Flexabenz Pain Relief

Flexabenz Pain Relief Uses, Dosage, Side Effects, Food Interaction and all others data.

Cyclobenzaprine Hydrochloride relieves skeletal muscle spasm of local origin without interfering with muscle function.

Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear. Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours. Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications. Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.

Diclofenac Eye Drops contains Diclofenac Sodium, a potent non-steroidal anti-inflammatory drug with analgesic property. Diclofenac Sodium produces anti-inflammatory effect by inhibiting cyclooxygenase activity with a reduction in the tissue prostaglandin ( such as PgE2 and Pg F2α) .

Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.

A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages.

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Linseed oil is a rich source of α-Linolenic acid extracted from the dried, ripened seeds of the flax plant Linum usitatissimum. Other fatty acids contained in linseed oil include palmitic acid, stearic acid, oleic acid and linolenic acid. Linseed oil is particularly susceptible to polymerization reactions upon exposure to oxygen in air due to a high content of di- and triunsaturated esters. It is used in drying processes, and is used in other industrial and commercial applications. It is an indirect additive used in food contact substances.

Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens. The compound was first extracted and isolated from plant species Gaultheria procumbens in 1843. It can be manufactured synthetically and it used as a fragrance, in foods, beverages, and liniments. It forms a colorless to yellow or reddish liquid and exhibits a characteristic odor and taste of wintergreen. For acute joint and muscular pain, methyl salicylate is used as a rubefacient and analgesic in deep heating liniments. It is used as a flavoring agent in chewing gums and mints in small concentrations and added as antiseptic in mouthwash solutions.

Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth.

Trade Name Flexabenz Pain Relief
Generic Ethanol + Linseed Oil + Menthol + Methyl Salicylate + Diclofenac + Cyclobenzaprine
Weight 12%w/v
Type Spray
Therapeutic Class
Manufacturer Macleods Pharmaceuticals
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Flexabenz Pain Relief
Flexabenz Pain Relief

Uses

Flexor is used for an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living.

Diclofenac Sodium ophthalmic preparation is used for-

  • Inhibition of miosis during cataract surgery.
  • Post-operative inflammation after cataract surgery and other ocular surgical procedures.
  • Pre-operative and post-operative prevention of cystoid macular edema (CME) associated with lens extraction & intraocular lens implantation.
  • Post-traumatic inflammation in penetrating and non- penetrating wounds (as an adjuvant to local anti-infective therapy).
  • Non-infected chronic conjunctivitis, keratoconjunctivitis.

For therapeutic neurolysis of nerves or ganglia for the relief of intractable chronic pain in such conditions as inoperable cancer and trigeminal neuralgia (tic douloureux), in patients for whom neurosurgical procedures are contraindicated.

Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.

Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.

Flexabenz Pain Relief is also used to associated treatment for these conditions: Muscle SpasmsActinic Keratosis (AK), Acute Arthritis, Acute Gouty Arthritis, Acute Migraine, Acute Musculoskeletal Pain, Ankylosing Spondylitis (AS), Common Cold, Fever, Gouty Arthritis, Inflammation, Inflammatory Disease of the Oral Cavity, Inflammatory Disease of the throat, Inflammatory Reaction of the Nerve, Joint Pain, Juvenile Idiopathic Arthritis (JIA), Menstrual Distress (Dysmenorrhea), Muscle Inflammation, Ocular Inflammation, Operation site inflammation, Osteoarthritis (OA), Osteoarthritis of the Knee, Pain, Pain, Nerve, Pericarditis, Photophobia, Postoperative pain, Primary Dysmenorrhoea, Radicular Pain, Rheumatic Pain, Rheumatism, Rheumatoid Arthritis, Seasonal Allergic Conjunctivitis, Soreness, Muscle, Spinal pain, Tendon pain, Vertebral column pain, Acute Musculoskeletal injury, Acute, moderate, severe Pain, Inflammatory, Localized soft tissue rheumatism, Mild to moderate joint pain, Mild to moderate pain, Minor pain, Perioperative miosisBacterial Infections, Obstructive Hypertrophic Cardiomyopathy, Skin Infections, Bacterial, Skin Irritation, Ethylene glycol overdose, Fat occlusion in central venous catheter, Methanol overdose, Hand Hygiene, Skin disinfectionAcute Muscle Pain, Arthritis, Back Pain Lower Back, Backache, Contusions, Joint Pain, Ligament pain, Muscle Inflammation, Muscle Injuries, Muscle Strain, Muscle swelling, Pain, Pain of the Bone and Bones, Pain, Nerve, Partial-Onset Seizures, Postherpetic Neuralgia, Soreness, Muscle, Sprains, Tendon pain, Minor aches, Muscle, joint pains

How Flexabenz Pain Relief works

The exact mechanism of action of cyclobenzaprine has not been fully elucidated in humans, and much of the information available regarding its mechanism has been ascertained from early animal studies. There is some evidence that cyclobenzaprine exerts its effects at the supraspinal level, specifically within the locus coeruleus of the brainstem, with little-to-no action at neuromuscular junctions or directly on skeletal musculature. Action on the brainstem is thought to result in diminished activity of efferent alpha and gamma motor neurons, likely mediated by inhibition of coeruleus-spinal or reticulospinal pathways, and ultimately depressed spinal cord interneuron activity.

