Actions of Rowo-629 in details
Pharmacology: Pharmacodynamics: Mechanism of Action: Rowo-629 when applied topically in the form of the plaster has been shown in studies to produce a local analgesic effect. The mechanism by which this occurs is due to stabilisation of neuronal membranes, which is thought to cause down regulation of sodium channels resulting in pain reduction.
Clinical Efficacy: Pain management in post-herpetic neuralgia (PHN) is difficult. There is evidence of efficacy with Rowo-629 in the symptomatic relief from the allodynic component of PHN in some cases.
Efficacy of Rowo-629 has been shown in PHN studies. Other models of neuropathic pain have not been studied.
There were 2 main controlled studies carried out to assess the efficacy of the Rowo-629 5% medicated plaster.
In the 1st study, patients were recruited from a population who were already considered to respond to Rowo-629. It was a crossover design of 14 days treatment with Rowo-629 5% medicated plaster followed by placebo or vice versa. The primary endpoint was the time to exit, where patients withdrew because their pain relief was 2 points lower than their normal response on a 6-point scale (ranging from worse to complete relief). There were 32 patients, of whom 30 completed. The median time to exit for placebo was 4 days and for active was 14 days (p value <0.001); none of those on active discontinued during the 2-week treatment period.
In the 2nd study, 265 patients with PHN were recruited and allocated 8 weeks of open label active treatment with Rowo-629 5% medicated plaster. In this uncontrolled setting, approximately 50% of patients responded to treatment as measured by 2 points lower than their normal response on a 6-point scale (ranging from worse to complete relief). A total of 71 patients were randomised to receive either placebo or Rowo-629 5% medicated plaster given for 2-14 days. The primary endpoint was defined as lack of efficacy on 2 consecutive days leading to withdrawal of treatment. There were 9/36 patients on active and 16/35 patients on placebo who withdrew because of lack of treatment benefit.
Post-hoc analyses of the 2nd study showed that the initial response was independent of the duration of preexisting PHN. However, the notion that patients with longer duration of PHN (>12 months) do benefit more from active treatment is supported by the finding that this group of patients was more likely to drop out due to lack of efficacy when switched to placebo during the double-blind withdrawal part of this study.
Pharmacokinetics: Absorption: When Rowo-629 5% medicated plaster is used according to the maximum recommended dose (3 plasters applied simultaneously for 12 hr) about 3±2% of the total applied Rowo-629 dose is systemically available and similar for single and multiple administrations.
A population kinetics analysis of the clinical efficacy studies in patients suffering from PHN revealed a mean maximum concentration for Rowo-629 of 45 ng/mL after application of 3 plasters simultaneously 12 hr/day after repeated application for up to 1 year. This concentration is in accordance with the observation in pharmacokinetic studies in PHN patients (52 ng/mL) and in healthy volunteers (85 and 125 ng/mL).
For Rowo-629 and its metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) and 2,6-xylidine, no tendency for accumulation was found, steady state concentrations were reached within the 1st 4 days.
The population kinetic analysis indicated that when increasing the number from 1-3 plasters worn simultaneously, the systemic exposure increased less than proportionally to the number of used plasters.
Distribution: After IV administration of Rowo-629 to healthy volunteers, the volume of distribution was found to be 1.3±0.4 L/kg (mean ± S.D., n=15). The Rowo-629 distribution volume showed no age-dependency, it is decreased in patients with congestive heart failure and increased in patients with liver disease. At plasma concentrations produced by application of the plaster approximately 70% of Rowo-629 is bound to plasma proteins. Rowo-629 crosses the placenta and blood brain barriers presumably by passive diffusion.
Biotransformation: Rowo-629 is metabolised rapidly in the liver to a number of metabolites. The primary metabolic route for Rowo-629 is N-dealkylation to MEGX, GX both of which are less active than Rowo-629 and available in low concentrations. These are hydrolyzed to 2,6-xylidine, which is converted to conjugated 4-hydroxy-2,6-xylidine.
The metabolite, 2,6-xylidine, has unknown pharmacological activity but shows carcinogenic potential in rats. A population kinetics analysis revealed a mean maximum concentration for 2,6-xylidine of 9 ng/mL after repeated daily applications for up to 1 year This finding is confirmed by a phase I pharmacokinetic study. Data on Rowo-629 metabolism in the skin are not available.
