Bella Capsules

Overview of Bella Capsules

Dosage Strength

  • Bella 1 (Bupropion HCl / Phentermine HCl / Topiramate / Naltrexone HCl / Methylcobalamin) (Slow Release) 65/20/15/8/1mg
  • Bella 2 (Bupropion HCl / Phentermine HCl / Topiramate / Naltrexone HCl / Methylcobalamin) (Slow Release) 65/37.5/15/8/1mg
  • Bella 3 (Bupropion HCl / Caffeine / Oxytocin / Topiramate / Naltrexone HCl / Methylcobalamin) 65mg/20mg/100IU/15mg/8mg/1mg
  • Bella 4 (Bupropion HCl / Phentermine HCl / Topiramate / Naltrexone HCl / Methylcobalamin) (Slow Release) 65/15/15/8/1mg
  • Bella Decaf (Bupropion HCl / Oxytocin / Topiramate / Naltrexone HCl / Methylcobalamin) 65mg/100IU/15mg/8mg/1mg
  • Bella Plus Decaf (Bupropion HCl / Metformin / Oxytocin / Topiramate / Naltrexone HCl / Methylcobalamin) 65mg/250mg/100IU/15mg/8mg/1mg

General Information

Bupropion HCl 
Bupropion is an aminoketone antidepressant that is taken orally. It is not a tricyclic antidepressant and has no relation to any other antidepressant. Bupropion has been well tolerated in patients with tricyclic antidepressant-induced orthostatic hypotension; nonetheless, it has a higher potential for producing seizures than other antidepressants. 1 Bupropion is also approved as a smoking cessation aid and is used off-label for addiction to smokeless tobacco. When paired with behavior modification, the medication has been found to help persons with COPD quit smoking. Bupropion is also used off-label for a variety of neurological/psychological conditions, such as ADHD 2 and neuropathic pain 3. Bupropion hydrochloride was approved by the FDA in December 1985, however it was taken off the market for several years due to concerns about drug-induced seizures. It was relaunched as an antidepressant (Wellbutrin) in July 1989, and later as a sustained-release formulation (i.e., Wellbutrin SR). In May 1997, Zyban, another sustained-release oral dose form, was approved for the treatment of smoking cessation. In 1999, Zyban was given a new indication for use in conjunction with nicotine transdermal systems (NTS) to alleviate the symptoms of smoking cessation. In August 2003, a controlled-release version (Wellbutrin XL) was approved as a once-daily treatment for serious depression in adults. 456 Wellbutrin XL was authorized by the FDA in June 2006 for the prevention of major depressive episodes in people with a history of seasonal affective disorder (SAD). The first prescription medicine approved for patients with a history of SAD is Wellbutrin XL. 7 The FDA approved a once-daily formulation of bupropion hydrobromide (Aplenzin) for depression in April 2008, and Aplenzin was approved for the prevention of seasonal major depressive episodes in patients with SAD in August 2012. Aplenzin is distinct from all previously marketed versions of bupropion hydrochloride salt.

Phentermine HCI
Phentermine is an oral sympathomimetic amine used as an adjuvant in the treatment of exogenous obesity for a brief period of time (e.g., 8—12 weeks). Phentermine has similar pharmacologic effects as amphetamines. The FDA approved phentermine resin complex in 1959, however it is no longer available in the United States. The FDA authorized phentermine hydrochloride in 1973. There was increasing interest in phentermine in combination with another anorectic, fenfluramine, for the treatment of obesity and substance misuse in the mid-1990s, although there is little scientific evidence to support this practice. The FDA issued a ‘Dear Health Care Professional’ letter on July 8, 1997, warning physicians about the development of valvular heart disease and pulmonary hypertension in women receiving the combination of fenfluramine and phentermine; fenfluramine was later withdrawn from the US market in the fall of 1997. The combination of phentermine and other anorectic medications for obesity has not been studied and is not recommended. In May 2011, the FDA authorized Surrenza, an orally disintegrating tablet containing phentermine hydrochloride, for the treatment of exogenous obesity. 8

