Presentation and Status in Health Basket
30 X 1 mg
30 X 2 mg
30 X 4 mg
Posology: Cadex may be administered in the morning or the evening.
Hypertension: Cadex is used in a once daily regimen: the initial dose is 1mg, to minimise the potential for postural hypotension and/or syncope. Dosage may then be increased to 2mg after an additional one or two weeks of therapy and thereafter, if necessary to 4mg. The majority of patients who respond to Cadex will do so at a dose of 4mg or less. Dosage can be further increased if necessary to 8mg or the maximum recommended dose of 16mg.
Benign prostatic hyperplasia: The recommended initial dosage of Cadex is 1mg given once daily to minimise the potential for postural hypotension and/or syncope. Depending on the individual patient’s urodynamics and BPH symptomatology dosage may then be increased to 2mg and thereafter to 4mg and up to the maximum recommended dose of 8mg. The recommended titration interval is 1-2 weeks. The usual recommended dose is 2-4mg daily.
Paediatric population: The safety and efficacy of doxazosin in children and adolescents have not been established.
Elderly patients: Normal adult dosage.
Patients with renal impairment: Since there is no change in pharmacokinetics in patients with impaired renal function, the usual adult dose of doxazosin is recommended. Doxazosin is not dialysable.
Patients with hepatic impairment: There are only limited data in patients with liver impairment and on the effect of drugs known to influence hepatic metabolism (e.g. cimetidine). As with any drug wholly metabolised by the liver, doxazosin should be administered with caution to patients with evidence of impaired liver.
Method of administration: Oral administration.
For the treatment of benign prostatic hyperthropy.
Doxazosin is contraindicated in:
Hypersensitivity to the active substance or other types of quinazolines (e.g. prazosin, terazosin), or to any of the excipients.
Patients with a history of orthostatic hypotension.
Patients with benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones.
Patients with hypotension (for benign prostatic hyperplasia indication only).
Doxazosin is contraindicated as monotherapy in patients with either overflow bladder or anuria with or without progressive renal insufficiency.
Postural Hypotension/Syncope: Initiation of Therapy – In relation with the alpha-blocking properties of doxazosin, patients may experience postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the commencement of therapy. Therefore, it is prudent medical practice to monitor blood pressure on initiation of therapy to minimise the potential for postural effects.
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.
Use in patients with Acute Cardiac Conditions: As with any other vasodilatory anti-hypertensive agent it is prudent medical practice to advise caution when administering doxazosin to patients with the following acute cardiac conditions:
– pulmonary oedema due to aortic or mitral stenosis
– high-output cardiac failure
– right-sided heart failure due to pulmonary embolism or pericardial effusion
– left ventricular heart failure with low filling pressure.
Use in Hepatically Impaired patients: As with any drug wholly metabolised by the liver, doxazosin should be administered with particular caution to patients with evidence of impaired hepatic function. Since there is no clinical experience in patients with severe hepatic impairment use in these patients is not recommended.
Use with PDE-5 Inhibitors: Concomitant administration of doxazosin with phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, and vardenafil) should be done with caution as both drugs have vasodilating effects and may lead to symptomatic hypotension in some patients. To reduce the risk of orthostatic hypotension it is recommended to initiate the treatment with phosphodiesterase-5-inhibitors only if the patient is hemodynamically stabilized on alpha-blocker therapy. Furthermore, it is recommended to initiate phosphodiesterase-5-inhibitor treatment with the lowest possible dose and to respect a 6-hour time interval from intake of doxazosin. No studies have been conducted with doxazosin prolonged release formulations.
Use in patients undergoing cataract surgery: The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.
Priapism: Prolonged erections and priapism have been reported with alpha-1 blockers including doxazosin in post marketing experience. If priapism is not treated immediately, it could result in penile tissue damage and permanent loss of potency, therefore the patient should seek immediate medical assistance.
Screening for Prostate Cancer: Carcinoma of the prostate causes many of the symptoms associated with BPH and two disorders can co-exist. Carcinoma of the prostate should therefore be ruled out prior to commencing therapy with doxazosin for treatment of BPH symptoms.
Cadex contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Hypertension: In clinical trials involving patients with hypertension, the most common reactions associated with doxazosin therapy were of a postural type (rarely associated with fainting) or non-specific.
Benign prostatic hyperplasia: Experience in controlled clinical trials in BPH indicates a similar adverse event profile to that seen in hypertension.
