Desvenlafaxine

Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine and has been marketed separately as a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant that is used to treat major depressive disorder ¹. Desvenlafaxine is believed to work by blocking the reabsorption of serotonin and norepinephrine (noradrenaline) neurotransmitters or chemical messengers in your brain, increasing their availability and potentially improving mood and relieving depression, anxiety, and chronic pain ², ³, ⁴. Desvenlafaxine current clinical indication is limited to treating major depressive disorder. Desvenlafaxine is also sometimes used off-label to treat hot flashes (hot flushes; sudden strong feelings of heat and sweating) in women who have experienced menopause (‘change of life’; the end of monthly menstrual periods). Desvenlafaxine may be prescribed for other uses; ask your doctor or pharmacist for more information. Because Desvenlafaxine is the major active metabolite of venlafaxine, there is little evidence to suggest that Desvenlafaxine is more effective or has a different activity or rate of adverse events as Venlafaxine.

Desvenlafaxine was approved for use in the United States in 2008 and is still used with more than 1 million prescriptions filled yearly ⁵.

Desvenlafaxine is available as extended-release (long-acting) tablets of 25, 50, or 100 mg in generic forms and under the brand name of Pristiq. Desvenlafaxine is usually taken once a day with or without food. The recommended Desvenlafaxine dosage in adults is 50 mg once daily; increasing the dose has not been shown to improve effectiveness. Take desvenlafaxine at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take desvenlafaxine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow Desvenlafaxine tablets whole with plenty of water; do not split, chew, crush, or dissolve them.

Desvenlafaxine controls depression, but does not cure it. It may take several weeks before you feel the full benefit of desvenlafaxine. Continue to take desvenlafaxine even if you feel well. Do not stop taking desvenlafaxine without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking Desvenlafaxine, you may experience withdrawal symptoms such as dizziness; confusion; nausea; headache; ringing in the ears; irritability; aggressive behavior; inability to control emotions; frequent mood changes; abnormally excited, difficulty falling asleep or staying asleep, diarrhea, anxiety; extreme tiredness; unusual dreams; seizures; sweating; uncontrollable shaking of a part of the body; blurred vision; or pain, burning or tingling in the hands or feet. Tell your doctor if you experience any of these symptoms while you are decreasing your dose of desvenlafaxine or soon after you stop taking desvenlafaxine.

While believed to be better tolerated than venlafaxine, desvenlafaxine appears to have a similar spectrum and frequency of side effects.

Common side effects of desvenlafaxine may include:

• dizziness, drowsiness, anxiety
• increased sweating (diaphoresis)
• nausea, decreased appetite, constipation
• sleep problems (insomnia)
• decreased sex drive, impotence, or difficulty having an orgasm.

Desvenlafaxine may cause serious side effects. See your doctor at once if you have:

• a seizure;
• easy bruising or bleeding (nosebleeds, bleeding gums), blood in your urine or stools, coughing up blood;
• blurred vision, eye pain or swelling, or seeing halos around lights;
• cough, chest discomfort, trouble breathing;
• low blood sodium–headache, confusion, problems with thinking or memory, weakness, feeling unsteady.

Desvenlafaxine may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. Desvenlafaxine may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you or your caregiver notice any of these unwanted effects, see your doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Desvenlafaxine may cause a serious condition called serotonin syndrome if taken together with some medicines. Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea. Do not use desvenlafaxine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), tryptophan, St. John’s wort, amphetamines, or some pain or migraine medicines (eg, meperidine, methadone, rizatriptan, sumatriptan, tramadol, Demerol®, Methadose®, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before using any other medicines with desvenlafaxine.

How does desvenlafaxine work?

Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine and has been marketed separately as a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant that is used to treat major depressive disorder ¹. Desvenlafaxine is the primary active metabolite of venlafaxine. Therefore, the two agents are structurally similar in that they both contain two chemical rings that are not next to each other ⁶. Test tube studies have shown that desvenlafaxine is ten times more selective for serotonin than for norepinephrine, making it similar to the drug duloxetine ⁶. Surprisingly, the drug that desvenlafaxine derives from, venlafaxine, has an affinity to serotonin 30 times more than it does to norepinephrine. The time to inhibit reuptake in serotonin and norepinephrine is known for duloxetine, milnacipran, and venlafaxine. However, no such data is available for desvenlafaxine. Like the other serotonin and norepinephrine reuptake inhibitors (SNRIs), there is a weak effect on dopamine and its reuptake ⁶.

