Uripas™

[Doxazosin Mesylate]

Uripas

Description / Properties

Therapeutic Indications Hypertension Doxazosin is indicated for the treatment of hypertension and can be used as the initial agent to control blood pressure in the majority of patients. In patients not adequately controlled on a single antihypertensive agent doxazosin may be used in combination with another agent such as a thiazide diuretic, a beta-blocker, a calcium antagonist or an angiotensin-converting enzyme inhibitor.

Benign Prostatic Hyperplasia Doxazosin is indicated for the treatment of clinical symptoms in benign prostatic hyperplasia (BPH) and for reduced, urinary flow associated with BPH. Doxazosin may be used in BPH patients who are either hypertensive or normotensive. While the blood pressure changes in normotensive patients with BPH are clinically insignificant, patients with hypertension and BPH have had both conditions effectively treated with doxazosin monotherapy.

Contraindication

Doxazosin is contraindicated in patients with a known hypersensitivity to quinazolines, doxazosin, or any of the inert ingredients.

Side Effects

Hypertension In controlled clinical trials, the most common reactions associated with doxazosin were of a postural type (rarely associated with syncope) or non-specific and included:

  • Ear and Labyrinth Disorders : vertigo Gastrointestinal Disorders: nausea General Disorders and Administration Site Conditions: asthenia, edema, fatigue, malaise
  • Nervous System Disorders: dizziness, headache, postural dizziness, somnolence, syncope
  • Respiratory, Thoracic and Mediastinal Disorders: rhinitis
  • Benign Prostatic Hyperplasia Experience in controlled clinical trials in BPH indicates a similar adverse event profile to that seen in hypertension. In post-marketing experience, the following additional adverse events have been reported:
  • Blood and Lymphatic Disorders: leukopenia, thrombocytopenia Ear and Labyrinth Disorders: tinnitus Eye Disorders: blurred vision Gastrointestinal Disorders: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, mouth dry, vomiting General Disorders and Administrations Site Conditions: pain.
  • Hepatobiliary Disorders: cholestasis, hepatitis, jaundice
  • Immune System Disorders: allergic reaction
  • Investigations: abnormal liver function tests, weight increase.
  • Metabolism and Nutrition: anorexia.
  • Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain, muscle cramps, muscle weakness, myalgia.
  • Nervous System Disorders: hypoesthesia, paresthesia, tremor.
  • Psychiatric Disorders: agitation, anxiety, depression, insomnia, nervousness.
  • Renal and Urinary Disorders: dysuria, hematuria, micturition disorder, micturition frequency, nocturia, polyuria, urinary incontinence.
  • Reproductive System and Breast Disorder: gynecomastia, impotence, priapism.
  • Respiratory, Thoracic and Mediastinal Disorders: bronchospasm aggravated, coughing, dyspnea, epistaxis
  • Skin and Subcutaneous Tissue Disorders: alopecia, pruritus, purpura, skin rash, urticaria
  • Vascular Disorders: hot flushes, hypotension, hypotension postural. The following additional adverse events have been reported in marketing experience among patients treated for hypertension but these, in general, are not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin: bradycardia, tachycardia, palpitation, chest pain, angina pectoris, myocardial infarction, cerebrovascular accidents, and cardiac arrhythmias.

    Warning and Precautions

    Postural Hypotension / Syncope As with all alpha-blockers, a very small percentage of patients have experienced postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the commencement of therapy (see section 4.2 Posology and Method of Administration). When instituting therapy with any effective alpha-blocker, the patient should be advised how to avoid symptoms resulting from postural hypotension and what measures to take should they develop. The patient should be cautioned to avoid situations where injury could result should dizziness or weakness occur during the initiation of doxazosin therapy.

    Impaired Hepatic Function As with any drug wholly metabolized by the liver, doxazosin should be administered with caution to patients with evidence of impaired hepatic function (see section 5.2 Pharmacokinetic Properties).

    Interaction with Other Medicaments and Other Forms of Interaction

    Most (98 % ) of plasma doxazosin is protein bound. In vitro data in human plasma indicate that doxazosin has no effect on protein binding of digoxin, warfarin, phenytoin or indomethacin. Doxazosin has been administered without any adverse drug interaction in clinical experience with thiazide diuretics, frusemide, beta-blockers, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycemic drugs, uricosuric agents, or anticoagulants. In an open-label, randomized, placebo controlled trial in 22 healthy male volunteers, the administration of a single 1 mg dose of doxazosin on day I of a four-day regimen of oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean AUC of doxazosin, and no statistically significant changes in mean Cmax and mean half-life of doxazosin. The 10% increase in the mean AUC for doxazosin with cimetidine is within intersubject variation (27%) of the mean AUC for doxazosin with placebo.

    Pregnancy and Lactation

    Although no teratogenic effects were seen in animal testing with doxazosin, reduced fetal survival was observed in animals at extremely high doses. These doses were approximately 300 times the maximum human recommended dose. Animal studies have shown that doxazosin accumulates in breast milk. As there are no adequate and well controlled studies in pregnant or nursing women, the safety of doxazosin during pregnancy or lactation has not yet been established. Accordingly, during pregnancy or lactation, doxazosin should be used only when in the opinion of the physician; the potential benefit outweighs the potential risk.

    Effects on Ability to Drive and Use Machines

    The ability to engage in activities such as operating machinery or operating a motor vehicle may be impaired, especially when initiating doxazosin therapy.

    Dosage

    Hypertension The full dosage range of doxazosin is 1-16 mg daily. It is recommended that therapy be initiated at I mg given once daily for one or two weeks to minimize the potential for postural hypotension and/or syncope (see section 4.4 Special Warnings and Special Precautions for Use). The dosage may then be increased to 2 mg once daily for an additional one or two weeks. If necessary the daily dosage should then be increased gradually at similar intervals to 4 mg, 8 mg, and 16 mg as determined by patient response to achieve the desired reduction in blood pressure. The usual dose is 2-4 mg once daily.

    Benign Prostatic Hyperplasia The recommended initial dosage of doxazosin is 1 mg given once daily to minimize the potential for postural hypotension and/or syncope (see section 4.4 Special Warnings and Special Precautions for Use). Depending on the individual patient's urodynamics and BPH symptomatology, dosage may then be increased to 2 mg and thereafter to 4 mg and up to the maximum recommended dose of 8 mg. The recommended titration interval is 1-2 weeks. The usual recommended dose is 2-4 mg once daily.

    Use in Elderly

    Normal adult dosage is recommended. Use In Renally Impaired Patients Since the pharmacokinetics of doxazosin are unchanged in patients with renal insufficiency and there is no evidence that doxazosin aggravates existing renal dysfunction, the usual dosages may be used in these patients.

    Use in Hepatically Impaired Patients See section 4.4 Special Warnings and Special Precautions for Use.

    Use In Children The safety and efficacy of doxazosin in children have not been established.

    Overdose

    Should overdosage lead to hypotension, the patient should be immediately placed in a supine, head down position. Other supportive measures should be performed if thought appropriate in individual cases. Since doxazosin is highly protein bound, dialysis is not indicated.

    Presentations Available

    Blister cards, with clear PVC coated with PVDC on one side, and printed aluminum foil on the other. Two blister cards of 10 tablets each in a carton.

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