Offers health care providers a new multimodal approach to
adult pain management
LONDON, Feb. 5, 2024
/PRNewswire/ -- Hikma Pharmaceuticals PLC (Hikma), the
multinational pharmaceutical company, announces the launch of
COMBOGESIC® IV (acetaminophen and ibuprofen) injection
in the US.
COMBOGESIC® IV is an intravenous, opioid-free pain
relief medicine that is a combination of 1,000 mg of acetaminophen
and 300 mg of ibuprofen, a nonsteroidal anti-inflammatory drug
(NSAID). It was approved by the US FDA in October 2023 for use in adults where an
intravenous route of administration is considered clinically
necessary for: (i) the relief of mild to moderate pain; and (ii)
the management of moderate to severe pain as an adjunct to opioid
analgesics.1
The American Society of Anesthesiology's (ASA) evidence-based
recommendations emphasize the importance of a multimodal approach
to pain management using multiple interventions with different
mechanisms of action that may offer additive or synergistic effects
to optimize pain relief.2
COMBOGESIC® IV offers health care providers a new,
non-opioid approach to pain management by combining active drug
substances with different mechanisms of action in a single
formulation, providing:
- Shorter onset to analgesia3
- Superior analgesia efficacy and comparable safety in common
adverse events3
- Sustained pain-management results3
In a Phase 3 clinical trial, COMBOGESIC® IV provided
more than double the pain relief than that of acetaminophen IV and
ibuprofen IV alone.3 Time to meaningful pain relief was
shorter in the COMBOGESIC® IV group than that in the
Ibuprofen IV or placebo groups.3 COMBOGESIC®
IV also allows for superior analgesia efficacy.3
"The approval of COMBOGESIC® IV is an important step
in providing hospitals and health care providers in the US with an
alternative treatment option for managing patients' pain," said Dr.
Bill Larkins, President of
Injectables, Hikma. "This is another example of how we continue to
expand our portfolio of critical medicines and we are pleased to
make this important new treatment option available for patients,
helping to put better health within reach, every day."
In 2021, Hikma signed an exclusive license and distribution
agreement with AFT Pharmaceuticals (AFT) for the commercialization
of COMBOGESIC® IV in the US. Under the trade name of
MAXIGESIC® IV outside of the
United States, COMBOGESIC® IV is licensed in over
100 countries and marketed in over 20 countries.
About COMBOGESIC® IV
COMBOGESIC®
IV is the only IV analgesic therapy formulated with 1,000 mg of
acetaminophen and 300 mg of ibuprofen, utilizing the synergistic
effect of both medicines for optimal pain relief.1 It offers health
care providers a new approach to multimodal analgesia by combining
active drug substances with different mechanisms of action that
harness additive or synergistic effects to provide more effective
pain relief compared with individual components used as
single-modality
interventions.1-3 COMBOGESIC® IV is
supplied as a readily available solution with no mixing required
for administration.1 It is administered as a 15-minute
IV infusion, every 6 hours as needed, not to exceed the maximum
total daily dose of 4,000 mg acetaminophen and 1,200 mg of
ibuprofen in 24 hours.1
Enquiries
|
Hikma
Pharmaceuticals PLC
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Susan
Ringdal
|
+44 (0)20 7399 2760/
+44 7776 477050
|
EVP, Strategic Planning
and Global Affairs
|
uk-investors@hikma.uk.com
|
|
|
Steve Weiss
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+1 732 788
8279
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David Belian
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+1 848 254
4875
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US Communications and
Public Affairs
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uscommunications@hikma.com
|
About Hikma
(LSE: HIK) (NASDAQ Dubai: HIK) (OTC: HKMPY) (rated
BBB-/stable S&P and BBB-/positive Fitch)
Hikma helps put better health within reach every day for
millions of people around the world. For more than 40 years, we've
been creating high-quality medicines and making them accessible to
the people who need them. Headquartered in the UK, we are a global
company with a local presence across the North America, the Middle East and North Africa (MENA) and Europe, and we use our unique insight and
expertise to transform cutting-edge science into innovative
solutions that transform people's lives. We're committed to our
customers, and the people they care for, and by thinking creatively
and acting practically, we provide them with a broad range of
branded and non-branded generic medicines. Together, our 8,800
colleagues are helping to shape a healthier world that enriches all
our communities. We are a leading licensing partner, and through
our venture capital arm, are helping bring innovative health
technologies to people around the world. For more information,
please visit: www.hikma.com
This product has been approved for marketing in
the United States by the US FDA.
