1. For relief of inflammation and pain in the following disorders and symptoms:
Rheumatoid arthritis, osteoarthritis, lower back pain, periarthritis of the shoulder, and
shoulder-arm-neck syndrome, toothache
2. For relief of postoperative, post-traumatic or post-exodontial pain and
inflammation
3. For antipyresis and relief of pain in the following disorder:
Acute upper respiratory, tract inflammation, (including acute upper. airway
inflammation, accompanying acute bronchitis)
 

Posology:
For indications (1 & 2) the usual adult dosage is 60 mg of loxoprofen sodium (as
anhydride) orally three times a day.
For p.r.n. use, administer 60-120 mg once orally. The dosage may be adjusted
according to the patient’s age and symptoms.
For indication (3) the usual adult dosage is 60 mg of loxoprofen sodium (as anhydride)
p.r.n. once orally.
The dosage may be adjusted according to the patient’s age and symptoms. In
principle, the recommended maximum daily dose of ROXONIN is twice daily
administration, and the total daily dose should not exceed 180 mg/day.
Use of ROXONIN on an empty stomach should be avoided.
Use in the Elderly
In as much as adverse reactions are likely to occur in elderly patients, ROXONIN should
be used with caution, e.g., starting at a low dose, while closely monitoring the
patient’s condition (see “Important Precautions”).
Pediatric Use
The safety of ROXONIN in low birth weight infants, newborn infants, Infants and
toddlers, Children and adolescents has not been established.
Precautions Concerning Use
When ROXONIN Tablets are dispensed, patients should be instructed to remove each
tablet from the PTP blister package before taking the drug. [It has been reported that
accidental ingestion of the blister package can lead to esophageal mucosal injury and
subsequent perforation caused by the pointed corner of the package, resulting in
serious complications such as mediastinitis.]
 

(ROXONIN is contraindicated in the following patients.) • Patients with peptic ulcers [Peptic ulcers may be aggravated due to reduced gastric blood flow resulting from inhibition of prostaglandin biosynthesis.] (See “Careful Administration”) • Patients with severe blood disorders [Platelet dysfunction may occur and the abnormality may be worsened.] • Patients with severe hepatic functions disorders [Hepatic function disorders have been reported with the use of ROXONIN, and the patient’s hepatic function disorder may be aggravated.] • Patients with severe renal impairment [Adverse reactions such as acute renal failure, nephrotic syndrome, etc. have been reported with the use of ROXONIN.] • Patients with severe cardiac function failure [Cardiac symptoms may be exacerbated because inhibition of prostaglandin biosynthesis in the kidneys may cause edema and an increase in circulating body fluid volume, with a consequent increase in cardiac work.] • Patients with a history of hypersensitivity to any ingredients of ROXONIN . • Patients with or with a history of aspirin-induced asthma (induction of asthmatic attack with non steroidal anti-inflammatory-analgesics, etc.) [May induce an aspirin-induced asthmatic attack.] • Women in the late stages of pregnancy [See “Use during Pregnancy, Delivery, or Lactation”]

