SmartRx Gaba-V Kit

Uses

Capsaicin is indicatd for- Rheumatoid arthritis, Osteoarthritis, Pain due to diabetic neuropathy, Joint pain, Post-herpetic neuralgia, Post-surgical neuropathic pain, Nerve Pain, Back pain, Muscle pain, Fibromyalgia, Bursitis, Pruritis (itching)

Gabapentin is used for-

• Epilepsy
• Neuropathic pain (e.g. postherpetic neuralgia) and other pain conditions
• Bipolar disorder
• Headache syndrome
• Spasticity in multiple sclerosis and spinal cord diseases

Others indication are:

• Alcohol withdrawal
• Schizoaffective disorder
• Post-traumatic stress disorder
• Agitation and behavioural disturbances
• associated with dementia
• Lesch-Nyhan syndrome
• Essential tremor
• Restless legs syndrome
• Brachioradial pruritus
• Hemichorea/hemiballismus
• Hot Flashes

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.

SmartRx Gaba-V Kit is also used to associated treatment for these conditions: Arthritis, Back Pain Lower Back, Backache, Bursitis, Contusions, Inflammatory Reaction caused by Rheumatism, Muscle Cramps, Musculoskeletal Pain, Osteoarthritis (OA), Periarthritis, Post-Herpetic Neuralgia (PHN), Rheumatic Pain, Soft Tissue Injury, Tendinitis, Acute nonspecific tenosynovitisPartial-Onset Seizures, Peripheral Neuropathic Pain, Postherpetic NeuralgiaAcute 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 SmartRx Gaba-V Kit works

Capsaicin has been shown to reduce the amount of substance P associated with inflammation - however this is not believed to be its main mechanism in the relief of pain . Capsaicin's mechanism of action is attributed to "defunctionalization" of nociceptor fibers by inducing a topical hypersensitivity reaction on the skin. This alteration in pain mechanisms is due to many of the following: temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fiber terminals.

The precise mechanism through which gabapentin exerts its therapeutic effects is unclear. The primary mode of action appears to be at the auxillary α2δ-1 subunit of voltage-gated calcium channels (though a low affinity for the α2δ-2 subunit has also been reported). The major function of these subunits is to facilitate the movement of pore-forming α1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons. There is evidence that chronic pain states can cause an increase in the expression of α2δ subunits and that these changes correlate with hyperalgesia. Gabapentin appears to inhibit the action of α2δ-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.

There is some evidence that gabapentin also acts on adenosine receptors and voltage-gated potassium channels, though the clinical relevance of its action at these sites is unclear.

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

SmartRx Gaba-V Kit dosage

18 years of age and older:Apply a thin film of Capsaicin cream to affected area 3 to 4 times daily. A burning sensation may occur upon application, but generally disappears with regular use. Application schedules of 3 to 4 times a day for 2 weeks provides optimum pain relief.

Neuropathic pain: 300 mg on day-1, then 300 mg twice on day-2, then 300 mg thrice on day-3, then increase the dose according to response in steps of 300 mg daily to maximum 1800 mg daily in three divided doses.

Partial seizure/epilepsy: 300 mg on day-1, then 300 mg twice on day-2, then 300 mg thrice on day-3, then increase the dose according to response in steps of 300 mg daily to maximum 2400 mg daily in three divided doses.

In case of children:

• For 3-12 years: 10 to 15 mg/kg, Incase of titration 25-35 mg/kg daily in 3 divided doses.
• Maintenance dose is 900 mg daily (body weight 26-36 Kg) or 1.2 gm daily (body weight 37-50 Kg).

Gabapentin can be taken orally with or without food.

Side Effects

Capsaicin may cause transient burning on application. This burning is observed more frequently when the application schedules are more than 3-4 times daily. The burning can be enhanced if too much cream is used and if it is applied just before or after a bath or shower.

Generally Gabapentin is well tolerated but a few side effects like fatigue, dizziness , ataxia, weight gain, peripheral edema, dry mouth and somnolence, may occur. Rarely it may cause fulminate hepatic failure, or aplasticanemia.

Toxicity

Acute oral LD50 and dermal LD50 in mouse are 47.2 mg/kg and >512 mg/kg, respectively . Capsaicin is shown to be mutagenic for bacteria and yeast .

Capsaicin can cause serious irritation, conjunctivitis and lacrimation via contact with eyes. It induces a burning sensation and pain in case of contact with eyes and skin. As it is also irritating to the respiratory system, it causes lung irritation and coughing as well as bronchoconstriction. Other respiratory effects include laryngospasm, swelling of the larynx and lungs, chemical pneumonitis,respiratory arrest and central nervous system effects such as convulsions and excitement . In case of ingestion, gastrointestinal tract irritation may be observed along with a sensation of warmth or painful burning . Symptoms of systemic toxicity include disorientation, fear, loss of body motor control including diminished hand-eye coordination, hyperventilation, tachycardia, and pulmonary oedema . Careful early decontamination is recommended and medical intervention should be initiated for any life-threatening symptoms. In case of contact, individual must be removed from the source of exposure and the contacted skin and mucous membranes should be thoroughly washed with copious amounts of water .

The oral TDLo of gabapentin in humans is 2.86 mg/kg and the LD₅₀ in rats has been found to be >8000 mg/kg. Symptoms of overdose are consistent with the drug's adverse effect profile and involve CNS depression (e.g. dizziness, drowsiness, slurred speech, lethargy, loss of consciousness) and gastrointestinal symptoms such as diarrhea. Management of overdose should involve symptomatic and supportive treatment. Gabapentin can be removed by hemodialysis - this may be of benefit in some patients, such as those with impaired renal function.

