Drugs List

Therapeutic Indications

Uses

HIV infection in adolescents with NRTI resistance: Second line treatment
Sexually acquired HIV infection in high risk patients: PrEP
Treatment of HIV infected adults

Antiretroviral combination therapy for the treatment of HIV-1 infected adults.

HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents.

Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents at high risk, in combination with safer sex practice.

Contraindications

Children under 12 years
Breastfeeding
Galactosaemia
Haemodialysis
Renal impairment - creatinine clearance below 30 ml/minute
Renal impairment - creatinine clearance below 60ml/minute - if HIV PrEP

Precautions and Warnings

Children under 18 years
Elderly
Weight below 35kg
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance 30-80ml/minute
Renal impairment in children under 18 years

Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm HIV negative status before and during pre-exposure prophylaxis
Must be used in combination with other antiretrovirals
Not all available brands are licensed for all age groups
Not all available brands are licensed for all indications
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Evaluate renal function before and during treatment
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor hepatic function in patients with hepatic impairment
Monitor renal function after 2-4 weeks, 3 months and 3-6 monthly thereafter
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
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Interrupt treatment if creatinine clearance below 50 ml/minute
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
Female: Ensure adequate contraception during treatment
Advise patient of importance of full compliance

Emtricitabine and tenofovir disoproxil should be avoided in patients with HIV-1 that is harbouring the K65R mutation.

Patients should have HIV status testing at least every 3 months for pre-exposure prophylaxis.

If HIV infection or HIV exposure is suspected, use of emtricitabine and tenofovir disoproxil for prophylaxis should be delayed for one month and HIV status reconfirmed before continuing prophylaxis treatment.

Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

Pregnancy and Lactation

Pregnancy

Use emtricitabine with tenofovir disoproxil with caution in pregnancy.

The limited amount of data available on the use of emtricitabine with tenofovir disoproxil in pregnancy indicates no foetal/neonatal toxicity associated with the combined therapy. Animal data do not suggest a risk of reproductive toxicity.

Emtricitabine crosses the placenta readily but the limited data show no evidence of teratogenicity in humans or animals. Tenofovir also crosses the placenta easily and Schaefer notes that the risk of foetal toxicity in humans is thought to be low, but there is a potential risk of bone density changes, and suggests that pregnant patients exposed to these drugs should be offered a detailed ultrasound to ascertain normal development of the foetus.

Briggs recommends that in the incidence of pregnancy occurring during therapy for HIV-1, combined antiretroviral therapy should continue, as withdrawal or interruption of therapy may increase the emergence of resistant viral strains. Treatment of the pregnant mother with monotherapy is considered inadequate. Briggs also recommends the use of zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.

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

Emtricitabine with tenofovir disoproxil is contraindicated in breastfeeding.

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Emtricitabine and tenofovir are excreted into breast milk. There is limited data on any impact this may have on the nursing infant.

LactMed indicates that where no other safe feeding replacement is available, the WHO guidelines recommend that all breastfeeding women with a HIV infection should be maintained on antiretroviral therapy at least for the duration of risk for mother-to-child-transmission.

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 pain
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Anaemia
Angioedema
Asthenia
Autoimmune disorders
Autoimmune hepatitis
Blood disorders
Bone pain
Creatine kinase increased
Decrease in bone mineral density
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Flatulence
Fractures
Graves' disease
Headache
Hepatic impairment
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hyperpigmentation of skin
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Maculopapular rash
Metabolic disorders
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Osteomalacia
Osteonecrosis
Pain
Pancreatitis
Proteinuria
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Renal failure
Rhabdomyolysis
Urticaria
Vesiculo-bullous reactions
Vomiting

Presentation

Oral formulations of emtricitabine and tenofovir disoproxil.

Drugs List

Therapeutic Indications

Uses

HIV infection in adolescents with NRTI resistance: Second line treatment
Sexually acquired HIV infection in high risk patients: PrEP
Treatment of HIV infected adults

Antiretroviral combination therapy for the treatment of HIV-1 infected adults.

HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents.

Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents at high risk, in combination with safer sex practice.