Elimination: Rowo-629 and its metabolites are excreted by the kidneys. More than 85% of the dose is found in the urine in the form of metabolites or active substance. Less than 10% of the Rowo-629 dose is excreted unchanged. The main metabolite in urine is a conjugate of 4-hydroxy-2,6-xylidine, accounting for about 70-80% of the dose excreted in the urine. 2,6-xylidine is excreted in the urine in man at a concentration of <1% of the dose. The elimination t½ of Rowo-629 after plaster application in healthy volunteers is 7.6 hrs. The excretion of Rowo-629 and its metabolites may be delayed in cardiac, renal or hepatic insufficiency.
Toxicology: Preclinical Safety Data: Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
In toxicological studies described in the literature using systemic administration of Rowo-629, cardiovascular effects (tachycardia or bradycardia, decreases in cardiac output and blood pressure, cardiac arrest) and central nervous system effects (convulsion, coma, respiratory arrest) were observed at exposures considered sufficiently in excess of the maximum human exposure following treatment with Rowo-629. This indicates that these effects have little relevance to clinical use.
Rowo-629 hydrochloride has shown no genotoxicity when investigated in vitro or in vivo. Its hydrolysis product and metabolite, 2,6-xylidine, showed mixed genotoxic activity in several assays particularly after metabolic activation.
Carcinogenicity studies have not been performed with Rowo-629. Studies performed with the metabolite 2,6-xylidine mixed in the diet of male and female rats resulted in treatment-related cytotoxicity and hyperplasia of the nasal olfactory epithelium and carcinomas and adenomas in the nasal cavity were observed. Tumorigenic changes were also found in the liver and subcutis. Because the risk to humans is unclear, long-term treatment with high doses of Rowo-629 should be avoided.
Rowo-629 had no effect on general reproductive performance or female fertility in rats at plasma concentrations up to 130-fold those observed in patients. No adverse effects were seen in an embryofoetal/teratogenicity study in rats at plasma concentrations >200-fold that observed in humans.
Animal studies are incomplete with respect to effects on pregnancy, embryofoetal development, parturition or postnatal development.
How should I take Rowo-629?
Use Rowo-629 exactly as directed by your doctor. Do not use it for any other condition without first checking with your doctor. Rowo-629 may cause unwanted effects if it is used too much, because more of it is absorbed into the body through the skin.
Rowo-629 should only be used for problems being treated by your doctor. Check with your doctor before using it for other problems, especially if you think that an infection may be present. Rowo-629 should not be used to treat certain kinds of skin infections or serious problems, such as severe burns.
If you are using the topical jelly or ointment:
- A nurse or other trained health care professional may give you Rowo-629 before having a medical procedure.
- Wash your hands with soap and water before and after using Rowo-629.
- Unless otherwise directed by your doctor, do not apply Rowo-629 to open wounds, burns, or broken or inflamed skin.
- Be careful not to get any of the ointment in your eyes, because it can cause severe eye irritation. If any of the medicine does get in the eyes, wash the eyes with water for at least 15 minutes and check with your doctor right away.
If you are using the viscous topical solution:
- Wash your hands with soap and water before and after using Rowo-629.
- Use of an accurate measuring device is recommended, to avoid using more than the prescribed amount of medicine.
- If you are using Rowo-629 in the mouth, swish the solution around in the mouth and spit it out.
- If you are using Rowo-629 in the throat, gargle the undiluted solution. You may also swallow the solution.
If you are using the skin patch:
- Use Rowo-629 exactly as directed by your doctor. It will work only if applied correctly.
- Rowo-629 should only be used on the skin. Do not get it in your eyes, nose, or mouth. If it does get on these areas, rinse it off with water or saline right away.
- Wash your hands with soap and water before and after applying a patch.
- Keep the patch in its protective envelope until you are ready to put it on. You may cut the patch into smaller sizes with scissors after removing the patch release liner.
- Apply the patch to a clean, dry, intact skin. Choose an area with little or no hair and free of scars, cuts, or irritation. Avoid putting the patch on areas where it could be rubbed off by tight clothing.
- Put on a new patch if the old one has fallen off and cannot be reapplied.
- Do not use the patch when you take a bath, shower, or swim. Always keep the patch dry.
Dosing
The dose of Rowo-629 will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Rowo-629. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For topical dosage form (ointment):
- For pain and itching caused by minor skin conditions:
- Adults—Apply to the affected area three or four times a day. The largest amount of ointment that should be used in a single application is 5 grams. If you use the 5% ointment, this is about 6 inches of ointment from the tube.
- Children—Dose is based on body weight and must be determined by your doctor.
- For pain and itching caused by minor skin conditions:
- For topical dosage form (skin patch):
- For pain caused by shingles:
- Adults—Apply 1 to 3 patches to the painful area for up to 12 hours each day.