This product approval does not confer the right on Hikma, or
any other party, to market this product outside the United States.
IMPORTANT SAFETY INFORMATION
WARNING:
HEPATOTOXICITY, CARDIOVASCULAR RISK, and GASTROINTESTINAL
RISK
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RISK OF MEDICATION
ERRORS: Take care when prescribing, preparing, and administering
COMBOGESIC® IV to avoid dosing errors which could result
in accidental overdose and death.
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HEPATOTOXICITY:
COMBOGESIC® IV contains acetaminophen. Acetaminophen has
been associated with cases of acute liver failure, at times
resulting in liver transplant and death. Most of the cases of liver
injury are associated with doses of acetaminophen that exceed 4,000
mg per day, and often involve more than one
acetaminophen-containing product.
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CARDIOVASCULAR RISK:
COMBOGESIC® IV contains ibuprofen, a nonsteroidal
anti-inflammatory drug (NSAID). NSAIDs cause an increased risk of
serious cardiovascular thrombotic events, including myocardial
infarction and stroke, which can be fatal. This risk may occur
early in treatment and may increase with duration of
use.
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•
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COMBOGESIC®
IV is contraindicated for treatment of peri-operative pain in the
setting of coronary artery bypass graft (CABG)
surgery.
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GASTROINTESTINAL RISK:
NSAIDs cause an increased risk of serious gastrointestinal adverse
events including bleeding, ulceration, and perforation of the
stomach or intestines, which can be fatal. These events can occur
at any time during use and without warning symptoms. Elderly
patients are at greater risk.
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CONTRAINDICATIONS
COMBOGESIC® IV is contraindicated in:
- Patients with previous demonstrated hypersensitivity to
acetaminophen, ibuprofen, other NSAIDs or to any of the
excipients/components of this product.
- Patients who have experienced asthma, urticaria, or
allergic-type reactions after taking aspirin or other NSAIDs.
Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been
reported in such patients.
- The treatment of peri-operative pain in the setting of coronary
artery bypass graft (CABG) surgery.
- Patients with severe hepatic impairment or severe active liver
disease.
WARNINGS & PRECAUTIONS
- Risk of Medication Errors. Take care when prescribing,
preparing, and administering COMBOGESIC® IV in order to
avoid dosing errors which could result in accidental overdose and
death. In particular, be careful to ensure that the dose in
milligrams (mg) and milliliters (mL) is not confused, the dosing is
based on weight for patients under 50 kg, infusion pumps are
properly programmed, and the total daily dose of acetaminophen from
all sources does not exceed maximum daily limits.
- Hepatotoxicity. (i) COMBOGESIC® IV
contains acetaminophen which has been associated with cases of
acute liver failure, at times resulting in liver transplant and
death. The risk of acute liver failure is higher in individuals
with underlying liver disease and in individuals who ingest alcohol
while taking acetaminophen. The use of COMBOGESIC® IV in
patients with hepatic impairment is not recommended. (ii)
COMBOGESIC® IV contains ibuprofen. Elevations of ALT or
AST (three or more times the upper limit of normal [ULN]) have been
reported in approximately 1% of NSAID-treated patients in clinical
trials. In addition, rare, sometimes fatal, cases of severe hepatic
injury, including fulminant hepatitis, liver necrosis, and hepatic
failure have been reported. Elevations of ALT or AST (less than
three times ULN) may occur in up to 15% of patients treated with
NSAIDs.
- Cardiovascular Thrombotic Events. Trials suggest that
NSAIDs, taken for up to 3 years, elevate the risk of serious
cardiovascular events like myocardial infarction and stroke. To
minimize these risks, the lowest effective dose for the shortest
duration possible should be used in these patients.
- Gastrointestinal Bleeding, Ulceration, and Perforation.
NSAIDs cause serious gastrointestinal (GI) adverse events including
inflammation, bleeding, ulceration, and perforation of the
esophagus, stomach, small or large intestine, which can be fatal.
These adverse events can occur at any time, with or without warning
symptoms. Avoid use in patients at higher risk. In concomitant use
with low-dose aspirin for cardiac prophylaxis, monitor patients
more closely for evidence of GI bleeding.
- Serious Skin Reactions. Acetaminophen, or NSAIDs may
cause serious skin reactions such as exfoliative dermatitis, acute
generalized exanthematous pustulosis (AGEP), Stevens-Johnson
Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be
fatal. These serious events may occur without warning. Inform
patients about the signs and symptoms and discontinue the use of
the drug at the first appearance of skin rash or any other sign of
hypersensitivity. COMBOGESIC® IV is contraindicated in
patients with previous serious skin reactions to acetaminophen or
NSAIDs.