More recently it has been suggested that inhibition of descending serotonergic pathways in the spinal cord via action on 5-HT2 receptors may contribute to cyclobenzaprine’s observed effects.

Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G2 which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.

PGE2 is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 act via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.

PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors. Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor. PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.

PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes.

Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves . This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.

Dosage

Flexabenz Pain Relief dosage

The usual dose is 5-10 mg three times daily given by mouth. The daily dose should not exceed 60 mg. Treatment for more than 2 or 3 weeks is not recommended.

Dose in elderly: Therapy with Flexor in the elderly should be initiated with a 5 mg dose and titrated slowly upward.

Dose in hepatic impairment: Flexor should be used with caution in subjects with mild hepatic impairment starting with the 5 mg dose and titrating slowly upward. The use of Flexor in subjects with moderate to severe impairment is not recommended.

Pediatric Use: Safety and effectiveness of Cyclobenzaprine Hydrochloride in pediatric patients below 15 years of age have not been established.

Ophthalmic (Adult)-

  • Postoperative ocular inflammation: Instill into the appropriate eye 4 times daily starting 24 hr after surgery for up to 28 days.
  • Inflammation and discomfort after strabismus surgery: Instill 1 drop 4 times daily for the 1st wk; then tid in the 2nd wk, bid in the 3rd wk, and as required for the 4th wk.
  • Pain and discomfort after radial keratotomy: Instill 1 drop before surgery followed by 1 drop immediately after surgery, and then 1 drop 4 times daily for up to 2 days.
  • Pain after accidental trauma: Instill 1 drop 4 times daily for up to 2 days.
  • Control of inflammation after argon laser trabeculoplasty:Instill 1 drop 4 times during the 2 hr before procedure followed by 1 drop 4 times daily, up to 7 days after procedure.
  • Prophylaxis of intra-operative miosis: Instill into appropriate eye 4 times w/in 2 hr before surgery.
  • Post-photorefractive keratectomy pain:Instill into the affected eye twice, an hr before surgery, then 1 drop twice at 5-min intervals immediately after surgery, then every 2-5 hr while awake for up to 24 hr.
  • Seasonal allergic conjunctivitis:Instill 1 drop before surgery followed by 1 drop immediately after surgery, and then 1 drop 4 times daily for up to 2 days.

Side Effects

The adverse reactions reported most frequently with Cyclobenzaprine Hydrochloride are drowsiness, dry mouth and dizziness. The incidence of these common adverse reactions is lower in the surveillance program than in the controlled clinical studies.

Mild to moderate burning sensation in 5-15% patients which is transient in nature and almost never necessitated discontinuation of treatment. Other less common side-effects are sensitivity to light, bad taste, feeling of pressure, allergic reactions etc.

Toxicity

The oral LD50 of cyclobenzaprine in mice and rats is 338 mg/kg and 425 mg/kg, respectively. Signs of overdose may develop rapidly after ingestion and commonly include significant drowsiness and tachycardia, with less common manifestations including tremor, agitation, ataxia, GI upset, and other CNS effects such as confusion and hallucinations. Potentially critical manifestations, though rare, include cardiac arrest or dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.

As the management of cyclobenzaprine overdose is complex and ever-changing, it is recommended that a poison control center be consulted prior to treatment. Typical management involves gastrointestinal decontamination, close cardiac monitoring, and monitoring for signs of CNS or respiratory depression. As cyclobenzaprine exists in relatively low concentrations in plasma, monitoring of drug plasma levels should not guide management and dialysis is likely of no value.

Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, and gastrointestinal bleeding. Hypertension, acute renal failure, respiratory depression and coma occur rarely. In case of overdose, provide supportive care and consider inducing emesis and administering activated charcoal if overdose occurred less than 4 hours prior.

Oral, rat LD50: 5628 mg/kg. Symptoms and effects of overdose include nausea, vomiting, CNS depression, acute respiratory failure or death and with chronic use, severe health problems, such as liver and brain damage.

Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination .

Precaution

Because of its atropine-like action, Cyclobenzaprine Hydrochloride should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic medication.

