xarelto Tag

Xarelto and Erectile Dysfunction: Personal Story

I was prescribed Xarelto (rivaroxaban) for deep vein thrombosis (DVT) following a treatment with heparin injections.

About two weeks after switching to Xarelto I noticed loss of libido, severe erectile dysfunction (very weak erections even after prolonged stimulation that almost immediately recede when stimulation ceases), reduced genital sensation, no response to sexual stimuli, premature ejaculation and sexual anhedonia (pleasureless orgasm) when an orgasm was achieved. It was like I had become completely asexual. Even nocturnal/morning erections had become extremely sparse and feeble, which was another way for me to confirm that there was something wrong on a physical rather than psychological level. To be more precise, the problem was not simply erectile dysfunction, but a sexual dysfunction with multiple manifestations.

The above dramatic changes took place in about 2 weeks after starting Xarelto (20 mg once per day), at a time when I was taking no other drug or supplement, and have persisted since discontinuing the drug (March 2017). Subtler issues also became more apparent, for example a sensation as if a low-intensity electric current was running through the penis, which was especially noticeably when lying down. Moreover, following an orgasm there would be a feeling of discomfort in the genital area, bordering on mild pain.

The host of sexuality-related side-effects I experienced can be aptly summed up in two words: chemical castration. Such was the extent and depth of change in such a short period of time. A severe “punishment” for an (intentionally?) misinformed medication user when in most countries even child molesters are exempt from such a “treatment“.

Surprisingly, such adverse effects were not listed on the a Xarelto patient information leaflet. But this should not come as much of a surprise, as it is alleged that Bayer Health Group and Johnson and Johnson (the pharmaceutical companies which developed the drug) were well aware of studies showing Xarelto had higher rates of serious side effects but failed to provide adequate warnings about the known side effects both to doctors and to patients [1]. And the side effects referred to here are the ones that quite often lead to death, i.e. internal bleeding. If they were reticent about such… lethal side effects, would they be eloquent about sexuality-related side effects? I very much doubt it… In fact, a Google search for Xarelto lawsuits gives plenty of results.  On March 25th, 2019, they settled for $775 million to get paid out to victims. [1]

Xarelto’s serious side effects have a long range, if one takes into account post-marketing reports: internal bleeding, wound infections, thrombocytopenia (platelet deficiency), hepatitis, Stevens-Johnson syndrome (severe skin reaction which can lead, among others, to multiple organ failure with a mortality rate of 7.5) [2]. In 2015, rivaroxaban accounted for the highest number of reported cases of serious injury among regularly monitored medications to the FDA’s Adverse Events Reporting System.

The vascular specialists I asked had no clue about such an adverse effect. I thought that this reaction would probably resolve when I stop the drug. The medication was discontinued on March 2017 and the condition has not resolved at all (last update: 5 April 2019). In effect, it has remained exactly as it was when it first appeared.

Following visits to urologists/andrologists, I was asked to check hormone levels for testosterone, prolactin, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG) and albumin.

There was nothing in the results that indicated why this problem had presented itself. In fact, my testosterone was 981 ng/dl, putting me at the top 2,5% of men.

The doctors said that the medical knowledge on these physiological mechanisms is limited; there are plenty of unknown chemical paths where this could go wrong. They don’t even know which are the chemical triggers of libido, apparently, this is not testosterone.

When I searched on EudraVigilance and FDA’s Adverse Event Reporting System (FAERS) I found that there was a number of Individual Case Safety Reports with same adverse reactions (one even included penile size reduced).

Currently, I am at a loss as what I should do to resolve the situation, or as to how the drug affected my organism and whether this can be remedied.

You have similar issues? What YOU can do to help yourself

I would encourage anyone to submit side effects directly or via one’s healthcare professional to the FDA (for people from the USA), RxISK (for people from all over the world; this is a very important resource as David Healy who founded it has undertaken research on similar conditions caused by other medications), EudraVigilance (for people from Europe), YellowCard (for people from the UK) and Kitrini Karta (for people from Greece) .

Why is this important? Because many side effects go under-reported, something which applies even more strongly to side effects relating to sexuality and the taboo and embarrassment that goes with it. The only way to raise awareness and find a possible cure is by having people who experienced the side effects report them.

