Methylnaltrexone (Subcutaneous)

As a opioid antagonist, Methylnaltrexone helps to reverse some of the side effects of opioid medications, such as constipation.


Methylnaltrexone, which is often marketed under the brand name Relistor, is a relatively new agent of peripherally acting opioid antagonists. It functions to reverse the negative side effects of some opioid-based medications without having an effect on their pain-killing properties or causing withdrawal symptoms.

Because Methylnaltrexone is a quaternary ammonium cation, it is impossible for it to cross the blood/brain barrier. It, therefore, has antagonist effects across the entire body and counteracts effects such as constipation and itching without interfering with the analgesic effects of the opioid in the brain. Despite this, a large proportion of analgesic effects are mediated by opioid receptions on sensory neurons particularly in conditions like surgical pain, arthritis or trauma. Methylnaltrexone could, therefore, increase pain in these circumstances.

The use of opioid medicines for four weeks or more can create incidences of severe constipation in the patient, which can cause serious complications if left untreated. Methylnaltrexone is FDA-approved for the treatment of constipation but is typically only resorted to when ordinary laxatives have failed. It binds to the same receptors as opioids like Morphine but instead blocks the effects of these drugs. It is chemically similar to naltrexone, although it cannot enter the brain as it carries a positive charge on its nitrogen atom.

This medicine was first developed in the late 70's and has been clinically approved since 2008. It is delivered via subcutaneous injection in patients who are in receipt of palliative care or are undergoing narcotic treatment for severe pain.

Type Of Medicine

  • Laxative

Conditions Treated

  • Opioid-induced constipation
  • Opioid-induced itching

Side Effects

Like most medications, Methylnaltrexone can cause some unwanted side effects alongside its desired effect. The most common side effects reported by patients undergoing treatment with this medication include the following:

  • Chills
  • Fear
  • Nervousness
  • Increased sweating
  • Diarrhea
  • Severe/persistent diarrhea
  • Yawning

Most patients only experience very minimal side effects while taking Methylnaltrexone, if they observe any at all. Methylnaltrexone is designed to alleviate symptoms of constipation which if left untreated can cause serious complications. As such, the benefits of using Methylnaltrexone are generally thought to outweigh the risks of experiencing temporary mild discomfort caused by side effects.

As the patient continues to take this medication as prescribed by a doctor, most of the previously mentioned side effects should subside. If they persist over a prolonged period or appear to get worse over time, the patient is advised to follow this up with their healthcare provider as soon as possible. A doctor or pharmacist may be able to recommend over the counter remedies or other treatments to alleviate side effects.

Other side effects experienced less frequently, albeit often enough to warrant a mention, include the following:

  • Bloated or full feeling
  • Headache
  • Muscular spasms
  • Feeling of pressure in the stomach
  • Runny nose
  • Swelling of the stomach or abdominal area
  • Vomiting

Because Methylnaltrexone can create feelings of fear and/or nervousness in the patient, they are advised to refrain from driving or operating heavy machinery while taking Methylnaltrexone until it has been observed that it is safe to do so. This is to prevent the patient or other road users from injury.

Not all side effects may have been reported. Patients who experience side effects which are not listed in the literature provided with this medication should inform their healthcare provider as soon as possible and report their findings to the FDA.


Like all medications, it is incredibly important for patients to only take Methylnaltrexone as directed by a qualified physician. This means that patients must avoid taking any more of the drug than advised, either in terms of dose size or frequency of use. Additionally, patients should be prepared to stop using this medication if advised to do so by a doctor, even if they still have a supply of the medication remaining.

Methylnaltrexone should be administered on an empty stomach, at least half an hour before the patient's first meal of the day. Once Methylnaltrexone has been administered, it is important for the patient to be in close proximity to toilet facilities, as bowel control can be difficult once the drug begins to take effect.

Dose sizes can vary according to the specific needs of the patient. It is therefore important for the patient to listen carefully to the instructions of the doctor at the time Methylnaltrexone is prescribed. The instructions printed on the side of the medication packaging can also be followed, as these should be similar. When determining the best dose size, a doctor will take a number of different factors into account. The medicine strength, number of doses per day, time between doses and length of time the patient is expected to be taking Methylnaltrexone will all play a role. The amount of opioid medication the patient is taking will also affect dose size.

While the manufacturers of Methylnaltrexone provide general dose instructions, it must be reiterated that these are simply guidelines which can be altered by the patient's doctor. Factors discussed between patient and physician will affect dose amounts.

The usual adult dose for opioid-induced constipation:

On average the patient should expect to receive approximately 12mg of Methylnaltrexone, subcutaneously, once a day. Prior to initiating Methylnaltrexone use, all other laxative therapy should be discontinued. Laxatives may be used as required for a suboptimal response after three days of Methylnaltrexone use. The use of Methylnaltrexone should be re-evaluated when the opioid regimen is changed. This helps to avoid any adverse reactions.

The usual adult dose for the prevention of constipation in patients with advanced illness:

Weight-based dosing should be used in patients with advanced illnesses. Methylnaltrexone may be administered every second day (or as and when required) but no more frequently than a single dose in any 24-hour period.

