Udenafil instructions for use, how to take?

This page is an instruction manual for the use of udenafil and all generics based on it, presented in the GENERICS catalog: Zudena 100, Zudena 200, Udaforce 100, Udaforce 200, and others. Their active ingredient is the same — udenafil. The mechanism of action, dosages, contraindications, and interactions are identical for all of these drugs.

What is udenafil

Udenafil is a synthetic compound from the group of PDE-5 (phosphodiesterase type 5) inhibitors, developed by the South Korean company Dong-A Pharmaceutical Co., Ltd (Seoul, Korea) under the trade name Zydena®. The drug was registered in the Republic of Korea in 2005 — it is the first PDE-5 inhibitor of Korean origin approved for the treatment of erectile dysfunction (ED).[1]

By its mechanism of action, udenafil belongs to the same pharmacological group as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra). However, udenafil has a unique pharmacokinetic profile: it combines a relatively rapid onset of action (30–60 minutes) with a long-lasting effect of up to 12 hours — an intermediate position between "short-acting" PDE-5 inhibitors (sildenafil, vardenafil) and long-acting tadalafil.[2]

In the GENERICS catalog, udenafil is presented in dosages of 100 mg and 200 mg from the manufacturers Sunrise Remedies and Fortune Health Care (India) — companies with GMP certification. Generics contain the same molecule, undergo production control, and cost significantly less than the original Zydena®.

How udenafil works

The mechanism of action of udenafil is identical to other PDE-5 inhibitors. Upon sexual arousal, the nerve endings of the penis release nitric oxide (NO), which triggers the synthesis of cyclic guanosine monophosphate (cGMP). It is cGMP that relaxes the smooth muscles of the vessels of the corpora cavernosa, ensuring blood flow and the formation of an erection.

The PDE-5 enzyme constantly destroys cGMP. In erectile dysfunction, its activity is excessive: cGMP breaks down faster than it is produced, and the erection does not reach the required hardness or quickly fades. Udenafil blocks PDE-5, allowing cGMP to accumulate and act longer. As a consequence, upon sexual arousal, the vascular response becomes fully functional.

Scheme: upon sexual arousal, nitric oxide is produced → triggers cGMP synthesis → relaxes blood vessels → erection. The PDE-5 enzyme destroys cGMP and dampens the process. Udenafil blocks PDE-5, preventing cGMP from being destroyed prematurely.

Important: udenafil, like all PDE-5 inhibitors, does not cause an erection on its own. Sexual arousal is necessary for its work. Without it, the drug does not work.[3]

Pharmacokinetics: why udenafil is "medium" in duration

Udenafil occupies a special niche among PDE-5 inhibitors. Understanding its pharmacokinetics helps to better plan the intake.

Absorption: after oral administration, udenafil is rapidly absorbed. Peak plasma concentration (Cmax) is achieved in 0.8–1.3 hours when taken on an empty stomach.[4] This is faster than tadalafil (Tmax about 2 hours) and comparable to vardenafil.

Half-life: udenafil is eliminated from the body monoexponentially with a terminal half-life (T1/2) of 7.3–12.1 hours.[4] This is significantly longer than sildenafil or vardenafil (~4 hours), but shorter than tadalafil (~17.5 hours). Such T1/2 determines the clinically significant duration of the effect up to 12 hours.

Metabolism: udenafil is metabolized predominantly by the CYP3A4 enzyme to form the active metabolite DA-8164, which possesses approximately half the pharmacological activity compared to the parent molecule.[5] This is important to consider when co-administered with CYP3A4 inhibitors or inducers.

Accumulation with multiple dosing: with daily use of udenafil, a steady-state state is achieved by day 5, while no significant accumulation of the drug is observed.[4]

Dosages

In clinical trials, udenafil was studied in the range of 25 to 200 mg. The GENERICS catalog presents two dosages.

