraindicated during breastfeeding.

Tenofovir disoproxil is known to be excreted in human breast milk, and the risk to the nursing infant is unknown. It is contraindicated by the manufacturer in breastfeeding mothers.

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

Side Effects

Abdominal distension
Abdominal pain
Acute tubular necrosis
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Blood disorders
Decrease in bone mineral density
Diabetes insipidus
Diarrhoea
Dizziness
Fanconi syndrome
Fatigue
Flatulence
Graves' disease
Headache
Hepatic impairment
Hepatic steatosis
Hepatitis
Hyperlactataemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in serum transaminases
Inflammatory reactions
Lactic acidosis
Metabolic disorders
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Opportunistic infections
Osteomalacia
Osteonecrosis
Pancreatitis
Proximal tubulopathy
Rash
Renal failure
Renal impairment
Rhabdomyolysis
Vomiting

Presentation

Oral formulations containing tenofovir disoproxil.

Drugs List

Therapeutic Indications

Uses

Chronic hepatitis B
HIV infection-combined with other antiretrovirals

HIV-1 infection in combination with other antiretroviral agents in adults and children aged 2 years and older.

Chronic hepatitis B in adults with compensated liver disease, with evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis.

Chronic hepatitis B in adults with evidence of lamivudine-resistant hepatitis B virus.

Chronic hepatitis B in adults with decompensated liver disease.

Chronic hepatitis B in children aged 2 years to 18 years with compensated liver disease and evidence of immune active disease including active viral replication and persistently elevated serum ALT levels, or histological evidence of moderate to severe inflammation and/or fibrosis.

Dosage

Adults

Children

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 2 years
Breastfeeding
Renal impairment - creatinine clearance below 10ml/minute
Renal impairment in children under 18 years

Precautions and Warnings

Children aged 2 to 18 years
Patients over 65 years
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Monitor HBV levels during and after treatment in patients with co-infection
Reduce dose in patients with creatinine clearance below 50ml/min
Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of Hepatitis B
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
HIV therapy: Must be used in combination with other antiretrovirals
If unknown HIV status,antibody testing should be offered prior to treatment
Not all available products are licensed for all age groups
Not all formulations are suitable for use in children under 12 years
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced with HIV/HBV management
Some formulations contain lactose
Monitor renal function prior to initiating treatment
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Hepatitis B:Monitor liver function for at least 6months after discontinuing
Monitor children exposed in utero for mitochondrial impairment
Monitor patients with renal impairment for toxic effects
Monitor renal function after 2-4 weeks, 3 months and 3-6 monthly thereafter
Monitor renal function in patients with renal impairment
Monitor renal function in patients with risk factors for renal impairment
Monitor serum phosphate levels
On discontinuation, may cause recurrence of hepatitis B
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
May cause weight gain
Risk of developing opportunistic infections
Raised ALTs may be due to HBV clearance
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Interrupt treatment if serum phosphate decreases to below 1 mg/dL
Suspend therapy if renal function deteriorates; reinstitute when normal
Advise patient not to take NSAIDs unless advised by clinician
Take another dose if vomiting occurs within one hour

If serum phosphate levels fall to less than 1.5mg/dl (0.48mmol/l) or creatinine clearance is decreased to less than 50ml/minute, renal function should be re-evaluated within 1 week (including measurements of blood glucose, blood potassium and urine glucose concentrations). If serum phosphate levels decrease to 1.0mg/dl (0.32mmol/l) or creatinine clearance is decreased to less than 50ml/minute an interruption of treatment may be considered necessary. Interrupting treatment should also be considered in case of progressive decline of renal function when no other cause has been identified.

Pregnancy and Lactation

Pregnancy

Use tenofovir disoproxil with caution during pregnancy.

The manufacturer permits the use of tenofovir disoproxil in pregnancy if it is considered clinically necessary, and states that no malformations or foetal/neonatal toxicity was found in human data, and no reproductive toxicity was evidenced in animal studies.

Briggs states that, although animal studies suggest there could be a risk of decreased growth, the risk to the foetus is low.

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 to 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 ).

Lactation

Tenofovir disoproxil is contraindicated during breastfeeding.

Tenofovir disoproxil is known to be excreted in human breast milk, and the risk to the nursing infant is unknown. It is contraindicated by the manufacturer in breastfeeding mothers.

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

Side Effects

Abdominal distension
Abdominal pain
Acute tubular necrosis
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Blood disorders
Decrease in bone mineral density
Diabetes insipidus
Diarrhoea
Dizziness
Fanconi syndrome
Fatigue
Flatulence
Graves' disease
Headache
Hepatic impairment
Hepatic steatosis
Hepatitis
Hyperlactataemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in serum transaminases
Inflammatory reactions
Lactic acidosis
Metabolic disorders
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Opportunistic infections
Osteomalacia
Osteonecrosis
Pancreatitis
Proximal tubulopathy
Rash
Renal failure
Renal impairment
Rhabdomyolysis
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 2018

Reference Sources

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 January 2018

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: Viread 33 mg/g granules. Gilead Sciences Ltd. Revised April 2019.
Summary of Product Characteristics: Viread 123mg tablets. Gilead Sciences Ltd. Revised April 2019.
Summary of Product Characteristics: Viread 163mg tablets. Gilead Sciences Ltd. Revised April 2019.
Summary of Product Characteristics: Viread 204mg tablets. Gilead Sciences Ltd. Revised April 2019.
Summary of Product Characteristics: Viread 245mg tablets. Gilead Sciences Ltd. Revised April 2019.
Summary of Product Characteristics: Tenofovir disoproxil 245mg tablets. Dr Reddy's Laboratories Ltd. Revised November 2018.
Summary of Product Characteristics: Tenofovir disoproxil 245mg tablets. Accord Healthcare Ltd. Revised January 2017.