The following undesirable effects have been observed and reported during treatment with doxazosin with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Infections and infestations: Common: respiratory tract infection, urinary tract infection.
Blood and the lymphatic system disorders: Very rare: leukopenia, thrombocytopenia.
Immune system disorders: Uncommon: allergic drug reaction.
Metabolism and nutrition disorders: Uncommon: gout, increased appetite, anorexia.
Psychiatric disorders: Uncommon: agitation, depression, anxiety, insomnia, nervousness.
Nervous system disorders: Common: somnolence dizziness, headache. Uncommon: cerebrovascular accident, hypoesthesia, syncope, tremor. Very rare: dizziness postural, paraesthesia.
Eye disorders: Very rare: blurred vision. Unknown: intraoperative floppy iris syndrome.
Ear and labyrinth disorders: Common: vertigo. Uncommon: tinnitus.
Cardiac disorders: Common: palpitation, tachycardia. Uncommon: angina pectoris, myocardial infarction. Very rare: bradycardia, cardiac arrhythmias.
Vascular disorders: Common: hypotension, postural hypotension. Very rare: hot flushes.
Respiratory, thoracic and mediastinal disorders: Common: bronchitis, cough, dyspnoea, rhinitis. Uncommon: epistaxis. Very rare: bronchospasm.
Gastrointestinal disorders: Common: abdominal pain, dyspepsia, dry mouth, nausea. Uncommon: constipation, flatulence, vomiting, gastroenteritis diarrhoea.
Hepato-biliary disorders: Uncommon: abnormal liver function tests. Very rare: cholestasis, hepatitis, jaundice.
Skin and subcutaneous tissue disorders: Common: pruritus. Uncommon: skin rash. Very rare: urticaria, alopecia, purpura.
Musculoskeletal, connective tissue and bone disorders: Common: back pain, myalgia. Uncommon: arthralgia. Rare: muscle cramps, muscle weakness.
Renal and urinary disorders: Common: cystitis, urinary incontinence. Uncommon: dysuria, micturition frequency, haematuria. Rare: polyuria. Very rare: increased diuresis, micturition disorder, nocturia.
Reproductive system and breast disorders: Uncommon: impotence. Very rare: gynecomastia, priapism. Unknown: retrograde ejaculation.
General disorders and administration site conditions: Common: asthenia, chest pain, influenza-like symptoms, peripheral oedema. Uncommon: pain, facial oedema. Very rare: fatigue, malaise.
Investigations: Uncommon: weight increase.
Phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil): Concomitant administration of doxazosin with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients. No studies have been conducted with doxazosin prolonged release formulations.
Doxazosin is highly bound to plasma proteins (98%). In vitro data in human plasma indicates that doxazosin has no effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin or indomethacin).
In vitro studies suggest that doxazosin is a substrate of cytochrome P450 3A4 (CYP 3A4). Caution should be exercised when concomitantly administering doxazosin with a strong CYP 3A4 inhibitor, such as clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole.
Conventional doxazosin has been administered without any adverse drug interaction in clinical experience with thiazide diuretics, furosemide, beta-blocking agents, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycaemic drugs, uricosuric agents, or anticoagulants. However, data from formal drug/drug interaction studies are not present.
Doxazosin potentiates the blood pressure lowering activity of other alpha-blockers and other antihypertensives.
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 1 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
For the hypertension indication:
Pregnancy: As there are no adequate and well-controlled studies in pregnant women, the safety of doxazosin during pregnancy has not yet been established. Accordingly, during pregnancy, doxazosin should be used only when, in the opinion of the physician, the potential benefit outweighs the potential risk. Although no teratogenic effects were seen in animal testing, reduced foetal survival was observed in animals at extremely high doses.
Lactation: The excretion of doxazosin in breast milk was demonstrated to be very low (with the relative infant dose less than 1%) however human data is very limited. A risk to the newborn or infant cannot be excluded and therefore doxazosin should be used only when in the opinion of the physician, the potential benefit outweighs the potential risk.
For the benign prostatic hyperplasia indication: This section is not applicable.
Should overdosage lead to hypotension, the patient should be immediately placed in a supine, head down position. Other supportive measures may be appropriate in individual cases.
If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressor should then be used. Renal function should be monitored and supported as needed.
Since doxazosin is highly protein bound, dialysis is not indicated.
Lactose: Cadex contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.