Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK
Oxybutynin is associated with anticholinergic central nervous system (CNS) effects (see section 4.8). Anticholinergic CNS effects (e.g., hallucinations, agitation, confusion, somnolence) have been reported; monitoring recommended especially in first few months after initiating therapy or increasing the dose; consider discontinuing therapy or reducing the dose if anticholinergic CNS effects develop.
Angioedema of the face, lips, tongue and/or larynx has been reported with oxybutynin. In some cases, angioedema occurred after the first dose. Angioedema associated with upper airway swelling has the potential to become life-threatening. If involvement of tongue, hypopharynx, or larynx occurs, oxybutynin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.
Oxybutynin should be given with caution in patients with the following conditions:
Oxybutynin should be used with caution in the frail elderly who may be more sensitive to the effects of oxybutynin. Anticholinergics should be used with caution in elderly patients due to the risk of cognitive impairment.
If urinary tract infection is present, an appropriate antibacterial therapy should be started.
Oxybutynin may aggravate tachycardia (and thus the symptoms of hyperthyroidism, congestive heart failure, cardiac arrhythmia, coronary heart disease, hypertension), cognitive disorders and symptoms of prostatic hypertrophy.
When oxybutynin is used in patients with fever or in high environmental temperatures, this can cause heat prostration, or heat stroke, due to decreased sweating.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Oxybutynin may reduce salivary secretions, which could result in dental caries, parodontotsis, or oral candidiasis.
As oxybutynin can cause angle-closure glaucoma, visual acuity and intraocular pressure should be monitored periodically during therapy. Patients should be advised to contact a physician immediately if they are aware of a sudden loss of visual acuity or ocular pain.
Oxybutynin hydrochloride is not recommended for use in children below age 5 years due to insufficient data on safety and efficacy.
There is limited evidence supporting the use of Oxybutynin in children with monosymptomatic nocturnal enuresis (not related to detrusor overactivity).
In children over 5 years of age, Oxybutynin hydrochloride should be used with caution as they may be more sensitive to the effects of the product, particularly the CNS and psychiatric adverse reactions.
The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity, such as amantadine and other anticholinergic antiparkinsonian medicinal products (e.g. biperiden, levodopa), antihistamines, antipsychotics (e.g. phenothiazines, butyrophenones, clozapine), quinidine, digitalis, tricyclic antidepressants, atropine and related compounds like atropinic antispasmodics and dipyridamole.Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. They may also antagonize the gastrointestinal prokinetic effects of metoclopramide and domperidone. Sublingual nitrates may fail to dissolve under the tongue owing to dry mouth, resulting in reduced therapeutic effect.
Oxybutynin is metabolised by cytochrome P450 isoenzyme CYP3A4. Concomitant administration with a CYP3A4 inhibitor can inhibit oxybutynin metabolism and increase oxybutynin exposure. Mean oxybutynin chloride concentrations were approximately 2 fold higher when Lyrinel XL was administered with ketoconazole, a potent CYP3A4 inhibitor. Other inhibitors of cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g. itraconazole and fluconazole) or macrolide antibiotics (e.g. erythromycin), may increase oxybutynin exposure. The clinical relevance of such potential interaction is not known. Caution should be used when such drugs are co-administered.
Concomitant use with cholinesterase inhibitors may result in reduced cholinesterase inhibitor efficacy.
Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as oxybutynin.
Interaction studies have only been performed in adults. It is not known whether the extent of interactions in the paediatric population is similar to that in adults.
There are no adequate data on the use of oxybutynin in pregnant women. Studies in animals have shown minor reproductive toxicity (see section 5.3). Lyrinel XL is not recommended during pregnancy.
When oxybutynin is used during breastfeeding, a small amount is excreted in the mother’s milk. The effect on newborns/infants is unknown. Use of Lyrinel XL during breastfeeding is therefore not recommended.
Reproduction studies with oral oxybutynin in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility.
Oxybutynin has minor influence on the ability to drive and use machines. Oxybutynin may produce drowsiness or blurred vision; therefore, patients should be cautioned regarding activities requiring mental alertness such as driving, operating machinery or performing hazardous work while taking this drug.