• 100 mg — standard therapeutic dose

The recommended starting dose for most men. In phase III clinical trials, it was the 100 mg dose that demonstrated a significant improvement in erectile function on the IIEF scale compared to placebo.[3] With a sufficient effect, there is no need to increase the dose.

• 200 mg — increased dose

It is used in case of insufficient response to 100 mg. No statistically significant difference in efficacy between 100 mg and 200 mg was found in a number of studies, but the frequency of side effects with 200 mg is higher.[3] Switching to 200 mg is justified only after evaluating several attempts to use 100 mg under optimal conditions.

The maximum frequency of administration is 1 time per day, regardless of the dosage.

How to take

Time of intake

The tablet is taken orally, with water, 30–60 minutes before planned sexual activity. Do not chew or crush. Due to rapid absorption (Tmax ~1 hour on an empty stomach), if necessary, intake is possible slightly later than for sildenafil — the effect will occur within the expected timeframe. Clinically significant action persists up to 12 hours after administration.[6]

What to drink with: only clean non-carbonated water (~200 ml). Grapefruit juice inhibits CYP3A4 in the gut and can increase the concentration of udenafil in the blood — it is better to avoid.

Influence of food

Udenafil has an important practical advantage: food does not significantly affect the completeness of its absorption (bioavailability). In a pharmacokinetic study, when taking 200 mg of udenafil with high-fat food, the total area under the "concentration-time" curve (AUC) did not change significantly compared to taking it on an empty stomach, although Cmax decreased by about 21% with a low-fat diet.[7] This means that udenafil can be taken regardless of food intake — unlike sildenafil, for which fatty food is a significant limitation.

Alcohol

Moderate alcohol consumption (1–2 glasses of wine) is not an absolute contraindication. However, both substances lower blood pressure, and their joint intake can increase dizziness or orthostatic hypotension. During the first doses of udenafil, it is recommended to abstain from alcohol in order to evaluate individual tolerance to the drug.

Efficacy

Overall efficacy (on demand)

In a key phase III randomized, placebo-controlled trial (167 patients with ED of various etiologies and severity, 12 weeks), udenafil at doses of 100 and 200 mg significantly improved erectile function scores on the IIEF scale compared to placebo.[3]

A meta-analysis of 5 randomized controlled trials (RCTs), involving a total of 1109 patients, confirmed: udenafil is significantly superior to placebo in improving the IIEF-EF score (mean difference 5.65 points; 95% CI: 4.41–6.89; p < 0.00001). No serious adverse events were recorded in any of the included studies.[8]

Efficacy up to 12 hours after dosing

A unique feature of udenafil is the preservation of a clinically significant effect 12 hours after administration. In a specially designed RCT (104 patients), men received udenafil 100 mg and attempted intercourse exactly 12 hours later. Compared with the placebo group, udenafil significantly improved erection maintenance (SEP Q3: udenafil 54.7% vs. placebo 28.3%; p < 0.0001). The change in IIEF-EF from baseline was also significantly higher in the udenafil group (4.40 ± 0.84 vs. −0.58 ± 0.67; p < 0.0001).[6]

With daily use

In addition to the "on demand" regimen, udenafil was studied in a daily dosing schedule. In a 12-week RCT, udenafil at doses of 50 mg and 75 mg once daily significantly improved IIEF-EF scores compared to placebo.[9] A 24-week study involving 346 patients confirmed the sustainability of the effect: the proportion of men who returned to normal erectile function (IIEF-EF ≥ 26) was 39.1% with a dose of 50 mg and 47.0% with a dose of 75 mg.[10]

In diabetes mellitus

In a randomized, double-blind, placebo-controlled study involving 174 patients with ED and diabetes mellitus (7 centers in Korea, 12 weeks of treatment), udenafil at doses of 100 and 200 mg statistically significantly improved IIEF-EF, SEP Q2, SEP Q3, and GAQ scores compared to placebo. Adverse events were mild in severity; the main ones were flushing, headache, nausea, and conjunctival hyperemia.[11]

In arterial hypertension on the background of hypotensive therapy

A separate RCT (165 patients with ED receiving hypotensive drugs) showed that udenafil at doses of 100 and 200 mg significantly improves erectile function without a significant impact on safety — the frequency and severity of adverse events in the udenafil and placebo groups did not differ significantly. Treatment did not affect either the number of hypotensive drugs taken or the previous experience of using PDE-5 inhibitors.[12]

It is important to understand: udenafil does not work with complete destruction of nerve innervation (for example, with severe diabetic neuropathy or complete transection of nerve bundles during surgery). In such cases, alternative treatment methods are considered.

