Phentermine

Mechanism of Action

Amphetamine-related anorexigenic agent; action in reducing appetite may be secondary to CNS effects that may involve stimulation of hypothalamus to release norepinephrine

Absorption

Peak plasma time: 3.0-4.4 hr (orally disintegrating tablet)

Elimination

Excretion: Urine (primarily)

Phentermine is a prescription medicine used for weight loss. It is taken for a limited amount of time by overweight adults, along with exercise and a low-fat diet. Phentermine belongs to a group of drugs called anorectics. It works by decreasing appetite.

Phentermine comes in tablet and capsule form. It is usually taken by mouth once daily in the morning before breakfast or 1 to 2 hours after breakfast.

Phentermine also is available as an orally disintegrating tablet and is usually taken in the morning, with or without food.

Common side effects of phentermine include dry mouth, fast heart beat, insomnia, and dizziness.

Do not drive or operate heavy machinery until you know how phentermine affects you.

Phentermine is part of the drug class:

• Centrally acting antiobesity products

Take phentermine exactly as prescribed.

Phentermine comes in tablet, capsule. It is usually taken by mouth once daily in the morning before breakfast or 1 to 2 hours after breakfast.

Phentermine also is available as an orally disintegrating tablet form and is usually taken in the morning, with or without food.

Taking phentermine in the evening can cause insomnia (trouble falling asleep or staying asleep), so phentermine should be taken in the morning.

With dry hands, gently remove the Suprenza (phentermine hydrochloride ODT) tablet from the bottle. Immediately place the tablet on top of the tongue where it will dissolve, then swallow with or without water.

Do not drink alcohol while taking phentermine.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of phentermine at the same time.

If you take too much phentermine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store phentermine at 20° to 25°C (68° to 77°F).
• Keep this and all medicines out of the reach of children.

Taking this medicine with other stimulant drugs that make you restless or hyperactive can worsen these effects. Ask your doctor before taking phentermine with diet pills, other stimulants, or medicine to treat attention deficit hyperactivity disorder (ADHD).

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with phentermine, especially:

• an antidepressant--citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline.

This list is not complete. Other drugs may interact with phentermine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Storage

Oral

15–30°C.a c

25°C (may be exposed to 15–13°C).a b

In the U.S.

• Adipex
• Adipex-P
• Atti-Plex P
• Fastin
• Ionamin
• Lomaira
• Phentercot
• Phentride
• Pro-Fast

Available Dosage Forms:

• Capsule, Extended Release
• Capsule
• Tablet, Disintegrating
• Tablet

Therapeutic Class: Appetite Suppressant, Centrally Acting

Chemical Class: Amphetamine Related

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. For phentermine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to phentermine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of phentermine is not recommended in children 16 years of age and younger. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of phentermine in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving phentermine.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using phentermine.

Interactions with Medicines

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 phentermine, it is especially important that your healthcare professional 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 phentermine 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.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Sibutramine
• Tranylcypromine

Using phentermine 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.

• Fenfluramine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

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

• Agitated state (very nervous or anxious) or
• Arrhythmias (abnormal heart rhythms), history of or
• Arteriosclerosis (hardening of the arteries), serious or
• Congestive heart failure, history of or
• Drug abuse or dependence, history of or
• Glaucoma or
• Heart or blood vessel disease (eg, coronary artery disease), history of or
• Hypertension (high blood pressure) that is not controlled, history of or
• Hyperthyroidism (overactive thyroid) or
• Stroke, history of—Should not be used in patients with these conditions.

• Allergy to tartrazine—Suprenza™ contains tartrazine. Patients with this condition may have an allergic reaction.

• Heart valve disease or
• Hypertension (high blood pressure) or
• Pulmonary hypertension (elevated pressure in the lungs)—Use with caution. May make these conditions worse.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Exogenous Obesity

Dosage should be individualized to obtain an adequate response with the lowest effective dose.

The usual adult dose is one tablet (37.5 mg) daily, as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast. The dosage may be adjusted to the patient’s need. For some patients, half tablet (18.75 mg) daily may be adequate, while in some cases it may be desirable to give half tablets (18.75 mg) two times a day.

Phentermine hydrochloride is not recommended for use in pediatric patients ≤ 16 years of age.

Late evening medication should be avoided because of the possibility of resulting insomnia.

The recommended maximum dosage of Phentermine hydrochloride is 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73m2). Avoid use of Phentermine hydrochloride in patients with eGFR less than 15 mL/min/1.73m2 or end-stage renal disease requiring dialysis [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Phentermine hydrochloride USP has the chemical name of α,α,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:

Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder which is soluble in water and lower alcohols, slightly soluble in chloroform and insoluble in ether.

Phentermine hydrochloride, an anorectic agent for oral administration, is available as a tablet containing 37.5 mg of Phentermine hydrochloride (equivalent to 30 mg of Phentermine base).

Phentermine hydrochloride tablets, USP contain the inactive ingredients corn starch, FD&C Blue #1, lactose monohydrate, magnesium stearate, povidone, pregelatinized starch, stearic acid and sucrose.

Mechanism of Action

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-amphetamine). Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics.” It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.

Pharmacodynamics

Typical of amphetamines include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.

Pharmacokinetics

Following the administration of Phentermine, Phentermine reaches peak concentrations (Cmax) after 3 to 4.4 hours.

