Pediatrics

We work together with practitioners, children, and their families to customize medications and meet specific needs.

Children pose many challenges when it comes to medication: they may resist having to take a medication, dislike the taste or texture, have difficulty swallowing solid dosage forms, and are fearful of injections.

The limited pediatric market for most drugs may be the leading reason for the lack of investment in drug development for this population by the pharmaceutical industry. Most medications are not labeled for pediatric populations, and when a medication is not approved for use in infants and children, it usually is not available in a suitable pediatric dosage form. Fortunately, our compounding pharmacy is able to help. We can compound oral medications into pleasantly flavored suspensions, solutions, concentrates, freezerpops, "gummy bears" or lozenges, in colors that entice the child to take the medication. A palatable formulation is more likely to improve compliance and minimize spillage or waste during administration. Lollipops are an ideal alternative to "swish and swallow" medications that need to be retained in the mouth for a prolonged period of time. Most drugs can be compounded into transdermal gels that can easily be applied to an appropriate site, such as the child's wrist, for absorption through the skin.

Professional compounding is not just diluting existing medications, or mixing powders with bases. We must consider physical and chemical properties of each active and inactive ingredient in order to prepare an effective and safe customized medication with the desired taste, color, fragrance, viscosity, uniformity, texture, and stability. The efficacy of any compounded medication is influenced by the technique and equipment used in preparing the formulation, the purity and quality of the ingredients, choice of vehicle (base), and proper use of additives such as penetration enhancers.

Emergence of resistant pathogens emphasizes the need for alternatives to antimicrobial agents for acne therapy. We can compound cosmetically-appealing customized formulations which can contain numerous medications to provide a synergistic effect for treatment of resistant acne.

Int J Dermatol 1995 Jun;34(6):434-7
Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.
Click here to access the PubMed abstract of this article.

J Dermatol 1996 Apr;23(4):243-6
Topical spironolactone reduces sebum secretion rates in young adults.
Click here to access the PubMed abstract of this article.

The use of medications to treat ADHD has greatly increased, yet the dosage requirements for many children differ from strengths that are commercially available. This often necessitates a midday dose at school, which can be embarrassing to a child. Slow-release dosage forms can be compounded to contain the precise dose of medication needed by each child.

Pediatr Clin North Am 1999;46:945-963
Management of stimulant medications in children with attention-deficit/hyperactivity disorder.
Click here to access the PubMed abstract of this article.

Autism spectrum disorder (ASD) is diagnosed on the basis of behavioral parameters, yet there are many underlying biomedical factors which can contribute to these symptoms. Therapies directed at these underlying factors may be helpful in decreasing symptoms of autism. For example, recent studies have found chronic inflammation in the brains of children with autism, raising the possibility that treatments directed against inflammation may be helpful.

The Autism Research Institute asked parents to rate the effectiveness of numerous biomedical treatments. As of 2008, over 26,000 parents had evaluated more than 80 interventions. Detoxification was considered helpful by 74% of parents. Other highly rated therapies included gluten/casein-free diet, food allergy treatment, methylcobalamin, and essential fatty acid therapy. It is thought that the earlier treatment is started, the better the results.

Gluten-Free and Casein-Free Preparations

Children with autism may benefit from a gluten-free and casein-free diet. Many commonly used medications contain gluten. Some probiotics contain casein. We can compound preparations that are free of gluten and casein to solve problems for sensitive individuals.

Therapy for Gut Dysbiosis

Autistic children frequently have abnormalities in gut permeability, defects or deficiencies in intestinal enzymes, and/or abnormal intestinal flora. Yeast overgrowth can be prevented or treated by oral administration of Lactobacillus or other probiotics. If response is insufficient, oral antifungals may be needed. Prescription medications can be compounded for oral administration to help reduce yeast in the gut. Compromised digestive function, often secondary to inflammation of the bowel, may lead to the absorption of toxins (“leaky gut”). Children can benefit from balanced nutrition, treatment of imbalanced gut flora, and enhancement of immune function.

Nutritional Therapy for Autism

Most children with autism have a need for increased amounts of vitamins, minerals, and some amino acids. Some detoxification agents may remove essential minerals, creating a need for additional minerals. Vitamin C, vitamin B6, vitamin A, omega-3 fatty acids, calcium, magnesium, zinc, and selenium are often needed in addition to a broad-spectrum vitamin/mineral supplement. Copper should be avoided in many cases, since the levels in autistic children are sometimes high. Amino acid, nutritional, and supplemental therapies can be customized for each child. Once the physician has determined the specific nutrients that are needed, compatible supplements can be combined in flavored suspensions to simplify administration.

