Medications for Obesity: Side Effects and Contraindications

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There are currently several medications on the market that have been approved by the U.S. Food and Drug Administration (FDA) for treating obesity. While they have been shown to have weight-loss benefits for eligible patients, they all have side effects--including some that are serious. Here are the potential side effects of which you should be aware, listed by medication:

Orlistat (Xenical®, Alli®)

Orlistat is available in both a prescription form (originally marketed as Xenical®) and a non-prescription, over-the-counter form (currently marketed under the brand name Alli®).

The difference between the two is a matter of dosage; the prescription product contains 120 mg of orlistat and was introduced in 1999 in the United States, while the over-the-counter version contains 60 mg of orlistat.

In a safety announcement dated May 26, 2010, the FDA stated that it was adding a new warning to the labels of both the prescription and over-the-counter versions of orlistat to make physicians and the public aware of “cases of severe liver injury that have been reported rarely with the use of this medication.” The FDA did note that a cause-and-effect relationship between taking orlistat and liver injury had not been definitively established.

Other side effects that have been reported with orlistat, primarily because it blocks dietary fat absorption, include oily spotting in bowel movements, flatulence, and sensing the urgency to move the bowels. These side effects are usually short-lived, however.

Orlistat may also block some absorbing fat-soluble vitamins, such as Vitamin A and Vitamin D, and beta-carotene, and thus patients taking orlistat may need to take a multivitamin or supplements to ensure that they are getting the adequate nutritional intake. According to the package insert for Xenical®, the vitamin supplement should be taken at least two hours before or after taking Xenical®.

There are also possible interactions between orlistat and medications such as cyclosporine and levothyroxine; patients taking these medications will need to take the doses several hours apart and be monitored for their respective conditions (such as thyroid function).

According to the package insert for Xenical®, orlistat is contraindicated (i.e., must not be taken) in pregnant patients, in patients with chronic malabsorption syndrome, and in patients with cholestasis (a medical condition in which bile flow from the liver to the duodenum is blocked).

Phentermine/Topiramate (Qsymia®)

The drug combination of phentermine plus extended-release topiramate, currently marketed under the brand name Qsymia®, is a prescription medication that was approved by the FDA in 2012.

Potentially serious concerns about safety have arisen from the clinical trials of phentermine/topiramate. Specifically, these concerns have included teratogenicity (causes birth defects) and higher resting heart rate. Preliminary data suggested that women who took topiramate, one component of this drug combination, during pregnancy were more likely to have infants with an orofacial cleft (such as cleft palate).

Thus, phentermine/topiramate should not be taken by pregnant women or by women who are planning to become pregnant, due to the risk of birth defects in the fetus.

Also, it is unknown whether or not phentermine/topiramate can be passed to a newborn via breast milk, and thus, nursing mothers are advised either to discontinue the drug or discontinue breastfeeding. Further, the use of phentermine/topiramate is not recommended in children.

Drug labeling for phentermine/topiramate recommends heart-rate monitoring on a regular basis, and recommends against the use of this drug in patients with recent or unstable cardiovascular disease. Heart disease in relation to weight-loss drugs is of particular concern due to the notorious history of heart valve defects with Fen-Phen (fenfluramine/phentermine), which was withdrawn from the market due to this disastrous side effect.

It is also important to note that the drug information accompanying phentermine/topiramate states that using this drug with another weight-loss medication, whether this be a prescription, over-the-counter medication or herbal preparation, has not been established to be safe.

The package insert also states that this drug is contraindicated in patients who have glaucoma or hyperthyroidism. In addition, it is contraindicated “during or within 14 days administering monoamine oxidase inhibitors” and in patients with “known hypersensitivity or idiosyncrasy to the sympathomimetic amines” (package insert).

Lorcaserin (Belviq®)

Lorcaserin, currently marketed under the brand name Belviq®, is a prescription drug that was also approved by the FDA in 2012.

Lorcaserin should not be taken by pregnant women or by women who are planning to become pregnant, due to the risk of birth defects in the fetus. Also, it is unknown whether or not lorcaserin can be passed to a newborn via breast milk, and thus, nursing mothers are also advised to take this into account when deciding whether or not to take the drug.

