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September 12, 2015

Sovaldi and Olysio

Medication Overview

In December 2013, the U.S. Food and Drug Administration approved two new drugs from a new class of drugs which help fight chronic hepatitis C infection: Olysio (generic name simeprevir, made by Janssen) and Sovaldi (generic name sofosbuvir, made by Gilead). Olysio is called a protease inhibitor, since it blocks a key viral enzyme and prevents the virus from multiplying. Sovaldi is called a polymerase inhibitor; it blocks a different viral enzyme. Both pills appear to help more people clear the virus from their system in a shorter time than did the older drugs for hepatitis C—and for the first time, some patients may be able to take oral medication and not require the weekly shots of interferon that has been the key medication used for Hep C for the past 15 years. Different factors must be considered to decide who can benefit from the new medications and who will not, or who has situations with Hep C that we’re not sure yet how best to treat. The following is a summary of some of the different hepatitis C variations and the current most advised “recipe” for which Sovaldi appears the best choice. The key factors are: what subtype (called genotype, where the viral genes differ and response to treatment differs); what prior treatment was tried, with what result? Is there a cirrhosis condition of the liver?

In late 2014, the FDA approved release of the medication from Gilead Pharmaceuticals called Harvoni, and also approved a combination of two drugs from two different companies, the drug Sovaldi and the drug Olysio. Sovaldi (generic name sofosuvir) is actually one ingredient in Harvoni. This drug, and Olysio (generic name simeprevir), were previously approved for Hepatitis C treatment but were developed to be used with other drugs which were problematic because of their side effects—older drugs ribavirin, and interferon (injections). Based on new research, it was clear that the new medication, Harvoni, or the new combination, Sovaldi + Olysio, get superior cure rates.

Sovaldi Treatment

Genotype 1 and 4

We treat for 12 weeks with 1 tablet Sovaldi daily, 400 mg each, and weekly interferon shots, daily ribavirin pills; Cure rates are 90%. For patients with cirrhosis, or who previously failed other treatments—with exception if boceprivir (Victrelis) or telaprevir (Incivek) didn’t work…then the choices need to be discussed.

Genotype 2

We use Sovaldi and ribavirin pills for 12 weeks, no interferon needed. Cure rate is about 95%.

Genotype 3

We use Sovaldi and ribavirin pills for 24 weeks, no interferon needed. Cure rate is about 85% (a 12 week program gets about 70% cure, so is NOT advised). Better treatments are likely to be available in later 2015 or 2016. The rates of cure are much lower if a genotype 3 patient has cirrhosis and only gets 24 weeks of treatment (about 60% at best); so in this situation we do need “triple therapy” to include interferon, and we treat with Sovaldi for 24 weeks combined with interferon, ribavirin and results are about 85% cure. Patients in stable condition will likely be asked to wait for better treatment late 2015 or 2016.

When treatment stops, because it won’t work:

At the 4th week if we detect 25 IU of hepatitis C in the quantitative RNA test, we stop ALL treatment; same at week 12, and at week 24 for those who need longer treatment.

How to take:

One must take medication once daily with or without food. If you forget a dose in the morning, it can be taken in the evening. It is extremely important to success of the medication, to avoid getting viral mutations, to not miss an entire day.

Side effects:

From the Sovaldi,there a few to no side effects. There is mainly a rash which develops much more easily with SUN EXPOSURE. SO: we advise sunscreen routinely when leaving home, and wearing long sleeves, hat during the period of Olysio treatment. Japanese and perhaps other Asian patients may be more sensitive to such rash. However, interferon and ribavirin can have substantial side effects. These are discussed in separate patient brochure and website, other information from the manufacturers of interferon and ribavirin. Fatigue, flu-like symptoms after the first injections, anemia, headache, loss of appetite, mood changes are quite common with interferon and anemia is common with ribavirin.

Solvadi & Olysio Treatment

If we do treat you, here is the basic info you need to know about Sovaldi + Olysio (S/O)

1. Sovaldi (Gilead Pharma) (genericname sofosuvir (“sof”) is a 400mg pill; Olysio (simeprivir) is a 150mg pill. Both drugs work against the virus directly and the combination prevents your virus developing resistance to the drugs.

2. Treatment is taken in most cases for 12 weeks and it is essential to take every single dose, preferably the same time of the day. Viruses can develop resistance quickly if the drug disappears from the body. The two pills are best taken with the firs meal of the day, important for good absorption to take the Olysio with food.

3. Who gets 12 weeks? Genotype 1 virus. People with other genotypes need to discuss options with us.People who were never treated before, with or without cirrhosis. People who tried but failed prior treatments, with no indication of cirrhosis

4. Who gets 24weeks? People who tried but failed prior treatments, who have indications of cirrhosis. Some patients with cirrhosis even if they’ve never been treated before.

5. Special cases People with severe kidney disease, for example need kidney dialysis. People who have HIV and also have hepatitis C

6. Precautions: Pregnancy: these are category C drugs so are used only if there are strong reasons that we shouldn’t wait till after pregnancy is completed

7. Side effects are very few: The 10% or so of patients in the FDA trials who reported fatigue or headache had minor degrees of these and it isn’t clear the drug caused these, more likely they were just what the patients had anyway. Same with the very low rates reported of nausea, diarrhea or dizziness—these are just symptoms people get commonly for any reason. Olysio will infrequently cause a rash which is much more likely to occur with sun exposure. So we advise limited time in the sun, very good sun screen (30-50 is fine), hat, long sleeves whenever possible, just for the period of treatment.

