Yentreve (Duloxetine)

How does it work?

Yentreve capsules contain the active ingredient duloxetine hydrochloride, which is a type of medicine called a combined serotonin and noradrenaline reuptake inhibitor. It is used to treat stress urinary incontinence (SUI) in women. SUI is the accidental leakage of urine when pressure in the bladder is increased suddenly, for example by coughing, sneezing, laughing, lifting or exercise.

The urethral sphincter is the muscle at the exit to the bladder that holds back urine. We normally relax it voluntarily when we want to urinate. However, there are various factors, for example pregnancy, childbirth and obesity, that can weaken the tone of the urethral sphincter, allowing it to leak out urine involuntarily when the pressure in the bladder increases.

Duloxetine is thought to work by increasing the tone of the urethral sphincter. It does this by its action on serotonin and noradrenaline in the spinal cord.

Serotonin and noradrenaline are compounds called neurotransmitters. They are stored in nerve cells and are involved in transmitting messages between the nerve cells. Neurotransmitters are released from nerve cells as a message is transmitted. Once the message has been transmitted, the nerve cells then reabsorb the neurotransmitter.

Duloxetine prevents serotonin and noradrenaline from being reabsorbed back into nerve cells in the spinal cord. This enhances the nerve messages that are sent to the urethral sphincter. These messages increase the tone of the urethral sphincter during the time that urine is being stored in the bladder. This makes it less likely to open slightly under stress such as coughing and allow urine to leak out. The sphincter can still be relaxed voluntarily when you want to pass urine.

Duloxetine is used to treat moderate to severe stress incontinence, and has been shown to reduce the frequency of episodes of leakage. It may be more effective if combined with a pelvic floor muscle re-training programme, and you should discuss this with your doctor. Duloxetine has not been shown to benefit mild SUI (less than 14 episodes of leakage per week).

What is it used for?

  • Moderate to severe stress urinary incontinence (SUI) in women.

Warning!

  • Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance. This medicine may make you feel sleepy or dizzy and so may reduce your ability to drive or operate hazardous machinery safely. If you do experience drowsiness this may be made worse by alcohol.
  • This medicine may cause a drop in blood pressure when moving from a lying or sitting position to sitting or standing, which may cause dizziness, light-headedness or fainting, particularly when you first start treatment. For this reason you should take care when moving from lying down to sitting or standing, particularly if you wake up in the night, until you know how this medicine affects you. If you feel dizzy or light-headed at any time during treatment, sit or lie down until the symptoms pass.
  • This medicine can cause some people's blood pressure to increase. It is recommended that that your blood pressure is monitored while you are taking this medicine if you suffer from heart disease or high blood pressure, especially during the first month of treatment.
  • Although this medicine is not used to treat depression, the active ingredient (duloxetine) also exists as an antidepressant, called Cymbalta. As with other antidepressant medicines, there have been isolated cases of people experiencing suicidal thoughts during or shortly after stopping treatment with duloxetine. For this reason, you should let your doctor know if you have any distressing thoughts or feelings, including depressive feelings or agitation, at any time while taking this medicine or after stopping treatment.
  • Medicines of this type have been associated with the development of unpleasant or distressing restlessness and the need to move, often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. If you experience these symptoms you should consult your doctor.
  • Medicines of this type may also cause the amount of sodium in the blood to drop - a condition called hyponatraemia. This can cause symptoms such as drowsiness, confusion, muscle twitching or convulsions. Elderly people may be particularly susceptible to this effect. There may also be an increased risk in people with liver cirrhosis and those who are dehydrated or taking diuretic medicines. You should consult your doctor if you develop any of these symptoms while taking this medicine so that your blood sodium level can be checked if necessary.
  • You should not suddenly stop taking this medicine, as this may cause withdrawal symptoms such as dizziness, pins and needles sensations, nausea, difficulty sleeping, intense dreams, headache, tremor, agitation or anxiety. Withdrawal symptoms are temporary and are not the same as addiction. They can usually be avoided by stopping the medicine gradually, usually over at least two weeks. Follow the instructions given by your doctor when it is time to stop treatment with this medicine.

Use with caution in

  • Elderly people.
  • Decreased kidney function.
  • Bipolar affective disorder (manic depression).
  • History of mania.
  • History of seizures, eg epilepsy.
  • Raised pressure in the eyeball, eg glaucoma or people at risk of glaucoma.
  • High blood pressure.
  • Heart disease.
  • People with bleeding tendencies.
  • People taking medicines to reduce blood clotting (anticoagulant or antiplatelet medicines, see below).