  • If patient weighs less than 38kg, they should receive 0.15mg of Methylnaltrexone per kg of body weight.
  • If patient weighs between 38kg and 62kg, they should receive 8mg of Methylnaltrexone.
  • If patient weighs between 62kg to 114kg, they should receive 12mg of Methylnaltrexone.
  • If patient weights more than 114kg, they should receive 0.15mg of Methylnaltrexone per kg of body weight.

Methylnaltrexone should be used at these doses for the treatment of constipation in adults with chronic non-cancer related pain, or those with illnesses in advanced stages who are receiving palliative care when the patient response to laxative therapy has not been sufficient.

There are no recommended dose sizes for patients under the age of 18 years. While Methylnaltrexone can be used in patients of 18 and younger, efficacy and safety has not been clinically established. The manufacturer, therefore, leaves the dose size and frequency for pediatric use at the discretion of the prescribing doctor.

Patients are warned against taking double doses. If the patient misses a dose, they should simply arrange for the next dose to be administered as soon as they realize. If it is closer to the time for the next dose to be taken, the patient should simply omit the missed dose and wait until the next scheduled dose.

If the patient experiences signs or symptoms of an overdose (fast or slow heartbeat, difficulty breathing, loss of consciousness, loss of coordination, severe nervousness) they may require immediate medical attention. In this case, the patient or their caregiver should contact emergency services on 911 or their local poison control center on 1800-222-1222.


All drugs have the potential to interact with other medications or chemicals within the human body. These interactions can change the effects of one or more of the involved medications. In some cases, this can result in one or more medications becoming ineffective in treating the condition they were prescribed to alleviate. In other cases, interactions can cause dangerous and even fatal side effects to occur. Because these risks exist, it is important for the patient to keep a detailed list of all medicines they are currently taking. This extends to over the counter remedies, herbal supplements, vitamins and complementary medicines as well as prescribed drugs.

There are currently no known drugs which interact with Methylnaltrexone. However, this does not mean that no interactions exist it merely means that no interactions have been clinically observed. Patients who feel one of their existing medications is interacting negatively with Methylnaltrexone are advised to inform their doctor and/or healthcare provider and to report their findings to the FDA.

Several disease interactions exist with Methylnaltrexone. Patients with intestinal obstruction, renal impairment (kidney disease) or hepatic impairment (liver disease) are advised to inform their doctor prior to undergoing treatment with Methylnaltrexone. In most cases, the Methylnaltrexone dose will need to be adjusted in order to avoid causing further impairment to the liver or kidneys in patients suffering from illnesses affecting these organs.


To ensure that Methylnaltrexone is safe for them, patients should inform their doctor if they have ever had one or more of the following conditions:

  • Stomach ulcer
  • Cancer
  • Perforations in the stomach or intestines
  • Colitis
  • Crohn's disease
  • Diverticulitis
  • Ogilvie's syndrome
  • Kidney disease
  • Liver disease

Because Methylnaltrexone can produce bowel movements within 20-30 minutes, patients are advised to be close to a restroom while using this medicine.

Methylnaltrexone is injected subcutaneously (under the skin). In many cases (during palliative care or when the patient is suffering from severe pain) this medication will be administered by a healthcare professional in a clinical setting, such as a hospital, hospice or doctor's surgery. However, some patients or their caregivers may be shown how to use injections at home. Patients should only self-administer this medicine when they fully understand how to use the injection equipment properly. The patient should also understand how to correctly dispose of syringes and needles. The patient's healthcare provider should show them the best places on the body to subcutaneously administer Methylnaltrexone. Patients are advised to use a different place on the body every time they inject and to avoid injecting into the same place twice in a row.

Patients should inform their doctor about any changes in weight. Methylnaltrexone doses for injection are based on the weight of the patient any drastic changes in weight could, therefore, affect the efficacy of the dose.


Methylnaltrexone for injection should be stored at room temperature away from sources of heat, moisture and light. It is therefore unsuitable for storage in a bathroom cabinet. Instead, it should be kept in a dedicated, locked medicine cabinet where possible. It should also be kept out of the reach of children and/or pets. Patients must not freeze vials or pre-filled syringes and should keep the medication in its original container.

Disposable needles and syringes should be used only once. Patients should follow FDA guidelines and adhere to state laws when it comes to disposing of used needles. A puncture-proof sharps container should be used for disposal. These containers can be safely disposed of at most local pharmacies.


Methylnaltrexone is a greatly beneficial drug, but it can also pose a risk to patients who do not communicate effectively with their healthcare providers and physicians. As a treatment designed to alleviate symptoms of constipation associated with opioid use, Methylnaltrexone creates a laxative effect when standard laxatives are insufficient. However, it can also cause a number of unwanted effects such as diarrhea, persistent yawning, stomach cramps, nausea and more. By producing feelings of nervousness and fear, it can impair the day-to-day functioning of the patient and put them in perilous situations if the correct precautions are not taken. Because of this, it is important for the patient to be upfront about their own medical history.

When taken correctly, Methylnaltrexone can help provide relief to the side effects of opioid use which are sometimes untreatable with standard laxatives. By alleviating symptoms of constipation, Methylnaltrexone allows the patient to enjoy a greater quality of life and healthier intestinal system which may not have been achievable by conventional means. To achieve this, patient and doctor must work together to find the most appropriate dose size and frequency of use.