1) Careful Administration (ROXONIN should be administered with caution in the
following patients.)
a) Patients with a history of peptic ulcers [since the use of ROXONIN may cause
recurrence of ulceration.]
b) Patients with peptic ulcer associated with chronic use of nonsteroidal antiinflammatory-analgesic agents whose clinical condition requires long-term
administration of ROXONIN and who are currently on misoprostol therapy
[ROXONIN must be administered with care while closely monitoring the clinical
condition of patients receiving this drug continuously, because peptic ulcers
may be refractory to treatment with misoprostol, which is indicated for
nonsteroidal antiinflammatory- analgesic drug-induced peptic ulceration.]
c) Patients with or with a history of blood disorders [since adverse reactions such
as hemolytic anemia are prone to occur.]
d) Patients with or with a history of hepatic function disorders [because
exacerbation or recurrence of the hepatic function disorders have been
reported with the use of ROXONIN.]
e) Patients with or with a history of renal impairment [since adverse reactions
such as edema, proteinuria, serum creatinine elevation or hyperkalemia have
been reported with the use of ROXONIN.]
f) Patients with cardiac dysfunction [See “CONTRAINDICATIONS”]
g) Patients with a history of hypersensitivity
h) Patients with bronchial asthma [as the disease state may be exacerbated.]
i) Patients with colitis ulcerative [as the disease state may be exacerbated.]
j) Patients with Crohn's disease [as the disease state may be exacerbated.]
k) Elderly subjects [See “Use in the Elderly”.]
2) Important Precautions
a) It is important to note that treatment with anti-inflammatory-analgesic agents
is a symptomatic treatment, not a causal treatment.
b) The following should be considered when using ROXONIN in the management
of chronic diseases (rheumatoid arthritis, osteoarthritis):
i) Patients receiving long-term medication should be followed by periodic
laboratory examinations (e.g., urinalysis, hematological examination, liver
function tests). If any abnormality is noted, appropriate measures such as
dosage reduction or withdrawal should be taken.
ii) Therapies other than drug treatment must also be considered.
c) The following should be considered in using ROXONIN in the management of
acute diseases:
i) The proper dosage regimen, depending on the degree of acute
inflammation, pain and fever, should be determined.
ii) Long-term use of the same drug(s) must be avoided in principle.
iii) If any causal treatment is available, should be undertaken preferentially.
Aimless treatment with ROXONIN should be avoided.
d) The patient’s clinical condition should be closely monitored with caution
against the development of adverse reactions. As an excessive decrease in
body temperature, collapse, coldness of limbs, etc. may be manifested in
patients using ROXONIN, the clinical status must be carefully monitored after
administration of the drug especially in elderly patients with a high-grade fever
or patients with a debilitating disease.
e) ROXONIN may mask the signs and symptoms of infections. Therefore, an
appropriate antibiotic should be used in combination to treat inflammation
due to infection, and the patient should be closely monitored and ROXONIN
administered with care.
f) It is recommended to avoid the concomitant use of other anti-inflammatoryanalgesic agents with ROXONIN.
g) In elderly patients pay special attention to adverse reactions. Careful
administration is necessary; for example, care should be taken to administer
the individual minimum effective dose.
3) Other Precautions
a) It has been reported that temporary sterility is observed in women receiving
long-term NSAID therapy
 

1. Drug Interactions Precautions for co-administration (ROXONIN should be
co-administered with care when administered with the following drugs.)

Pregnancy
• ROXONIN should be administered to women who are or are possibly pregnant
only when the anticipated therapeutic benefits are considered to outweigh any
potential risk. [The safety of this ROXONIN in these populations has not been
established.]
• ROXONIN should not be used in women in the late stages of pregnancy. [Delayed
parturition has been reported in an animal tudy (in rats).]
• Fetal arterial vasoconstriction has been reported in a study on rats receiving the
drug in the late stages of gestation.
Lactation
• Administration of this drug to nursing mothers should be avoided. If
administration of this drug is judged to be essential, nursing should be
discontinued. [Preclinical studies have showed that loxoprofen is excreted into
milk in rats.]
 

Some undesirable effects (e.g. dizziness or sleepiness), have been reported.
To be safe, should be careful when driving and using machine.
 

