Qsymia Weight Loss Breakthrough: How It Works to Melt Fat Fast!

Qsymia is a prescription medication approved for long-term weight management in individuals with obesity or who are overweight with at least one weight-related medical condition. It combines two active pharmaceutical ingredients: phentermine and topiramate. This article delves into the mechanism of action of Qsymia, how it facilitates weight loss, its administration, potential side effects, contraindications, and other crucial aspects.

What is Qsymia?

Qsymia is an oral medication taken once daily. It is indicated for patients with a body mass index (BMI) of 30 or above, or 27 or greater in the presence of at least one weight-related medical condition, such as hypertension, Type 2 diabetes, fatty liver disease, or sleep apnea. The drug combines phentermine and topiramate in an extended-release formulation.

Active Ingredients

Qsymia combines two active ingredients, each with its own mechanism, that work synergistically to promote weight loss:

Phentermine: First introduced in 1959 as part of an anti-obesity combination drug, phentermine is a sympathomimetic amine anorectic. It is closely related to amphetamines and functions as a central nervous system stimulant and appetite suppressant (anorexiant). Phentermine acts on the brain to suppress appetite, augmenting the release of neurotransmitters like norepinephrine and epinephrine. These neurotransmitters transmit signals to the brain, decreasing hunger and increasing the sensation of fullness.
Topiramate: Topiramate was discovered in 1979 but was not released for commercial use until 1996. It is an antiepileptic medication known to impact appetite and metabolism. While its precise mechanism concerning weight loss is not entirely clear, it is theorized to affect neural pathways governing appetite and food cravings. Topiramate's mechanism of action involves multiple pathways. It acts as an anticonvulsant, lowering the seizure threshold and stabilizing membranes by acting on high-voltage-activated calcium channels and voltage-gated sodium channels. It also has an augmenting effect on GABA-A receptors and weakly inhibits carbonic anhydrase, in addition to antagonizing glutamate receptors.

Mechanism of Action for Weight Loss

The synergy between phentermine and topiramate within Qsymia is thought to be the key to its weight loss effectiveness. It is thought Qsymia may increase the activity of the neurotransmitter GABA (γ-aminobutyric acid), which is a chemical messenger in your brain. This can suppress your appetite and make you feel more full. Phentermine is classified as a sympathomimetic amine, central nervous system stimulant and appetite suppressant (anorexiant) and and acts on the brain to suppress your appetite.

Phentermine and topiramate have been used separately in various ways. Phentermine on its own has been used for short-term treatment of obesity in combination with exercise and caloric restriction. In addition, Topiramate has been used to treat partial-onset or primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome, and as a prophylactic treatment of migraine headaches.

Administration

Qsymia is available as oral capsules in various strength combinations (i.e., 3.75 mg/23 mg, 7.5 mg/46 mg, 11.25 mg/69 mg, and 15 mg/92 mg of phentermine mg/topiramate mg ER). It is recommended to take this medication in the morning to prevent insomnia.

Typically, treatment begins with a low dose, progressively increasing every two weeks until reaching the optimal dose of 7.5/46 mg of phentermine/topiramate. Every 12 weeks, a re-evaluation of weight loss progress is recommended. When discontinuing Qsymia at the 15/92 mg dose, it's important to taper the dosage gradually. This involves taking a dose every other day for at least one week before stopping completely.

The medication's initiation begins with the lowest dose of 3.75 mg/23 mg phentermine mg/topiramate mg ER.
Continue on the lowest dose for 14 days, then increase to the 7.5 mg/46 mg phentermine mg/topiramate mg ER dosage.
Reevaluate in 12 weeks.
If 3% weight loss is not achieved after 12 weeks on the 7.5 mg/46 mg phentermine mg/topiramate mg ER dosage, discontinue or escalate the dose to 11.25 mg/69 mg every morning for 14 days.

Individuals with moderate kidney and/or liver diseases should not exceed a dose higher than 7.5/46 mg of phentermine/topiramate.