Diclofenac eye drops may mask the signs of infection. So physicians should be alert to the development of infections in patients receiving the drug. During prolonged use, it is recommended that physicians conduct periodic examinations of the eye, including measurement of the intraocular pressure. Contact lenses should not be worn during treatment.

Interaction

Plasma concentration may be increased with the use of cimetidine, diltiazem, disulfiram, methylphenidate, ritonavir, and verapamil. Side-effects are increased by adrenaline, amiodarone, general anesthetics, SSRIs, antihistamines, antimuscarinics, antipsychotics, anxiolytics and hypnotics, clozapine, disopyramide, diuretics, flecainide, MAOIs, moclobemide, moxifloxacin, nefopam, nicorandil, noradrenaline, phenothiazine, pimozide, procainamide, propafenone, quinidine, selegiline, sibutramine, sotalol, terfenadine, thioridazine, and tramadol. Effects of adrenergic neurone blockers, clonidine, barbiturates, nitrates, and primidone are reduced while effects of baclofen, opioid analgesics, and thyroid hormones are enhanced with concomitant use of cyclobenzaprine. Carbamazepine and rifampicin may increase metabolism of cyclobenzaprine. Effects may be antagonized by oestrogens. Avoid use with brimonidine, entacapone, artemether with lumefantrine, or sibutramine. CNS effects may be enhanced by other CNS depressants.

No drug interaction is reported. There should be at least 5 minutes interval when another ophthalmic solution (e.g., steroid) is given.

Volume of Distribution

The volume of distribution of cyclobenzaprine is approximately 146 L. The combination of high plasma clearance despite a relatively long half-life observed with cyclobenzaprine is suggestive of extensive tissue distribution.

Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2 L/kg. The volume of the central compartment is 0.04 L/kg. Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration. There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable.

After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier.

Elimination Route

The oral bioavailability of cyclobenzaprine has been estimated to be between 0.33 and 0.55. Cmax is between 5-35 ng/mL and is achieved after 4 hours (Tmax). AUC over an 8 hour dosing interval was reported to be approximately 177 ng.hr/mL.

Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged . Many topical formulations are absorbed percutaneous and produce clinically significant plasma concentrations. Absorption is dose proportional over the range of 25-150 mg. Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further. Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h.

Rapidly absorbed.

Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% .

Half Life

The effective half-life of cyclobenzaprine in young healthy subjects is approximately 18 hours. These values are extended in the elderly and those with hepatic insufficiency, with a mean effective half-life of 33.4 hours and 46.2 hours in these groups, respectively.

The terminal half-life of diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h.

The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication.

Clearance

The approximate plasma clearance of cyclobenzaprine is 0.7 L/min.

Diclofenac has a plasma clearance 16 L/h.

Elimination Route

After administration of a radio-labeled dose of cyclobenzaprine, 38-51% of radioactivity was excreted in the urine while 14-15% was excreted in the feces. Cyclobenzaprine is highly metabolized, with only approximately 1% of this same radio-labeled dose recovered in the urine as unchanged drug. Metabolites excreted in the urine are likely water-soluble glucuronide conjugates.

Diclofenac is mainly eliminated via metabolism. Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs.

Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).

Pregnancy & Breastfeeding use

Pregnancy: Pregnancy category B. This drug should be used during pregnancy only if clearly needed.

Lactation: Caution should be exercised when Cyclobenzaprine Hydrochloride is administered to a nursing mother.

The safety of Diclofenac eye drops in pregnancy & lactation has not been established and its use therefore is not recommended unless the potential benefit to the mother outweighs the possible risk to the child.

Contraindication

Recent MI, arrhythmias, severe liver disease.

Hypersensitivity to any of the components Like other non steroidal anti-inflammatory agents, Diclofenac Sodium eye drops is contraindicated in patients in whom attacks of asthma, urticaria or acute rhinitis have been observed following application of acetyl salicylic acid or other cyclo-oxygenase inhibitors

Special Warning

Dose in hepatic impairment: Cyclobenzaprine should be used with caution in subjects with mild hepatic impairment starting with the 5 mg dose and titrating slowly upward. The use of Cyclobenzaprine in subjects with moderate to severe impairment is not recommended.

Acute Overdose

Although rare, deaths may occur from over dosage with Cyclobenzaprine Hydrochloride. Signs and symptoms of toxicity may develop rapidly after Cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible.

Accidental ingestion of Diclofenac Sodium presents virtually no risk of unwanted effects, since one 5 ml bottle of eye drop solution contains only 5 mg of Diclofenac Sodium, which is equivalent to about 3% of the recommended maximum oral dose for adults.

Storage Condition

Close the bottle immediately after use. Do not use for more than four weeks after opening. Store at room temperature.

Innovators Monograph

You find simplified version here Flexabenz Pain Relief


*** Taking medicines without doctor's advice can cause long-term problems.
Share