Topiramate
Topiramate is an antiepileptic medication (AED) that is taken orally and is used to treat partial-onset, generalized primary tonic-clonic seizures as well as as an additional therapy in Lennox-Gastaut syndrome. It is structurally distinct from other AEDs and is produced from the naturally occurring monosaccharide D-fructose. Topiramate, unlike other AEDs, appears to prevent the spread of seizures rather than raising the seizure threshold. Topiramate has several mechanisms of action, which may explain why it is beneficial in patients with diverse seizures who have failed to respond to other medications. Topiramate is still being explored as an add-on therapy and as a monotherapy in a variety of refractory epilepsies in children and adults, including infantile spasms linked with West syndrome. It is also used to prevent migraines in adults and children. Topiramate may have a ‘off-label’ function in the treatment of eating disorders such as binge-eating disorder, tics owing to Tourette’s syndrome or other chronic tic disorders, or drug misuse disorders such as alcohol dependency. 91011121314151617

Naltrexone HCI
Naltrexone is an opiate receptor antagonist that is taken orally. It is generated from thebaine and has a structure that is quite similar to oxymorphone. Similarly to parenteral naloxone, naltrexone is a pure antagonist (no agonist activities are visible), but naltrexone has better oral bioavailability and a significantly longer duration of action than naloxone. In clinical settings, naltrexone is used to help patients who are known opiate abusers maintain an opiate-free condition. Patients who use naltrexone as part of a comprehensive vocational rehabilitation program or other compliance-enhancing program gain the most from it. Unlike methadone or LAAM, naltrexone does not improve medication adherence or avoid withdrawal. Naltrexone has been utilized in the treatment of rapid and ultrarapid detoxification. By providing opiate antagonists, these treatments are intended to precipitate withdrawal. These approaches are expected to reduce the risk of relapse while also allowing for the rapid implementation of naltrexone maintenance and psychosocial assistance. Under general anesthesia or strong sedation, ultrarapid detoxification is conducted. While various studies have been conducted to investigate the role of alternative detoxification procedures, a standardized procedure involving appropriate drugs and dose, safety, and effectiveness in comparison to normal detoxification techniques has not been found. 18 In individuals being treated for alcoholism, naltrexone promotes abstinence, prevents relapse, and reduces alcohol consumption. When used with conventional therapy, naltrexone may only produce a minor improvement in result in some alcoholic individuals. In 1984, the FDA approved naltrexone as an adjuvant treatment for patients who were addicted to opiate agonists. In January 1995, the FDA approved naltrexone for the treatment of alcoholism. In April 2006, the FDA authorized Vivitrol, a once-monthly injectable naltrexone formulation used to assist reduce alcohol cravings. In October 2010, the FDA approved Vivitrol for the prevention of recurrence to opioid dependency following opioid detoxification.

Methylcobalamin
Methylcobalamin, also known as vitamin B12, is a B-vitamin. It can be found in a wide range of foods, including fish, shellfish, meats, and dairy products. Although the terms methylcobalamin and vitamin B12 are used interchangeably, vitamin B12 is also available in the form of hydroxocobalamin, a less widely prescribed medicinal product (see Hydroxocobalamin monograph), and methylcobalamin. Methylcobalamin is used to treat pernicious anemia and vitamin B12 deficiency, as well as in the Schilling test to measure vitamin B12 absorption. Vitamin B12 is a B vitamin that is present in foods such as beef, eggs, and dairy products. Deficiency is uncommon in healthy people; nevertheless, the elderly, devout vegetarians (i.e., vegans), and those with malabsorption issues are more likely to become deficient. Anemia, digestive difficulties, and irreversible nerve damage may ensue if vitamin B12 deficiency is not treated with a vitamin B12 supplement.

Methylcobalamin, the most chemically complicated of all vitamins, is a water-soluble, organometallic molecule with a trivalent cobalt ion bound inside a corrin ring, which, while similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two pyrrole rings directly connected. Co is the central metal ion (cobalt). Methylcobalamin cannot be produced by plants or animals; the only species that possess the enzymes required for methylcobalamin production are bacteria and archaea. When opposed to animal tissues, higher plants do not concentrate methylcobalamin from the soil, making them a poor supply of the chemical.