Clinical Trial Outcomes

The outcomes from clinical trials conducted for Qsymia approval are quite promising. They reveal significant weight loss in the majority of individuals who were prescribed doses of 7.5/46 mg and 15/92 mg of phentermine/topiramate. In 56-week long clinical trials, patients lost on average 14.5 kg (32 lb) using Qsymia 15 / 92 mg plus diet and exercise, and about 5 inches off of their waist. However, it's essential to keep in mind that a significant portion of individuals may regain the weight they've lost once they discontinue the treatment. This highlights the importance of maintaining a balanced diet and a consistent exercise routine even after completing a Qsymia regimen.

Adverse Effects

The likelihood of experiencing side effects increases with higher doses of the medication. While not everyone experiences all potential side effects, it's important to remain informed about potential changes that may arise while taking Qsymia. The most common adverse events reported in clinical trials are dry mouth, constipation, and paresthesia.

Qsymia has a number of potential side effects.

Topiramate may cause severe hypohidrosis and hyperthermia. Avoid combination with anticholinergics which can increase the risk of hyperthermia.
Phentermine/topiramate may cause an increased resting heart rate of up to 20 bpm. Any patient with a history of the cardiac or cerebrovascular disease should use caution. Therefore, it is important to monitor heart rate in all patients taking phentermine/topiramate. Appetite suppressants drugs such as phentermine are associated with valvular heart disease.
Phentermine/topiramate can lead to psychiatric and cognitive disturbances. Mood disorders, including anxiety, depression, or insomnia, may occur with use. Clinicians should monitor patients for suicidal ideations and behaviors, depressed mood, and increased anxiety. It has also been associated with insomnia. Any history of a mood disorder may increase the risk of recurrence with the use of this drug. Phentermine/topiramate has been associated with cognitive impairment causing lapses in memory and judgment. In addition, the patient's ability to concentrate may also be affected.
Acute myopia associated with secondary angle-closure glaucoma may occur with use. Monitoring for increased intraocular pressure will help prevent permanent vision loss if an event occurs.
Elevated serum creatinine may occur. As a result, there is an increased risk of hypokalemia. Obtain periodic blood chemistry panels to monitor for changes. Topiramate is a weak carbonic anhydrase inhibitor; therefore, it can lead to metabolic acidosis, hypokalemia and may lead to the development of nephrolithiasis.
Due to decreased appetite, hypoglycemia may occur, especially in patients with type-2 diabetes mellitus.
Central nervous system (CNS) depression has been noted, and it is advised to avoid other CNS depressants such as alcohol to avoid adverse effects such as dizziness and impaired coordination. Abrupt withdrawal of phentermine/topiramate combination may trigger seizures. Therefore, therapy should be withdrawn gradually to minimize the potential of increased seizure frequency.

A rare side effect of Qsymia is the development of self-harming thoughts and behaviours.

Contraindications

Use of phentermine/topiramate is contraindicated in individuals who are suffering from glaucoma, those who have shown hypersensitivity to any part of the combination drugs, those with a history of hyperthyroidism, women who are pregnant, and those who have recently used a monoamine oxidase inhibitor as it may lead to hypertensive crisis.

Qsymia and MAOIs must never be taken simultaneously as it can cause dangerous elevation of blood pressures. There must be a 14-day period after stopping MAOIs before starting Qsymia.

The inhaled anesthetics such as isoflurane, desflurane, and sevoflurane are to be used cautiously in patients taking phentermine/topiramate as the risk for ventricular tachycardia increases.

Read also: Weight Loss Meds & BCBS

The use of phentermine/topiramate is contraindicated when patients are on a current regimen of isocarboxazid, linezolid, phenelzine, procarbazine, or transdermal selegiline due to the risk of hypertensive episodes.

Phentermine-topiramate can cause dangerous interactions with drugs. For example, selective serotonin reuptake inhibitors (SSRI) can cause serotonin syndrome when combined with phentermine/topiramate. This can lead to high body temperature, agitation, sweating, tremors, dilated pupils, hyperreflexia, and diarrhea. In severe cases, this could be life-threatening, especially with seizures, high fever, irregular heartbeat, and unconsciousness.