Not to be used in

  • Children and adolescents under 18 years of age.
  • Liver disease resulting in decreased liver function.
  • Severely decreased kidney function.
  • Uncontrolled high blood pressure.
  • Pregnancy.
  • Breastfeeding.
  • People who have taken a monoamine oxidase inhibitor (MAOI) antidepressant medicine in the last 14 days.
  • People taking the medicines fluvoxamine, ciprofloxacin or enoxacin.
  • Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency (Yentreve capsules contain sucrose).

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • This medicine has not been studied in pregnant women. The risk to the developing foetus is unknown, however, if the medicine is used near term it may cause withdrawal symptoms in the newborn baby. Yentreve should not be used during pregnancy. Seek medical advice from your doctor if you get pregnant or plan to get pregnant while you are taking this medicine.
  • This medicine passes into breast milk. It should not be used by breastfeeding mothers. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

  • Disturbances of the gut such as nausea, constipation, diarrhoea, vomiting or indigestion.
  • Dry mouth.
  • Fatigue.
  • Insomnia.
  • Dizziness.
  • Headache.
  • Decreased appetite and weight loss.
  • Decreased sex drive, problems with orgasm.
  • Hot flushes.
  • Increased sweating.
  • Anxiety, nervousness, agitation.
  • Sleepiness.
  • Tremor.
  • Blurred vision.
  • Itching.
  • Feeling of weakness or lethargy.
  • Thirst.
  • Muscle twitching.
  • Cold hands or feet.
  • Inflammation of the liver (hepatitis).
  • Increased blood pressure or heart rate.

See also warnings above. The side effects listed may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

The following medicines may increase the blood level of duloxetine and so should not be taken in combination with this medicine:

  • ciprofloxacin
  • enoxacin
  • fluvoxamine.

Yentreve must not be taken at the same time as, or within 14 days of taking a monoamine oxidase inhibitor (MAOI) antidepressant, for example phenelzine, tranylcypromine or isocarboxacid. In addition, this type of antidepressant should not be started until at least five days after stopping Yentreve.

This medicine should not be used at the same time as a medicine called Cymbalta, which also contains duloxetine, but is used for depression.

Side effects may be more common if this medicine is used in combination with the antidepressant moclobemide, or the herbal remedy for depression St John's wort (Hypericum perforatum). These medicines are not recommended for use in combination with Yentreve.

There may be an increased risk of a rare side effect called the serotonin syndrome if Yentreve is taken with any of the following medicines, which also enhance the activity of serotonin in the central nervous system. These medicines are not recommended for use in combination with Yentreve:

  • SSRI antidepressants, eg fluoxetine, paroxetine
  • tricyclic antidepressants such as clomipramine or amitriptyline
  • venlafaxine
  • tryptophan
  • tramadol
  • triptans for migraine, eg sumatriptan.

The use of Yentreve in combination with antidepressant medicines, particularly any of those those mentioned above, is not recommended. If your doctor wants you to start taking an antidepressant, it is recommended that Yentreve is stopped gradually first.

There may be an increased risk of drowsiness or sedation if this medicine is taken with any of the following medicines (which can also cause drowsiness):

  • antipsychotics, eg haloperidol
  • barbiturates, eg phenobarbital
  • benzodiazepines, eg diazepam
  • opioid painkillers, eg morphine, codeine
  • sedating antihistamines, eg chlorphenamine
  • sleeping tablets, eg zopiclone.

There may be an increased risk of bleeding if duloxetine is taken by people who are taking any of the following medicines, which are known to affect the ability of the blood to clot:

  • anticoagulants (to prevent and treat blood clots) such as warfarin
  • antiplatelet medicines (to "thin the blood") such as aspirin, dipyridamole or clopidogrel
  • non-steroidal anti-inflammatory drugs (NSAIDs) eg ibuprofen, diclofenac.

There may be an increased risk of side effects on the liver if this medicine is taken in combination with medicines that can affect the liver.

Duloxetine may increase the blood levels of the following medicines:

  • flecainide
  • metoprolol
  • propafenone
  • risperidone
  • tricyclic antidepressants such as nortriptyline, amitriptyline or imipramine.

Other medicines containing the same active ingredient

In the UK there are currently no other medicines for treating SUI that contain duloxetine as the active ingredient.

Cymbalta contains duloxetine, but is used to treat depression, not SUI.