Brufen Mr

Uses

Ibuprofen is used

• For the treatment of sign and symptoms of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and other non-rheumatoid arthropathies,
• For the treatment of non-articular rheumatic conditions, such as frozen shoulder, bursitis, tendinitis, tenosynovitis and low back pain,
• For the treatment of soft tissue injuries such as sprain, strain and post operative pain
• For the treatment of dysmenorrhoea,
• For the treatment of dental pain.
• For the treatment of cold & fever.

It is used in the symptomatic treatment of painful muscle spasm associated with musculoskeletal conditions and as an adjunct in the management of spasticity associated with multiple sclerosis or spinal cord disorders.

Brufen Mr is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Common Cold, Cystic Fibrosis (CF), Fever, Gastric Ulcer, Gouty Arthritis, Headache, Insomnia, Juvenile Idiopathic Arthritis (JIA), Menstrual Distress (Dysmenorrhea), Migraine, Mild pain, Nasal Congestion, Osteoarthritis (OA), Pain, Pain, Acute, Pain, Inflammatory, Patent Ductus Arteriosus (PDA), Pericarditis, Primary Dysmenorrhoea, Rheumatoid Arthritis, Severe Pain, Sinus pressure, Mild to moderate pain, Minor aches and pains, Moderate PainAcute Low Back Pain, Drug Withdrawal Headache, Insomnia, Migraine, Pain, Seizures, Spasticity, Muscle, Withdrawal From Addictive Substance; Detoxification

How Brufen Mr works

The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway.

Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.

Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at Alpha-2 adrenergic receptor sites. This drug is centrally acting and leads to a reduction in the release of excitatory amino acids like glutamate and aspartate, which cause neuronal firing that leads to muscle spasm. The above reduction and excitatory neurotransmitter release results in presynaptic inhibition of motor neurons. The strongest effect of tizanidine has been shown to occur on spinal polysynaptic pathways. The anti-nociceptive and anticonvulsant activities of tizanidine may also be attributed to agonist action on Alpha-2 receptors. Tizanidine also binds with weaker affinity to the Alpha-1 receptors, explaining its slight and temporary effect on the cardiovascular system .

Dosage

Brufen Mr dosage

Oral Administrations-

For Children:

• 20 mg per kg body weight daily in divided doses. In children weighing less than 30 kg the total daily dosage should not exceed 500 mg. If gastrointestinal disturbances occur Ibuprofenshould be given with food or milk.
• 1-2 years: 1/2 tea spoonful (2.5 ml) 3-4 times daily;
• 3-7 years: 1 tea spoonful (5 ml) 3-4 times daily;
• 8-12 years: 2 tea spoonful (10 ml) 3-4 times daily. Ibuprofenis not recommended for children under 1 year.

For adult:

• For arthritic pain: The dosage range is from 0.9 to 2.4 g per day. The usual dose is 400 mg, 3-4 times per day, preferably after food. The dose may be raised to a maximum of 2.4 g daily depending on the severity of symptom at the time of initiating drug therapy or as patients fail to respond. After a satisfactory response has been achieved the patients dose should be reviewed and adjusted as required and tapered gradually.
• For mild to moderate pain: 400 mg 6 hourly or as demanded by the condition.
• For dysmenorrhoea: 400 mg every 4 hours or as demanded by the condition.

Topical Administrations-

Pain and inflammation associated with musculoskeletal and joint disorder: As 5% cream, foam, gel, spray soln or 10% gel: Apply onto affected area.

The usual initial daily dose is 2 mg as a single dose. The daily dose may be increased thereafter according to response in steps of 2 mg at intervals of at least 3 to 4 days, usually up to 24 mg daily given in 3 to 4 divided doses. The maximum recommended dose is 36 mg daily.

Side Effects

Usually Ibuprofen has a low incidence of side effects. The most frequent side effects are gastrointestinal disturbances. Peptic ulceration and gastrointestinal bleeding have occasionally been reported. Other side effects include headache, dizziness, nervousness, skin rash, pruritus, drowsiness, insomnia, blurred vision and other ocular reactions, hypersensitivity reaction, abnormal liver function test, impairment of renal function, agranulocytosis and thrombocytopenia.

Tizanidine Hydrochloride may cause drowsiness, fatigue, dizziness, dry mouth, nausea, gastrointestinal disturbances, hypotension. Bradycardia, insomnia, hallucinations and altered liver enzymes, and rarely acute hepatitis have also been reported.

Toxicity

The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).

The reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig.