Many children with autism are zinc deficient. Zinc deficiency affects taste perception and children then become averse to eating certain foods and taking supplements. In this case, transdermal preparations can be very helpful by completely bypassing the oral route of administration. Commonly needed nutrients which can easily be given in a transdermal form include vitamin A, vitamin D, and zinc.

Glutathione is the major antioxidant in cells and is important for detoxification and elimination of environmental toxins. Its active form is reduced in about 80 percent of autistic children. Oxidative stress, a suspected contributor in many disease processes like heart disease and cancer, also plays a role in autism, and occurs when antioxidants are not present in sufficient levels to clear the body of free radicals. Free radicals can damage cells in the brain, gastrointestinal tract and immune system. Children with low glutathione levels may be more vulnerable to this damage, so supplementation with oral or transdermal glutathione and other antioxidants may be beneficial.

Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with ASD.

J Child Neurol. 2008 May;23(5):482-5.
Melatonin for Insomnia in Children With Autism Spectrum Disorders.
Click here to access the PubMed abstract of this article.

Detoxification (including chelation)

Some children with autism may suffer from heavy metal toxicity, and may potentially benefit from therapies which support detoxification. Some may also benefit from chelation (removal of heavy metals). Oral DMSA (dimercaptosuccinic acid) is approved by the FDA for treating lead poisoning in children as young as one year of age. It has also been demonstrated to be able to bind and remove a wide range of toxic metals, including mercury, arsenic, tin, nickel, and antimony. Oral DMSA has been used off-label for this purpose. It is important to monitor kidney and liver function and complete blood counts when using DMSA, and although rare, serious side effects may occur.

Please note: These therapies have not been approved by the FDA for the treatment of autism, and should be used only under direct supervision of an experienced and knowledgeable health care professional after parents or guardians have received adequate information and given consent.

www.autism.com

Ann Neurol 2005;57:67–81
Neuroglial activation and neuroinflammation in the brain of patients with autism.
Click here to access the PubMed abstract of this article.

Ann N Y Acad Sci. 2007 Jun;1107:92-103.
Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder.
Click here to access the PubMed abstract of this article.

Cell Mol Neurobiol. 2004 Apr;24(2):219-41
Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism.
Click here to access the PubMed abstract of this article.

Neuroendocrinology Letters 2002;23:303-8
Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.
Click here to access the PubMed abstract of this article.

Dev Brain Dysfunction 1997;10:40-43
Biochemical parameters in autistic children.

J Inherit Metab Dis.1993;16(4):762-770 Pediatrics 1995;95:255-8

Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

J Nutr Env Med 2000;10:25-32
Sulphur metabolism in autism.

Low Dose Naltrexone (LDN) and Autism

ASC (autism spectrum conditions) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviors induced in animals or humans by opiate administration, including decreased socialization, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behavior of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason. A review of the literature from 2010 until 2013 concluded that naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in the majority of the participants.

J Intellect Disabil Res. 2015 Apr;59(4):293-306.
Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review.
Click here to access the PubMed abstract of this article.

Approximately two-thirds of infants experience diaper rash (dermatitis). Customized diaper rash preparations -ointments, powders, or creams- can be compounded to treat each child’s specific symptoms, using ingredients which will protect the skin from additional irritation, soothe and encourage healing, and prevent secondary infections. Skin protectants (zinc oxide, petrolatum) provide a physical barrier against external irritants such as urine or gastrointestinal enzymes in stool. Antifungal creams can be used when a yeast (Candida) infection is suspected.

We can also compound a bile acid sequestrant, such as cholestyramine ointment, to prevent skin irritation, which is especially helpful for ostomy patients.

Ann Pharmacother 1996 Sep;30(9):954-6
Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
Click here to access the PubMed abstract of this article.

