What are the most common Spedra side effects? What to expect and when to seek help

DoktorABC editorial team

Accurate, up-to-date health information written by our editorial team and reviewed by UK-registered prescribers.

How common are side effects with Spedra?

Side effects with Spedra are common but mostly mild. In clinical trials, around 30 to 40% of men taking Spedra reported at least one side effect, compared with around 25% of men taking a placebo. The majority were minor and did not cause men to stop treatment.

The most commonly reported side effects were headache, flushing, and nasal and sinus congestion. Most adverse events in clinical studies were mild to moderate in severity and resulted in infrequent discontinuations: 2.8% of participants taking avanafil 100 mg stopped treatment due to side effects in the largest general population trial. 

The SmPC also notes that in the long-term extension study, the percentage of patients experiencing adverse reactions decreased with increasing length of exposure, suggesting that many effects reduce over time as the body adjusts to the medicine. 

Overall adverse events were more frequent in subjects with a lower body mass index. The clinical significance of this observation is not fully established.

How frequently are side effects experienced

The table below is drawn from the adverse reaction tables in both the Spedra 100 mg and 200 mg SmPCs. Frequency categories follow the standard MedDRA convention used in UK product information.

Always read the full patient information leaflet supplied with your medication for a complete list of side effects.

Do side effects change with dose?

The 100 mg and 200 mg Spedra SmPCs list identical adverse reaction frequency bands in their side effect tables. This means the published SmPC data does not provide dose-specific percentages distinguishing what proportion of men experience each side effect at 100 mg versus 200 mg separately.

What the SmPC does state is that in overdose studies, adverse reactions were similar to those seen at lower doses but incidence rates and severities were increased. This suggests a general dose-response relationship, but specific percentage comparisons between 100 mg and 200 mg are not available from the current UK product information and should not be inferred.

The appropriate dose for any individual is a prescriber decision, based on response to the starting dose and individual tolerability. Do not adjust your dose independently. If you are experiencing significant side effects, speak to your prescriber before making any change.

How long do side effects last?

Most side effects of Spedra are related to its vasodilatory mechanism and occur within the first few hours after taking the tablet, corresponding to the period of peak drug concentration. Avanafil has a half-life of approximately six to 17 hours, meaning most effects will reduce as the medicine clears the body over the course of the day. 

Headache, flushing, and nasal congestion typically occur within the first hour or two and resolve within a few hours. The long-term extension study showed that the overall proportion of patients experiencing adverse reactions decreased with increasing duration of treatment, suggesting that many effects settle with regular use.

If side effects are persistent, severe, or occur beyond the expected timeframe, contact your prescriber.

Serious side effects and red flags

The following symptoms are uncommon or rare but require prompt action. Stop taking Spedra and seek immediate medical attention if any of these occur.

Sudden vision loss or significant visual disturbance:
Cases of non-arteritic anterior ischaemic optic neuropathy (NAION), a condition of the optic nerve that can cause sudden vision loss, have been reported in connection with the use of PDE5 inhibitors. No cases were reported during the clinical trials of avanafil specifically, but the risk cannot be excluded based on class-level data. If you experience any sudden visual deficit, stop taking Spedra immediately and seek urgent medical attention. Men who have previously experienced NAION in one eye must not use Spedra. 

Sudden hearing loss:
Sudden decrease or loss of hearing, which may be accompanied by tinnitus (ringing in the ears) and dizziness, has been reported in temporal association with the use of PDE5 inhibitors. The SmPC advises stopping Spedra and seeking prompt medical attention if this occurs. 

Priapism (prolonged erection):
An erection lasting four hours or more requires immediate medical attention. Priapism was not reported during avanafil clinical trials but has been observed with other PDE5 inhibitors. If untreated, it can cause permanent damage to penile tissue. 

Chest pain during or after sexual activity:
Sexual activity carries a degree of cardiac risk. If you experience chest pain during or after sexual activity, stop sexual activity immediately and seek medical attention. Men with significant cardiovascular conditions should discuss the cardiac safety of sexual activity with their doctor before taking Spedra. 

Signs of a serious allergic reaction:
Hypersensitivity reactions are uncommon but possible. Stop taking Spedra and seek medical help immediately if you develop swelling of the face, lips, tongue, or throat, difficulty breathing, or a severe rash.

Interactions with Spedra: what to avoid and what requires caution

Avanafil is metabolised predominantly by the CYP3A4 enzyme system. A number of medicines and substances affect how avanafil is processed by the body, and some combinations carry serious risks. 

Absolute contraindications: never combine with Spedra

Nitrates and nitric oxide donors: Co-administration of avanafil with any form of organic nitrate or nitric oxide donor is absolutely contraindicated. This includes glyceryl trinitrate (GTN), isosorbide mononitrate, isosorbide dinitrate, nicorandil, molsidomine, and amyl nitrite (poppers). The combination can cause a serious and potentially life-threatening drop in blood pressure. The SmPC states that in a life-threatening situation where nitrate administration is medically necessary, at least 12 hours should have elapsed since the last dose of Spedra before nitrate administration is considered. 

