Tenofovir disoproxil (as the fumarate)

Generic name
Tenofovir disoproxil (as the fumarate)
Brand name
ATC Code
J05AF07
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Tenofovir disoproxil (as the fumarate)

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

 

  2-12 years (n=23)
6.5 mg/kg		 12-18 years (n=8)
245 mg 
Cmax (μg/ml) 0.24 ± 0.13 0.38 ± 0.13
AUCtau (μg·h/ml) 2.59 ± 1.06 3.39 ± 1.22

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Chronic hepatitis B
  • Oral
    • 2 years up to 12 years
      • 6.5 mg/kg/day in 1 dose. Max: 245 mg/day.
      • Duration of treatment:

        Length of treatment in HBeAg-positive patients: continue at least up to 12 months after HBeAg seroconversion or until HBsAg seroconversion has occurred or until signs of loss of effectiveness;

        Length of treatment in HBeAg-negative patients: continue at least until HBsAg seroconversion or until signs of loss of effectiveness.

    • 12 years up to 18 years and ≥ 35 kg
      • 245 mg/day in 1 dose
      • Duration of treatment:

        Length of treatment in HBeAg-positive patients: continue at least up to 12 months after HBeAg seroconversion or until HBsAg seroconversion has occurred or until signs of loss of effectiveness;

        Length of treatment in HBeAg-negative patients: continue at least until HBsAg seroconversion or until signs of loss of effectiveness.

    • 2 years up to 12 years
      [1]
      • 6.5 mg/kg/day in 1 dose. Max: 245 mg/day.
      • Duration of treatment:

        Length of treatment in HBeAg-positive patients: continue at least up to 12 months after HBeAg seroconversion or until HBsAg seroconversion has occurred or until signs of loss of effectiveness;

        Length of treatment in HBeAg-negative patients: continue at least until HBsAg seroconversion or until signs of loss of effectiveness.
Treatment HIV infection
  • Oral
    • ≥ 12 years and ≥ 35 kg
      • 245 mg/day in 1 dose

Renal impaiment in children > 3 months

Use of the granules is preferred over use of the tablet. Interval prolongation does not give optimal results and may lead to increased toxicity and possibly an inadequate response.

Granulate 33 mg/g, under control of tenofovir level:

  • GFR ≥50: dose adjustment not required.
  • GFR 30-50: 50% of normal reversal dose, interval between 2 doses: 24 hours.
  • GFR 20-30: 25% of normal reversal dose, interval between 2 doses: 24 hours.
  • GFR 10-20: 10% of normal reversal dose, interval between 2 doses: 24 hours.
  • GFR <10: general advice is not given.
Clinical consequences

With impaired renal function, the AUC of tenofovir increases. This increases the risk of adverse reactions.

Clinical effects:
Risk of toxicity increases. Adjustment of dosage affects trough level. If the trough level is not sufficiently high, antiviral activity may not be sufficient; this may result in resistance.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Decreases in bone mineral density have been reported in children; in addition, proximal tubulopathy is more common in children.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Renal function: Do not initiate treatment in children with renal impairment; discontinue treatment if renal impairment develops in children. If serum phosphate levels in children fall to < 0.96 mmol/l within one week reassess renal function including glucose and potassium levels in blood and glucose in urine (in view of proximal tubulopathy). If renal or bone abnormalities exist/appear, consult a paediatric nephrologist about interrupting treatment. In children, always discontinue treatment with the development of renal impairment. In children, there is uncertainty regarding the long-term effects of renal toxicity; reversibility has not yet been adequately established.

Effect on bone: In children, there is still uncertainty about the long-term effects of changes in bone mineral density (BMD) on long-term bone health, and the risk of fractures in the future. Bone abnormalities, such as osteomalacia, which may manifest as persistent or progressive bone pain, and in rare cases may well contribute to the development of fractures, may be related to tenofovir disoproxil-induced proximal renal tubulopathy.

In chronic hepatitis B

Balance the decision to treat a child based on the needs of the individual patient and on the value of the histologic information available before initiation. In children with compensated liver disease, the serum ALT should be persistently elevated for at least 6 months (in HBeAg-positive disease) or 12 months (in HBeAg-negative disease) prior to treatment. The long-term benefits of virologic suppression with continued treatment should be weighed against the risks of long-term treatment, including the potential for emergence of resistant hepatitis B virus and the long-term uncertainties regarding renal and bone toxicity. Consult clinically relevant guidelines in this area as necessary.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

DIRECT ACTING ANTIVIRALS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Nucleosides and nucleotides excl. reverse transcriptase inhibitors
J05AB01
J05AB12
J05AB06
J05AB16
J05AB04
J05AB11
J05AB14
Phosphonic acid derivatives
J05AD01
Protease inhibitors
J05AE08
J05AE10
J05AE07
J05AE02
J05AE04
J05AE03
J05AE01
Nucleoside and nucleotide reverse transcriptase inhibitors
J05AF06
J05AF02
J05AF09
J05AF10
J05AF05
J05AF04
J05AF13
J05AF13
J05AF01
Non-nucleoside reverse transcriptase inhibitors
J05AG06
J05AG03
J05AG04
J05AG01
J05AG05
Neuraminidase inhibitors
J05AH02
J05AH01
Antivirals for treatment of HIV infections, combinations
J05AR02
J05AR20
J05AR13
J05AR25
J05AR18
J05AR19
J05AR03
J05AR09
J05AR10
Other antivirals
J05AX28
J05AX12
J05AX07
J05AX09
J05AX08
J05AX24
ANTIVIRALS FOR TREATMENT OF HIV INFECTIONS, COMBINATIONS
J05AR02
J05AR20
J05AR13
J05AR25
J05AR18
J05AR19
J05AR03
J05AR09
J05AR10
Integrase inhibitors
J05AJ04
Antivirals for treatment of HCV infections
J05AP54
J05AP57
J05AP51
J05AP08
J05AP55

References

  1. Gilead Sciences International Limited, SmPC Viread (EU/1/01/200/003) Rev56; 12-05-2021, www.geneesmiddeleninformatiebank.nl
  2. Bamford, A., et al (PENTA Steering Committee) (2015), Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life., HIV Med., doi:10.1111
  3. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children., Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection., https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/overview-0?view=full, April 11, 2022
  4. NKFK Workinggroup Acute Kidney Impairment, Extrapolation of KNMP risk analysis "Impaired renal function" for adults to children, 20 Dec 2021

Changes

Therapeutic Drug Monitoring


Overdose