Merck Receives FDA Approval for ISENTRESS® (raltegravir) for Pediatric Oral Suspension
January 8, 2014 8:30 am ET
Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today that the U.S. Food and Drug Administration (FDA)
recently approved ISENTRESS® for oral suspension, a new
pediatric formulation of Merck’s integrase inhibitor. With this
approval, ISENTRESS is now indicated in combination with other
antiretroviral (ARV) agents for the treatment of HIV-1 infection in
patients four weeks of age and older. The use of other active agents
with ISENTRESS is associated with a greater likelihood of treatment
response. The oral suspension may be used in patients as young as four
weeks of age, weighing at least 3 kg to less than 20 kg. The safety and
efficacy of ISENTRESS have not been established in infants less than
four weeks of age. Formulations of ISENTRESS for specific populations
now include oral suspension, chewable tablets and film-coated tablets.
“We are very pleased that ISENTRESS can now be a part of a treatment
regimen for HIV-1 infected infants and children as young as four weeks
of age,” said Hedy Teppler, executive director, Clinical Research, Merck
Merck anticipates that the oral suspension formulation will be available
in the United States during the third quarter of 2014.
Important Selected Safety Information
ISENTRESS does not cure HIV-1 infection or AIDS.
Severe, potentially life-threatening and fatal skin reactions have been
reported. This includes cases of Stevens-Johnson syndrome,
hypersensitivity reaction and toxic epidermal necrolysis. Immediately
discontinue treatment with ISENTRESS (raltegravir) and other suspect
agents if severe hypersensitivity, severe rash, or rash with systemic
symptoms or liver aminotransferase elevations develop and monitor
clinical status, including liver aminotransferases closely.
Immune reconstitution syndrome can occur, including the occurrence of
autoimmune disorders with variable time to onset, which may necessitate
further evaluation and treatment.
ISENTRESS chewable tablets contain phenylalanine, a component of
aspartame, which may be harmful to patients with phenylketonuria.
Co-administration of ISENTRESS with drugs that are strong inducers of
uridine diphosphate glucuronosyltransferase (UGT1A1) may result in
reduced plasma concentrations of raltegravir. Co-administration of
ISENTRESS and other drugs may alter the plasma concentration of
raltegravir. The potential for drug-drug interactions (DDIs) must be
considered prior to and during therapy. Co-administration or staggered
administration (by 2 hours) of aluminum and/or magnesium
hydroxide-containing antacids and ISENTRESS is not recommended.
Rifampin, a strong inducer of UGT1A1, reduces plasma concentrations of
ISENTRESS. Therefore, the dose of ISENTRESS for adults should be
increased to 800 mg twice daily during coadministration with rifampin.
There are no data to guide co-administration of ISENTRESS with rifampin
in patients below 18 years of age.
The most commonly reported (≥2%) drug-related clinical adverse reactions
of moderate to severe intensity in treatment-naïve adult patients
receiving ISENTRESS compared with efavirenz were insomnia (4% vs 4%),
headache (4% vs 5%), nausea (3% vs 4%), fatigue (2% vs 3%) and dizziness
(2% vs 6%), respectively. In treatment-experienced adult patients
receiving ISENTRESS, the most commonly reported (≥2% in either treatment
group) drug-related clinical adverse reactions of moderate to severe
intensity and at a higher incidence compared with placebo was headache
(2% vs 1%). Intensities were defined as follows: Moderate (discomfort
enough to cause interference with usual activity); or Severe
(incapacitating with inability to work or do usual activity). In
treatment-experienced children and adolescents four weeks through 18
years of age receiving ISENTRESS, the frequency, type and severity of
drug-related adverse reactions were comparable to those observed in
Grade 2 to 4 creatine kinase laboratory abnormalities were observed in
patients treated with ISENTRESS. Myopathy and rhabdomyolysis have been
reported. Use with caution in patients at increased risk of myopathy or
rhabdomyolysis, such as patients receiving concomitant medications known
to cause these conditions and patients with a history of rhabdomyolysis,
myopathy or increased serum creatine kinase.
Rash occurred more commonly in treatment-experienced subjects receiving
regimens containing ISENTRESS (raltegravir) plus darunavir/ritonavir,
compared to subjects receiving ISENTRESS without darunavir/ritonavir or
darunavir/ritonavir without ISENTRESS. However, rash that was considered
drug-related occurred at similar rates for all three groups. These
rashes were mild to moderate in severity and did not limit therapy;
there were no discontinuations due to rash.
ISENTRESS should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. To monitor
maternal-fetal outcomes of pregnant patients exposed to ISENTRESS, an
Antiretroviral Pregnancy Registry has been established. Physicians are
encouraged to register patients by calling 1-800-258-4263.
ISENTRESS is Merck’s integrase inhibitor for the treatment of HIV-1
infection in adult and pediatric patients ages four weeks and older and
weighing at least 3 kg as part of combination HIV therapy. ISENTRESS
works by inhibiting the insertion of HIV-1 DNA into human DNA by the
integrase enzyme and has demonstrated rapid antiviral activity. Inhibiting
integrase from performing this essential function limits the ability of
the virus to replicate and infect new cells. ISENTRESS is now
approved as part of combination therapy in more than 76 countries for
use in treatment-naïve adult patients with HIV-1 and in more than 114
countries for use in treatment-experienced adult patients with HIV-1.
ISENTRESS, in combination therapy, for use in children and adolescents
with HIV-1 ages two years and older has also been approved for use in 35
countries. Merck is continuing to move forward with filings of ISENTRESS
for oral suspension in additional countries around the world.
To assist patients taking ISENTRESS, Merck offers the SUPPORT™ program,
which provides personal support and patient advocacy regarding
individual reimbursement issues. For more information about the SUPPORT™
program, please visit www.merckhelps.com
or call 1-800-850-3430.
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This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
Risks and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
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United States and internationally; global trends toward health care cost
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including obtaining regulatory approval; Merck’s ability to accurately
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Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be
found in Merck’s 2012 Annual Report on Form 10-K and the company’s other
filings with the Securities and Exchange Commission (SEC) available at
the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for ISENTRESS (raltegravir) at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf
and Patient Information for ISENTRESS at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf.
ISENTRESS® is a registered trademark of
Merck & Co., Inc., Whitehouse Station, N.J., USA
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