LD50 information

Oral LD50 (rat): 414 mg/kg; Subcutaneous LD50 (rat): 282 mg/kg; Oral LD50 (mouse): 235 mg/kg

Use in pregnancy

Animal studies have determined that this drug causes fetal harm . Studies have not been performed in humans, and it is advisable to ensure that tizanidine use in pregnant women should be reserved for cases in which possible benefit clearly outweighs the possible risk to mother and unborn child .

Use in breastfeeding

In studies of rat models, this tizanidine was found excreted in the breastmilk with a milk-to-blood ratio of 1.8:1 . In young nursing rats, abnormal results were obtained in tests indicative of central nervous system function. Various developmental changes that may have been attributable to the drug were observed. It is unknown whether tizanidine is excreted in human milk. It is a lipid-soluble drug, however, and likely to be excreted into breast milk .

Carcinogenesis and mutagenesis

No signs of carcinogenicity were observed in two dietary studies performed in rodent models. Tizanidine was given to mice for 78 weeks at doses reaching a maximum 16 mg/kg (equivalent to twice the maximum recommended human dose). In addition, the drug was given to rats for 104 weeks at doses reaching 9 mg/kg (equivalent to 2.5 times the maximum recommended human dose). There was a lack of a statistically significant increase in the occurrence of tumors in either study group .

Tizanidine was not found to be mutagenic or clastogenic in several laboratory essays, including the bacterial Ames test, the mammalian gene mutation test, in addition to the chromosomal aberration test in Chinese hamster cells and several other assays .

Precaution

Ibuprofen should be given with caution to patients with bleeding disorders, cardiovascular diseases, peptic ulceration or a history of such ulceration and in those who are receiving coumarin anticoagulants and in patients with renal or hepatic impairment.

Patients with impaired kidney or liver function; when patients drive a vehicle or operate machinery.

Interaction

Increased risk of GI bleeding with warfarin, corticosteroids, SSRIs and aspirin. May reduce the natriuretic effects of diuretics. Reduced antihypertensive effect of ACE inhibitors and angiotensin II receptor antagonists. May increase toxicity of lithium and methotrexate. Increased nephrotoxicity with ciclosporin and tacrolimus.

Alcohol or other CNS depressants may enhance the CNS effects of Tizanidine. There may be an additive hypotensive effect when Tizanidine is used in patients receiving antihypertensive therapy.

Volume of Distribution

The apparent volume of distribution of ibuprofen is of 0.1 L/kg.

Extensively distributed throughout the body. The average steady-state volume of distribution is 2.4 L/kg .

Elimination Route

It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption.

When orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract. The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration.

This drug undergoes significant first-pass metabolism. After the administration of an oral dose, tizanidine is mostly absorbed. The absolute oral bioavailability of tizanidine is measured to be about 40% .

Effect of food on absorption

Food has been shown to increase absorption for both the tablets and capsules. The increase in absorption with the tablet (about 30%) was noticeably higher than the capsule (~10%). When the capsule and tablet were administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet . It is therefore advisable to take this drug with food for increased absorption, especially in tablet form.

Half Life

The serum half-life of ibuprofen is 1.2-2 hours. In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours.

Approximately 2.5 hours .

Clearance

The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage.

A note on renal impairment

Tizanidine clearance is found to be decreased by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. This drug should be used with caution in patients with renal impairment .

Elimination Route

Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose. The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose.

In summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment.

This drug is mainly eliminated by the kidney .

Pregnancy & Breastfeeding use

Ibuprofen is not recommended during pregnancy or for use in nursing mothers.

Tizanidine has no teratogenic effects in rats and rabbits. As there have been no controlled studies in pregnant women, it should not be used during pregnancy unless the benefit clearly outweighs the risk. Although only small amounts of Tizanidine are excreted in animal milk, lactating women should not take Tizanidine.

Contraindication

Ibuprofen should not be given to patients with hypersensitivity to lbuprofen and to individuals who show nasal polyps, angioedema, bronchospastic reactivity to aspirin or other non-steroidal anti-inflammatory drug. Ibuprofen is contraindicated in patients with active or previous peptic ulceration & gastro-intestinal ulceration or bleeding.

Tizanidine Hydrochloride is contraindicated to the patients who have known hypersensitivity to this drug and in case of severe hepatic impairment.

Acute Overdose

Gastric lavage, correction of blood electrolytes (if necessary). There is no specific antidote for Ibuprofen

Children: Experience in children is limited and the use of Tizanidine in this patient group is not recommended.

Elderly: Renal clearance in the elderly may in some cases be significantly decreased. Caution is therefore indicated when using in elderly patients.

Storage Condition

Keep in a cool & dry place. Keep out of the reach of children.

Store in a cool & dry place, protected from light & moisture. Do not freeze. Keep all medicines out of the reach of children.

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