Side effects

The profile of adverse reactions of udenafil is typical for the class of PDE-5 inhibitors and is dose-dependent. According to a meta-analysis of 5 RCTs, the most common adverse events associated with taking the drug were flushing (5.6% vs. 1.8% in the placebo group) and headache (3.1% vs. 0%). No serious adverse events were recorded in any of the included studies.[8]

Common (in 2–10% of patients)

Flushing (redness of the face and neck), headache, nasal congestion, nausea. These reactions are caused by vasodilation — the expansion of blood vessels as the main mechanism of action of the drug. As a rule, they are mild or moderate and pass on their own.

Uncommon (0.1–2%)

Dizziness, dyspepsia, conjunctival hyperemia (redness of the eyes). In a pharmacokinetic study with multiple dosing, a slight impairment of color discrimination in the blue-green range of the spectrum was detected; it disappeared on its own with subsequent doses and was regarded as clinically insignificant.[4]

Rare but serious (<0.1%)

As with the entire class of PDE-5 inhibitors, isolated cases of priapism (painful erection lasting more than 4 hours), NAION (non-arteritic anterior ischemic optic neuropathy), and sudden hearing loss have been described. A causal relationship between the last two complications and udenafil intake has not been established. If any of these symptoms occur, immediate medical attention is required.

Impairment of color perception and vision: udenafil has a molecular structure similar to sildenafil, however, in a pharmacokinetic study, transient color vision impairment was detected only in the multiple dosing group and evaluated as clinically insignificant. In clinical trials for the treatment of ED, visual disturbances were not a characteristic side effect of udenafil.

Contraindications

Absolute (must not be taken under any circumstances)

• Nitrates in any form — nitroglycerin, isosorbide dinitrate/mononitrate, and any other organic nitrates or nitric oxide donors. The combination of udenafil with nitrates sharply increases the decrease in blood pressure — up to a life-threatening collapse. This is the most critical contraindication for the entire class of PDE-5 inhibitors.
• Riociguat (Adempas®) — a soluble guanylate cyclase stimulator used in pulmonary hypertension. Co-administration with PDE-5 inhibitors is contraindicated.
• Severe cardiovascular diseases in which sexual activity is contraindicated: unstable angina, myocardial infarction (<3 months), stroke (<6 months), severe heart failure (NYHA class III–IV), uncontrolled arterial hypertension (>170/110 mmHg) or hypotension (<90/50 mmHg), uncontrolled arrhythmias.
• Severe hepatic impairment — udenafil is metabolized by CYP3A4 in the liver; with severe liver dysfunction, clearance is sharply reduced.
• Loss of vision in one eye due to a history of NAION.
• Hypersensitivity to udenafil or excipients.
• Age under 18 years.

Relative (require caution and consultation with a doctor)

• Stable CAD, chronic heart failure of NYHA class I–II, controlled hypertension — use is possible after assessing cardiac risk.
• Anatomical deformities of the penis (Peyronie's disease, severe curvature, cavernous fibrosis) — increased risk of priapism.
• Diseases predisposing to priapism: sickle cell anemia, leukemia, multiple myeloma.
• Retinitis pigmentosa.
• Moderate or severe renal impairment — data on udenafil are limited; treatment should start with the minimum dose.
• Moderate hepatic impairment — dose reduction is required.
• Drug interactions
• Critically dangerous — absolute contraindication

Nitrates and nitric oxide donors. Co-administration of udenafil with any organic nitrates (nitroglycerin, isosorbide dinitrate/mononitrate, amyl nitrite, etc.) is categorically contraindicated. The interaction leads to sharp and potentially life-threatening hypotension. With regular intake of nitrates, udenafil is completely contraindicated.