Caffeine
Caffeine is a naturally occurring xanthine derivative that is utilized as a stimulant of the central nervous system and respiratory system, as well as a moderate diuretic. Other xanthine derivatives include theophylline, a bronchodilator, and theobromine, a chemical found in cocoa and chocolate. Caffeine can be found in a variety of beverages including soft drinks. Caffeine is frequently mixed with analgesics or ergot alkaloids to treat migraine and other types of headache. Caffeine is also available without a prescription in medicines advertised to relieve sleepiness or mild water retention. Caffeine was originally licensed for use in a medicine product by the FDA in 1938. It is used as a respiratory stimulant in infants with prematurity apnea, both orally and parenterally. Within 24 hours of dosing, caffeine reduces the frequency of apneic episodes by 30—50%. 19 Caffeine is favored over theophylline in newborns because of its ease of administration, consistent oral absorption, and broad therapeutic window. Cafcit®, a commercial preparation of parenteral caffeine, was licensed by the FDA in October 1999 for the treatment of prematurity apnea after years of only being available under orphan drug status (e.g., Neocaf). The FDA has maintained the approved prescription formulation’s orphan drug status.

Oxytocin
Endogenous oxytocin is a hormone released by the hypothalamic supraoptic and paraventricular nuclei and stored in the posterior pituitary. It promotes uterine smooth muscle contraction during pregnancy and causes milk ejection after milk has been produced in the breast. Mating, parenting, and social behaviors have all been linked to oxytocin. Because oxytocin is released during intercourse in both men and women, it is thought to be important in sexual bonding. The hormone is thought to facilitate the emotional attachment between mother and child in addition to assisting nursing and the birthing process. 20 Oxytocin has also been investigated in autism and may be related to the social and developmental deficits associated with the disorder. 21 In clinical practice, oxytocin is most commonly administered to induce and intensify labor and to reduce postpartum bleeding. Intranasal oxytocin formulations, which were used to increase postpartum milk ejection, are no longer made in the United States. The FDA authorized oxytocin in 1962.

Metformin
Metformin is an oral biguanide anti-diabetic medicine that is comparable to phenformin, which was pulled off the market in the United States in 1977 due to the development of lactic acidosis. However, the chance of this adverse effect is significantly lower with metformin. 22 Metformin’s activities differ from, but complement, those of sulfonylureas and other diabetes treatments. Metformin was reported to produce comparable glycemic control to glyburide in type 2 diabetes. notwithstanding the fact that it resulted in a higher prevalence of stomach issues 23 Metformin has been shown to be effective in the treatment of polycystic ovarian syndrome (PCOS); it lowers blood androgen levels, restores normal menstrual periods and ovulation, and may increase conception rates. 24 Furthermore, limited evidence suggest that it may postpone puberty in girls with precocious puberty and menarche in females with early-normal puberty. 2526 Metformin versus comprehensive lifestyle adjustment has been studied in people with impaired glucose tolerance, and while both lower the incidence of diabetes, lifestyle intervention has a stronger effect. 27 Although lifestyle management is highly beneficial, most patients who utilize it alone fail within the first year of illness. As a result, a joint consensus protocol for the management of type 2 diabetes mellitus developed by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes recommends starting metformin with lifestyle modifications as soon as possible after diagnosis. Metformin was selected as the first medication therapy because of its efficacy, safety, and low cost. 282930 Furthermore, in a follow-up study to the UKPDS, researchers discovered that after 10-years of resuming typical care, patients originally randomized to metformin therapy had a 33% relative reduction (RR 0.67, 95 percent CI 0.51—0.89; p=0.005) in the risk of myocardial infarction and a 27% relative reduction (RR 0.73, 95 percent CI 0.59—0.89; p=0.002) in the risk of death from any cause as 31 Metformin was first launched in Europe in the 1950s, but the FDA did not authorize it until December 1994. It is approved as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin for type 2 diabetes. In January 2001, the regular-release pills were approved for usage in children over the age of ten. In September 2003, an oral solution (Riomet) was approved. Glucophage XR was approved in October 2000, Fortamet was approved in April 2004, and Glumetza was approved in June 2005, each with its own drug delivery method (see Pharmacokinetics section). When compared to regular-release metformin, extended-release versions provide comparable glucose control but have the advantage of once-daily treatment. Another benefit is a claim of fewer adverse events, specifically gastrointestinal-related adverse events (i.e., flatulence, diarrhea); however, larger trials comparing regular-release metformin to extended-release metformin are needed to confirm these claims, as current trial results are conflicting. 323334

