—Alan Franciscus, Editor-in-Chief
This month’s column, I am going to take a different path: I will
report on the drugs in development and the most common side effects
reported as well as offer some self-help tips to help manage the less
severe ones. In addition, I will report on a new drug combination that
was approved in Japan.
BMS Approval in Japan
On July 7, 2014 the Japanese Ministry of
Health, Labor and Welfare (MHLW) approved Daklinza (daclatasvir—HCV NS5A
inhibitor) and Sunvepra (asunaprevir—HCV protease inhibitor) for the
treatment of chronic hepatitis C genotype 1 for a treatment period of
24 weeks. According to a Bristol-Myers Squibb (BMS) company press
release, of the HCV genotype 1b patients treated 84.7% were cured. The
number of people in Japan with hepatitis C is estimated at 1.2
million, and approximately 70% have HCV genotype 1b. Among patients 65
years of age or older who were either interferon-ineligible or
intolerant, 91.9% were cured. In the patients with compensated
cirrhosis the cure rates were 90.9%. The treatment discontinuation
rate due to adverse events was 5%. The rate of serious adverse events
(SAEs)reported was 5.9%, and the press release stated that “few SAEs
were experienced by more than one patient.”
• Nasopharyngitis: The most
common side effect (30.2%) reported in the study was nasopharyngitis
(upper respiratory system inflammation, infection, the common cold).
Self-help tips: Standard care for the common cold – bed rest, over-the-counter cold remedies, and nasal sprays including saline.
AbbVie / Gilead
The Food and Drug Administration (FDA) is expected to approve
Gilead’s sofosbuvir/ledipasvir by October 10, 2014, and AbbVie’s 3D
combination by December 22, 2014. The new oral combination therapies
have higher cure rates, lower side effects and shorter treatment
durations than some of the current drug regimes. However, all drugs
have side effects and this article will focus on the most frequent side
effects reported in the Phase 3 clinical trials. For this article, I
am going to combine the most frequent side effects reported for both
drugs in the clinical trials. It is important to know, however, that
in clinical trials every symptom is reported whether or not it is
related to the study drug, so you could potentially have a symptom of
hepatitis C during the study period that would be listed as a side
effect of the study drug. Another issue is that many times the
patient population of clinical studies is made up of patients who are
typically ‘the easiest to treat.’ Therefore, many health issues and
side effects may not emerge until the medications are taken by many more
people with the condition who may have a wide range of other health
issues that may affect the tolerability, adherence and side effects of
the newly approved drugs. Another issue is that the side effects
listed in the Phase 3 studies are not rated by severity so some of them
might be mild and others might be severe. However, the number of
people who discontinued treatment due to side effects in both Gilead’s
AbbVie’s Phase 3 clinical trials was less than 1% which would
indicate that the majority of side effects were mild to moderate.
Below are some of the most frequent side effects that occurred and
some common tips for managing them. If you do experience these side
effects or others that become more than annoying they should be
reported to a medical provider before they become worse.
• Fatigue: The most common symptom of hepatitis C
is fatigue and it is also the most common side effect of the new
medications. Fatigue can range from feeling mildly tired to feeling
totally exhausted. It can interfere with almost every area of life
including work, family and social interactions and it can also lead to
anxiety, depression and isolation.
Self-help tips: Be sure to get enough sleep and daily
exercise. Take short naps (no more than 10 to 20 minutes and do not
nap too close to bedtime). Make sure the fatigue is not caused by
something else—talk with your medical provider. Ask for help! Get
organized! Try deep breathing—watch your breathing. Many people who
are tired and stressed hold their breath which can lead to more stress
• Headache: The second most common side effect of the new medications is headache.
Self-help tips: Limit caffeine in coffee, sodas, teas,
chocolate, and tobacco. Avoid loud noises, bright lights and strong
odors. Cold compresses on the head may help. Use over-the-counter pain
aids. If a headache is very painful or persists over time talk to a
• Insomnia: This is a common symptom of hepatitis
C that is also a common side effect of the new all-oral therapies.