The most common adverse reactions reported during clinical trials by >5% of patients were dry mouth, constipation, diarrhoea, headache, somnolence and dizziness.
Serious adverse reactions associated with oxybutynin include anticholinergic central nervous system effects (see section 4.4).
The safety of Lyrinel XL was evaluated in five double-blind, controlled (i.e. placebo or active comparator) clinical trials for the management of overactive bladder, in which 759 adult subjects received doses ranging from 5 to 20 mg/day. Additionally, safety was evaluated in one open-label (i.e. active comparator) clinical trial, in which 60 paediatric subjects received doses of 10 or 15 mg/day. Table 1 below reflects the adverse drug reactions reported with Lyrinel XL in clinical trials in adults and from postmarketing experience. Adverse drug reactions reported in the paediatric clinical trial are shown in Table 2.
Table 1. Adverse drug reactions reported in clinical trials in adults and from postmarketing experience:
Common: Urinary tract infection
Uncommon: Hypersensitivity
Not Known*: Anaphylactic reaction
Uncommon: Anorexia, Fluid retention, Decreased appetite
Common: Insomnia
Uncommon: Hallucinations, Confusional state, Agitation, Memory impairment
Not Known*: Psychotic disorder, Anxiety, Nightmares, and Paranoia, symptoms of depression, dependence (in patients with history of drug or substance abuse)
Common: Somnolence, Dizziness, Headache, Dysgeusia
Uncommon: Convulsions
Not Known*: Cognitive disorders
Common: Vision blurred, Dry eye
Uncommon: Angle closure glaucoma
Not Known*: Mydriasis, Ocular hypertension
Common: Palpitations
Uncommon: Arrhythmia, Tachycardia
Uncommon: Hypertension, Flushing
Common: Oropharyngeal pain, Cough, Nasal dryness, Dry throat
Uncommon: Dysphonia, Nasal congestion, Throat irritation
Very Common: Dry mouth
Common: Gastroesophageal reflux disease, Abdominal pain, Dyspepsia, Constipation, Diarrhoea, Nausea, Flatulence
Uncommon: Dysphagia, Abdominal discomfort, Frequent bowel movements, Vomiting
Not Known*: Pseudo-obstruction in patients at risk (elderly or patients with constipation and treated with other medicinal products that decrease intestinal motility)
Common: Dry skin, Pruritus
Uncommon: Urticaria, Rash
Not Known*: Angioedema, Hypohidrosis
Common: Dysuria, Urinary hesitation
Uncommon: Urinary retention, Residual urine
Not Known*: Impotence
Common: Fatigue
Uncommon: Chest discomfort, Mucosal dryness, Thirst
Common: Residual urine volume+
Uncommon: Fall
Not Known*: Heat stroke
* Cannot be estimated from the available clinical data.
+ The bundled term residual urine volume consists of the preferred terms residual urine volume and residual urine volume increased.
The following postmarketing adverse reactions listed in Table 1 are from postmarketing reports only (not seen in clinical trials), with the frequency category estimated from clinical trial safety data comprising 759 patients: hallucinations, agitation, memory impairment, and convulsions. These estimates represent the upper limit of the 95% CI.
As with other oxybutynin formulations, dry mouth was the most frequently reported adverse drug reaction. However, in clinical studies, dry mouth has been less frequently reported with Lyrinel XL than with oxybutynin immediate release formulations. For patients who required final doses of 5 or 10 mg of Lyrinel XL, the relative incidence of dry mouth that occurred at any dose level was 1.8 times lower compared with patients who required final doses >10 mg.
The safety of Lyrinel XL was evaluated in 60 paediatric subjects (age range 5 to 15 years; dose range 10-15 mg/day) who participated in an open-label, active control, three-arm clinical trial. Adverse drug reactions reported by Lyrinel XL-treated paediatric subjects in this clinical trial are shown in Table 2.
Table 2. Adverse drug reactions reported in clinical trials with paediatric subjects:
Common: Anorexia
Common: Insomnia
Common: Headache
Common: Flushing
Very Common: Constipation
Common: Diarrhoea
Common: Rash, Pruritus
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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