(Including reports on adverse reactions the incidence of which cannot be calculated)
Adverse reactions to this drug were reported in 409 (3.03%) of 13,486 patients
treated. The major adverse reactions reported were gastrointestinal symptoms
(Stomach discomfort, abdominal pain, nausea and/or vomiting, anorexia, etc.: 2.25%);
edema (0.59%); rash, urticaria, etc. (0.21%); and sleepiness (0.10%). [At the end of
reexamination period1) and at the latest approval of indications 2-7)]
(1) Clinically significant adverse reactions (incidence unknown)
i) Shock and anaphylactoid symptoms: Shock and anaphylactoid symptoms
(decreased blood pressure, urticaria, edema of the larynx, dyspnea,etc.) have
been reported with the use of ROXONIN. Patients should be carefully
monitored during treatment. If any abnormal symptoms occur in a patient
being treated with ROXONIN, ROXONIN should be discontinued and
appropriate therapies should be initiated immediately.
ii) Hemolytic anemia, leukopenia, and thrombocytopenia: Hemolytic anemia,
leukopenia, and thrombocytopenia have been reported with the use of
ROXONIN. Patients should be carefully followed by hematological
examination, etc. during treatment. If any abnormal symptoms occur in a
patient being treated with ROXONIN, ROXONIN should be discontinued and
appropriate therapies should be initiated immediately.
iii) Oculomucocutaneous syndrome and toxic epidermal necrolysis:
Oculomucocutaneous syndrome (Stevens-Johnson syndrome) and toxic
epidermal necrolysis (Lyell syndrome) have been reported with the use of
ROXONIN. Patients should be carefully monitored during treatment. If any
abnormal symptoms occur in a patient being treated with ROXONIN,
ROXONIN should be discontinued and appropriate therapies should be
initiated immediately.
iv) Acute renal failure, nephrotic syndrome and interstitial nephritis: Acute
renal failure, nephrotic syndrome and interstitial nephritis have been
reported with the use of ROXONIN. Patients should be carefully monitored
during treatment. If any abnormal symptoms occur in a patient being treated
with ROXONIN, ROXONIN should be discontinued and appropriate therapies
should be initiated immediately. ROXONIN should be used with special
caution in such patients because hyperkalemia may appear in association
with acute renal failure.
v) Cardiac failure congestive: Cardiac failure congestive has been reported with
the use of ROXONIN. Patients should be carefully monitored during
treatment. If any abnormal symptoms occur in a patient being treated with
ROXONIN, ROXONIN should be discontinued and appropriate therapies
should be initiated immediately.
vi) Interstitial pneumonia: Interstitial pneumonia with manifestations of fever,
cough, dyspnea, chest X-ray abnormalities, and eosinophilia have been
reported with the use of ROXONIN. If these signs/findings are observed in a
patient being treated with ROXONIN, ROXONIN should be discontinued and
appropriate therapies such as corticosteroid medication, should be initiated
immediately.
vii) Gastrointestinal bleeding: Serious peptic ulceration or gastrointestinal
bleeding from the small intestine and/or large intestine, e.g., hematemesis,
melena and hematochezia, and consequent shock has been reported with the
use of ROXONIN. Patients should be carefully monitored during treatment. If
any abnormal symptoms occur in a patient being treated with ROXONIN,
ROXONIN should be discontinued and appropriate therapies should be
initiated immediately.
viii)Gastrointestinal perforation: Gastrointestinal perforation has been reported
with the use of ROXONIN. If epigastric pain, abdominal pain, etc. are noted in
a patient being treated with ROXONIN, ROXONIN should be discontinued and
appropriate therapies should be initiated immediately.
ix) Hepatic function disorders, and jaundice: Hepatic function disorders
including jaundice, increased serum levels of AST (GOT), ALT (GPT) and  -GTP,
or fulminant hepatitis have been reported with the use of ROXONIN. Patients
should be carefully monitored during treatment. If any abnormal symptoms
occur in a patient being treated with ROXONIN, ROXONIN should be
discontinued and appropriate therapies should be initiated.
x) Asthmatic attack: Acute respiratory disorders such as asthmatic attack have
been reported with the use of ROXONIN. Patients should be carefully
monitored during treatment. If any abnormal symptoms occur in a patient
being treated with ROXONIN, ROXONIN should be discontinued and
appropriate therapies should be initiated immediately.
xi) Aseptic meningitis: Aseptic meningitis including fever, headache, nausea and
vomiting, nuchal rigidity, clouding of consciousness, etc. has been reported
with the use of ROXONIN. Patients should be carefully monitored during
treatment. If any abnormal symptoms occur in a patient being treated with
ROXONIN, ROXONIN should be discontinued and appropriate therapies
should be initiated immediately. (in particular, the adverse event is likely to
occur in the patients with systemic lupus erytgematosus or mixed connective
tissue disease).
(2) Clinically significant adverse reactions reported in association with the use of
other non steroidal anti-inflammatory-analgesic drugs
i) Aplastic anemia: Aplastic anemia has been reported in association with the
use of other non-steroidal anti-inflammatory-analgesic drugs.