8. Drug interactions: To get the best blood levels of Sovaldi/Olysio, a. If you need an antacid, keep it 4 or more hours away from the Harvoni b. If you need an acid controller like Pepcid, Zantac take at the same time, or 12 hours away, from Harvoni and don’t use more than 80mg ofPepcid (famotidine) or 300 mg of Zantac (ranitidine) per dayuvastatin) c. If you need omeprazole (Prilosec) type acid blockers (PPI drugs), common in people with GERD/reflux, the advice is take only 20 mg and to take Harvoni and the PPI acid blocker together 30 minutes before first meal of the day. d. If you take the heart medicine digoxin, the blood level of digoxin might increase and it needs to be measured after 7-10 days on Harvoni to see if digoxin dose needs to be reduced. e. If you have to take certain seizure drugs then we shouldn’t use Harvoni, it will often be ineffective (carbamazepine , phenytoin , phenobarbital , oxcarbazepine ) f. Cholesterol drugs: not advised to use Harvoni with Crestor (rosuvastatin), usually the statin can be dropped for 12 or 24 weeks with little harm, or a different low potency statin used instead. g. HIV drugs have special instructions. Sometimes is fine to use with Harvoni, with monitoring for side effects of tenofovir (Viread), sometimes best NOT to use Harvoni.

9.Pregnancy Class C: This means use Sovaldi + Olysio only if there is a good reason to treat during pregnancy instead of waiting. There are no indications this is harmful but we have very limited experience and can’t “prove”safety.

10.Breast feeding: Appears safe although small amounts of the drug likely do get to the baby

Additional Information:

Pregnancy Precautions: the ribavirin is severely toxic to developing fetus, and TWO methods of birth control are required, with monthly pregnancy tests, during the treatment when ribavirin is used. It doesn’t matter which partner is taking treatment. A negative pregnancy test before starting treatment is essential also. Contraception should NOT be hormonal type. Contraception should be maintained for 6 months AFTER ribavirin treatment has finished.

Cost: if the medication is covered by your plan, in combination with a co-pay discount card, out of pocket costs should be limited to $25 or less. The drug cost though is about SEVEN HUNDRED FIFTY DOLLARS A PILL. Patients with Medicare plans may in some cases have very high co-payments for which they cannot use a co-pay discount card. We don’t yet know whether MediCal will cover Sovaldi.

Lab Monitoring: Very critical to keep regular with lab tests; this is weekly for first 4 weeks, then typically monthly if anemia doesn’t become a major issue. We cannot renew medication prescriptions if lab monitoring is not being followed properly.

Drug Interactions: there are a few that we have to be careful about, mainly some drugs for seizure disorders, HIV infection or the drug rifampin. The herbal St Johns wart should not be used and no new prescription or herbal drug started without consulting the physician overseeing your hepatitis C treatment.

Special Situations 1. Chronic kidney disease, dialysis patients. We don’t know yet what doses of Sovaldi is prudent, and ribavirin is not a safe drug without major dose modifications. 2. Sovaldi with ribavirin can be given for patients with hepatocellular cancer awaiting liver transplantation. 3. Sovaldi seems effective in patients who also have HIV. The possibility of drug interactions must be thought through very carefully if treatment for both diseases is carried out. 4. The heart drug amiodarone is a problem for patients who would take Sovaldi; in fact serious very slow heart rate can develop so at present we do NOT give the two drugs together.

Future Treatments Based on a small experimental trial, the combination of Olysio and Sovaldi with no other medication, or with just ribavirin pills without interferon shots, have shown cure rates 93% to 100%, and we have found that this combination is a good choice for some people. MANY other drugs are being tested, in combinations of each other and in combinations with older drugs, to see what the best outcomes are with the least side effects. If treatment presently doesn’t seem right for a particular patient, we may well have new options coming along quite regularly during the next few years. Individuals interested in hepatitis C treatment, or re-treatment, with the new medications should call us to make appointments. The details are complicated and potential side effects, costs and monitoring details need to be fully understood.

Testing for a Cure :We measure the viral levels at 4 weeks to be sure drug is working and again at 12 weeks. In those taking it 24 weeks we measure again at 24 weeks, at end of treatment in either case. IT IS VERY RARE to detect any virus at end of treatment. We check again 12 weeks (3 months) after end of treatment: negative (no virus) means CURE. Ordinarily we don’t need to run virus tests again. Note that the antibody test for hepatitis C, which is how you were first diagnosed, can still be positive longterm and there is no reason to check it.

Cure Rates: 94-99%, the lower number in those with cirrhosis who had failed prior treatment, and got 12 weeks of Harvoni. The cure rate is 98-99% in these people with 24 weeks of treatment.

Follow up after treatment: If hepatitis C didn’t cause cirrhosis by the time it was treated or the amount of scar tissue was not close to that of cirrhosis, just usual health care and usual checkups. However, even after hepatitis C cure, people who had cirrhosis or advanced fibrosis should still see GI or liver specialists periodically and should have liver ultrasound tests, most commonly every 6 months, because there is still a risk of liver cancer (hepatocellular carcinoma) developing in the liver with cirrhosis. Early detection means treatment is available that can either save lives or at least extend lives substantially. Also, people with cirrhosis still have other risks for other complications and should take certain precautions and be seen by specialists periodically even if they seem fine and feel normal.