References

1.Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacotherapy 1992;12:18-22.
2.Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry 2005;57:793-801.
3.Semenchuk MR, Sherman S, Davis B. Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Neurology 2001;57:1583-1588.
4.Institute for Clinical Systems Improvement (ICSI). Major depression in adults for mental health care. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 May. Available on the World Wide Web at www.guideline.gov
5.Care Management Institute, Kaiser Permanente. Adult primary care depression guidelines. Oakland (CA): Kaiser Permanente; 2004 Apr. Retrieved October 27, 2005. Available on the World Wide Web at www.guidelines.gov
6.American Psychiatric Association. Practice guidelines for the treatment of patients with major depressive disorder. Am J Psychiatry 2000;157(4 Suppl):1-45.
7.Modell JG, Rosenthal NE, Harriett AE, et al. Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biol Psychiatry 2005;58:658-67.
8.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.
9.Topamax (topiramate) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Jun.
10.Trokendi XR (topiramate extended-release capsules) package insert. Rockville, MD: Supernus Pharmaceuticals; 2020 Nov.
11.Qudexy XR (topiramate) package insert. Maple Grove, MN: Upsher-Smith Laboratories; 2021 Feb.
12.Silberstein SD, Holland S, Freitag F, et al. Evidence based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Report of the quality standards subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012;78:1337-1345.
13.American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache 2018;59:1-18.
14.Oskoui M, Pringsheim T, Billinghurst L, et al. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2019 [Epub ahead of print]
15.McElroy SL. Pharmacologic treatments for binge-eating disorder. J Clin Psychiatry 2017;78:14-19.
16.Work Group on Alcohol Use Disorder, American Psychiatric Association. Practice guideline for the pharmacological treatment of patients with alcohol use disorder. American Psychiatric Association 2018. Available on the web at https://psychiatryonline.org/doi/pdf/10.1176/appi.books.9781615371969.
17.Pringsheim T, Okun MS, Muller-Vahl K, et al. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019;92:896-906.
18.O’Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998;279:229-234.
19.Scanlon JEM, Chin KC, Morgan MEI, et al. Caffeine or theophylline for neonatal apnea? Arch Dis Child 1992;67:425-8.
20.Cabanac M, Pfaff DW, Ogawa S, et al. Neural oxytocinergic systems as genomic targets for hormones and as modulators of hormone-dependent behaviors. Results Probl Cell Differ 1999;26:91-105.
21.Modahl C, Green L, Fein D, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry 1998;43:270-277.
22.Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995;18:779-84.
23.Hermann LS, Scherstein B, Bitzen PO, et al. Therapeutic comparison of metformin and sulfonylurea, alone, and in various combinations. A double-blind controlled study. Diabetes Care 1994;17:1100-9.
24.Kosasa TS. Making a Case for Metformin. OB/GYN 2003;48:69-80.
25.Ibanez L, Ong K, Valls C, et al. Metformin treatment to prevent early puberty in girls with precocious puberty. J Clin Endocrinol Metab 2006;91:2888-91.
26.Ibanez L, Valls C, Ong K, et al. Metformin therapy during puberty delays menarche, prolongs puberal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty. J Clin Endocrinol Metab 2006;0:2068-73.
27.Doggrell SA. Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect. Expert Opin Pharmacother 2002;3:1011-3.
28.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes
29.American Diabetes Association. Standards of medical care in diabetes-2012. Diabetes Care 2012;35(suppl1):S11-S63.
30.American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care 2014;37(suppl1):S14-S80.
31.Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89.
32.Blonde L, Dailey GE, Jabbour SA, et al. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Curr Med Res Opin 2004; 20(4):565-72.
33.31285
34.Wagstaff AJ, Figgit DP. Extended-release metformin hydrochloride. Single composition osmotic tablet formulation. Treat Endocrinol 2004;3:327-32.
35.Bryant SG, Guernsey BG, Ingrim NB. Review of bupropion. Clin Pharm 1983;2:525-37.
36.Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Sellersville, PA: Teva Pharmaceuticals; 2013 Jan.