Read also an article posted on RXisk about  Xarelto and sex.

Alternatives to Xarelto

If you are still taking Xarelto, or any other anticoagulant, including novel oral anticoagulants (NOACs) and you feel it is impacting your health negatively, then you can consult your doctor in order to switch medication. NOACs are the new kids on the block and their side-effects have not been fully documented yet. For decades the drugs available for anticoagulation were heparin and coumarins (warfarin—brand name Coumadin—mainly in the US and acenocoumarol—brand name Sintrom—in Europe).

If your physician is unsure regarding the way to switch medication, you can direct them to the leaflet switching between anticoagulants.

Bear in mind that switching medication for a particular side effect, for example erectile dysfunction or loss of libido, does not automatically guarantee that you will be rid of that side effect.
Firstly, you should have the relevant hormone and blood tests to exclude any other factors. Secondly, it appears that other anticoagulants may have similar side-effects—for example have a look at one of the comments below for Eliquis (apixaban).

Chinese Traditional Medicine formula

If you want to endeavour beyond Western medicine, traditional Chinese medicine (TCM) has a formula for anticoagulation called Bu Yang Huang Wu Tang (补阳还五汤) which can be taken in pill format or you can boil the herbs. This formula contains Angelica sinensis (dong quai, 当归) which contains coumarins. It should be noted that you cannot take this formula when you are taking any other form of anticoagulation as it can and will increase the risk of bleeding. Useful reference:  Traditional Chinese medicine formula activates blood circulation and prevents DVT (deep venous thrombosis).

Hirudotherapy (leeches)

The Chinese and the Greeks—among others—have used leeches as a therapy for thrombosis. Leeches contain a powerful anticoagulant named hirudin and hirudotherapy (leech therapy) is akin to taking heparin injections.

Other symptoms

Another symptom that started after taking Xarelto and persisted since, was a kind of skin rash that appeared in my forehead, more pronounced on the right side. I never had such a skin rash on my forehead or any other place of my body. A dermatologist I consulted had no idea what it was or what it was.

Drugs with similar side-effects

Interestingly, there are other medications that recently proved to have similar effects, like finasteride, causing post-finasteride syndrome (more about it by the Post-Finasteride Syndrome Foundation) and isotretinoin (Accutane, an acne medicine), causing post-retinoid sexual dysfunction (PRSD). And there are some papers on Endocrine Journal and International Journal of Risk & Safety in Medicine making the connection: 

• Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?
• Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases
• One hundred and twenty cases of enduring sexual dysfunction following treatment

Dr David Healy who wrote the book Pharmageddon and created the RxISK website makes a suggestion of nerve damage, and specifically of c-fibers in a presentation regarding sexual problems caused by post-SSRI sexual dysfunction. I was particularly touched by a comment to that video: 

…not only do they destroy ability to experience physical affection. They also stop ability to feel love, empathy, compassion, regret, human connection. They make you a shell of a human being. In fact they take away the essential essence of being human. Beyond unconscionable.

If one were to coin a term for this issue, since it is a kind of drug-induced erectile dysfunction /  medication-induced erectile dysfunction or more aptly drug-induced sexual dysfunction / medication-induced sexual dysfunction, it would be rivoraxaban-induced sexual dysfunction (RISD) / rivoraxaban-induced erectile dysfunction (RIED) or post-rivoraxaban sexual dysfunction (PRSD) / post-Xarelto sexual dysfunction (PXSD).

Another potential avenue of investigation has to do with ion channels (thanks to Heather for the clue) as they affect erection in a number of ways.

To put all this into context, such sexuality-related issues affect the individual on a scale that goes far beyond the sexual plane [4]:

Brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (for example, monetary, artistic, musical, altruistic, and transcendent pleasures).

Which is hardly an original concept and has very aptly been described by Nietzsche, in the Twilight of the Idols (Raids of an Untimely Man, §8):

For there to be art, for there to be any aesthetic activity and observation, one psychological prerequisite is indispensable: intoxication. Intoxication must have already heightened the sensitivity of the whole machine: otherwise, no art will be forthcoming. All kinds of intoxication, as different as their causes may be, have this power: above all, the intoxication of sexual excitement, that oldest and most primordial form of intoxication.

