Drugs List

Therapeutic Indications

Uses

HIV infection - combination therapy

Contraindications

Children under 12 years
Children with body weight under 40kg
Breastfeeding
First trimester of pregnancy
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Females of childbearing potential
Depression
Hepatic impairment
Hepatitis B
Hepatitis C
Psychiatric disorder
Second trimester of pregnancy
Third trimester of pregnancy

Treatment does not prevent risk of transmission of HIV
Treatment should be initiated by doctor experienced in HIV management
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Blood lipid and glucose levels may increase requiring treatment
Monitor children exposed in utero for mitochondrial impairment
Monitor for signs of osteonecrosis
Monitor levels of hepatic enzymes and bilirubin
On discontinuation, may cause recurrence of hepatitis B
Autoimmune diseases may occur during treatment
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Advise patient not to take St John's wort concurrently
Avoid antacids/mineral supplements 2 hrs after or 6 hrs before dose
Advise patients that hypersensitivity reactions may be life threatening

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

Dolutegravir and lamivudine is contraindicated during the first trimester of pregnancy. Use dolutegravir and lamivudine with caution during the second and third trimester of pregnancy.

The manufacturer does not recommend the use of dolutegravir and lamivudine during the first trimester of pregnancy due to the potential risk of neural tube defects to the infant. The manufacturer also recommends that dolutegravir and lamivudine should be used in the second and third trimester of pregnancy only if the potential benefits justifies the potential risk to the foetus.

At the time of writing there are limited data on the use of dolutegravir in pregnant women. The effect of dolutegravir on human pregnancy is unknown. Reproductive toxicity studies in animals have shown dolutegravir to cross the placenta. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

The MHRA states that due to results from an observational study there is evidence of an increased risk of neural tube defects in babies born to mothers who became pregnant while taking dolutegravir. They advise that dolutegravir should not be prescribed to women seeking to become pregnant and that pregnancy should be excluded in women of child bearing potential before starting dolutegravir. Women of childbearing potential are advised to use effective contraception throughout treatment with dolutegravir.

Animal studies indicate that lamivudine may inhibit cellular DNA replication.

Lactation

Dolutegravir and lamivudine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of dolutegravir and lamivudine during breastfeeding to avoid the potential risk of HIV transmission to the infant.

In order to avoid HIV transmission, it is recommend that infants are not breastfed by HIV infected women. It is not known if dolutegravir is excreted into human milk. Lamivudine is excreted into breast milk, the low levels ingested by the infant are likely to result in sub-optimal antiviral effect. At the time of writing there are no evidence that the low concentrations in human milk leads to adverse reactions in the breastfed infant.

Side Effects

Abdominal discomfort
Abdominal pain
Alopecia
Anaemia
Anxiety
Arthralgia
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Elevated amylase levels
Fatigue
Flatulence
Headache
Hepatitis
Hypersensitivity reactions
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Muscle disorders
Myalgia
Nausea
Neutropenia
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Rash
Red cell aplasia
Rhabdomyolysis
Somnolence
Thrombocytopenia
Vomiting

Presentation

Oral formulations containing dolutegravir and lamivudine.

Drugs List

Therapeutic Indications

Uses

HIV infection - combination therapy

Dosage

This fixed dose presentation should not be used in patients that require dose adjustments due to drug to drug interactions. The individual preparations of dolutegravir is available in cases where discontinuation or dose adjustment is needed. For further information, refer to the individual monograph of each preparation.

Adults

Children

Additional Dosage Information

Contraindications

Children under 12 years
Children with body weight under 40kg
Breastfeeding
First trimester of pregnancy
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Females of childbearing potential
Depression
Hepatic impairment
Hepatitis B
Hepatitis C
Psychiatric disorder
Second trimester of pregnancy
Third trimester of pregnancy

Treatment does not prevent risk of transmission of HIV
Treatment should be initiated by doctor experienced in HIV management
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Blood lipid and glucose levels may increase requiring treatment
Monitor children exposed in utero for mitochondrial impairment
Monitor for signs of osteonecrosis
Monitor levels of hepatic enzymes and bilirubin
On discontinuation, may cause recurrence of hepatitis B
Autoimmune diseases may occur during treatment
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Advise patient not to take St John's wort concurrently
Avoid antacids/mineral supplements 2 hrs after or 6 hrs before dose
Advise patients that hypersensitivity reactions may be life threatening

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

Dolutegravir and lamivudine is contraindicated during the first trimester of pregnancy. Use dolutegravir and lamivudine with caution during the second and third trimester of pregnancy.

The manufacturer does not recommend the use of dolutegravir and lamivudine during the first trimester of pregnancy due to the potential risk of neural tube defects to the infant. The manufacturer also recommends that dolutegravir and lamivudine should be used in the second and third trimester of pregnancy only if the potential benefits justifies the potential risk to the foetus.

At the time of writing there are limited data on the use of dolutegravir in pregnant women. The effect of dolutegravir on human pregnancy is unknown. Reproductive toxicity studies in animals have shown dolutegravir to cross the placenta. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

The MHRA states that due to results from an observational study there is evidence of an increased risk of neural tube defects in babies born to mothers who became pregnant while taking dolutegravir. They advise that dolutegravir should not be prescribed to women seeking to become pregnant and that pregnancy should be excluded in women of child bearing potential before starting dolutegravir. Women of childbearing potential are advised to use effective contraception throughout treatment with dolutegravir.

Animal studies indicate that lamivudine may inhibit cellular DNA replication.

Lactation

Dolutegravir and lamivudine is contraindicated during breastfeeding.

The manufacturer does not recommend the use of dolutegravir and lamivudine during breastfeeding to avoid the potential risk of HIV transmission to the infant.

In order to avoid HIV transmission, it is recommend that infants are not breastfed by HIV infected women. It is not known if dolutegravir is excreted into human milk. Lamivudine is excreted into breast milk, the low levels ingested by the infant are likely to result in sub-optimal antiviral effect. At the time of writing there are no evidence that the low concentrations in human milk leads to adverse reactions in the breastfed infant.

Side Effects

Abdominal discomfort
Abdominal pain
Alopecia
Anaemia
Anxiety
Arthralgia
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Elevated amylase levels
Fatigue
Flatulence
Headache
Hepatitis
Hypersensitivity reactions
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Muscle disorders
Myalgia
Nausea
Neutropenia
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Rash
Red cell aplasia
Rhabdomyolysis
Somnolence
Thrombocytopenia
Vomiting

Further Information

Last full review date: September 2019.

Reference Sources

MHRA Drug Safety Update December 2015 - Volume 9, Issue 5A
Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/485099/Drug_Safety_Update_Dec_2015.pdf
Last Accessed: 09 August 2019

Summary of Product Characteristics: Dovato 50mg/300mg film-coated tablets. ViiV Healthcare UK Ltd. Revised July 2019.