37.Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006;318:604-610.
38.Filippi L, Fiorini P, Daniotti M. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI). BMC Pediatrics 2012;12:144-155.
39.American College of Obstetrics and Gynecology (ACOG). ACOG Practice Bulletin Number 10: Clinical Management Guidelines for Obstetrician-Gynecologists. Induction of labor. Washington, DC: American College of Obstetricians and Gynecologists; November 1999.
40.Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.
41.Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.
42.Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2019 Nov.
43.Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2020 May.
44.Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.
45.Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.
46.Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.
47.Daviss WB, Perel JM, Rudolph GR, et al. Steady-state pharmacokinetics of bupropion SR in juvenile patients. J Am Acad Child Adolesc Psychiatry 2005;44:349-57.
48.Rosenfeld WE, Doose DR, Walker SA. A study of topiramte pharmacokinetics and tolerability in children with epilepsy. Pediatr Neurol 1999;20:339-344.
49.Manitpisitkul P, Shalayda K, Todd M. Pharmacokinetics and safety of adjunctive topiramate in infants (1-24 months) with refractory partial-onset seizures: a randomized, multicenter, open-label phase 1 study. Epilepsia 2013;54:156-164.
50.Mikaeloff Y, Rey E, Soufflet C. Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years. Epilepsia 2004;45:1448-1452.
51.Castano G, Mas R, Nodarse M, et al. One-year study of the efficacy and safety of policosanol (5 mg twice daily) in the treatment of type II hypercholesterolemia. Curr Ther Res 1995;56:296-304.
52.Filippi L, la Marca G, Fiorini P. Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy. Epilepsia 2009;50:2355-2361.
53.Cafcit (caffeine citrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Dec.
54.Charles BG, Townsend SR, Steer PA, et al. Caffeine citrate treatment for extremelypremature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther Drug Monit 2008; 30:709–16
55.Sawynok J, Yaksh T. Caffeine as an Analgesic Adjuvant: A Review of Pharmacology and Mechanisms of Action. Pharmacol Rev 1993; 45(1): 43 – 85.
56.Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions – A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.
57.Spitzer AR. Evidence-Based Methylxanthine Use in the NICU. Clin Perinatol 2012. 39: 127-148.
58.Aldridge A, Aranda JV, Neims AH. Caffeine metabolism in the newborn. Clin Pharmacol Ther; 1979 25(4):447-53.
59.Al-Alaiyan S, Al-Rawithi S, Raines D et al. Caffeine Metabolism in Premature Infants. Journal of Clinical Pharmacology; 2001 41(6): 620-7.
60.Lee T, Charles B, Steer P, et al. Population pharmacokinetics of intra-venous caffeine in neonates with apnea of prematurity. Clin Pharmacol Ther. 1997;61:628–640.
61.Pearlman SA, Duran C, Wood MA, et al. Caffeine pharmacokinetics in preterm infants older than 2 weeks. Dev Pharmacol Ther 1989;12:65–9.
62.Glucophage®/Glucophage® XR (metformin) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2009 Jan.
63.Robert F, Fendri S, Hary L,et al. Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects. Diabetes Metab 2003;Gerich JE. Oral hypoglycemic agents. N Engl J Med 1989;321:1231—45.:279–83.
64.Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.
65.Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American HeartAssociation Council on Cardiovascular Disease in the Young Congenital Heart Defects Committee and the Council on Cardiovascular Nursing. Circulation 2008; 117: 2407-23.
66.Wigal SB. Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults. CNS Drugs 2009;23:21-31.
67.Spencer T, Biederman J, Steingard R, et al. Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 1993;32:211-4.
68.US Food and Drug Administration (FDA). FDA Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. Retrieved Dec 22, 2016. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery
69.Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2009:CD001055
70.Massachusetts General Hospital Center for Women’s Mental Health. National Pregnancy Registry for Psychiatric Medications. Available on the World Wide Web at: https://womensmentalhealth.org/research/pregnancyregistry/.
71.Haas JS, Kaplan CP, Barenboim D, et al. Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use. Tob Control 2004;13:52-6.