Although there is no experience of acute overdosage with loxoprofen sodium hydrate,
it may be expected that the signs and symptoms mentioned under Adverse Reactions
would be more pronounced.
There exists no specific antidote for loxoprofen sodium hydrate, overdose should be
countered by conventional measures to reduce absorption (eg gastrolavage and
charcoal) and speed up elimination.

In the case of an actual or suspected overdose, patients should be observed and
appropriate hydration maintained. Symptomatic and supportive treatments should be
used.

General properties
Loxoprofen sodium hydrate has excellent analgesic, anti-inflammatory and antipyretic
properties, with particularly potent pain-relieving activity. This drug is a prodrug
which, after being absorbed from the gut, is biotransformed into an active metabolite
to exert its actions.
1. Analgesic effect
i) Loxoprofen sodium hydrate has been demonstrated to show an ED50 value
of 0.13 mg/kg in the Randoll-Selitto test (inflamed paw pressuring method:
rat, p.o.), the analgesic effect being 10 to 20 times as potent as the
reference drugs ketoprofen, naproxen and indomethacin.
ii) As assessed using the rat thermal inflammatory pain test (rat, p.o.),
loxoprofen sodium hydrate showed an ID50 value of 0.76 mg/kg and
proved to be as potent as naproxen and 3 to >5 times more potent than
ketoprofen and indomethacin.
iii) In the chronic arthritis pain test (rat, p.o.), loxoprofen sodium hydrate
produced the most profound analgesic effect (ED50: 0.53 mg/kg), 4 to 6
times more potent as compared with indomethacin, ketoprofen and
naproxen.
iv) The analgesic action of this drug is peripheral.
2. Anti-inflammatory effect
Loxoprofen sodium hydrate produces an anti-inflammatory effect essentially
comparable with the effects of ketoprofen and naproxen on acute and chronic
inflammations such as carrageenin-induced edema (rat) and adjuvant arthritis
(rat).
3. Antipyretic effect
Loxoprofen sodium hydrate was demonstrated to exert an antipyretic effect,
essentially comparable with the effects of ketoprofen and naproxen and about
three times more potent than the effect of indomethacin on yeast-induced
fever (rat).
4. Mechanism of action
Inhibition of prostaglandin biosynthesis constitutes the mechanism of action
of this drug, the site of action being cyclo-oxygenase. When administered
orally, loxoprofen sodium hydrate is absorbed from the gastrointestinal tract
as an unchanged compound with only a modest gastric-mucosal irritation. It is
then rapidly biotransformed into the active metabolite trans-OH form (SRS
coordination) with a potent inhibitory effect on prostaglandin biosynthesis to
exert its pharmacologic effects.
 

Absorption and Metabolism
In sixteen healthy adult volunteers, ROXONIN tablets was absorbed rapidly following
a single 60-mg oral dose, and loxoprofen (unchanged drug) and its trans-OH form
(active metabolite) were demonstrated in blood. The time to peak plasma
concentration was about 30 minutes for loxoprofen and about 50 minutes for the
trans-OH form, with an approximate half-life of 1 hour and 15 minutes for both
compounds.

No safety information
 

Low Substituted Hydroxypropylcellulose, Red Ferric Oxide, Lactose hydrate,
Magnesium Stearate
 

Not applicable.
 

4 years

stored below 30°C.
 

Forming Aluminium / Aluminium blister pack.
Packs of 20 tablets
 

No special requirements.