Oral Viscous Budesonide (OVB) for Treatment of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is a disease most likely due to an immunologic response to ingested and inhaled allergens. Presenting symptoms of EE often mimic those of gastroesophageal reflux disease (GERD) and include vomiting, dysphagia, pain, and food impaction. However, because the treatment of EE and GERD differs, it is important to distinguish between them. Swallowed topical steroids, such as fluticasone propionate, have been administered using a metered-dose inhaler (MDI) without a spacer, with instructions to not inhale, but to puff and swallow, thus delivering a topical antiinflammatory product to the esophageal mucosa. Although effective in lowering eosinophil levels, this technique of administering aerosolized corticosteroids, which are often bitter to taste, may be complicated for young children, and twice daily administration is necessary. However, this treatment is attractive because only 1% of the steroid is absorbed systemically and it undergoes rapid hepatic processing. The main potential side effect is oral/esophageal Candida infection that developed in 3 of 20 patients in one series.1

Budesonide is a corticosteroid with high topical anti-inflammatory activity but low systemic activity due to extensive hepatic metabolism. Aceves et al. of Children’s Hospital and the Department of Pediatrics, University of California, San Diego, reported the successful treatment of EE using an oral viscous suspension of budesonide in 2 patients who were unable to utilize fluticasone propionate for developmental reasons.2

Researchers noted: “Our data suggest that OVB is an effective and safe treatment for young children with proven EE. It may have advantages over other therapies in that it is palatable, its volume (8–12 ml) provides pan-esophageal mucosal coverage, and it requires only once daily administration.”3 The increased viscosity of OVB may prolong budesonide’s contact time with the esophageal mucosa. No significant adverse events were reported. Morning cortisol levels were within normal limits.

1 J Pediatr Gastroenterol Nutr 1998;27:90–3.
Treatment of eosinophilic esophagitis with inhaled corticosteroids.
Click here to access the PubMed abstract of this article.

2 J Allergy Clin Immunol 2005;116:705–6.
Topical viscous budesonide suspension for treatment of eosinophilic esophagitis.
Click here to access the PubMed abstract of this article

3 Am J Gastroenterol. 2007 Oct;102(10):2271-9.
Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children.
Click here to access the PubMed abstract of this article.

Athlete's foot, jock itch, and onychomycosis (fungal nail) are common, particularly in athletes. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties." Various synergistic combinations are used for antifungal therapy.

J Med Microbiol 2000 Sep;49(9):831-40
Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
Click here to access the PubMed abstract of this article.

Concerns about emerging resistance and the potential harm of using permethrins have prompted a search for effective pediculicidal therapies that are not harmful to children with repeated use. An herbal formulation has been shown to be effective for head lice. Ivermectin can also be compounded for topical application or as an oral dose titrated for each patient for the treatment of head lice and scabies.

Clin Exp Dermatol 2002 Jun;27(4):264-7
Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.
Click here to access the PubMed abstract of this article.

Twenty six male and female patients aged 5 to 17 years had head lice infestation confirmed by eggs presence and received treatments with a single 200 microgram/kg oral dose of. At day 14 after treatment, 20 had responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients appeared clear of infestation (27%), but 4 of the 6 patients with no eggs at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 may be appropriate.

Trop Med Parasitol 1994 Sep;45(3):253-4
Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
Click here to access the PubMed abstract of this article.

Two hundred scabies patients were randomly allocated to receive either oral ivermectin in a single dose of 200 micrograms/kg body weight, or 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindane group showed a similar response. Oral ivermectin is easy to administer as a single oral dose, induces an early and effective improvement in signs and symptoms, and compliance is accordingly increased.

J Dermatol 2001 Sep;28(9):481-4
Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.
Click here to access the PubMed abstract of this article.

Isr Med Assoc J. 2002 Oct;4(10):790-3
The in vivo pediculicidal efficacy of a natural remedy.
Click here to access the PubMed abstract of this article.

Resistant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy.

Therapy with 10% KOH was found to be effective and safe in the treatment of molluscum contagiosum (MC) in children, although a stinging sensation was reported by most children during the trial and some developed hyper- or hypopigmentation after treatment at the site of the lesions.

Pediatr Dermatol. 1999 May-Jun;16(3):228-31.
Treatment of molluscum contagiosum with potassium hydroxide: a clinical approach in 35 children. Romiti R et al.
Click here to access the PubMed abstract of this article.

In an attempt to reduce the side effects (stinging sensation & hyper- or hypopigmentation) found with use of 10% KOH, a new trial of 20 children used a less concentrated KOH solution (5%) for treatment of molluscum contagiosum (MC). The 5% KOH aqueous solution proved to be as effective as and less irritating than 10% KOH, and spared children from more aggressive physical modalities of treatment.

Pediatr Dermatol. 2000 Nov-Dec;17(6):495.
Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum. Romiti R, Ribeiro AP, Romiti N.
Click here to access the PubMed abstract of this article.