72.Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: a case of a possible infant seizure. J Clin Psychiatry 2004;65:881-2.
73.Baab SW, Peindl KS, Piontek CM, et al. Serum bupropion levels in 2 breastfeeding mother-infant pairs. J Clin Psychiatry 2002;63:910-11.
74.Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161:1066-78.
75.DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children’s health. Pediatrics. 2004;113:1007-1015.
76.Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.
77.Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Sellersville, PA: Teva Pharmaceuticals; 2013 Jan.
78.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.
79.Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2010 April.
80.Steiner E, Villen T, Hallberg M, et al. Amphetamine secretion in breast milk. Eur J Clin Pharmacol 1984;27:123-4.
81.Kelly TE, Hackett PH. Acetazolamide and sulfonamide allergy: a not so simple story. High Alt Med Biol 2010;11:319-323.
82.Brackett CC. Sulfonamide allergy and cross-reactivity. Curr Allergy Asthma Rep 2007;7:41-48.
83.Platt D, Griggs RC. Use of acetazolamide in sulfonamide-allergic patients with neurologic channelopathies. Arch Neurol 2012;69:527-529.
84.Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. New Engl J Med 2003;349:1628-35.
85.Ben-Zeev B, Watemberg N, Augarten A, et al. Oligohydrosis and hyperthermia: a pilot study of a novel topiramate adverse effect. J Child Neurol 2003;18:254-7.
86.Yamamoto Y, Takahashi Y, Imai K. Risk factors for hyperammonemia in pediatric patients with epilepsy. Epilepsia 2013;54:983-989.
87.The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.
88.Food and Drug Administration MedWatch. Topamax (topiramate): label change – risk for development of cleft lip and/or cleft palate in newborns. Retrieved March 4, 2011. Available on the World Wide Web http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245777.htm
89.Ohman I, Vitols S, Luef G, et al. Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations. Epilepsia 2002;43:1157-60.
90.Naltrexone (naltrexone hydrochloride) package insert. Hazelwood, MO: Mallinckrodt, Inc. 2009 Feb.
91.Vivitrol (naltrexone extended release injectable suspension) package insert. Waltham, MA: Alkermes, Inc.; 2021 Mar.
92.Revia (naltrexone hydrochloride) package insert. Pomona, NY: Duramed Pharmaceuticals, Inc. 2013 Oct.
93.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.
94.Bhatia J. Current options in the management of apnea of prematurity. Clin Pediatr 2000;39:327-36.
95.Erenberg A, Leff RD, Haack DG, et al. Caffeine Citrate for the Treatment of Apnea of Prematurity: A Double-Blind, Placebo-Controlled Study. Pharmacotherapy 2000;20(6):644–652.
96.Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006;166:965-971.
97.Christian MS, Brent RL. Teratogen update: evaluation of the reproductive and developmental risks of caffeine. Teratology 2001;64:51-78.
98.Hadeed A, Siegel S. Newborn cardiac arrhythmias associated with maternal caffeine use during pregnancy. Clin Pediatr 1993;32:45-7.
99.Le Guennec JC, Billon B. Delay in caffeine elimination in breast-fed infants. Pediatrics 1987;79:264-8.
100.Berlin CM, Denson HM, Daniel CH, et al. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics 1984;73:59-63.
101.Tyrala EE, Dodson WE. Caffeine secretion into breast milk. Arch Dis Child 1979;54:787-800.
102.Hill RM, Craig JP, Chaney MD, et al. Utilization of over-the-counter drugs during pregnancy. Clin Obstet Gynecol 1977;20:381-94.
103.Awake (caffeine) tablet package insert. Deerfield, IL: Walgreen Co. 05/214.
104.Mangesi L, Dowswell T. Treatments for breast engorgement during lactation. Cochrane Database Syst Rev. 2010;9:CD006946.
105.Bodmer M, Meier C, Krahenbuhl S, et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia. Diabetes Care 2008;31:2086-91.
106.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the ADA and EASD. Diabetes Care 2012. Epub ahead of print, doi: 10.2337/dc12-0413
107.Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011;34:1432-1437.
108.Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. BMJ 2007;335(7618):497 Epub 2007 Aug 30
109.Ting RZ, Szeto CC, Chan MH, et al. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975-9.
110.Vanky E, Zahlsen K, Spigset O, et al. Placental passage of metformin in women with polycystic ovary syndrome. Fertil Steril 2005;83:1575-8.