Normally serotonin and norepinephrine (noradrenaline) neurotransmitters (chemical messengers) in your brain, that play a role in mood, alertness, and other bodily functions, after their release, they’re typically reabsorbed by the sending neuron in a process called reuptake. Serotonin and norepinephrine reuptake inhibitors (SNRIs) work by blocking the reuptake of both serotonin and norepinephrine, which increases their levels in your brain neurons ⁷, ³. By blocking (inhibiting) reabsorption or reuptake of both serotonin and norepinephrine neurotransmitters (chemical messengers) in your brain, more serotonin and norepinephrine are active in your brain contributing to the therapeutic effects of SNRIs in depression and anxiety, however, the exact mechanism is not known.

Metabolism

The half-life of desvenlafaxine is 11 hours, and it metabolizes through the liver with a small amount broken down via the cytochrome P450 system ¹. Since CYP enzymes are not significantly involved in its metabolism, there is not as large of a concern for drug-drug interaction as compared to its counterparts. Renal excretion is a major route of desvenlafaxine elimination. Nearly 45% of desvenlafaxine is unchanged when eliminated in the urine. It is important to consider treating with a lower dose when dealing with patients who have moderate to severe kidney impairment or end-stage renal disease ⁶.

Desvenlafaxine uses

Desvenlafaxine is a FDA-approved drug to treat major depressive disorder in adults ⁸, ⁹. For healthy women who have contraindications to estrogen, doctor can use desvenlafaxine off-label to treat hot flashes during menopause ¹⁰.

What to know before taking Desvenlafaxine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make.

People with depression or mental illness may have thoughts about suicide. Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults during short-term studies. Tell your doctor right away if you have any sudden changes in mood or behavior, or thoughts about suicide. Do not stop using desvenlafaxine without first asking your doctor.

You should know that desvenlafaxine is very similar to another serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine (Effexor). You should not take these medications together.

Do not take desvenlafaxine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan], linezolid (Zyvox), methylene blue, phenelzine [Nardil], selegiline [Emsam, Zelapar], tranylcypromine [Parnate]). Do not start taking desvenlafaxine within 14 days after you stop using an monoamine oxidase (MAO) inhibitor. Wait 7 days after stopping desvenlafaxine before you start taking an monoamine oxidase (MAO) inhibitor. If you take them together or do not wait the proper amount of time, you may develop confusion, agitation, restlessness, stomach or bowel symptoms, a sudden high body temperature, an extremely high blood pressure, or severe seizures.

The presence of other medical problems may affect the use of Desvenlafaxine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with mania and depression)
• Bleeding problems
• Angle-closure glaucoma. You should know that Desvenlafaxine may cause angle-closure glaucoma, a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision. Talk to your doctor about having an eye examination before you start taking Desvenlafaxine. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, see your doctor or get emergency medical treatment right away.
• Heart or blood vessel disease
• Hyperlipidemia (high cholesterol or triglycerides in the blood)
• Hypertension (high blood pressure)
• Hyponatremia (low sodium levels in the blood)
• Interstitial lung disease
• Mania or hypomania
• Seizures
• Stroke
• Tachycardia (fast heartbeat): Use with caution. May make these conditions worse.
• Kidney disease
• Liver disease: Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Alcohol can make the side effects from desvenlafaxine worse.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to Desvenlafaxine, venlafaxine (Effexor) or any other medicines. Also tell your doctor if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. Ask your pharmacist or check the Medication Guide for a list of the ingredients. For non-prescription products, read the label or package ingredients carefully.

Children

Appropriate studies have not been performed on the relationship of age to the effects of desvenlafaxine in the pediatric population. Safety and efficacy have not been established.

Elderly

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of desvenlafaxine in the elderly. However, elderly patients are more likely to have low blood pressure, hyponatremia (low sodium in the blood), and age-related kidney problems, which may require an adjustment in the dose for patients receiving desvenlafaxine.

Pregnancy

Some antidepressants may harm your baby if you take them during pregnancy or while you’re breastfeeding. If you are pregnant, are thinking about getting pregnant or are breastfeeding, talk to your doctor about the benefits and possible risks of antidepressants. Don’t stop taking your medicine without talking with your doctor first.

If you become pregnant while taking desvenlafaxine, see your doctor. Desvenlafaxine may cause problems in newborns following delivery if it is taken during the last months of pregnancy. Do not start or stop desvenlafaxine without asking your doctor. If you are pregnant, your name may be listed on a pregnancy registry to track the effects of desvenlafaxine on the baby.

Desvenlafaxine is a category C drug, which means that tests done on animals have shown an adverse effect on the fetus, and there are no well-controlled studies in pregnant women. Still, possible benefits may justify the use of the drug in pregnant women despite the risks.