These studies showed that 5% imiquimod cream and 10% KOH solution are equally effective in treating molluscum contagiosum, although KOH has a faster onset of action.

Ann Dermatol. 2010 May;22(2):156-62. Epub 2010 May 17.
An open, randomized, comparative clinical and histological study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Seo SH, Chin HW, Jeong DW, Sung HW.
Click here to access the PubMed abstract of this article.

Indian J Dermatol Venereol Leprol. 2008 Nov-Dec;74(6):614-8.
An open, nonrandomized, comparative study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Metkar A, Pande S, Khopkar U.
Click here to access the PubMed abstract of this article.

Orally administered anti-emetics can be difficult for a nauseated child to "keep down", and rectal suppositories may not be well accepted by children. Even persistent nausea can often be effectively controlled by using a combination of medications tailored to meet an individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more.

Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.

US Pharmacist, August 1999; 74-5

Topical anesthesia is needed for common pediatric procedures such as suturing, wound cleaning, and injection administration. The ideal topical anesthetic would provide complete anesthesia following a simple pain-free application, not contain narcotics or controlled substances, and have an excellent safety profile. The combination of topical anesthetics lidocaine and tetracaine and the vasoconstrictor epinephrine has been used successfully for anesthesia prior to suturing linear scalp and facial lacerations in children. A triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") has also been reported to be effective when applied prior to laser and cosmetic procedures. Convenience of application without need for occlusion is an advantage of these topical anesthetics.

The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children."

Pediatrics 1995 Feb;95(2):255-8
Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application.

Cosmetic Dermatology 2003 Apr;16(4):35-7
Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics

Sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with Pulmonary arterial hypertension (PAH), and this medication can be compounded as a stable oral suspension.

Circulation. 2005 Jun 21;111(24):3274-80
Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study.
Click here to access the PubMed abstract of this article.

Am J Health Syst Pharm. 2006 Feb 1;63(3):254-7
Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children.
Click here to access the PubMed abstract of this article.

Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are medical emergencies. Mortality and poor neurologic outcome are directly associated with the duration of seizure activity. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Diazepam rectal gel was developed due to the need for non-injection-based delivery; however, the aesthetics of rectal delivery are not popular with patients and caregivers. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures at home or when actively seizing patients arrive in the emergency room. There are many factors that a practitioner and compounding pharmacist must consider when choosing a benzodiazepine for intranasal administration, including solubility of the drug, ease of passing the blood-brain barrier, and pharmacokinetic/pharmacodynamic profiles. Concentration is important as the nasal cavity can retain approximately 0.1-0.15 ml.

Under ideal conditions, most medication is absorbed from the nasal cavity and into the bloodstream within 15 to 20 minutes, thus generally avoiding the first-pass gut metabolism. Increased nasal mucus production is commonly observed with actively seizing patients, so it may be prudent to suction mucus from the nasal cavity prior to administration of intranasal midazolam. Intranasal midazolam has been extensively studied in epilepsy patients. Various devices have been used to deliver 0.2 mg/kg of midazolam injection intranasally.

Morbidity and mortality, as well as health-care resources and expenses associated with treatment of epileptic patients, could be reduced if an effective and safe transmucosal treatment was available for use by caregivers.

Neurotherapeutics. 2009 Apr;6(2):352-8.
Intranasal delivery of antiepileptic medications for treatment of seizures.
Click here to access the PubMed abstract of this article.

Midazolam nasal spray has been used to reduce procedural anxiety in children, anxiety-related dyspnea, and to prevent MRI-induced claustrophobia.

Intranasal Midazolam for Managing Prolonged Seizures Intranasal midazolam is a safe and practical alternative to rectal diazepam for managing prolonged seizures in non-hospitalized patients.

J Intellect Dev Disabil 2006 Sep;31(3):131-8
Community use of intranasal midazolam for managing prolonged seizures.
Click here to access the PubMed abstract of this article.

Am J Emerg Med 2006 May;24(3):343-6
Intranasal midazolam therapy for pediatric status epilepticus.
Click here to access the PubMed abstract of this article.

• BLT or LAT topical gel or spray
• Cholestyramine ointment
• Clotrimazole in DMSO solution
• Fluconazole/Ibuprofen topical
• Ivermectin topical KOH solution - 5% and 10%
• Nicotinamide/Spironolactone topical
• Promethazine transdermal gel
• Urea 40% plasters

The above list is just a few of the preparations that we can compound for pediatric use. We work together with prescriber and patient to solve problems, and all formulations are customized per prescription to meet the unique needs of each child.