Specific Populations Renal Impairment Cumulative urinary excretion of Phentermine under uncontrolled urinary pH conditions was 62% to 85%.
Systemic exposure of Phentermine may increase up to 91%, 45%, and 22% in patients with severe, moderate, and mild renal impairment, respectively [see Dosage and Administration (2.2) and Use in Specific Populations (8.6)].

Drug Interactions In a single-dose study comparing the exposures after oral administration of a combination capsule of 15 mg Phentermine and 92 mg topiramate to the exposures after oral administration of a 15 mg Phentermine capsule or a 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of Phentermine. However in the presence of topiramate, Phentermine Cmax and AUC increase 13% and 42%, respectively.

Available in tablets containing 37.5 mg Phentermine hydrochloride (equivalent to 30 mg Phentermine base). Each Phentermine hydrochloride tablet for oral administration is white with blue specks, capsule shaped, bisected and debossed “5030” on one side and debossed “V” on the reverse side.

Tablets are packaged in bottles of 30 (NDC 43547-404-03), 100 (NDC 43547-404-10) and 1000 (NDC 43547-404-11).

You may report side effects to Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).

Keep out of the reach of children.

Hypersensitivity or idiosyncrasy to phentermine, other sympathomimetic amines or any component of the formulation; history of cardiovascular disease (eg, arrhythmias, heart failure, coronary artery disease, stroke, uncontrolled hypertension); hyperthyroidism; glaucoma; agitated states; history of drug abuse; use during or within 14 days following MAO inhibitor therapy; pregnancy; breast-feeding

Capsule, tablet (excluding Lomaira):

eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; systemic exposure may be increased; use with caution.

eGFR 15 to 29 mL/minute/1.73 m2: Maximum dose: 15 mg/day.

eGFR <15 mL/minute/1.73 m2: Avoid use (has not been studied).

End-stage renal disease (ESRD) requiring dialysis: Avoid use (has not been studied).

Tablet (Lomaira only): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); systemic exposure may be increased; use with caution.

Concerns related to adverse effects:

• CNS effects: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Heart failure: In a scientific statement from the American Heart Association, phentermine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).

• Primary pulmonary hypertension (PPH): A rare, frequently fatal disease of the lungs, PPH has been reported to occur in patients receiving a combination of phentermine and fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; rare cases of PPH have been reported in patients taking phentermine alone. Discontinue in patients experiencing new-onset dyspnea, chest pain, syncope, or lower extremity edema.

• Valvular heart disease: Serious regurgitant cardiac valvular disease (primarily affecting the mitral, aortic, and/or tricuspid valves) has been reported to occur in patients receiving a combination of phentermine and fenfluramine or dexfenfluramine. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; rare cases of valvular heart disease have been reported in patients taking phentermine alone.

Disease-related concerns:

• Cardiovascular disease: Avoid stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry. Use with caution in patients with mild hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate.

• Diabetes: Use with caution in patients with diabetes mellitus; antidiabetic agent requirements (eg, insulin or oral hypoglycemic agents) may be decreased with anorexigens and concomitant dietary restrictions.

• Renal impairment: Use caution in patients with renal impairment; an increase in exposure is expected. Avoid use in patients with eGFR <15 mL/minute/1.73 m2, including end-stage renal disease (ESRD) requiring dialysis (has not been studied).

• Seizure disorders: Avoid or use with caution in patients with history of seizures (Apovian 2015).

• Tourette syndrome: Use with caution in patients with Tourette syndrome; stimulants may unmask tics.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use caution in this age group due to the risk for causing dependence, hypertension, angina, and myocardial infarction.

Dosage form specific issues:

• Tartrazine: Some products may contain tartrazine Some products may contain tartrazine (FDC yellow #5), which may cause allergic reactions in patients with sensitivity (caution in patients with asthma or aspirin hypersensitivity).

Other warnings/precautions:

• Abuse potential: Phentermine is pharmacologically related to the amphetamines, which have a high abuse potential; prolonged use may lead to dependency. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize possibility of overdose.

• Appropriate use: Phentermine is not approved for long-term use. Clinicians should carefully examine the potentially benefits against potential risks associated with use of medications in this class. Consult weight loss guidelines for current pharmacotherapy recommendations. Therapy should be used in conjunction with a comprehensive weight management program.

• Tolerance: Tolerance to the anorectic effect usually develops within a few weeks; discontinue use when tolerance develops, do not exceed recommended dosage in an attempt to overcome tolerance.

Use of phentermine is contraindicated during pregnancy (lack of potential benefit and possible fetal harm). Limited information is available about the use of phentermine in pregnancy (Jones 2002; McElhatton 2006). An increased risk of adverse maternal and fetal outcomes is associated with obesity; however, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience anxiety, constipation, diarrhea, dry mouth, insomnia, bad taste, decreased libido, sexual dysfunction, or agitation. Have patient report immediately to prescriber behavioral changes, angina, tachycardia, abnormal heartbeat, mood changes, tremors, shortness of breath, swelling of arms or legs, vision changes, severe dizziness, passing out, or severe headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

• May be used short-term as an aid to weight-loss in addition to exercise, behavioral modification, and caloric restriction. Recommended only for people with an initial BMI of equal or more than 30 kg/m2, or 27 kg/m2 with risk factors for a cardiovascular event (such as controlled high blood pressure, diabetes, or high cholesterol).