Riociguat is contraindicated in combination with any PDE-5 inhibitors.

Require dose adjustment or increased caution

CYP3A4 inhibitors. Udenafil is metabolized primarily by CYP3A4. When co-administered with ketoconazole (a strong CYP3A4 inhibitor), the Cmax of udenafil increased by 1.9 times, and the AUC — by 3.2 times.[5] A similar interaction should be expected with other potent CYP3A4 inhibitors: itraconazole, erythromycin, clarithromycin, ritonavir, and other HIV protease inhibitors, as well as grapefruit juice. If combination is necessary, start with the minimum dose of udenafil.

Alpha-blockers (doxazosin, tamsulosin — used for prostate adenoma). Both drugs lower blood pressure; a joint additive hypotensive effect can cause orthostatic hypotension. Start with the minimum dose of udenafil only after achieving a stable effect from the alpha-blocker.

Hypotensive drugs. In a study in patients receiving antihypertensive therapy, udenafil was used without significant enhancement of hypotension; nevertheless, blood pressure should be monitored, especially at the beginning of treatment.[12]

Have practically no effect on pharmacokinetics

CYP3A4 inducers (rifampicin and similar) can theoretically reduce the concentration of udenafil in the blood and weaken the effect. Detailed clinical data on this interaction for udenafil are not available; one should be guided by general principles for CYP3A4 substrates.

If you are taking several medications, be sure to consult your doctor or pharmacist. Special attention should be paid to drugs for the heart, pressure, antifungals, and antibiotics.

Special patient groups

Elderly men (65+)

Clinical trials of udenafil included men of a wide age range (including those over 65 years old). With age, the clearance of PDE-5 inhibitors may decrease. It is recommended to start with a dose of 100 mg and switch to 200 mg only if necessary.

Diabetes mellitus

Udenafil is effective in diabetic ED, which is confirmed by a specialized clinical study.[11] The response to treatment in this group is usually slightly lower than in patients without diabetes — this is characteristic of the entire class of PDE-5 inhibitors. With insufficient effect of 100 mg, a transition to 200 mg is permissible in agreement with the doctor.

Arterial hypertension

Controlled hypertension on the background of drug therapy is not an absolute contraindication. Udenafil was studied in patients taking hypotensive drugs and demonstrated an acceptable safety profile.[12] The key condition is to exclude nitrates from the hypotensive therapy.

Renal impairment

Specific clinical data on udenafil in renal failure are insufficient. Based on general principles for PDE-5 inhibitors, with mild to moderate renal failure, dose adjustment is probably not required; with severe — one should start with the minimum dose under medical supervision.

Hepatic impairment

Since the metabolism of udenafil is carried out mainly by CYP3A4 in the liver, impairment of its function reduces the clearance of the drug and increases systemic exposure. In moderate hepatic impairment, it is recommended to start with a dose of 100 mg; in severe — udenafil is contraindicated.

What to do if...

...the drug did not work

The most common reasons for the lack of effect:

• Too short waiting time — the drug was taken less than 30 minutes before intercourse.
• Insufficient sexual arousal — udenafil enhances the natural response to stimulation, but does not replace it.
• High anxiety during the first use — the psychological component really reduces efficacy.
• Drinking with juice, especially grapefruit juice, or alcohol — both factors affect pharmacokinetics.

Recommendations: evaluate efficacy after at least 4–8 attempts under optimal conditions. If 100 mg consistently does not give results, consider 200 mg. If the lack of effect persists, consult a doctor to find out the cause of ED.

