CIALIS® (Tadalafil) is an oral medication which is presented in tablet form used in the treatment of erectile dysfunction. It selectively inhibits cyclic guanosine monophosphate (cGMP). Tadalafil with the empirical formula C22H19N304 has molecular weight of 389.41. The structural formula for Tadalafil is represented below:
The IUPAC nomenclature of Tadalafil is (6R-trans)-6-(1,3-benzodioxol-5-yl)- 2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino [1', 2':1,6] pyrido[3,4-b]indole-1,4-dione. It comes in the crystalline form which is slightly soluble in ethanol but insoluble in water.
Cialis is presented as almond-shaped, film-coated tablets for oral use. Each tablet of Cialis contains 5, 10, or 20mg of the active substance Tadalafil and other excipients (Inactive ingredients or adjuvant materials) such as lactose monohydrate, hydroxypropyl cellulose, croscarmellose sodium, microcrystalline cellulose, hypromellose, magnesium stearate, titanium dioxide, talc, sodium lauryl sulfate, triacetin and iron oxide.
Mechanism of Action
Erection during sexual activity is caused by elevated blood flow to the tissues of the penis resulting from the relaxation of the arteries in the penis and the smooth muscle corpus cavernosal. This response is elicited as a result of the release of the neurotransmitter Nitric oxide from the endothelial cells and nerve terminals, which in turn stimulates the production of cyclic GMP in the smooth muscle cells. The chemical entity is responsible for the smooth muscle relaxation and the enhanced blood flow to the corpus cavernosum. The blockage of phosphodiesterase 5 (PDE5), strengthens erectile function by increasing the production of cGMP. Tadalafil blocks the Phosphodiesterase type 5 pathways. Because sexual arousal or stimulation is required for the release of nitric oxide, the blockage of PED5 by Tadalafil has no significant effect in the absence of sexual arousal.
Indications and usage
Cialis is indicated for the treatment of erectile dysfunction.
Nitrates - The administration of Tadalafil to patients who are placed on any form of nitrate medication, either intermittently or regularly is contraindicated. Clinical trials and research showed that Tadalafil potentiated the hypotensive effect of organic nitrates. This is explained to be as a result of the resultant effects of nitrates and Tadalafil on the cGMP/nitric oxide pathway.
Hypersensitivity - Cialis is contraindicated in patients with an established hypersensitivity to Tadalafil or any other component of the tablet.
The cardiovascular status of the patients must be considered by physicians before Tadalafil is prescribed, since there is a potential cardiovascular risk associated with vigorous sexual activity. Therefore, the treatment of erectile dysfunction using CIALIS should be discouraged in Men who have been cautioned to downplay sexual activity because of their cardiovascular status.
In the evaluation of erectile dysfunction, adequate medical assessment must be conducted to identify possible underlying causes as well as the appropriate treatment options.The following should be considered before prescribing Cialis:
Caution is advised when Phosphodiesterase type 5 inhibitors and other analogs are administered concomitantly with alpha blockers. CIALIS which mechanism of action is by inhibiting PDE5 and alpha-adrenergic blocking agents are both vasodilators capable of causing sharp reduction in blood-pressure. When two potent vasodilators are co-administered, a gross effect on blood pressure should be expected.
In patients with renal insufficiency or end-stage renal disease (ESRD), the dose of CIALIS should be limited to 5mg and frequency of dosage should not be more than once daily.
Patients who are down with moderate or mild hepatic impairment, the dose of CIALIS prescribed should not be more than 10 mg. Because of inadequate information in this group of patient, the use of CIALIS is not recommended.
Effects of Other Drugs on CIALISCytochrome P450 Inhibitors
CIALIS is a substrate of and extensively metabolized by CYP3A4. Research has shown that drugs that inhibit CYP3A4 delay the metabolism of Tadalafil in the body leading to increased exposure of the anti-erectile dysfunction agent to targeted receptors.
Ketoconazole - Ketoconazole often administered as 400mg daily is a potent inhibitor of CYP3A4, elevated Tadalafil single dose 20-mg exposure (AUC) by 314% and Cmax by 24%, when compared with the values gotten when Tadalafil 20-mg was administered alone.
Cytochrome P450 Inducers
Clinical trials have shown that drugs that induce the enzyme CYP3A4 can decrease duration of action of Tadalafil by speeding up its rate of metabolism.Rifampin- A CYP3A4 inducer usually administered 600 mg, decreased the single-dose exposure of Tadalafil 10-mg (AUC) by 86% and Cmax by 44%, compared to the values gotten when Tadalafil 10 mg is administered alone. Other CYP3A4 inducers include phenytoin, phenobarbital and carbamazepine which would decrease the duration of action of Tadalafil alike.
The following adverse reactions were reported when Tadalafil was taken in a placebo-controlled clinical trial
Pain in limb
Dosage and administrations
The recommended dose for Cialis in most patients is 10 mg, taken 30 minutes prior to sexual activity. The dose may however be increased to 20 mg or reduced to 5 mg, depending on the subject tolerability. Frequency of dosing should not exceed once daily.