Ingredients:
Tadalafil 20 mg
Excipients: Lactose, Avicel, Kollidon K30, Talc, Magnesium stearate, Primellose, Aerosil, Sodium lauryl sulfate, HPMC E15, PEG 6000, Titanium dioxide, Sunset yellow lake, Tartrazine lake, Patent dye q.s 1 tablet.
Dosage form: Film coated tablet.
Presentations: A carton contains 5 boxes. Each box of 2 blisters x 2 film coated tablets.
Indications
Mitalis is indicated in cases of erectile dysfunction (impotence) in adult males (the persistent or repeated inability to attain or maintain an erection sufficient for satisfactory sexual performance).
Contraindications
- Hypersensitivity to the active substance or to any of the excipients.
- Co-administration with organic nitrates in any form.
- Women.
- Children aged younger than 18 years.
- Patients with hepatic impairment.
- Patients with moderate and severe renal impairment (creatinine clearance CrCl ≤ 50 ml/min).
Pharmacodynamics:
Priapism is a haemodynamic process based on smooth muscle relaxation in the corpora cavernosa and arterioles. Sexual stimulation triggers release of nitric oxide from endothelial cells and the cavernous nervous terminals in the corpora cavernosa. Nitric oxide activates guanylate cyclase, thereby increasing the synthesis of cyclic guanosine monophosphate (cGMP) in the corpora cavernosa. Cyclic guanosine monophosphate acts to relax smooth muscles in the corpora cavernosa thereby increasing blood flow to the penis, leading to erection. Cyclic guanosine monophosphate is destroyed under the action of phosphodiesterase type 5 (PDE5) which promotes erectile function by increasing the amount of cGMP in the corpora cavernosa. Mitalis (tadalafil) acts to inhibit phosphodiesterase type 5 (PDE5).
Because nitric oxide is only released in the corpora cavernosa under sexual stimulation, the PDE5 inhibitory effect of tadalafil is not present without sexual stimulation. Mitalis works to enhance the body's natural response to sexual stimulation.
Pharmacokinetic properties
- Tadalafil is readily absorbed after oral administration and the mean maximum observed plasma concentration (Cmax) is achieved at a median time of 2 hours after dosing.
- Tadalafil is widely distributed into body tissues. 94% of tadalafil in plasma is bound to proteins. Protein binding is not affected by impaired renal function.
- Tadalafil is predominantly metabolized in the liver. The major circulating metabolite is the methylcatechol glucuronide.
- The mean half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Precautions
- Tadalafil has systemic vasodilatory properties that may result in transient decreases in blood pressure. Physicians should carefully consider whether their patients with certain underlying conditions, such as left ventricular outflow obstruction (such as aortic stenosis or idiopathic undiagnosed aortic valve hypertrophy) could be adversely affected by such vasodilatory effects including phosphodiesterase type 5 inhibitors.
- Tadalafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
- Because there are no data establishing the safety of tadalafil in the following subpopulations, the drug is not recommended in those with severe hepatic failure, end-stage renal disease requiring hemodialysis; in those with resting hypotension (<90/50 mmHg) or hypertension (170/110 mmHg); in those with cardiac failure, a history of stroke or a recent (within 6 months) myocardial infarction, unstable angina; in those with retinal degenerative diseases such as retinitis pigmentosa.
- Because both alpha and tadalafil are vasodilators. In patients who are taking alpha blockers concomitant administration of tadalafil may lead to symptomatic hypotension in some patients. If the patient is stabilized with alpha blockers, tadalafil should be used at the lowest dose.
- The drug should be used with caution in patients with bleeding disorders, progressive duodenal ulcer.
- Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance.
Interactions
- Tadalafil metabolism is principally mediated by CYP3A4 (major route) and 2C9 (minor route). Co-administration of potent cytochrome inhibitors of P450 3A4 (CYP3A4), such as ketoconazole, itraconazole, erythromycin and clarithromycin with tadalafil can significantly increase plasma sildenafil concentrations.
- In contrast, co-administration of CYP34A inhibitors, including rifampicin, phenytoin and carbamazepine with tadalafil can significantly decrease plasma tadalafil concentrations.
Effects on ability to drive and use machines
No well-controlled studies on the effects on the ability to drive and use machines have been performed. As headache, dizziness and drowsiness were reported, patients should be aware of how they might be affected by tadalafil, before driving or using machines.
Dosage & administration
Method of administration:
Tadalafil is for oral use only and can be taken with or without food.
Dosage:
- The recommended dose of tadalafil is 1 tablet, taken at least 30 minutes prior to sexual activity. The maximum dose frequency is once per day. Its effect can last up to 36 hours after oral dosing. It is not recommended for continuous daily.
- Men with renal impairment
Dose adjustments are not required in patients with mild renal impairment (creatinine clearance higher than 50 ml/minute).
Dosage: Patients using other medicinal products:
- The recommended dose of tadalafil as needed is not more than 10 mg every 72 hours for patients receiving drugs concomitantly that are potent cytochrome P450 isoenzyme CYP3A4 such as ketoconazole or HIV-protease inhibitor. In patients who anticipate a frequent use of tadalafil a once daily regimen, the dose should not exceed 2.5 mg.
- The initial recommended dose of tadalafil is 5 mg in patients taking an alpha-blocker.
Undesirable effects
The adverse reactions reported were transient, and generally mild or moderate.
· Common:
- Headache, flushing and indigestion.
- Visual disturbances such as blurred vision, photophobia, chromatopsia, cyanopsia, eye irritation, and eye pain and redness.
· Uncommon:
- Dizziness, insomnia, anxiety, dizziness, epistaxis, nasal congestion, fever and gastrointestinal disturbances such as diarrhea and vomiting. Priapism can occur.
- Skin rash, erythema, hair loss, back pain or leg pain, muscle aches, edema, water retention, paresthesias and urinary tract infections.
- Difficulty breathing, cough, rhinitis, sinusitis, bronchitis and cellulitis can occur. Sudden hearing loss has been also reported.
· Rare:
- Retinal hemorrhage, Non-arteritic anterior ischaemic optic neuropathy (NAION) that causes permanent blindness.
- Anemia, leucopenia, gynaecomastia, frequent urination or urinary incontinence, bloody urine and seizures.
- Cerebral hemorrhage and transient ischemia.
- Palpitations, syncope, hypertension, hypotension and severe cardiovascular events including myocardial infarction, arrhythmia, tachycardia, unstable angina, sudden death from the heart.
Inform your doctor about any side effects that may occur during the treatment.
Overdose
In cases of overdose, standard supportive measures should be adopted, as required. Haemodialysis contributes negligibly to tadalafil elimination.
Shelf-life: 36 months from the manufacturing.
Storage: Store in cool dry places, below 300C, protect from direct light.
Specifications: Manufacturer’s