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DRUG INTERACTIONS
CORNER Daniel S. Streetman, Section
Advisor
Treatment failure with dapsone/ferrous oxalate–minocycline
interaction?
Key point: Case report of infection relapse in a
patient with HIV taking minocycline and clarithromycin for toxoplasmic
encephalitis (TE) and dapsone/ferrous oxalate
(Disulone—sanofi-aventis) for primary prevention of
Pneumocystitis jirovecii infection suggests an interaction
between minocycline and dapsone/ferrous oxalate.
Finer points: A 38-year-old man with HIV (CD4 count
23/mm3 [2%]; plasma HIV viral load 12,900 copies/mL) and diagnosed with
TE began treatment with pyrimethamine 50 mg per day and sulfadiazone 4 g
per day but developed a fever and rash. TE therapy was discontinued and
the fever and rash resolved. Alternative treatment for TE was provided
with clarithromycin 500 mg twice daily and minocycline 200 mg daily. In
addition, the patient was started on dapsone/ferrous oxalate 50 mg daily
for primary prophylaxis of pneumocystis pneumonia. The patient responded
to the TE therapy as indicated by MRI and clinical response. A month
later, the patient began taking tenofovir (Viread—Gilead),
emtricitabine (Emtriva—Gilead), lopinavir (Kaletra—Abbott),
and ritonavir. About 2 years later, the patient presented with partial
seizures and was diagnosed with relapse of TE. At that time, he was
taking emtricitabine/tenofovir (Truvada—Gilead),
lopinavir/ritonavir (Aluvia—Abbott), clarithromycin, minocycline,
and dapsone/ferrous oxalate. On admission to the hospital, atovaquone
750 mg 4 times daily was started and dapsone/ferrous oxalate was
discontinued because the patient’s CD4 count was greater than
200/mm3. Analysis of frozen plasma samples taken a few days
before admission revealed a therapeutic clarithromycin concentration of
2.2 mg/L (therapeutic range, 1–3 mg/L), but a subtherapeutic
minocycline level of 0.3 mg/L (therapeutic range, 3–4 mg/L). The
patient claimed that he adhered to his medication regimens; medication
adherence was considered good because of the patient’s response to
antiretroviral therapy.
What you need to know: Treatment of TE with
minocycline and clarithromycin is suggested as alternative therapy for
patients who cannot tolerate first-line therapy. Disulone is a
formulation of dapsone available in France that also contains ferrous
oxalate. Iron is likely added to prevent the development of iron
deficiency anemia that may be associated with long-term use of dapsone;
however, concurrent use of iron and minocycline may result in decreased
antimicrobial and iron effectiveness. Decreased absorption of either
product can result from chelation in the gastrointestinal tract. In the
United States, dapsone is available as a generic product and does not
contain iron; no brand formulations of oral dapsone are marketed in the
United States.
What your patients need to know: Explain to patients
taking minocycline and iron products concurrently that this combination
may decrease the effectiveness of both medications. Tell patients to
talk to their prescriber before beginning iron supplementation.
Source: Gallien S et al. Drug-to-drug
interaction between dapsone and minocycline: an unusual cause of relapse
of toxoplasmic encephalitis in an HIV-infected patient. Scand J
Infect Dis. 2009;1–3. Epub ahead of print.
Posted September 30, 2009
Joe Sheffer (jsheffer@aphanet.org)
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