Raltegravir

Iron (supplements)

A spacing between the drugs is required.

No pharmaceutical opinion available for this interaction.

Mechanism

Iron (supplements) could bind (chelation) to raltegravir and reduce its absorption .

Raltegravir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

Raltegravir 400 mg BID : Administration with iron supplements should be separated by at least 4 hours.

Monitor for clinical efficacy.

Raltegravir HD 1200 mg QD : Association not recommended.

See the case report and the comments.

Alternative solution(s)

Iron (supplements)

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Monitor

Tests

CD4+

Viral load HIV

Raltegravir plasma level

Pharmacokinetic parameters

Comment

We lack information in the literature on the interaction between raltegravir and iron to make clear recommendations. However, we do know that chelation is possible and may lead to a possible decrease in absorption and effectiveness. As a precautionary measure to ensure proper concentration of raltegravir, raltegravir spacing of at least 4 hours with iron should be considered.

Ref #3083 : A case report describes a 39-year-old HIV-1-infected man who experienced virologic failure while receiving a raltegravir-containing antiretroviral regimen with concomitant calcium administration. For drug interaction reasons, the patient was switched from a PI-based regimen to raltegravir/tenofovir/emtricitabine and calcium carbonate (1 g-vitamin D3 400 IU 3 times/day) was added for prevention of osteoporosis. After 10 months of an undetectable viral load and clinical evidence of a high level of adherence on this regimen, the patient developed detectable HIV-1 RNA levels with documented resistance to raltegravir. His antiretroviral therapy was changed back to a protease inhibitor-based regimen, and his HIV-1 RNA level rapidly resuppressed. Therapeutic drug monitoring at the time of virologic failure showed lower than expected raltegravir concentrations at 5 hour post dose, but tenofovir and emtricitabine concentrations were within the expected range. The authors suggest that calcium binding to the divalent metal ion-chelating motif of raltegravir may have led to subtherapeutic raltegravir levels in this patient.

Use of iron supplements with raltegravir HD 1200 mg QD is not recommanded because studies with antacids containing divalent cations have shown a more pronounced reduction in raltegravir Cmin when given with raltegravir HD 1200 mg QD compared to raltegravir 400 mg BID. A similar effect with divalent cations containing supplements cannot be excluded.

Reference
  • 2416
    Raltegravir (Isentress, Isentress HD), Merck, Quebec, Canada, 21 juin 2017.
  • 2857
    Raltegravir (Isentress), European public assessment report (EPAR) Product Information, London, United Kingdom, sept 2013.
  • 3083
    Roberts JL, et al. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacother, 2011, 31(10): 298e-302e.
  • 3443
    Reynolds H, Lewis J, Egan D, Chaponda M, Else L et al. The effect of antacids and multivitamins on raltegravir. CROI 2018, Boston, MA USA, March 4–7, 2018. Abstract #470.