Insomnia can lead to fatigue, headaches and a whole host of other
Self-help tips: Stay away from caffeine, as mentioned
above, especially too close to bedtime. Avoid a partner who snores or
makes a lot of noise when they sleep. The room should be dark, and
not too cold or hot. Don’t eat too much food before bed but don’t go
to bed hungry. Establish healthy and regular sleeping habits—going to
bed the same time every night, developing a routine such as reading a
non-stimulating book before bedtime, trying to turn off your mind
before bedtime. If you find that you can’t sleep, get up and do
something boring; then go back to bed. Chronic insomnia can be
effectively treated with medications.
• Nausea: Feeling sick to your stomach is a common symptom of hepatitis C as well as a side effect of the all-oral therapies.
Self-help tips: Eat some dry crackers; avoid
food and odors that act as triggers; stay away from spicy, greasy, and
deep-fried foods. Eat small frequent healthy meals instead of three
large meals a day. Chew food slowly; try over-the counter medications
for nausea; try peppermint, chamomile, or ginger tea to help calm the
stomach; chew or suck on ginger. Acupuncture or acupressure (also
wristbands) may offer relief. The BRATT diet (bananas, rice,
applesauce, toast and tea) is also recommended.
• Asthenia (lack of muscle strength): This can go hand in hand with fatigue and can lead to balance issues and accidents that can be dangerous.
Self-help tip: Be careful when getting up from a
sitting position and when walking. Talk to your medical provider if
this issue becomes worse.
• Diarrhea: Persistent diarrhea can be much more
than annoying—it can lead to and exacerbate many of the symptoms above
and can affect the absorption of medications and nutrients.
Self-help tip: Drink plenty of clear fluids
(water, weak tea or broth); eat popsicles or gelatin, eat small
frequent meals, keep track of bowel moments; eat banana and potatoes
(high in potassium); stay away from high-fiber foods such as
whole-grain breads and cereals, spicy, fried and greasy food, alcohol,
caffeinated drinks and tobacco products. Try the BRATT diet (see
• Rash/ Pruritus (itching): The rash seen in the
all-oral therapies is not as severe as the rashes seen in previous HCV
drug combinations and was only reported in a minority of patients.
Self-help tips: There are many strategies to
combat dry skin and rashes including, and most importantly, drinking
clear fluids; avoid soap—especially scented soaps; apply moisturizer
especially after a shower; avoid hot showers and baths; oatmeal baths
and lotions can sooth the itching. Over-the-counter antihistamines can
relieve the itching.
• Irritability: Persistent irritability can be a sign of or a precursor to depression.
Self-help tip: Try deep breathing, meditation and prayer. If irritability worsens talk to a professional.
• Cough: A cough can simply be from a dry throat or could possibly be a symptom of a cold or lung infection.
Self-help tip: Drink plenty of clear fluids as
listed above; suck on cough drops; If the cough is persistent or if
there is a fever—see a doctor.
Janssen (Olysio) / Gilead (Sovaldi)
Janssen submitted a supplemental new drug application (sNDA) to the
Food and Drug Administration (FDA) in June. On July 15, 2014, Janssen
announced that the FDA designated the sNDA a Priority Review.
The most common side effects of Sovaldi are discussed above. The
most common side effect of Olysio is rash and photosensitivity. Rash
is discussed above. Photosensitivity is discussed below.
• Photosensitivity: basically means that your skin
is allergic to the sun. This is caused by many different drugs or
substances that trigger a person’s immune system to react to the sun.
The symptoms can be a mild rash to itchy red bumps and welts. It can
last for minutes, hours or days. If the rash becomes serious it should
be evaluated by a medical provider. There is no particular
diagnostic test for photosensitivity—diagnosis is usually made by
observing the skin rash. However, a physician may want to get at the
cause and do certain other tests. But since the cause is known to be a
reaction to Olysio it is unlikely that further testing will be done.
Self-help tip: Treatment consists of avoiding the
sun, wearing clothing to prevent exposure to the sun and the use of
corticosteroid ointments to relieve the pain and itching. In severe
cases UV light therapy might offer some relief. After treatment the
condition will resolve.
Source: HCV Advocate Newsletter August 2014