Drugs List

Therapeutic Indications

Uses

Antiretroviral combination therapy-HIV infected adults and children over 12

Contraindications

Children under 12 years
Children weighing less than 35kg
Breastfeeding
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 70ml/min

Precautions and Warnings

Children under 18 years
Patients over 65 years
Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Renal impairment - creatinine clearance 70-90ml/minute
Severe hepatic impairment

Switch to more suitable alternative before planned pregnancy
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
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 renal function every 4 weeks during first year, then every 3 months
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
Neonate exposed in utero: Risk of mitochondrial dysfunction
Advise patient to seek advice at first indications of pregnancy
Discontinue if creatinine clearance falls below 50 ml/minute
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
Advise patient not to take St John's wort concurrently
Avoid antacids within 4 hours of dose
Female: Non-hormonal contraception or minimum 30mcg oestrogen advised
Take another dose if vomiting occurs within one hour

Female patients of childbearing potential should use either a hormonal contraceptive containing at least 30 micrograms ethinylestradiol and containing norgestimate as the progestogen or should use an alternative reliable method of contraception.

Creatinine clearance should be calculated and urine glucose and urine protein should be determined in all patients before initiating treatment, then every 4 weeks during the first year of therapy and then every 3 months thereafter.

Avoid use with concurrent or recent use of nephrotoxic drugs (e.g. cidofovir, aminoglycosides, foscarnet, vancomycin, ganciclovir, etc) and/or NSAIDs. If concomitant use is unavoidable, renal function should be monitored weekly.

Discontinuation of therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis. Patients co-infected with HIV and HBV who discontinue therapy should be closely monitored with both clinical and laboratory follow up for at least several months after stopping treatment. If appropriate, initiation of hepatitis B therapy may be warranted. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.

Patients who experience a confirmed increase in serum creatinine of greater than 26.5 micromoles/l (0.3mg/dl) from baseline should be closely monitored for renal safety.

If serum phosphate is less than 0.48mmol/l (1.5mg/dl) or creatinine clearance is decreased to less than 70ml/minute, renal function should be re-evaluated within one week, including measurements of blood glucose, blood potassium and urine glucose concentrations. The manufacturer suggests to discontinue therapy in these patients unless potential benefit of therapy outweighs the possible risks of continuing.

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

Elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets are contraindicated during pregnancy.

The manufacturer does not recommend elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil treatment to be initiated during pregnancy and women who become pregnant during therapy with this product should be switched to an alternative regimen.

Treatment with cobicistat and elvitegravir during second and third trimester of pregnancy has shown to substantially lower elvitegravir exposure, which may result in virological failure and increase the risk of transmission of HIV from the mother to infant.

Animal studies do not indicate direct or indirect harmful effects of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil with respect to pregnancy, foetal development, parturition or postnatal development.

Lactation

Elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets are contraindicated in breastfeeding.

HIV is known to be transmitted in milk. HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease.

It is not known if elvitegravir or cobicistat are excreted in human milk. Emtricitabine and tenofovir have been shown to be excreted in human milk. Animal studies have shown that elvitegravir, cobicistat and tenofovir are excreted in milk.

At the time of writing there is limited published information regarding the use of elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets during breastfeeding.

Side Effects

Abdominal distension
Abdominal pain
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Constipation
Creatine kinase increased
Decreased appetite
Depression
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Fatigue
Flatulence
Graves' disease
Headache
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hyperglycaemia
Hyperlactataemia
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase of liver transaminases
Inflammatory reactions
Insomnia
Lactic acidosis
Maculopapular rash
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Osteomalacia
Osteonecrosis
Pain
Pancreatitis
Proteinuria
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Renal failure
Rhabdomyolysis
Serum creatinine increased
Skin discolouration
Suicidal tendencies
Urticaria
Vomiting

Presentation

Oral formulations of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil.