Even if we see sexual energy from a spiritual point, its existence is the actual rocket fuel for spirituality (Swami Kriyananda, The New Path):

If the sex drive were taken away from you, you would see that you had lost your greatest friend. You would lose all interest in life. Sex was given to make you strong. If a boxer were to fight only weaklings, he too would grow weak in time. It is by fighting strong men that he develops strength. The same is true in your struggle with the sex instinct. The more you master it, the more you will find yourself becoming a lion of happiness.

Would Gods live a life deprived of pleasure? Not even them, according to Simonides (from Fragments, 71):

What human life is desirable without pleasure, or what lordly power? Without it not even the life of the gods is enviable.

(Τίς γὰρ ἁδονᾶς ἄτερ θνατῶν βίος ποθεινὸς ἢ ποία τυραννίς; τᾶς ἄτερ οὐδὲ θεῶν ζηλωτὸς αἰών.)

No wonder that many lesser mortals suffering from iatrogenic sexual dysfunction syndromes (like Oly) choose to take their own lives.

The words of yet another PSSD sufferer perfectly echo my feelings:

The effect of living with PSSD is devastating. It has destroyed two relationships. Relationships with women end up being like an asexual friendship, with sex being like a pleasure-less boring chore, with no emotional connection or lust whatsoever.

To wrap it up, I wonder whether there is any way to find out what is the status of the other people who reported the same issue; so if you are facing a similar situation, kindly get in touch.

You can see screenshots of the Individual Case Safety Reports at the end of this post.

Xarelto and Erectile Dysfunction: FDA reports

Erectile dysfunction is found among people who take Xarelto, especially for people who are 60+ old , have been taking the drug for 1 – 6 months, also take medication Amlodipine, and have Stroke. This study is created by eHealthMe based on reports of 119,666 people who have side effects when taking Xarelto from FDA, and is updated regularly (from ehlealthme.com).

Blood thinners and Erectile Dysfunction

There is not much data available on blood thinners in general, (including novel oral anticoagulants – NOACs) and erectile dysfunction or sexual dysfunction.  Some blood thinners may even have the opposite effect of priapism (this applies to any varieties of heparin like  low-molecular-weight heparin or unfractioned heparin which are administered with an injection). From a paper:

Treatment with the coumarin derivative, warfarin, was suggested to be associated with an increased risk of ED in elderly men, but in this study only a few patients were actually treated with warfarin. Therefore, although information regarding anticoagulants and erectile function is lacking. […] Evidence regarding effect on erectile function of lipid-lowering drugs, anticoagulants, antithrombotics, and antiarrhythmic therapy is sparse and not conclusive.

It is no surprising if such issues are under-reported given the novelty of some of these drugs and the taboo associated with it or the tendency of physicians to attribute them to a pre-existing condition or “psychological” reasons. You can see in the comments below a mention from a visitor who sent an e-mail regarding another NOAC, Eliquis (apixaban).

Possible treatments for Xarelto-induced erectile dysfunction

Since the issues that arise from the use of Xarelto are much more complex than erectile dysfunction, PDE5 inhibitors like sildenafil (Viagra), tadalafil (Cialis) and the like are not likely to give anything more than an artificial erection which would not improve the quality of sensation.

If we accept the conjecture that anhedonic symptoms are due to some sort of nerve damage (as posited by David Healy above regarding PSSD) then there is nothing available on the market. In a trial stem cells were used for erectile dysfunction which was the result of radical prostatectomy (interestingly, exclusion criteria for this study was treatment with anticoagulants and lack of sexual interest). Another new option is the intracavernosal injection of platelet-rich plasma, as illustrated in a review of currently available modalities for erectile dysfunction.

Drugs that may cause erectile dysfunction /sexual dysfunction

Here is a list of drugs [3] (which will be edited here by me to update with new data) that may cause impotence/erectile dysfunction/sexual dysfunction:

Antidepressants and other psychiatric medicines

Amitriptyline (Elavil)
Amoxapine (Asendin)
Buspirone (Buspar)
Chlordiazepoxide (Librium)
Chlorpromazine (Thorazine)
Clomipramine (Anafranil)
Clorazepate (Tranxene)
Desipramine (Norpramin)
Diazepam (Valium)
Doxepin (Sinequan)
Fluoxetine (Prozac)
Fluphenazine (Prolixin)
Imipramine (Tofranil)
Isocarboxazid (Marplan)
Lorazepam (Ativan)
Meprobamate (Equanil)
Mesoridazine (Serentil)
Nortriptyline (Pamelor)
Oxazepam (Serax)
Paroxetine (Paxil, Seroxat)
Phenelzine (Nardil)
Phenytoin (Dilantin)
Sertraline (Zoloft)
Thioridazine (Mellaril)
Thiothixene (Navane)
Tranylcypromine (Parnate)
Trifluoperazine (Stelazine)

Antihistamine medicines

(certain classes of antihistamines are also used to treat heartburn)

Cimetidine (Tagamet)
Dimenhydrinate (Dramamine)
Diphenhydramine (Benadryl)
Hydroxyzine (Vistaril)
Meclizine (Antivert)
Nizatidine (Axid)
Promethazine (Phenergan)
Ranitidine (Zantac)

High blood pressure medicines and diuretics (water pills)

Atenolol (Tenormin)
Bethanidine
Bumetanide (Bumex)
Captopril (Capoten)
Chlorothiazide (Diuril)
Chlorthalidone (Hygroton)
Clonidine (Catapres)
Enalapril (Vasotec)
Furosemide (Lasix)
Guanabenz (Wytensin)
Guanethidine (Ismelin)
Guanfacine (Tenex)
Haloperidol (Haldol)
Hydralazine (Apresoline)
Hydrochlorothiazide (Esidrix)
Labetalol (Normodyne)
Methyldopa (Aldomet)
Metoprolol (Lopressor)
Nifedipine (Adalat, Procardia)
Phenoxybenzamine (Dibenzyline)
Phentolamine (Regitine)
Prazosin (Minipress)
Propranolol (Inderal)
Reserpine (Serpasil)
Spironolactone (Aldactone)
Triamterene (Maxzide)
Verapamil (Calan)
Thiazides are the most common cause of impotence among the high blood pressure medicines. The next most common cause is beta blockers. Alpha blockers tend to be less likely to cause this problem.

Parkinson disease medicines

Benztropine (Cogentin)
Biperiden (Akineton)
Bromocriptine (Parlodel)
Levodopa (Sinemet)
Procyclidine (Kemadrin)
Trihexyphenidyl (Artane)

Chemotherapy and hormonal medicines

Antiandrogens (Casodex, Flutamide, Nilutamide)
Busulfan (Myleran)
Cyclophosphamide (Cytoxan)
Ketoconazole
LHRH agonists (Lupron, Zoladex)

Other medicines

Aminocaproic acid (Amicar)
Atropine
Clofibrate (Atromid-S)
Cyclobenzaprine (Flexeril)
Cyproterone
Digoxin (Lanoxin)
Disopyramide (Norpace)
Estrogen
Finasteride (Propecia, Proscar, Avodart)
Furazolidone (Furoxone)
H2 blockers (Tagamet, Zantac, Pepcid)
Indomethacin (Indocin)
Isotretinoin (Accutane, Roaccutane)
Lipid-lowering agents
Licorice
Metoclopramide (Reglan)
NSAIDs (ibuprofen, etc.)
Orphenadrine (Norflex)
Prochlorperazine (Compazine)
Pseudoephedrine (Sudafed)
Sumatriptan (Imitrex)

Opiate analgesics (painkillers)

Codeine
Fentanyl (Innovar)
Hydromorphone (Dilaudid)
Meperidine (Demerol)
Methadone
Morphine
Oxycodone (Oxycontin, Percodan)

Recreational drugs

Alcohol
Amphetamines
Barbiturates
Cocaine
Marijuana
Heroin
Nicotine

Impotence caused by medications; drug-induced erectile dysfunction; drug-induced sexual dysfunction; prescription medicines and impotence; prescription medicines and sexual dysfunction

Screens from Pharmacovigilance databases

[1] WJB Associates – side effects of Xarelto – see also NYTIMES article

[2] Xarelto Serious Side Effects

[3] Drugs that may cause impotence

[4] Kringelbach ML. The hedonic brain: a functional neuroanatomy of human pleasure. In: Kringelbach ML, Berridge KC, editors. Pleasures of the Brain. Oxford, UK: Oxford University Press; 2010. See also: Neurobiology of sexual desire