Multi-drug overdoses involving gabapentin, particularly in combination with other CNS depressants such as opioids, can result in coma and death - this possibility should be considered when managing overdosage.

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

Capsaicin cream should not be applied to broken or irritated skin. Applied area should not be tightly bandaged. Do not get on mucous membranes and into eyes or on contact lenses. If this occurs, rinse the affected area thoroughly with water. Do not apply the cream on the heat treated area as this may increase the burning sensation. In case of accidental ingestion, seek physician advice immediately.

Patients should be instructed to take Gabapentin only as prescribed. While using Gabapentin patients should be instructed either not to drive a car or to operate other complex machinery until they have gained sufficient experiences about Gabapentin whether or not it affects their mental and/or motor performance adversely.

Interaction

Antacids may reduce the bioavailability of Gabapentin by up to 20%. Cimetidine may alter its reanal excretion. Gabapentin does not interact with other anti-epileptic drug or with oral contraceptive preparations.

Volume of Distribution

The apparent volume of distribution of gabapentin after IV administration is 58±6 L. The drug is found in the CSF in concentrations approximately 9-20% of the corresponding plasma concentrations and is secreted into breast milk in concentrations similar to that seen in plasma.

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

Oral: Following oral administration, capsaicin may be absorbed by a nonactive process from the stomach and whole intestine with an extent of absorption ranging between 50 and 90%, depending on the animal . The peak blood concentration can be reached within 1 hour following administration . Capsaicin may undergo minor metabolism in the small intestine epithelial cells post-absorption from the stomach into the small intestines. While oral pharmacokinetics information in humans is limited, ingestion of equipotent dose of 26.6 mg of pure capsaicin, capsaicin was detected in the plasma after 10 minutes and the peak plasma concentration of 2.47 ± 0.13 ng/ml was reached at 47.1 ± 2.0 minutes .

Systemic: Following intravenous or subcutaneous administration in animals, the concentrations in the brain and spinal cord were approximately 5-fold higher than that in blood and the concentration in the liver was approximately 3-fold higher than that in blood .

Topical: Topical capsaicin in humans is rapidly and well absorbed through the skin, however systemic absorption following topical or transdermal administration is unlikely . For patients receiving the topical patch containing 179 mg of capsaicin, a population analysis was performed and plasma concentrations of capsaicin were fitted using a one-compartment model with first-order absorption and linear elimination. The mean peak plasma concentration was 1.86 ng/mL but the maximum value observed in any patient was 17.8 ng/mL .

Absorption of gabapentin is thought to occur solely via facilitated transport by the LAT1 transporter within the intestines. As this process is saturable, the oral bioavailability of gabapentin is inversely proportional to the administered dose - the oral bioavailability of a 900mg/day regimen is approximately 60%, whereas a 4800mg/day regimen results in only 27% bioavailability. The T_max of gabapentin has been estimated to be 2-3 hours. Food has no appreciable effect on gabapentin absorption.

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

Following oral ingestion of equipotent dose of 26.6 mg of pure capsaicin, the half life was approximately 24.9 ± 5.0 min . Following topical application of 3% solution of capsaicin, the half-life of capsaicin was approximately 24 h . The mean population elimination half-life was 1.64 h following application of a topical patch containing 179 mg of capsaicin .

The elimination t_1/2 of gabapentin in patients with normal renal function is 5-7 hours. In patients with reduced renal function, the elimination t_1/2 may be prolonged - in patients with a creatinine clearance of 16,17

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

Both the plasma clearance and renal clearance of gabapentin are directly proportional to the patient's creatinine clearance due to its primarily renal elimination.

Elimination Route

It is proposed that capsaicin mainly undergoes renal excretion, as both the unchanged and glucuronide form. A small fraction of unchanged compound is excreted in the feces and urine. In vivo animal studies demonstrates that less than 10 % of an administered dose was found in faces after 48 h .

Gabapentin is eliminated solely in the urine as unchanged drug. Cimetidine, an inhibitor of renal tubular secretion, reduces clearance by approximately 12%, suggesting that some degree of tubular secretion is involved in the renal elimination of gabapentin.

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

The safety of Capsaicin during pregnancy or lactation has not been established in either humans or animals.

Pregnancy: Gabapentin is a pregnancy category C drug; it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Gabapentin may be secreted through the breast milk like many other drugs , so it should be used in women who are nursing, only if the benefits clearly outweigh the risks.

Contraindication

Capsaicin cream is contraindicated on broken or irritated skin. It is also contraindicated in patients with known hypersensitivity to capsaicin or any of the excipients used in this product.

Gabapentin is contraindicated in patients who have known hypersensitivity to the drug.

Special Warning

Use in Children: Safety and effectiveness of Gabapentin in the management of neuropathic pain in pediatric patients have not been established. Safety and effectiveness of Gabapentin in the management of seizures in pediatric patients below the age of 3 years have not been established.

Renal impaired patient: In case of renal impaired patient Gabapentin doses must be reduced :

• CrCl >60 ml/min: 1200 mg/daily in 3 divided doses
• CrCl 30-60 ml/min: 600 mg/daily in 2 divided doses
• CrCl 15-30 ml/min: 300 mg/daily single dose
• CrCl <15 ml/min: 150 mg/daily single dose or 300 mg/every alternate day
• Heamodialysis: maximum 300 mg after each dialysis Gabapentin can be taken orally with or without food.

Acute Overdose

Sufficient information on overdose of Capsaicin is not available.

Storage Condition

Keep at cool and dry place, away form light. Keep out of the reach of children.

Tablets should be stored below 25° C and protected from light & moisture

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