Drugs List

Therapeutic Indications

Uses

Antiretroviral combination therapy-HIV infected adults and children over 12

Dosage

Adults

Children

Patients with Renal Impairment

Contraindications

Children under 12 years
Children weighing less than 35kg
Breastfeeding
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance below 70ml/min

Precautions and Warnings

Children under 18 years
Patients over 65 years
Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Renal impairment - creatinine clearance 70-90ml/minute
Severe hepatic impairment

Switch to more suitable alternative before planned pregnancy
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
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 renal function every 4 weeks during first year, then every 3 months
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
Neonate exposed in utero: Risk of mitochondrial dysfunction
Advise patient to seek advice at first indications of pregnancy
Discontinue if creatinine clearance falls below 50 ml/minute
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
Advise patient not to take St John's wort concurrently
Avoid antacids within 4 hours of dose
Female: Non-hormonal contraception or minimum 30mcg oestrogen advised
Take another dose if vomiting occurs within one hour

Female patients of childbearing potential should use either a hormonal contraceptive containing at least 30 micrograms ethinylestradiol and containing norgestimate as the progestogen or should use an alternative reliable method of contraception.

Creatinine clearance should be calculated and urine glucose and urine protein should be determined in all patients before initiating treatment, then every 4 weeks during the first year of therapy and then every 3 months thereafter.

Avoid use with concurrent or recent use of nephrotoxic drugs (e.g. cidofovir, aminoglycosides, foscarnet, vancomycin, ganciclovir, etc) and/or NSAIDs. If concomitant use is unavoidable, renal function should be monitored weekly.

Discontinuation of therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis. Patients co-infected with HIV and HBV who discontinue therapy should be closely monitored with both clinical and laboratory follow up for at least several months after stopping treatment. If appropriate, initiation of hepatitis B therapy may be warranted. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.

Patients who experience a confirmed increase in serum creatinine of greater than 26.5 micromoles/l (0.3mg/dl) from baseline should be closely monitored for renal safety.

If serum phosphate is less than 0.48mmol/l (1.5mg/dl) or creatinine clearance is decreased to less than 70ml/minute, renal function should be re-evaluated within one week, including measurements of blood glucose, blood potassium and urine glucose concentrations. The manufacturer suggests to discontinue therapy in these patients unless potential benefit of therapy outweighs the possible risks of continuing.

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

Elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets are contraindicated during pregnancy.

The manufacturer does not recommend elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil treatment to be initiated during pregnancy and women who become pregnant during therapy with this product should be switched to an alternative regimen.

Treatment with cobicistat and elvitegravir during second and third trimester of pregnancy has shown to substantially lower elvitegravir exposure, which may result in virological failure and increase the risk of transmission of HIV from the mother to infant.

Animal studies do not indicate direct or indirect harmful effects of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil with respect to pregnancy, foetal development, parturition or postnatal development.

Lactation

Elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets are contraindicated in breastfeeding.

HIV is known to be transmitted in milk. HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease.

It is not known if elvitegravir or cobicistat are excreted in human milk. Emtricitabine and tenofovir have been shown to be excreted in human milk. Animal studies have shown that elvitegravir, cobicistat and tenofovir are excreted in milk.

At the time of writing there is limited published information regarding the use of elvitegravir with cobicistat, emtricitabine and tenofovir disoproxil tablets during breastfeeding.

Counselling

Advise patients if a dose is missed within 18 hours of the time it is usually taken, the patient should take the missed dose with food as soon as possible and resume the normal dosing schedule. If the dose is missed by more than 18 hours and it is almost time for the next dose, the patient should not take the missed dose and resume the usual dosing schedule.

Advise patients if they vomit within 1 hour of taking a dose, another dose should be taken.

Advise patient not to take NSAIDs unless advised by clinician.

Advise patient to seek advice at first indications of pregnancy.

Side Effects

Abdominal distension
Abdominal pain
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Constipation
Creatine kinase increased
Decreased appetite
Depression
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Fanconi syndrome
Fatigue
Flatulence
Graves' disease
Headache
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hyperglycaemia
Hyperlactataemia
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase of liver transaminases
Inflammatory reactions
Insomnia
Lactic acidosis
Maculopapular rash
Muscle weakness
Myopathy
Nausea
Nephritis
Neutropenia
Osteomalacia
Osteonecrosis
Pain
Pancreatitis
Proteinuria
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Renal failure
Rhabdomyolysis
Serum creatinine increased
Skin discolouration
Suicidal tendencies
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 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.

Summary of Product Characteristics: Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets. Gilead Sciences Ltd. Revised April 2019

MHRA Drug Safety Update April 2019
Available at: https://www.mhra.gov.uk
Last accessed: 22 May 2019

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 July 2018