Dosage

When one of the active substances needs to be discontinued or when dosage needs to be modified, separate preparations of emtricitabine and tenofovir disoproxil are available. For further information, refer to the individual Summary of Product Characteristics of these medicinal products.

Not all available brands are licensed for all age groups.

Adults

Children

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 12 years
Breastfeeding
Galactosaemia
Haemodialysis
Renal impairment - creatinine clearance below 30 ml/minute
Renal impairment - creatinine clearance below 60ml/minute - if HIV PrEP

Precautions and Warnings

Children under 18 years
Elderly
Weight below 35kg
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance 30-80ml/minute
Renal impairment in children under 18 years

Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm HIV negative status before and during pre-exposure prophylaxis
Must be used in combination with other antiretrovirals
Not all available brands are licensed for all age groups
Not all available brands are licensed for all indications
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Evaluate renal function before and during treatment
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor hepatic function in patients with hepatic impairment
Monitor renal function after 2-4 weeks, 3 months and 3-6 monthly thereafter
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
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Interrupt treatment if creatinine clearance below 50 ml/minute
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
Female: Ensure adequate contraception during treatment
Advise patient of importance of full compliance

Emtricitabine and tenofovir disoproxil should be avoided in patients with HIV-1 that is harbouring the K65R mutation.

Patients should have HIV status testing at least every 3 months for pre-exposure prophylaxis.

If HIV infection or HIV exposure is suspected, use of emtricitabine and tenofovir disoproxil for prophylaxis should be delayed for one month and HIV status reconfirmed before continuing prophylaxis treatment.

Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

Pregnancy and Lactation

Pregnancy

Use emtricitabine with tenofovir disoproxil with caution in pregnancy.

The limited amount of data available on the use of emtricitabine with tenofovir disoproxil in pregnancy indicates no foetal/neonatal toxicity associated with the combined therapy. Animal data do not suggest a risk of reproductive toxicity.

Emtricitabine crosses the placenta readily but the limited data show no evidence of teratogenicity in humans or animals. Tenofovir also crosses the placenta easily and Schaefer notes that the risk of foetal toxicity in humans is thought to be low, but there is a potential risk of bone density changes, and suggests that pregnant patients exposed to these drugs should be offered a detailed ultrasound to ascertain normal development of the foetus.

Briggs recommends that in the incidence of pregnancy occurring during therapy for HIV-1, combined antiretroviral therapy should continue, as withdrawal or interruption of therapy may increase the emergence of resistant viral strains. Treatment of the pregnant mother with monotherapy is considered inadequate. Briggs also recommends the use of zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.

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

Emtricitabine with tenofovir disoproxil is contraindicated in breastfeeding.

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Emtricitabine and tenofovir are excreted into breast milk. There is limited data on any impact this may have on the nursing infant.

LactMed indicates that where no other safe feeding replacement is available, the WHO guidelines recommend that all breastfeeding women with a HIV infection should be maintained on antiretroviral therapy at least for the duration of risk for mother-to-child-transmission.

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 pain
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Anaemia
Angioedema
Asthenia
Autoimmune disorders
Autoimmune hepatitis
Blood disorders
Bone pain
Creatine kinase increased
Decrease in bone mineral density
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Flatulence
Fractures
Graves' disease
Headache
Hepatic impairment
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hyperpigmentation of skin
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Maculopapular rash
Metabolic disorders
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Osteomalacia
Osteonecrosis
Pain
Pancreatitis
Proteinuria
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Renal failure
Rhabdomyolysis
Urticaria
Vesiculo-bullous reactions
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: October 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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: Truvada film-coated tablets. Gilead Sciences Ltd. Revised December 2018.
Summary of Product Characteristics: Ictastan 200mg/245mg film-coated tablets. Accord UK Ltd. Revised June 2018.

MHRA Drug Safety Update 14 December 2015. 'Antiretroviral medicines: updated advice on body-fat changes and lactic acidosis'
Available at: https://www.mhra.gov.uk
Last accessed: 26 October 2016

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 October 2018

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
Emtricitabine Last revised: 31 July 2018
Last accessed: 13 October 2016

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
Tenofovir Last revised: 01 October 2018
Last accessed: 15 October 2018