Uromax

Interactions with herbal products have not been formally investigated.

Interactions with foods have not been formally investigated.

Interactions with other drugs have not been formally investigated.

Interactions with laboratory tests have not been formally investigated.

Oxybutynin is metabolized through the cytochrome P450 system, specifically the 3A4 enzymes. Inhibitors of these enzymes may alter the pharmacokinetics of Uromax. The clinical significance of this is unknown. Alcohol may increase drowsiness.

There is a dose-response relationship for the reduction in episodes of urinary incontinence, with the greatest reduction at a daily dose of Uromax 15 mg. This is also the dose associated with the highest level of patient satisfaction, even though anticholinergic side effects also increase with increasing dose.

The recommended initial dose of Uromax is 10-15 mg once a day. The dose may be adjusted in 5 mg increments according to individual efficacy and tolerability. The maximum recommended daily dose is 20 mg.

Uromax is designed to allow once daily dosing. If frequency, urgency or incontinence repeatedly occurs at the end of a dose interval, it is generally an indication for a dosage increase, not more frequent administration.

Dose adjustments should be based on the patient's clinical response. Because of the sustained release properties of Uromax, dose adjustments should generally be separated by 48 hours. Uromax may be taken with or without food. In debilitated patients or patients with impaired hepatic or renal function, it is advisable to initiate at the lowest dose and to increase carefully according to tolerance and response.

Uromax tablets should be swallowed intact with the aid of liquids. The tablets should not be crushed, chewed or divided.

If a patient forgets to take one or more doses, they should take their next dose at the normal time and in the normal amount.

Other adverse effects reported with other formulations of oxybutynin are: impotence, increased ocular tension, interference with normal heat regulation, mood changes, suppression of lactation, tachycardia, drug idiosyncrasies that may include dermal manifestations or paralysis of the ciliary muscles of the eye causing blurred vision.

colitis, eructation, increased appetite, liver function tests abnormal, melena, mouth ulceration, tongue disorder.

abnormal vision, conjunctivitis, eye pain, iritis, mydriasis, tinnitus.

arthritis, joint disorder.

hair disorder, nail disorder, skin discolouration, sweating decreased, urticaria, vesiculobullous rash.

abdomen enlarged, allergic reaction, face edema, lack of drug effect, malaise.

hiccup, increased upper airway secretion, lung disorder.

cystitis, nocturia, urethral pain, urethritis, urinary urgency.

The most frequent adverse effects of oxybutynin are those related to its anticholinergic (antimuscarinic) effects, most notably dry mouth and pharyngitis. Although the incidence of dry mouth increased with increasing dose, in Uromax clinical trials, patient satisfaction also improved at higher doses because of corresponding improvement in control of urinary incontinence.

akathisia, anxiety, circumoral paresthesia, confusion, depression, libido decreased, nervousness, paresthesia.

creatinine increased, generalized edema.

During the first two or three days of overactive bladder symptom relief, patients may experience dry mouth, constipation, drowsiness or blurred vision. Provided these symptoms are not intolerable, patients should be encouraged to continue at the same dose for a few days since these symptoms tend to decrease in severity, or even disappear, over time. If excessive dry mouth, constipation, drowsiness or blurred vision persists, the dose should be reduced by 5 mg. If it is necessary to reduce the dose, it may be possible to carefully increase it again after three or four days if the symptoms of overactive bladder are not being well controlled.

migraine, syncope.

Available data does not suggest a difference in the balance between efficacy and adverse event profile in patients over the age of 65 years and less than 65 years.

No data is available on use in children.

Each yellow, round, film coated tablet, engraved with “U” on one side and a number corresponding to the mg strength on the other, contains: oxybutynin chloride 10 mg. Nonmedicinal ingredients: cetostearyl alcohol, dibasic calcium phosphate dihydrate, dye blend yellow, hydroxyethyl cellulose, magnesium stearate, methacrylic acid copolymer Type C, microcrystalline cellulose, sodium alginate, talc and triethyl citrate; film coating: hydroxypropyl methylcellulose, polyethylene glycol, polysorbate 80, synthetic yellow iron oxide and titanium dioxide. Opaque plastic bottles of 100.

Each pink, oval, film coated tablet, engraved with “U” on one side and a number corresponding to the mg strength on the other, contains: oxybutynin chloride 15 mg. Nonmedicinal ingredients: cetostearyl alcohol, dibasic calcium phosphate dihydrate, dye blend yellow, hydroxyethyl cellulose, magnesium stearate, methacrylic acid copolymer Type C, microcrystalline cellulose, sodium alginate, talc and triethyl citrate; film coating: hydroxypropyl methylcellulose, polyethylene glycol, polysorbate 80, synthetic red iron oxide, titanium dioxide. Opaque plastic bottles of 100.

Uromax should be used with caution in debilitated patients.

Use with caution in patients with renal impairment.

Use with caution in patients with hepatic impairment.

The symptoms of prostatic hypertrophy may be aggravated following administration of oxybutynin.

Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In such cases, treatment with oxybutynin would be inappropriate and possibly harmful.

Administer with caution to patients with hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition.

Administration of oxybutynin in large doses to patients with ulcerative colitis may suppress intestinal motility to the point of producing a paralytic ileus and precipitate or aggravate toxic megacolon, a serious complication of the disease.

Oxybutynin may cause drowsiness.

Use with caution in patients with autonomic neuropathy.

When oxybutynin is administered in the presence of high environmental temperature, it can cause heat prostration (fever and heat stroke due to decreased sweating).

Oxybutynin may produce drowsiness or blurred vision. Patients should be cautioned regarding activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work while taking this drug, until it is clear that their ability to do so is not impaired. Alcohol or other sedative drugs may enhance the drowsiness caused by oxybutynin.