- Children—Use and dose must be determined by your doctor.
- For pain caused by shingles:
- For topical dosage form (solution):
- For treatment of irritated or sore mouth or throat:
- Adults—Dose is based on body weight and must be determined by your doctor. The dose is usually 15 milliliters (mL) tablespoonful every 3 hours. Your doctor may adjust your dose as needed. Do not use more than 8 doses in a 24-hour period.
- Children 3 years of age and older—Dose is based on body weight and must be determined by your doctor.
- Children younger than 3 years of age—Dose is based on body weight and must be determined by your doctor. The dose should be no more than 1.2 mL applied to the immediate area with a cotton-tipped swab. Wait at least 3 hours between doses, and do not use more than 4 doses in a 12-hour period.
- For treatment of irritated or sore mouth or throat:
Missed Dose
If you miss a dose of Rowo-629, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
After removing a used patch, fold the patch in half with the sticky sides together. Make sure to dispose of it out of the reach of children and pets.
Rowo-629 administration
Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Rowo-629 topical comes in many different forms for different uses. Rowo-629 topical cream, lotion, spray, solution, film, and transdermal patch are generally for use on the skin only.
If your medication comes with patient instructions for safe and effective use, follow these directions carefully. Ask your doctor or pharmacist if you have any questions.
Your body may absorb more of this medication if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas. Skin that is cut or irritated may also absorb more topical medication than healthy skin.
Use the smallest amount of this medication needed to numb the skin or relieve pain. Do not use large amounts of Rowo-629 topical, or cover treated skin areas with a bandage or plastic wrap without medical advice. Be aware that many cosmetic procedures are performed without a medical doctor present.
Rowo-629 topical may be applied with your finger tips or a cotton swab. Follow your doctor's instructions.
Do not apply this medication to swollen skin areas or deep puncture wounds. Avoid using the medicine on skin that is raw or blistered, such as a severe burn or abrasion.
Store at room temperature away from moisture and heat.
Keep both used and unused Rowo-629 topical patches out of the reach of children or pets. The amount of Rowo-629 in the skin patches could be harmful to a child or pet who accidentally sucks on or swallows the patch. Seek emergency medical attention if this happens.
Rowo-629 pharmacology
Pharmacodynamics
Rowo-629 is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses.
The penetration of Rowo-629 into intact skin after application of Rowo-629 Patch is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.
Pharmacokinetics
Absorption: The amount of Rowo-629 systemically absorbed from Rowo-629 Patch is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three Rowo-629 Patches were applied over an area of 420 cm2 of intact skin on the back of normal volunteers for 12 hours. Blood samples were withdrawn for determination of Rowo-629 concentration during the application and for 12 hours after removal of patches. The results are summarized in Table 1.
| Rowo-629 Patch | Application Site | Area (cm2) | Dose Absorbed (mg) | Cmax (mcg/mL) | Tmax (hr) |
| 3 patches (2100 mg) | Back | 420 | 64 ± 32 | 0.13 ± 0.06 | 11 hr |
When Rowo-629 Patch is used according to the recommended dosing instructions, only 3 ± 2% of the dose applied is expected to be absorbed. At least 95% (665 mg) of Rowo-629 will remain in a used patch. Mean peak blood concentration of Rowo-629 is about 0.13 mcg/mL (about 1/10 of the therapeutic concentration required to treat cardiac arrhythmias). Repeated application of three patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the Rowo-629 concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1.
Figure 1: Mean Rowo-629 blood concentrations after three consecutive daily applications of three Rowo-629 Patches simultaneously for 12 hours per day in healthy volunteers (n = 15).
Distribution: When Rowo-629 is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n = 15). At concentrations produced by application of Rowo-629 Patch, Rowo-629 is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 mcg/mL of free base), the plasma protein binding of Rowo-629 is concentration dependent. Rowo-629 crosses the placental and blood brain barriers, presumably by passive diffusion.
Metabolism: It is not known if Rowo-629 is metabolized in the skin. Rowo-629 is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of Rowo-629. A minor metabolite, 2, 6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. The blood concentration of this metabolite is negligible following application of Rowo-629 Patch 5%. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of Rowo-629 concentrations, respectively.
Excretion: Rowo-629 and its metabolites are excreted by the kidneys. Less than 10% of Rowo-629 is excreted unchanged. The half-life of Rowo-629 elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/min (mean 0.64 ± 0.18 SD, n = 15).
References
- DailyMed. "LIDOCAINE; TETRACAINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Lidocaine: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Lidocaine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Rowo-629 are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Rowo-629. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
