Other Warnings/Precautions

• Phentermine-topiramate can cause fetal toxicity; women of childbearing potential should obtain a negative pregnancy test before treatment and monthly thereafter and use effective contraception

• If a patient develops a sustained increase in resting heart rate while taking phentermine/topiramate, the dose should be reduced or the medication should be discontinued

• May cause an increase in serum creatinine; if persistent elevations in creatinine occur during phentermine-topiramate treatment, the dose should be reduced or the medication should be discontinued

• Phentermine-topiramate has not been studied in combination with insulin; weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues, and medication adjustments may be necessary

• Warn patients and their caregivers about the possibility of activation of suicidal ideation and advise them to report such side effects immediately

Do Not Use

• If patient is pregnant

• If patient has glaucoma

• If patient has hyperthyroidism

• If patient is taking an MAOI

• If there is a proven allergy to phentermine or topiramate

PHENTERMINE-TOPIRAMATE: SPECIAL POPULATIONS

Renal Impairment

• Maximum dose is 7.5 mg/46 mg per day in patients with moderate to severe impairment

• Not studied or recommended for use in patients with end-stage renal disease

Hepatic Impairment

• Maximum dose is 7.5 mg/46 mg per day in patients with moderate impairment

• Not recommended for use in patients with severe impairment

Cardiac Impairment

• Not systematically evaluated in patients with cardiac impairment

• Not recommended for patients with recent or unstable cardiac or cerebrovascular disease

Elderly

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy have not been established

• Not recommended for use in children or adolescents

Pregnancy

• Risk Category X [contraindicated]

• There is an increased risk of cleft lip/palate with topiramate

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended to discontinue drug or bottle feed

PHENTERMINE-TOPIRAMATE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients who have had past weight loss on either active compound alone may experience a more robust weight loss effect and better tolerability on the combination of phentermine with topiramate than with administration of either drug alone

Potential Disadvantages

• Patients with a history of kidney stones or risks for metabolic acidosis

• Women who are pregnant or wish to become pregnant

• Patients with a history of past stimulant abuse

Primary Target Symptoms

• Excess weight

Pearls

• Has perhaps the largest effect size on weight loss of drugs available for the treatment of obesity

• Could theoretically be effective in binge-eating disorder

• Because of the teratogenic risk with phentermine-topiramate, it is available only through a Risk Evaluation and Mitigation Strategy (REMS) program; only certified pharmacies may distribute it

Suggested Reading

Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med 2012;367(17):1577–9.

Cosentino G, Conrad AO, Uwaifo GI. Phentermine and topiramate for the management of obesity: a review. Drug Des Devel Ther 2011;7:267–87.

Holes-Lewis KA, Malcolm R, O’Neil PM. Pharmacotherapy of obesity: clinical treatments and considerations. Am J Med Sci 2013;345(4):284–8.

Shin JH, Gadde KM. Clinical utility of phentermine/topiramate (QsymiaTM) combination for the treatment of obesity. Diabetes Metab Syndr Obes 2013;6:1319.

PIMOZIDE

PIMOZIDE: THERAPEUTICS

Brands

• Orap

see index for additional brand names

Generic?

Not in U.S.

Class

• Tourette’s syndrome/tic suppressant; conventional antipsychotic (neuroleptic, dopamine 2 antagonist)

Commonly Prescribed for

(bold for FDA approved)

• Suppression of motor and phonic tics in patients with Tourette syndrome who have failed to respond satisfactorily to standard treatment

• Psychotic disorders in patients who have failed to respond satisfactorily to standard treatment

How the Drug Works

• Blocks dopamine 2 receptors in the nigrostriatal dopamine pathway, reducing tics in Tourette’s syndrome

• When used for psychosis, can block dopamine 2 receptors in the mesolimbic dopamine pathway, reducing positive symptoms of psychosis

How Long Until It Works

• Relief from tics may occur more rapidly than antipsychotic actions

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior

If It Works

✽ Is a second-line treatment option for Tourette’s syndrome

✽ Is a secondary or tertiary treatment option for psychosis or other behavioral disorders

• Should evaluate for switching to an antipsychotic with a better/risk benefit ratio

If It Doesn’t Work

• Consider trying one of the first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride, asenapine, iloperidone, lurasidone)

• Consider trying another conventional antipsychotic

• If 2 or more antipsychotic monotherapies do not work, consider clozapine

Best Augmenting Combos for Partial Response or Treatment Resistance

✽ Augmentation of pimozide has not been systematically studied and can be dangerous, especially with drugs that can either prolong QTc interval or raise pimozide plasma levels

Tests

✽ Baseline EKG and serum potassium levels should be determined

✽ Periodic evaluation of EKG and serum potassium levels, especially during dose titration

• Serum magnesium levels may also need to be monitored

✽ Since conventional antipsychotics are frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0–29.9) or obese (BMI ≥30)

• Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100–125 mg/dL), diabetes (fasting plasma glucose >126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol, and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management

✽ Monitor weight and BMI during treatment

✽ Consider monitoring fasting triglycerides monthly for several months in patients at high risk for metabolic complications and when initiating or switching antipsychotics

✽ While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different antipsychotic

• Should check blood pressure in the elderly before starting and for the first few weeks of treatment

• Monitoring elevated prolactin levels of dubious clinical benefit

• Patients with low white blood cell count (WBC) or history of drug-induced leucopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months and pimozide should be discontinued at the first sign of decline of WBC in the absence of other causative factors