Bupropion is one of the two active ingredients of weight loss drug Contrave. One Contrave tablet contains 90 mg of bupropion hydrochloride. It is majorly antidepressant and decreases appetite thus works well in the treatment of obesity. In combination with naltrexone hydrochloride, it forms Contrave, which is a trending weight loss regimen these days.

History and clinical studies:

Bupropion is first discovered by Nariman Mehta in 1969. In 1989, US approved this molecule for medical use. Earlier, FDA approved sustained release formula was released. Later on, it is combined with hydrochloride (HCl) to form bupropion hydrochloride and used as extended release formula. In combination with hydrochloride (HCl), it is used in Contrave & it is approved by US FDA in 2014 as weight loss drug, effective in weight loss, in combination with low-fat balanced diet and regular physical exercise.

Through clinical research, it is discovered that bupropion minimizes the effects of sympathomimetic and anticholinergic and cardiac effects of antidepressant drugs. Burroughs Wellcome patented this drug in 1974 (GlaxoSmithKline). It is a chemical derivative of diethylpropion, which is used as anorectic.

When the drug is approved in 1985 by FDA, it showed seizures when administered in a dosage of 400 mg to 600 mg. Because of this, bupropion was removed from the market in 1986. Later on, in 1989, the drug was again introduced in maximum daily dose as 450 mg. Then a sustained release tablet was launched specifically to treat smoking habit.

The most recent formula of the drug is extended release form. Because of this, it lowers the risk of seizures when used for therapeutic purpose. The drug is also approved by US FDA for seasonal affective disorder in 2006.

The molecule is studied for its therapeutic usage to treat obesity. When clinical trials were done to assess its effects on depressive disorders, it is observed that there is no weight gain in patients treated with bupropion as compared to other patients taking other antidepressant drugs and as compared to placebo. A placebo-controlled study conducted 3 times to evaluate bupropion’s effects on weight loss and it showed demonstrated the effect on weight loss in overweight and obese women as compared to placebo (2% to 10% body weight depends on bupropion dose, type of diet and treatment duration).

As per a recent 16-week trial on overweight adolescent, bupropion proved to be superior in weight reduction. Thus its use in weight loss pill Contrave is justified.

How bupropion works:

Bupropion is an aminoketone, works as “norepinephrine and dopamine reuptake inhibitor” and its structure is similar to Cathinone. Through preclinical study, it is observed that bupropion enhances monoaminergic neurotransmission action through its inhibitory effect on DA and NE reuptake inhibitors. The combination with hydrochloride (HCl) dissolves easily in gastrointestinal (GI) tract & thus increases its absorption in the blood stream.

Pharmacokinetic profile of bupropion in Contrave:  

After oral administration of Contrave in healthy individuals, the peak concentration of bupropion and time to reach peak concentration is 168 ng/ml in three hours. If you take Contrave taken after a meal with high-fat level, there is much increase in systemic exposure, Hence Contrave administration is not recommended post taking high-fat food.

Excretion: In urine 83%, in feces 10%

Indications:

Bupropion hydrochloride (independent or in combination with other components such as naltrexone) is the solution if you are suffering from any of the below-mentioned disease/conditions:

  • Obesity, overweight
  • Depression
  • Anxiety
  • Discontinue smoking
  • ADHD (Attention deficit hyperactivity disorder)
  • Sexual dysfunction
  • Neuropathic pain

Contrave is in huge demand nowadays as a chronic weight management solution along with reduced calorie intake in the diet and regular exercise.

Interaction with other drugs and diseases: 

There are certain drugs and disease with which bupropion interacts and causes harmful effects if taken together. Here go the details:

  • Diseases: Hepatic diseases, mania, seizures, depression, psychosis, closed angle glaucoma, history of head injury, renal dysfunction, weight loss in patients suffering from anorexia, malnutrition.
  • Drugs: Aripiprazole, metoprolol, esomeprazole, amphetamine, MAO inhibitors, dextroamphetamine, acetaminophen, duloxetine, escitalopram, alprazolam, cetirizine are common drugs which have interaction with bupropion.
  • Alcohol, nicotine: increases blood pressure, may cause seizures and chest pain if taken with alcohol or nicotine.

Precautions: 

Inform your physician well about your medical history before starting the treatment, specifically in following conditions:

  • Lab tests: If the patient is taking Contrave, It may cause false-positive amphetamine in urine drug test due to bupropion.
  • If the patient is taking MAO inhibitors, it should be stopped before 14 days of starting Contrave treatment to avoid hypertensive reactions.
  • If the patient is elderly, should be monitored regularly for BP, Pulse rate while on medication.
  • Pregnancy: bupropion falls under FDA category C of pregnancy, so it is not known whether it is harmful to unborn baby. The risk of congenital heart disease to the baby is in question. However, you need to inform your physician as a precaution.
  • Breastfeeding mothers: Though there is no proven effect of the drug on milk production, There is a risk of seizures to a breastfeeding infant.
  • Bupropion is cytochrome P450 2D6 isozyme inhibitor and metabolized by CYP2B6 isozyme. When starting medication metabolized by CYP2B6 in a patient already taking Contrave, start with the lower dose of medicine and titrate with care. Contrary to this, if starting Contrave in a patient who is already taking a drug which is metabolized by CYP2B6, original medicine dose should be reduced.

Hence you are advised to be careful to avoid these interactions if you are taking any of above-mentioned drugs and/or already suffering from any of these diseases before taking Contrave.

Adverse reactions:

  • Suicidal thoughts
  • Neuropsychiatric disorders
  • Mania
  • Depression
  • Seizures
  • Homicidal thoughts
  • Arrhythmia
  • Glaucoma
  • Severe hypertension
  • Stevens-Johnson syndrome
  • Hypersensitivity
  • Anaphylaxis
  • Erythema
  • Headache
  • Nausea
  • Dizziness
  • Vomiting
  • Tinnitus
  • Anorexia
  • Abdominal pain
  • Weight loss

Overdose:

If a patient by mistakenly takes an overdose and shows symptoms such as difficulty in breathing, please call your doctor or emergency medical services. Overdose can also happen if a patient is already taking medication which contains bupropion (e.g. Wellbutrin), and it is contraindicated to advise him/her Contrave in such scenario.

Since bupropion hydrochloride (HCl) causes seizures in high dose, you should be overly cautious when administering Contrave with an antidepressant, antipsychotic drugs. Monitor the patient continuously if the patient is taking these drugs along with Contrave, so that any adverse reaction can be controlled.

Disclaimer: This article does not recommend to take or not to take the drug bupropion and the content is not intended to be a substitute for professional medical advice or treatment. Please visit your physician for any medical advice.