The two new drugs are Olysio (simeprevir) capsules and Sovaldi (sofosbuvir) tablets. Both work by stopping the replication of the Hepatitis C virus.

Olysio 150 mg capsules are a once-daily treatment that must be used in combination with pegylated interferon (peginterferon alfas like Pegasys or Pegintron) and ribavirin. It cannot currently be used as monotherapy, which means it can’t be used alone. Sovaldi 400 mg tablets are a once-daily treatment that can be used without the injectable peginterferon alfa. This is novel and helpful in hepatitis therapy because the peginterferon alfa injectable often contributes to patients not finishing their course of Hep C therapy due to the unfavorable side effects.

Based on a side-by-side review if disparate studies, Sovald appears to be more versatile than Olysio as it is approved for treatment of genotypes 1, 2, 3 and 4. Also, for genotype 2 and 3, Sovaldi can be taken with ribavirin alone, excluding the need for interferon altogether. (Interferon, perhaps the most dreaded component of HCV therapy, is administered by injection and many side effects.  On the other hand, Olysio must always be used in combination with interferon and ribavirin for the duration of either 24 weeks (for treatment-naive patients) or 48 weeks (for patients previously exposed to HCV therapy). However ,it cannot be used with many retroviral drugs.

Using the two together is beginning to be explored, with early results showing efficacy in even hard-to-treat cases. In early January, the New England Journal published a study of the combination of these two drugs. he New England Journal of Medicine, investigators designed a Phase II open-label study of Gilead Sciences’ recently approved nucleotide analogue NS5B polymerase inhibitor Sovaldi and Bristol-Myers Squibb’s NS5A replication complex inhibitor daclatasvir.

Sulkowski MS, et al “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection” N Engl J Med 2014; 370: 211-221.

Sovaldi, Prescribing Information 2014

Megace has long been shown to help weight gain in cancer and AIDS. More recently, Megace ES came on the market. The advantage is in the concentrated dose that Megace ES offers. It is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

The recommended adult initial dosage of Megace ES (megestrol acetate) oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). The equivalent Megace dose it 800 mg and requires 20 ml. These drugs are are bioequivalent in a fed state.
However,  in unfed patients Megace ES achieved 5 times greater peak plasma levels than Megace suspension. Additionally, the study demonstrated that a lower volume of Megace ES achieved maximum blood concentration more rapidly than the currently available oral suspension products.

However, the two products were not directly compared in regard to clinical effectiveness and it is not known if this pharmacokinetic advantages translate into any clinical advantage.

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While retrospective studies indicate that long-term steroid use increases the risk of PCP infection it is not known how these patients should be prophylaxed. The threshold for potential infection that warrants prophylaxis with its costs in side effects and expense is unknown, and the critical amount of immunosuppression necessary to increase risk for PCP is also unknown. Prophylaxis has been suggested for patients immunosuppressed owing to an underlying disease or immunosuppressive therapy. In some cancer centers, patients who receive corticosteroid therapy for longer than 4 weeks at a dose equivalent to 20 mg of prednisone per day are routinely are given PCP prophylaxis, as well as those in high-risk groups such as bone marrow transplant recipients and children with ALL.

In 2009, Kovacs and Masur summarized the first 100 years since identification of Pneumocystis. They concluded that in HIV-negative patients there is no reliable laboratory marker for risk of this infection, but that in these patients PCP is more likely to be an acute illness causing severe respiratory distress of rapid onset when compared with HIV-positive patients. That makes routine prophylaxis more reasonable. Their recommended approach is to use PCP prophylaxis in patients receiving at least 20 mg of prednisone per day for at least 1 month. They also note that steroid therapy can accelerate symptomatic and physiologic improvement and improve survival in patients with moderate or severe PCP. Since steroids are in themselves immunosupressive, management of corticosteroids in PCP-infected patients is quite complex.

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