...side effects occurred

• Mild side effects (flushing, headache, nasal congestion) — as a rule, pass on their own within a few hours. Next time you take it, try reducing the dose.
• Dizziness or a feeling of a sharp drop in pressure — lie down, raise your legs above heart level, drink water. If the condition does not improve, seek medical attention.
• Chest pain after taking — call an ambulance immediately. Do not take nitroglycerin: its co-administration with udenafil causes a critical drop in pressure. Be sure to inform the medical staff about taking udenafil and the time of its intake.

...the erection does not go away (priapism)

If the erection is painful and does not subside within 2–3 hours after stopping sexual activity, this is an emergency situation. Do not wait 4 hours. Immediately contact the nearest emergency department. Treatment started in the first 4–6 hours, as a rule, allows to completely preserve the function. Delay threatens irreversible damage to the corpora cavernosa. This is a rare complication (<0.1%), but it is important to know about it in advance.

...an excessive dose was taken (overdose)

There is no specific antidote. Symptoms of overdose are an increase in side effects: severe headache, sharp drop in pressure, dizziness, nausea.

Lie down and rest. With a significant drop in pressure or loss of consciousness, call an ambulance. Tell the doctor what dose you took and when. Do not take nitrates. The drug is eliminated on its own as the concentration decreases (T1/2 ~7–12 hours).

...you missed a dose

Udenafil is taken "on demand" — only before planned sexual activity. The concept of a "missed dose" does not apply to it in the standard regimen. If you use udenafil in a daily dosing schedule as prescribed by a doctor and miss a dose, take it as soon as possible, but do not double the dose the next day.

Storage conditions

Store at a temperature not exceeding 30°C, in a dry place, protected from direct sunlight. Keep out of reach of children. The expiration date is indicated on the package; do not use the drug after its expiration.

Udenafil-based drugs in the GENERICS catalog:

All listed drugs contain udenafil as an active substance. This instruction applies to all of them. The differences between brands lie in the manufacturer and excipients; the mechanism of action, indications, contraindications, and interactions are identical.

• Zudena 100 — udenafil 100 mg (Sunrise Remedies)
• Zudena 200 — udenafil 200 mg (Sunrise Remedies)
• Udaforce 100 — udenafil 100 mg (Fortune Health Care)
• Udaforce 200 — udenafil 200 mg (Fortune Health Care)

If premature ejaculation is also relevant to you along with ED, consider the combination drug Super Zudena (udenafil + dapoxetine) or a separate intake of dapoxetine — these are drugs for prolonging intercourse, solving both tasks. Udaforce-D from Fortune Health Care works in a similar way.

If you are interested in comparing udenafil with other molecules, see the sections sildenafil, tadalafil, vardenafil, and avanafil, as well as our review of drugs for potency.

The information on this page is for informational purposes only and does not replace consultation with a doctor. Before using any udenafil-based drug for the first time, consult a urologist or general practitioner — especially in the presence of cardiovascular diseases, taking other medications, or chronic illnesses.

Frequently Asked Questions

How does Udenafil differ from Sildenafil and Tadalafil?

All three molecules work by the same mechanism — they block PDE-5. The key difference of udenafil is its intermediate pharmacokinetic profile: it begins to act about as quickly as sildenafil (in 30–60 minutes), but the effect persists significantly longer — up to 12 hours. This is longer than sildenafil (~4–6 hours) or vardenafil (~5–6 hours), but shorter than tadalafil (up to 36 hours). Another practical advantage: the bioavailability of udenafil is practically unaffected by fatty food — unlike sildenafil, for which a fatty dinner can significantly delay the onset of the effect.

How long does it take for Udenafil to start working?

Peak blood concentration is achieved approximately 0.8–1.3 hours after taking on an empty stomach.[4] The first clinically significant effect in most men is within 30–60 minutes. For a reliable result, it is recommended to take the tablet 30–60 minutes before intimacy. When taken with food, absorption is slightly slowed down, but bioavailability does not change significantly.

Is it possible to take Udenafil every day?