As an agonist of the serotonin receptor, lorcaserin is termed a “serotonergic drug,” and therefore there is the potential risk of serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions. This risk increases when used in combining other serotonergic drugs or drugs that impair the metabolism of serotonin. These may include other medications such as tricyclic antidepressants, dietary supplements like St. John’s Wort, monoamine oxidase inhibitors (MAOIs), triptans or bupropion, among many others.

It is thus important to note that the drug information accompanying lorcaserin states that using lorcaserin with another weight-loss medication, whether this be a prescription or over-the-counter medication, has not been established to be safe. Furthermore, the safety of lorcaserin when it comes to cardiovascular events has not yet been established, although the FDA has asked the company that makes and markets lorcaserin to monitor this.

Naltrexone/Bupropion (Contrave®)

This medication, known by the brand name Contrave®, is a combination of two other drugs, naltrexone hydrochloride, and bupropion hydrochloride. Contrave® was approved by the FDA on September 10, 2014.

The FDA has given Contrave® a black box warning because it contains bupropion. This warning notes that there can be an increased risk of suicidal thoughts and behaviors associated with antidepressant drugs, including bupropion. The warning also notes that “serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.”

Common side effects reported during the clinical trials with Contrave® included nausea, vomiting, constipation, diarrhea, headache, dizziness, insomnia and dry mouth.

The FDA’s news release noted that Contrave® can cause seizures and should therefore not be used in patients with seizure disorders. Another serious potential side effect is a possible increase in blood pressure and heart rate on Contrave®; for this reason, the medication is contraindicated in patients with uncontrolled high blood pressure. Blood pressure and pulse should be monitored while a patient is taking Contrave®. In addition, other products containing bupropion should not be taken along with Contrave®.

Because of its naltrexone component, Contrave® is also contraindicated in patients who are taking opioids or who are being treated for opioid dependence. Patients who are abruptly discontinuing benzodiazepines, alcohol, barbiturates, or antiepileptic drugs should also not take Contrave®.

Contrave® is also contraindicated in women who are pregnant or trying to become pregnant.

Liraglutide (Saxenda®)

On December 23, 2014, the FDA approved liraglutide as a treatment option for chronic weight management. This medication, which is an injection, is being marketed under the brand name Saxenda®.

The FDA has issued a black-box warning on Saxenda®, stating that tumors of the thyroid gland have been observed in studies on rodents, but that it is unknown whether or not Saxenda® can cause these tumors in humans.

Serious side effects that have been reported in patients taking Saxenda® include pancreatitis (inflammation of the pancreas, which can be life-threatening), gallbladder disease, kidney disease, and suicidal thoughts. Additionally, Saxenda® can raise heart rate, and the FDA advises that is be discontinued in any patient who experiences a sustained increase in resting heart rate.

The most common side effects of Saxenda® that were seen in the clinical trials were nausea, constipation, vomiting, diarrhea, decreased appetite, and low blood sugar (hypoglycemia).

Due to the theoretical risk of thyroid tumors, Saxenda® should not be taken by patients who have a rare endocrine disorder known as multiple endocrine neoplasia syndrome type 2 (MEN-2), or by patients who have a personal or family history of a type of thyroid cancer known as medullary thyroid carcinoma (MTC).

Others who should not take Saxenda® include children (the FDA is currently requiring clinical trials to evaluate the safety and efficacy in children), women who are pregnant or breastfeeding, and anyone who has ever had a serious hypersensitivity reaction to liraglutide or to any of the product components of Saxenda®.


XENICAL[package insert]. Genetech, Inc. 2013.

Colman E, Golden J, Roberts M, Egan A, et al. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. Published October 10, 2012, at

QSYMIA [package insert]. Mountain View, CA: Vivus, Inc; 2012-2013.

BELVIQ [package insert]. Woodcliff Lake, NJ: Eisai Inc; 2012.

U.S. Food and Drug Administration. FDA approves weight-management drug Contrave. Accessed online at on September 11, 2014.

FDA news release. FDA approves weight-management drug Saxenda. Accessed online at on January 6, 2015.

Saxenda prescribing information. Novo Nordisk. Accessed online at on January 7, 2015.

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