Special Warnings and Precautions

Pregnancy: Phentermine and topiramate can cause fetal harm. Data from pregnancy registries and epidemiology studies indicate that a fetus exposed to topiramate in the first trimester of pregnancy has an increased risk of oral clefts (cleft lip with or without cleft palate). If a patient becomes pregnant while taking phentermine/topiramate ER, treatment should be discontinued immediately, and the patient should be apprised of the potential hazard to a fetus. Females of reproductive potential should have a negative pregnancy test before starting phentermine/topiramate ER and monthly thereafter during phentermine/topiramate ER therapy. Phentermine/topiramate ER is contraindicated in pregnancy. Real-world data suggests that Qsymia can be harmful to a developing fetus. Its use during the first trimester of pregnancy has been associated with an increased risk of cleft palate/cleft lip.
Glaucoma: In rare instances, Qsymia has been linked to closed-angle glaucoma. Individuals with a known history of glaucoma should refrain from using this medication.
Cardiovascular Issues: Individuals with high blood pressure and type 2 diabetes should exercise caution when considering Qsymia. It can lower blood sugar and raise blood pressure.
Electrolyte Imbalance: Qsymia may lead to an increase in sodium bicarbonate and creatinine levels in the blood while decreasing potassium levels.
Increased Heart Rate: In the US, the drug label contains warnings for increased heart rate.
Suicidal Behavior and Ideation: The drug label contains warnings for suicidal behavior and ideation.
Mood and Sleep Disorders: The drug label contains warnings for mood and sleep disorders.

Monitoring

Renal impairment: Clinicians need to consider the glomerular filtration rate(GFR) for patients with renal impairment. No dose adjustment is indicated if an individual has a GFR or CrCl greater or equal to 50 mL/min. For individuals with a GFR less than 50 mL/min, it is recommended that dosing should not exceed 7.5 mg/46 mg (phentermine/topiramate) per day.
Hepatic impairment: It is important to consider the Child-Pugh score for individuals with hepatic impairment. A Child-Pugh score of 5 or 6 indicates that no adjustment needs to be made. If the Child-Pugh score is 7 to 9, then it is recommended that dosing should not exceed 7.5 mg/46 mg (phentermine/topiramate) per day. If the Child-Pugh score is 10 to 15, indicating severe impairment, it is advised to avoid using phentermine/topiramate.
Monitor for weight reduction and changes in heart rate. Clinicians should periodically monitor a comprehensive metabolic panel, arterial blood gas analysis, and serum electrolytes to check for non-anion gap hyperchloremic metabolic acidosis.
Monitor for flank pain and hematuria as long-term treatment with topiramate can increase the risk of nephrolithiasis.

Drug Interactions

Qsymia and non-potassium sparing diuretics both contribute to a reduction in your body's potassium levels.

While safe to use birth control pills concurrently with Qsymia, these pills might exhibit increased concentration in the body.

Avoid the use of Qsymia with other drugs that inhibit carbonic anhydrase (e.g., zonisamide, acetazolamide or methazolamide).

Overdose

In acute topiramate overdose, the most frequent clinical features reported are drowsiness, vertigo, agitation, and mydriasis. In severe overdose, secondarily generalized tonic-clonic seizures followed by deep coma, somnolence, bradykinesia have been reported. Mild to moderate metabolic acidosis has been observed with topiramate overdose. Treatment of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Acidification of the urine increases phentermine excretion. Intravenous phentolamine has been suggested for severe hypertension. Activated charcoal has been shown to adsorb topiramate. Hemodialysis is an efficacious means of removing topiramate from the body. Currently, there is no specific antidote for phentermine-topiramate overdose. Therefore, treatment for overdose is largely supportive, focusing on the airway, breathing, and circulation. It is important to note that current AHA guidelines of cardiopulmonary resuscitation (CPR) recommend following order CAB (circulation-airway-breathing).

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