- Drug Rash with Eosinophilia and Systemic Symptoms
(DRESS). Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS) has been reported in patients taking NSAIDs such as
COMBOGESIC® IV. Some of these events have been fatal or
life-threatening.
- Hypersensitivity and Anaphylactic Reactions. There have
been post marketing reports of hypersensitivity and anaphylaxis,
including life-threatening anaphylaxis associated with the use of
acetaminophen.
- Hypertension. NSAIDs can lead to onset of new
hypertension or worsening of pre-existing hypertension, either of
which may contribute to the increased incidence of CV events.
- Heart Failure and Edema. Studies have demonstrated an
increase in hospitalizations for heart failure in NSAID-treated
patients compared to placebo-treated patients. Additionally, in a
study of patients with heart failure, NSAID use increased the risk
of MI, hospitalization for heart failure, and death. Additionally,
fluid retention and edema have been observed in some patients
treated with NSAIDs. Use of ibuprofen may blunt the CV effects of
several therapeutic agents used to treat these medical
conditions.
- Renal Toxicity and Hyperkalemia. Long-term
administration of NSAIDs has resulted in renal papillary necrosis
and other renal injury. Renal toxicity has also been seen in
patients in whom renal prostaglandins have a compensatory role in
the maintenance of renal perfusion. Increases in serum potassium
concentration, including hyperkalemia, have been reported with use
of NSAIDs, even in some patients without renal impairment. No
information is available regarding the use of
COMBOGESIC® IV in patients with advanced renal
disease.
- Exacerbation of Asthma Related to Aspirin Sensitivity.
Patients with asthma may have aspirin-sensitive asthma which may
include chronic rhinosinusitis complicated by nasal polyps; severe
bronchospasm, which can be fatal and/or intolerance to aspirin and
other NSAIDs. Because cross-reactivity between aspirin and other
NSAIDs has been reported in such aspirin-sensitive patients,
COMBOGESIC® IV is contraindicated in patients with this
form of aspirin sensitivity.
- Fetal Toxicity: Premature Closure of Fetal Ductus
Arteriosus. Avoid use of COMBOGESIC® IV in pregnant
women at about 30 weeks gestation and later. COMBOGESIC®
IV increases the risk of premature closure of the fetal ductus
arteriosus at approximately this gestational age.
- Fetal Toxicity: Oligohydramnios/Neonatal Renal
Impairment. Use of COMBOGESIC® IV at about 20 weeks
gestation or later in pregnancy may cause fetal renal dysfunction
leading to oligohydramnios and, in some cases, neonatal renal
impairment.
- Hematologic Toxicity. Anemia has occurred in
NSAID-treated patients. This may be due to occult or gross GI blood
loss, fluid retention, or an incompletely described effect on
erythropoiesis. NSAIDs included in COMBOGESIC® IV may
increase the risk of bleeding events.
- Masking of Inflammation and Fever. Activity of
COMBOGESIC® IV in reducing inflammation, and possibly
fever, may diminish the utility of diagnostic signs in detecting
infections.
- Ophthalmological Effects. If a patient develops
ophthalmological complaints while receiving COMBOGESIC®
IV, the drug should be discontinued, and the patient should have an
ophthalmologic examination.
- Increased Risk of Hepatotoxicity with Concomitant Use of
Other Acetaminophen-containing Products. COMBOGESIC®
IV should not be used concomitantly with other acetaminophen
containing products.
- Use with Alcohol. COMBOGESIC® IV should not
be used concomitantly with alcoholic beverages.
- Laboratory Monitoring. Consider monitoring patients on
NSAID treatment with a CBC and a chemistry profile as clinically
indicated.
ADVERSE REACTIONS
The most common
TEAEs (occurring in ≥ 3% of COMBOGESIC®
IV -treated participants) were related to the infusion
site (infusion site pain, infusion site extravasation), or
affected the gastrointestinal (nausea, vomiting, constipation) or
nervous (dizziness, headache, somnolence) systems. Other skin and
subcutaneous-related TEAEs (pruritis, hyperhidrosis) also affected
around 2 to 3% of the study population, as did procedural nausea
and polyuria.
DRUG INTERACTIONS
A number of known or potential
interactions between COMBOGESIC® IV and other drugs/drug
classes exist. Please refer to the Drug Interactions in the
Prescribing Information for further information.