111.Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum
112.Coetzee EJ, Jackson WPU. Metformin in management of pregnant insulin-dependent diabetics. Diabetologia 1979;16:421-425.
113.American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 60: Pregestational diabetes mellitus. Obstet Gynecol 2005;105:675-85.
114.American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 30: Gestational diabetes. Obstet Gynecol 2001;98:525-38.
115.Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:457.
116.Balani J, Hyer SL, Rodin DA, et al. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 2009;26:798-802.
117.Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia 2002;45:1509-14.
118.Gardiner SJ, Kirkpatrick CMJ, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003;73:71-7.
119.Briggs GG, Ambrose PJ, Nageotte MP, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005;105:1437-41.
120.Glueck CJ, Salehi M, Sieve L, et al. Growth, motor, and social development in breast- and formula- fed infants of metformin-treated women with polycystic ovary syndrome. J Pediatr 2006;148:628-32.
121.Everett J. Use of oral antidiabetic agents during breastfeeding. J Hum Lact 1997;13:319-21.
122.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
123.Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Physician; 64:119-26.
124.Food and Drug Administration Adverse Event Reporting System. Potential signals of serious risks/new safety information identified from the FDA adverse event reporting system (FAERS): July – September 2017. Available on the worldwide web at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm592379.htm
125.Descamps V, Ranger-Rogez S. DRESS syndrome. Joint Bone Spine 2014;81:15-21.
126.Spriet S, Banks TA. Drug reaction with eosinophilia and systemic symptoms syndrome. Allergy Asthma Proc 2015;36:501-5.
127.Institute for Safe Medication Practices (ISMP). Acute Care ISMP Medication Safety Alert 2018;23:1-2.
128.Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.
129.Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2010 April.
130.Lomaira (phentermine hydrochloride) package insert. Newton, PA: KVK-Tech, Inc.; 2016 Sept.
131.Hendricks EJ, Srisurapanont M, Schmidt SL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes (Lond). 2014;38:292-298.
132.Depakote (divalproex sodium tablets) package insert. North Chicago, IL: AbbVie Inc.; 2020 May.
133.Page RL, Bainbridge JL. Intractable Epistaxis Associated with Topiramate Administration. Ann Pharmacother. 2006; Accessed online on July 5, 2006. Published Online, 5 July 2006. Available on the World Wide Web at: www.theannals.com, DOI 10.1345/aph.1H078
134.Kossoff EH, Pyzik PL, Furth SL. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002;43:1168-1171.
135.Groeper K, McCann ME. Topiramate and metabolic acidosis: a case series and review of the literature. Paediatr Anaesth 2005;15:167-70.
136.Wilner A, Raymond K, Pollard R. Topiramate and metabolic acidosis. Epilepsia 1999;40:792-5.
137.Nawrot P, Jordan S, Eastwood J, et al: Effects of caffeine on human health. Food Addit Contam 2003;20:1-30.
138.Schmidt B, Roberts RS, Davis P, et al. Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2006; 354:2112-2121.
139.lane AJ, Coombs RC, et al. Effect of caffeine on neonatal splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed 1999;80:F128–F129.
140.Bhatt-Mehta V, Schumacher RE. Treatment of apnea of prematurity. Pediatr Drugs 2003;5:195-210.
141.Caffeine tablets alertness aid supplement (product label). Woonsocket RI, CVS; 2012.
142.Pollak C, Bright D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111:42-46.
143.Davis R, Osorio I: Childhood caffeine tic syndrome. Pediatrics 1998;101:E4.
144.Prolab Caffeine supplement product label. Chatsworth, CA Prolab Nutrition Inc; 2012.
145.Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386–99.
146.Pitocin (oxytocin) package insert. Rochester, MI: JHP Pharmaceuticals, LLC; 2014 Sept.
147.Curless RV, Beaumont DM, Sinar EJ, et al. Subarachnoid hemorrhage mimicking acute water intoxication during labour augmented by oxytocin infusion. Br J Clin Pract 1990;44(12):637-638.

Legal Disclaimer: All information presented in this website is intended for informational purposes only and not for the purpose of rendering medical advice.

Get Started For $99 Initial Provider Consult