Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Treatment of adults infected with HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors, lamivudine or tenofovir.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Renal impairment - creatinine clearance below 50ml/minute

Precautions and Warnings

Major risk factors for decreased bone mineral content
Patients over 65 years
Decompensated liver disease
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatitis B
Lactose intolerance
Pregnancy
Severe hepatic impairment

Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
Before initiating screen all patients for hepatitis B infection
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Monitor renal function prior to initiating treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Evaluate renal function if signs of proximal renal tubulopathy occur
Hepatitis B:Monitor liver function for at least 6months after discontinuing
Monitor renal function in patients with risk factors for renal impairment
On discontinuation, may cause recurrence of hepatitis B
Advise patient to report bone pain, pain in extremities or fractures
Advise patients to report muscle pain/tenderness/weakness
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
Risk of developing opportunistic infections
Discontinue if creatinine clearance falls below 50 ml/minute
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently

Lamivudine and tenofovir disoproxil and doravirine should be avoided with concurrent or recent use of nephrotoxic medical products e.g. high dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs). Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.

In patients at risk of renal dysfunction, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose and urine protein be assessed prior to initiation and frequently during treatment.

Assessment of bone mineral density should be considered for patients who have a history of pathological bone fracture or other risk factors for osteoporosis or bone loss.

Bone abnormalities may be associated with proximal renal tubulopathy, if bone abnormalities are suspected, appropriate consultation and evaluation should occur.

Pregnancy and Lactation

Pregnancy

Use lamivudine and tenofovir disoproxil and doravirine with caution during pregnancy.

The manufacturer recommends to avoid the use of lamivudine and tenofovir disoproxil and doravirine during pregnancy as a precautionary measure, and to monitor maternal-foetal outcomes in any patients exposed to doravirine during pregnancy. Encouraging physicians to register patients to the Antiretroviral Pregnancy Registry.

Animal studies with doravirine do not indicate direct or indirect harmful effects with respects to reproductive toxicity. Animal studies with tenofovir disoproxil do not indicate direct or indirect harmful effects with respects to reproductive toxicity. However, animal studies with lamivudine show an increase in early embryonic deaths, and may inhibit cellular DNA replication.

Lactation

Lamivudine and tenofovir disoproxil and doravirine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of lamivudine and tenofovir disoproxil and doravirine during breastfeeding, and that mothers should be instructed to not breastfeed due to the potential HIV-1 transmission and potential adverse reactions in the infant.

It is unknown if doravirine is excreted into breast milk. Lamivudine and tenofovir disoproxil are excreted into breast milk. There is limited published information regarding the use of lamivudine and tenofovir disoproxil and doravirine during breastfeeding.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Acute interstitial nephritis
Acute kidney injury
Acute tubular necrosis
Aggression
Alanine aminotransferase increased
Allergic dermatitis
Alopecia
Anaemia
Angioedema
Anxiety
Arthralgia
Aspartate aminotransferase increased
Asthenia
Attention disturbances
Changes in mood
Chest pain
Chills
Confusion (transient)
Constipation
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Fatigue
Fever
Flatulence
Gastrointestinal disorder
Haemoglobin decrease
Hallucinations
Headache
Hepatic steatosis
Hepatitis
Hypertension
Hypertonia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Impaired memory
Impaired renal tubular function
Insomnia
Irritability
Lactic acidosis
Malaise
Muscle disorders
Muscle weakness
Musculoskeletal pain
Myalgia
Myopathy
Nasal symptoms
Nausea
Nephritis
Nephrogenic diabetes insipidus
Nephrolithiasis
Neutropenia
Nightmares
Osteomalacia
Pain
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Pustular rash
Rash
Rectal tenesmus
Red cell aplasia
Renal calculus
Renal disorders
Renal failure
Rhabdomyolysis
Rosacea
Sleep disturbances
Sleep walking
Soft faeces
Somnolence
Suicidal tendencies
Thirst
Thrombocytopenia
Tonsillar hypertrophy
Vomiting

Presentation

Oral formulation of lamivudine and tenofovir disoproxil and doravirine.

Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Treatment of adults infected with HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors, lamivudine or tenofovir.

