Tadalafil should NOT be used in

(B) Patient on Nitrates therapy[?]Sildenafil, Tadalfil, Vardenafil & Avanafil are the only approved & effective oral agents for the treatment of Erectile Dysfunction.oThese 4 drugs markedly improved the management of erectile dysfunction, because they are effective for the treatment of a broad range of causes, including psychogenic, diabetic, vasculogenic, post-radical prostatectomy (nerve-sparing procedures), & spinal cord injury.oThese are Selective & Potent Inhibitors of PDE-5, the predominant phosphodiesterase isoform found in the penis.DrugOnset of ActionHalf-lifeDoseAdverse EffectsContraindicationsTadalafilTmax,30-60 min Duration, 12-36 h Plasma concentration Not affected by food or ETOH17.5 h10 mg, 20 mg; 2.5 or 5 mg or daily doseHeadache,dyspepsia,back pain,nasalcongestion,myalgiaNitratesHypotensionCardiovascular risk factorsRetinitis pigmentosaChange dose with some antiretroviralsShould be on stable dose of alpha blockers[?]Significant Drug Interactions & Contraindications:oPhosphodiesterase 5 (PDE5) inhibitors include Sildenafil (Viagra), Vardenafil (Levitra), & Tadalafil (Cialis).-The administration of any of these drugs with doses of any Nitrate is contraindicated.-The combination can cause dangerously low blood pressure.[?]Contraindications of Tadalafil Black 80 mg:oThe consumption of this drug is chiefly avoided due to some medical issues in men like:-Abnormal conditions or deformity of genitals-Hypersensitivity problem to any ingredient of this drug.-Heart related problems-Severe renal insufficiency-History of stroke & heart attack-Severe pulmonary disorders.-Patients with history of AMI/stroke/fatal arrhythmias <6 month Nitrates - total contraindication/PDEIs in small dose + spacing at least 24 hrs (48 hrs with Tadalafil) for fear of developing IHD/AMI due to severe hypotension.oPrecautions for Tadalafil:-With alpha blockers (except Tamsulosin) - orthostatic hypotension.-With hepato/renal insufficiency.-With Pyronie's disease-With bleeding tendencies (leukemia's, hemophilia, Vitamink K deficiency, Antiphospholipid syndrome... etc).-With quinidine, procainamide, amiodarone (class I & III antiarhtmics) (Vardenafil).-Dose adjustment; when using drugs that have interaction on hepatic livery microsomal enzymes i.e., inhibitors or inducers.-Retinitis pigmentosa.OTHER OPTIONS[?]Nitrates are vasodilators acts by producing vascular smooth muscle relaxation through cGMP pathway.-Cyclic GMP is hydrolyzed to 5 GMP by PDE5-Tadalafil is a Phosphodiesterase 5 (PDE5) inhibitors-Inhibition of PDE5 prolongs and accentuates the cGMP in smooth muscle causes relaxation.-Taking tadalafil with vasodilator drug like nitrate can cause sudden & serious decrease in blood pressure.oTadalafil in treatment of Pulmonary Arterial Hypertension is used to improve haemodynamics & excercise ability oTadalafil in treatment of Sexual dysfunction like Erectile dysfunction is treated by5-20 mg taken 1-2 h before sex, is now the standard treatment for maintaining erections.oRemember1-Combination with vasodilators results in sudden changes of blood pressure values:-Tadalafil relaxes muscles of the blood vessels and increases blood flow to particular areas of the body.-Used to treat erectile dysfunction, and symptoms of benign prostatic hypertrophy-Also in treatment of Pulmonary Arterial Hypertension is used to improve haemodynamics & excercise ability.oWhen given alone to men with severe coronary artery disease, these drugs have modest effects on blood pressure, producing >10% fall in systolic, diastolic & mean systemic pressures & in pulmonary artery systolic & mean pressures.oSildenafil, tadalafil & vardenafil all have a significant & potentially dangerous interaction with organic nitrates, the therapeutic actions of which are mediated via their conversion to NO with resulting increases in cyclic GMP.oIn the presence of a PDE5 inhibitor, nitrates cause profound increases in cyclic GMP and can produce dramatic reductions in blood pressure.