The symptoms of hyperthyroidism may be aggravated following administration of oxybutynin.

Because the safety of Uromax tablets in children has not been evaluated, use of the drug in this age group should be with appropriate caution.

Oxybutynin may produce blurred vision.

The safety of Uromax in pregnancy has not been established. Therefore, it should not be used in women of childbearing potential, unless, in the opinion of the physician, the expected benefit to the patient outweighs the possible risk to the fetus.

It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Uromax is administered to a nursing woman.

The symptoms of coronary heart disease, congestive heart failure, cardiac arrhythmias, tachycardia and hypertension may be aggravated following administration of Uromax.

Although not reported for immediate-release or controlled-release oxybutynin formulations, newer antimuscarinic agents used in the treatment of urinary incontinence have been reported to prolong the QT/QTc interval of the electrocardiogram. Some drugs that cause QT/QTc prolongation may increase the risk of the rare, but serious ventricular arrhythmia—torsades de pointes. Patients at risk for QT/QTc prolongation, such as those with clinically relevant heart failure, long QT syndrome, recent significant hypokalemia, or receiving other drugs known to prolong QT/QTc, should be appropriately monitored when receiving oxybutynin. Patients who develop prolonged QT/QTc or symptoms of possible arrhythmia such as dizziness, palpitations, or fainting should be evaluated electrocardiographically and for electrolyte disturbances.

Protect from moisture. Protect from high humidity.

Store at room temperature (15-30°C).

Keep in a safe place out of the reach of children.

Protect from exposure to light.

Plasma concentrations of oxybutynin decline biexponentially following intravenous or oral administration. The volume of distribution is 193 L after intravenous administration of 5 mg oxybutynin chloride.

Oxybutynin is rapidly absorbed from the gastrointestinal tract when given orally. There is inter-individual variability in absorption and it is increased in the presence of food. The terminal plasma elimination half-life of oxybutynin ranges from 2 to 3 hours in healthy individuals to 5 hours in frail elderly individuals.

The rate of absorption of oxybutynin was lower with Uromax than with immediate-release oxybutynin tablets under both fasting and fed conditions, while the extent of absorption of Uromax and immediate-release oxybutynin are equivalent under fed and fasted conditions.

At steady-state, the maximum plasma oxybutynin concentration was lower and the minimum concentration higher with Uromax (15 mg once daily) than with immediate-release oxybutynin (5 mg q8h) (Relative C_max 75%; Relative C_min 220%). Fluctuation in plasma oxybutynin concentrations was lower with Uromax than with immediate-release oxybutynin (135% vs. 319%). Extent of absorption was higher with Uromax than with immediate-release oxybutynin (Relative AUC 136%) but concentrations of the metabolite N-desethyloxybutynin were lower (Relative AUC 76%; Relative C_max 54%) and fluctuation was less with Uromax than immediate-release oxybutynin (148% vs. 255%).

Oxybutynin chloride is a tertiary amine ester with anticholinergic (antimuscarinic), as well as direct spasmolytic and local anesthetic properties. It depresses spontaneous activity of smooth muscle and inhibits contractions produced by non-cholinergic stimulation. It does not have blocking effects at skeletal neuromuscular junctions or autonomic ganglia (nicotinic effects).

In vitro studies of isolated detrusor muscle or intact bladder preparations from several animal species have demonstrated that oxybutynin competitively antagonizes smooth muscle contraction due to acetylcholine or parasympathetic nerve stimulation. In vitro studies of bladder homogenates demonstrate that oxybutynin binds to muscarinic receptor sites.

Oxybutynin also has a direct inhibitory effect on smooth muscle. In vitro studies using isolated detrusor or intact bladder preparations have demonstrated oxybutynin-induced reductions in spontaneous and non-cholinergically induced contractions of the detrusor, with a potency greater than that of atropine. Oxybutynin also demonstrates local anesthetic effects.

The combination of anticholinergic, spasmolytic and local anesthetic actions make oxybutynin a therapeutically useful agent in the treatment of urinary incontinence.

In patients with urinary incontinence, urodynamic studies have demonstrated that oxybutynin increases maximal bladder capacity, detrusor compliance, and volume at first bladder contraction and first desire to void, and decreases maximum detrusor pressure. These effects are associated with decreases in urgency, frequency of micturition and incontinence episodes.

In a steady-state pharmacokinetic study, stimulated saliva output over 24 hours, was greater with Uromax than immediate-release oxybutynin, and subjective evaluations of dry mouth severity were lower with Uromax than immediate-release oxybutynin, indicating less propensity for anticholinergic side effects with Uromax.

The duration of effect of Uromax tablets is 24 hours. Once daily dosing with Uromax provides comparable reductions in micturition frequency, urgency and incontinence episodes to immediate-release oxybutynin, given three times per day. Uromax produced a significant reduction (62%) in night-time incontinence episodes but immediate-release oxybutynin did not. In a study comparing fixed doses of 5, 10 or 15 mg, the reduction in episodes of urinary incontinence was greatest at a daily dose of 15 mg. This was also the dose associated with the greatest level of overall control of urinary symptoms (urgency, frequency and incontinence) and with the highest rating of patient satisfaction, in consideration of both efficacy and side effects.

Only negligible amounts of the parent compound are excreted renally.

Oxybutynin is metabolized through the cytochrome P450 system, specifically the 3A4 enzymes. Oxybutynin is extensively metabolized in the liver and gut wall. The parent compound and the metabolite (N-desethyloxybutynin) are both active and are equipotent. The most abundant but inactive metabolite is phenylcyclohexylglycolic acid.