- Drugs That Interfere with Hemostasis. Ibuprofen and
anticoagulants such as warfarin have a synergistic effect on
bleeding. The concomitant use of ibuprofen and anticoagulants have
an increased risk of serious bleeding compared to the use of either
drug alone. Concomitant use of drugs that interfere with serotonin
reuptake and an NSAID may potentiate the risk of bleeding more than
an NSAID alone.
- Aspirin. There is no consistent evidence that concurrent
use of aspirin mitigates the increased risk of serious CV
thrombotic events associated with NSAID use. The concurrent use of
aspirin and an NSAID increases the risk of serious gastrointestinal
(GI) events.
- ACE Inhibitors, Angiotensin Receptor Blockers, and
Beta-Blockers. NSAIDs may diminish the antihypertensive effect
of ACE inhibitors, ARBs, or Beta-Blockers.
- Diuretics. NSAIDs can reduce the natriuretic effect of
loop diuretics and thiazides in some patients.
- Lithium. NSAIDs produced an elevation of plasma lithium
levels and a reduction in renal lithium clearance. Monitor patients
for signs of lithium toxicity.
- Methotrexate. Concomitant use of NSAIDs and methotrexate
may increase the risk for methotrexate toxicity (e.g., neutropenia,
thrombocytopenia, renal dysfunction). Monitor patients for
methotrexate toxicity.
USE IN SPECIFIC POPULATIONS
- Females and Males of Reproductive Potential. Use of
acetaminophen may cause reduced fertility in males and females of
reproductive potential. It is not known whether these effects on
fertility are reversible. The use of NSAIDs may delay or prevent
rupture of ovarian follicles. Consider withdrawal of
NSAID-containing products in women who have difficulties conceiving
or who are undergoing investigation of infertility.
- Geriatric Use. Because elderly patients are more likely
to have decreased renal function, care should be taken in dose
selection, and it may be useful to monitor renal function. Elderly
patients (65 years and older) are at greater risk for
NSAID-associated serious cardiovascular, gastrointestinal, and/or
renal adverse reactions. If the anticipated benefit for the elderly
patient outweighs these potential risks, start dosing at the low
end of the dosing range, and monitor patients for adverse
effects.
- Hepatic Impairment. Use of COMBOGESIC® IV in
patients with hepatic impairment is not recommended.
- Renal Impairment. The use of COMBOGESIC® IV
in these patients is not recommended as it may hasten the
progression of renal dysfunction in patients with pre-existing
renal disease.
INDICATIONS AND USAGE
COMBOGESIC® IV is
indicated in adults (over age 18) where an intravenous route of
administration is considered clinically necessary for:
- The relief of mild to moderate pain.
- The management of moderate to severe pain as an adjunct to
opioid analgesics.
LIMITATIONS OF USE
COMBOGESIC® IV is
indicated for short-term use of five days or less.
Patient counseling information should be shared with the patient
prior to administration. For additional information, please refer
to the Package Insert for full Prescribing Information, available
on www.hikma.com.
To report an adverse event or product complaint, please contact
us at us.hikma@primevigilance.com or call 1-877-845-0689 or
1-800-962-8364. Adverse events may also be reported to the FDA
directly at 1-800-FDA-1088 or www.fda.gov/medwatch.
Manufactured by:
S.M. Farmaceutici SRL
Zona Industriale, 85050 Tito (PZ), Italy
Distributed by:
Hikma Pharmaceuticals
USA Inc.
Berkeley Heights, NJ 07922 USA
COMBOGESIC® is a registered trademark of AFT
Pharmaceuticals Limited.
© 2024 Hikma Pharmaceuticals USA
Inc. All rights reserved.
Document identification number: HK-2471-v3
1 COMBOGESIC® IV (acetaminophen 1000 mg and
ibuprofen 300 mg) [package insert].
2 Chou R, Gordon DB, de Leon-Casasola OA, et al.
Management of post operative pain: a clinical practice guideline
from the American pain society, the American society of regional
anesthesia and pain medicine, and the American society of
anesthesiologists' committee on regional anesthesia, executive
committee, and administrative council. J Pain.
2016;17:131-157.
3 Daniels SE, Playne R, Stanescu I, Zhang J,
Gottlieb IJ, Atkinson HC. Efficacy and safety of an intravenous
acetaminophen/ibuprofen fixed-dose combination after bunionectomy:
A randomized, double-blind, factorial, placebo-controlled trial.
Clinical Therapeutics. 2019;41(10).
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SOURCE Hikma Pharmaceuticals USA Inc.