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Renal impairment - creatinine clearance below 50ml/minute

Precautions and Warnings

Major risk factors for decreased bone mineral content
Patients over 65 years
Decompensated liver disease
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatitis B
Lactose intolerance
Pregnancy
Severe hepatic impairment

Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
Before initiating screen all patients for hepatitis B infection
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Monitor renal function prior to initiating treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Evaluate renal function if signs of proximal renal tubulopathy occur
Hepatitis B:Monitor liver function for at least 6months after discontinuing
Monitor renal function in patients with risk factors for renal impairment
On discontinuation, may cause recurrence of hepatitis B
Advise patient to report bone pain, pain in extremities or fractures
Advise patients to report muscle pain/tenderness/weakness
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
Risk of developing opportunistic infections
Discontinue if creatinine clearance falls below 50 ml/minute
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently

Lamivudine and tenofovir disoproxil and doravirine should be avoided with concurrent or recent use of nephrotoxic medical products e.g. high dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs). Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.

In patients at risk of renal dysfunction, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose and urine protein be assessed prior to initiation and frequently during treatment.

Assessment of bone mineral density should be considered for patients who have a history of pathological bone fracture or other risk factors for osteoporosis or bone loss.

Bone abnormalities may be associated with proximal renal tubulopathy, if bone abnormalities are suspected, appropriate consultation and evaluation should occur.

Pregnancy and Lactation

Pregnancy

Use lamivudine and tenofovir disoproxil and doravirine with caution during pregnancy.

The manufacturer recommends to avoid the use of lamivudine and tenofovir disoproxil and doravirine during pregnancy as a precautionary measure, and to monitor maternal-foetal outcomes in any patients exposed to doravirine during pregnancy. Encouraging physicians to register patients to the Antiretroviral Pregnancy Registry.

Animal studies with doravirine do not indicate direct or indirect harmful effects with respects to reproductive toxicity. Animal studies with tenofovir disoproxil do not indicate direct or indirect harmful effects with respects to reproductive toxicity. However, animal studies with lamivudine show an increase in early embryonic deaths, and may inhibit cellular DNA replication.

Lactation

Lamivudine and tenofovir disoproxil and doravirine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of lamivudine and tenofovir disoproxil and doravirine during breastfeeding, and that mothers should be instructed to not breastfeed due to the potential HIV-1 transmission and potential adverse reactions in the infant.

It is unknown if doravirine is excreted into breast milk. Lamivudine and tenofovir disoproxil are excreted into breast milk. There is limited published information regarding the use of lamivudine and tenofovir disoproxil and doravirine during breastfeeding.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Acute interstitial nephritis
Acute kidney injury
Acute tubular necrosis
Aggression
Alanine aminotransferase increased
Allergic dermatitis
Alopecia
Anaemia
Angioedema
Anxiety
Arthralgia
Aspartate aminotransferase increased
Asthenia
Attention disturbances
Changes in mood
Chest pain
Chills
Confusion (transient)
Constipation
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Fatigue
Fever
Flatulence
Gastrointestinal disorder
Haemoglobin decrease
Hallucinations
Headache
Hepatic steatosis
Hepatitis
Hypertension
Hypertonia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Impaired memory
Impaired renal tubular function
Insomnia
Irritability
Lactic acidosis
Malaise
Muscle disorders
Muscle weakness
Musculoskeletal pain
Myalgia
Myopathy
Nasal symptoms
Nausea
Nephritis
Nephrogenic diabetes insipidus
Nephrolithiasis
Neutropenia
Nightmares
Osteomalacia
Pain
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Pustular rash
Rash
Rectal tenesmus
Red cell aplasia
Renal calculus
Renal disorders
Renal failure
Rhabdomyolysis
Rosacea
Sleep disturbances
Sleep walking
Soft faeces
Somnolence
Suicidal tendencies
Thirst
Thrombocytopenia
Tonsillar hypertrophy
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: April 2019

Reference Sources

Summary of Product Characteristics: Delstrigo 100mg/300mg/245mg film-coated tablets. Merck Sharp & Dohme Limited. Revised June 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
Doravirine Last revised: 03 December 2018
Last accessed: 04 April 2019

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
Lamivudine Last revised: 31 October 2018
Last accessed: 04 April 2019

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: 07 February 2019
Last accessed: 04 April 2019