Riociguat: Co-administration with this guanylate cyclase stimulator is contraindicated due to the risk of symptomatic hypotension. 

Potent CYP3A4 inhibitors: Co-administration with potent inhibitors of CYP3A4 is contraindicated. This includes ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin. These medicines significantly increase avanafil exposure: ketoconazole increased avanafil AUC 14-fold and ritonavir increased it 13-fold. 

Medicines and substances requiring caution or dose adjustment

Moderate CYP3A4 inhibitors: Medicines such as erythromycin, diltiazem, fluconazole, verapamil, amprenavir, aprepitant, and fosamprenavir increase avanafil exposure to a clinically relevant but lesser degree. When taking a moderate CYP3A4 inhibitor, the maximum recommended dose of avanafil is 100 mg, with a minimum interval of 48 hours between doses. This is a prescriber decision; do not adjust your dose independently.

Alpha-blockers: Medicines used for benign prostatic hyperplasia or high blood pressure, including doxazosin, tamsulosin, and alfuzosin, can cause additional blood pressure lowering when combined with avanafil. The SmPC advises that in men who are stable on alpha-blocker therapy and starting Spedra, treatment should be initiated at the lowest dose of 50 mg. 

Alcohol: Drinking alcohol while taking Spedra can cause a more significant drop in blood pressure than either would alone. This increases the risk of dizziness, light-headedness, or fainting. The SmPC advises caution with alcohol, and it is worth being aware of this particularly in social situations where you might be drinking before or after taking the tablet.

Grapefruit juice: Grapefruit juice is a weak inhibitor of CYP3A4 and may increase avanafil exposure. The SmPC advises avoiding grapefruit juice within 24 hours before taking avanafil. 

CYP3A4 inducers: Medicines that induce CYP3A4, including rifampicin, carbamazepine, phenobarbital, efavirenz, and bosentan, may reduce the efficacy of avanafil by lowering its plasma concentration. Concomitant use is not recommended. 

Other ED treatments: Combining Spedra with other PDE5 inhibitors or other treatments for erectile dysfunction has not been studied and is not recommended. 

How Spedra’s side effects compare to sildenafil and tadalafil

All three PDE5 inhibitors share a broadly similar class-level side effect profile. The most commonly reported effects across all three are headache, flushing, and nasal congestion. However, there are some clinically meaningful differences.

Visual disturbances are more commonly associated with sildenafil than with avanafil or tadalafil. This reflects sildenafil’s comparatively lower selectivity for PDE5 over PDE6 in the retina. Avanafil’s high PDE5 selectivity (greater than 100-fold over PDE6) is thought to explain why visual colour disturbance, which is listed as common with sildenafil, is not reported as a common effect of avanafil. 

Back pain and myalgia are more specifically associated with tadalafil than with avanafil or sildenafil, and are listed as common in the tadalafil SmPC. With avanafil, back pain is listed as uncommon and myalgia as rare. 

Dyspepsia is listed as common with both sildenafil and tadalafil, but only as uncommon with avanafil. 

An important limitation: NICE ESNM45 notes explicitly that there are no direct head-to-head comparisons between avanafil and other PDE5 inhibitors, and that indirect comparisons are limited by differences in study design and populations. The observations above are drawn from separate SmPCs and should be treated as indicative rather than definitive comparative evidence.

How to report a suspected side effect

If you experience a side effect you believe may be related to Spedra, you can report it to the MHRA via the Yellow Card scheme, or by searching for MHRA Yellow Card in the Google Play or Apple App Store. 

Reporting suspected side effects helps the MHRA monitor the ongoing safety profile of licensed medicines in real-world use. You do not need to be certain the medicine caused the effect to make a report.

Conclusion

The side effect profile of Spedra is broadly consistent with the PDE5 inhibitor class. Headache, flushing, and nasal congestion are the most commonly reported effects and are typically mild, short-lived, and reduced with continued use. Serious side effects are uncommon, but sudden vision loss, sudden hearing loss, prolonged erection, and chest pain each require immediate medical attention.

The most clinically important practical points are the absolute contraindication with nitrates and potent CYP3A4 inhibitors, the need for caution with alpha-blockers, the interaction with alcohol, and the requirement to avoid grapefruit juice within 24 hours of a dose. Disclosing your full medication list to your prescriber before starting Spedra is the most reliable way to avoid clinically significant interactions.

If you have concerns about side effects, contact your prescriber rather than adjusting your dose or stopping treatment independently.

FAQ

The DoktorABC medical advisory board

Dr. Roland Ruiken

Medical advisor, Norway

Dr. Viktor Simunovic

Medical advisor, Croatia

To the medical advisory board