Yes, udenafil was studied in a daily dosing regimen (at doses of 50 and 75 mg) and demonstrated efficacy in 12- and 24-week courses.[9][10] This distinguishes it from sildenafil and vardenafil, for which a daily regimen is non-standard. Nevertheless, for continuous daily use, tadalafil 5 mg is used more often — it was specially developed for this scheme. Daily intake of udenafil should be agreed with a doctor.

What is better: Udenafil 200 mg or Tadalafil 20 mg for a long-lasting effect?

Both options provide a long-lasting action, but tadalafil's duration is significantly longer — up to 36 hours compared to 12 hours for udenafil. If maximum "freedom in time" is needed, it is more logical to choose tadalafil 20 mg. Udenafil 200 mg is preferred for those who want a shorter, but still long window of action without drug accumulation with frequent use. Both are well tolerated with food. The choice is determined by individual preferences and the pattern of sexual life.

Is Udenafil addictive?

No. Udenafil is not a hormone and not a psychoactive substance. Physical dependence is not formed during its use. After stopping the drug, erectile function returns to its baseline level. Psychological "pill dependence" is not a pharmacological phenomenon, but a behavioral feature that is overcome when working with anxiety.

Sources

• [1] Salem EA, Kendirci M, Hellstrom WJ. Udenafil, a long-acting PDE5 inhibitor for erectile dysfunction. Curr Opin Investig Drugs. 2006;7(7):661–669. PubMed: 16869121
• [2] Cho MC, Paick JS. Udenafil for the treatment of erectile dysfunction. Ther Clin Risk Manag, 2014; 10: 341–354. PMC: 4027935
• [3] Paick JS, Kim SW, Yang DY, et al. The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. J Sex Med. 2008;5(4):946–953. PubMed: 18221288
• [4] Kim BH, Lim HS, Chung JY, et al. Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. Br J Clin Pharmacol. 2008;65(6):848–854. PubMed: 18318773
• [5] Shin KH, Chung YJ, Kim BH, et al. Effect of ketoconazole on the pharmacokinetics of udenafil in healthy Korean subjects. Br J Clin Pharmacol. 2010;69(3):307–310. PubMed: 20233203
• [6] Ahn TY, Park JK, Lee SW, et al. Efficacy of udenafil for the treatment of erectile dysfunction up to 12 hours after dosing: a randomized placebo-controlled trial. J Sex Med. 2010;7(6):2209–2216. PubMed: 20412426
• [7] Kim TE, Lim KS, Kim BH, et al. Effect of food on the pharmacokinetics of the oral phosphodiesterase 5 inhibitor udenafil for the treatment of erectile dysfunction. Br J Clin Pharmacol. 2009;68(6):882–888. PubMed: 19660002
• [8] Liu T, Xing J, Du Y. Efficacy and safety of udenafil for erectile dysfunction: a meta-analysis of randomized controlled trials. Urology. 2012;80(2):306–312. PubMed: 22497982
• [9] Seo KK, Kim SW, Paick JS, et al. Efficacy and safety of once-daily dosing of udenafil in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial. Eur Urol. 2011;60(2):380–387. PubMed: 21458153
• [10] Kim SW, Paick JS, Seo KK, et al. Efficacy of once-daily administration of udenafil for 24 weeks on erectile dysfunction: results from a randomized multicenter placebo-controlled clinical trial. J Sex Med. 2015;12(6):1462–1469. PubMed: 25736397
• [11] Moon DG, Yang DY, Lee CH, et al. A therapeutic confirmatory study to assess the safety and efficacy of Zydena (udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus. J Sex Med. 2011;8(7):2048–2061. PubMed: 21554549
• [12] Hwang TI, Lin YC, Chiang HS, et al. The efficacy and safety of udenafil [Zydena] for the treatment of erectile dysfunction in hypertensive men taking concomitant antihypertensive agents. J Sex Med. 2010;7(4 Pt 1):1463–1471. PubMed: 19694927

The sources describe the udenafil molecule and apply to all drugs based on it — both the original Zydena® and generics.