Some neonates exposed to Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), or Selective Serotonin Reuptake Inhibitors (SSRIs) late in the third trimester had clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. This clinical picture is consistent with either direct toxic effect of SSRIs and SNRIs, drug discontinuation syndrome, or serotonin syndrome.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established.

Breastfeeding

There are no adequate studies in women for determining infant risk when using Desvenlafaxine during breastfeeding. Modest doses of desvenlafaxine are excreted into breastmilk, but serum drug levels of breastfed infants are less than 10% of simultaneous maternal levels ¹¹. Total drug exposure of breastfed infants is about half of that experienced by breastfed infants whose mothers are taking venlafaxine ¹². With the related drug venlafaxine, newborn infants of mothers who took the drug during pregnancy sometimes experienced poor neonatal adaptation as seen with other antidepressants such as selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitor (SNRI). Similar effects may occur with desvenlafaxine. Monitor breastfed infants for excessive sedation and adequate weight gain if this drug is used during lactation, especially newborn or preterm infants.

Ten infants ranging in age from 0.9 to 12.7 months were breastfed (8 exclusively) during maternal use of desvenlafaxine in doses of 50 to 150 mg daily or an average of 1.2 mg/kg daily ¹¹. Mothers were also taking lorazepam (n = 6), quetiapine (n = 5), lamotrigine (n = 2), levonorgestrel (n = 2), domperidone (n = 1), and temazepam (n = 1). Infants were studied after an average of 9 days of exposure (range 4 to 35 days) of desvenlafaxine exposure via breastmilk ¹¹. At the time of the study, 7 of the 10 infants were at a lower growth percentile than at the time of birth. Examination by a pediatrician found that all infants were healthy and had Denver developmental scores that matched their age on the day of the study ¹².

A woman with depressive type schizoaffective disorder was taking lurasidone 40 mg at night and desvenlafaxine 50 mg daily after giving birth. She exclusively breastfed her infant. The infant’s growth and development was good during a follow-up period of 39 days ¹³.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking Desvenlafaxine, it is especially important that your doctor know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using Desvenlafaxine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bromopride
• Isocarboxazid
• Linezolid
• Methylene Blue
• Metoclopramide
• Ozanimod
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Tranylcypromine

Using Desvenlafaxine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Alfentanil
• Almotriptan
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Anileridine
• Apixaban
• Ardeparin
• Argatroban
• Aripiprazole
• Aspirin
• Atomoxetine
• Bemiparin
• Benzhydrocodone
• Benzphetamine
• Betrixaban
• Bivalirudin
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buspirone
• Butorphanol
• Cangrelor
• Carbamazepine
• Carvedilol
• Celecoxib
• Certoparin
• Chlorpheniramine
• Choline Salicylate
• Cilostazol
• Plus many more not on this list.

The following nonprescription or herbal products may interact with desvenlafaxine:

• St. John’s wort
• Aspirin
• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn);
• Tryptophan
• Dextromethorphan.

Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking desvenlafaxine. Do not start any of these medications while taking desvenlafaxine without discussing with your doctor.

Desvenlafaxine dosage

The dose of Desvenlafaxine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of Desvenlafaxine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (extended-release tablets)

• For depression
  • Adults: 50 milligrams (mg) once a day. Your doctor may adjust your dose as needed.
  • Children: Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of Desvenlafaxine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Desvenlafaxine side effects

Desvenlafaxine may cause side effects. See your doctor if any of these symptoms are severe or do not go away:

• constipation
• loss of appetite
• dry mouth
• dizziness
• sleepiness
• extreme tiredness
• unusual dreams
• yawning
• difficulty falling asleep or staying asleep
• sweating
• uncontrollable shaking of a part of the body
• pain, burning, numbness, or tingling in part of the body
• enlarged pupils (black circles in the centers of the eyes)
• sexual problems in males; decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation
• sexual problems in females; decreased sex drive, or delayed orgasm or unable to have an orgasm
• difficulty urinating

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, see your doctor immediately:

• rash
• hives
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• difficulty swallowing or breathing
• fast heartbeat
• cough
• chest, arm, back, neck, or jaw pain
• fever
• coma (loss of consciousness for a period of time)
• seizures
• fever, sweating, confusion, fast or irregular heartbeat, severe muscle stiffness or twitching, agitation, hallucinations, loss of coordination, nausea, vomiting, or diarrhea
• unusual bleeding or bruising
• nosebleeds
• small red or purple dots on the skin
• headache
• difficulty concentrating
• memory problems
• confusion
• weakness
• increased falls
• fainting

Desvenlafaxine may cause other side effects. See your doctor if you have any unusual problems while taking desvenlafaxine.

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