Pediatrics

We work together with practitioners, children, and their families to customize medications and meet specific needs.

Children pose many challenges when it comes to medication: they may resist having to take a medication, dislike the taste or texture, have difficulty swallowing solid dosage forms, and are fearful of injections.

The limited pediatric market for most drugs may be the leading reason for the lack of investment in drug development for this population by the pharmaceutical industry. Most medications are not labeled for pediatric populations, and when a medication is not approved for use in infants and children, it usually is not available in a suitable pediatric dosage form. Fortunately, our compounding pharmacy is able to help. We can compound oral medications into pleasantly flavored suspensions, solutions, concentrates, freezerpops, "gummy bears" or lozenges, in colors that entice the child to take the medication. A palatable formulation is more likely to improve compliance and minimize spillage or waste during administration. Lollipops are an ideal alternative to "swish and swallow" medications that need to be retained in the mouth for a prolonged period of time. Most drugs can be compounded into transdermal gels that can easily be applied to an appropriate site, such as the child's wrist, for absorption through the skin.

Professional compounding is not just diluting existing medications, or mixing powders with bases. We must consider physical and chemical properties of each active and inactive ingredient in order to prepare an effective and safe customized medication with the desired taste, color, fragrance, viscosity, uniformity, texture, and stability. The efficacy of any compounded medication is influenced by the technique and equipment used in preparing the formulation, the purity and quality of the ingredients, choice of vehicle (base), and proper use of additives such as penetration enhancers.

©Storey Marketing. Used with permission. All rights reserved.

Emergence of resistant pathogens emphasizes the need for alternatives to antimicrobial agents for acne therapy. We can compound cosmetically-appealing customized formulations which can contain numerous medications to provide a synergistic effect for treatment of resistant acne.

Int J Dermatol 1995 Jun;34(6):434-7
Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.
Click here to access the PubMed abstract of this article.

J Dermatol 1996 Apr;23(4):243-6
Topical spironolactone reduces sebum secretion rates in young adults.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

The use of medications to treat ADHD has greatly increased, yet the dosage requirements for many children differ from strengths that are commercially available. This often necessitates a midday dose at school, which can be embarrassing to a child. Slow-release dosage forms can be compounded to contain the precise dose of medication needed by each child.

Pediatr Clin North Am 1999;46:945-963
Management of stimulant medications in children with attention-deficit/hyperactivity disorder.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

Autism spectrum disorder (ASD) is diagnosed on the basis of behavioral parameters, yet there are many underlying biomedical factors which can contribute to these symptoms. Therapies directed at these underlying factors may be helpful in decreasing symptoms of autism. For example, recent studies have found chronic inflammation in the brains of children with autism, raising the possibility that treatments directed against inflammation may be helpful.

The Autism Research Institute asked parents to rate the effectiveness of numerous biomedical treatments. As of 2008, over 26,000 parents had evaluated more than 80 interventions. Detoxification was considered helpful by 74% of parents. Other highly rated therapies included gluten/casein-free diet, food allergy treatment, methylcobalamin, and essential fatty acid therapy. It is thought that the earlier treatment is started, the better the results.

Gluten-Free and Casein-Free Preparations

Children with autism may benefit from a gluten-free and casein-free diet. Many commonly used medications contain gluten. Some probiotics contain casein. We can compound preparations that are free of gluten and casein to solve problems for sensitive individuals.

Therapy for Gut Dysbiosis

Autistic children frequently have abnormalities in gut permeability, defects or deficiencies in intestinal enzymes, and/or abnormal intestinal flora. Yeast overgrowth can be prevented or treated by oral administration of Lactobacillus or other probiotics. If response is insufficient, oral antifungals may be needed. Prescription medications can be compounded for oral administration to help reduce yeast in the gut. Compromised digestive function, often secondary to inflammation of the bowel, may lead to the absorption of toxins (“leaky gut”). Children can benefit from balanced nutrition, treatment of imbalanced gut flora, and enhancement of immune function.

Nutritional Therapy for Autism

Most children with autism have a need for increased amounts of vitamins, minerals, and some amino acids. Some detoxification agents may remove essential minerals, creating a need for additional minerals. Vitamin C, vitamin B6, vitamin A, omega-3 fatty acids, calcium, magnesium, zinc, and selenium are often needed in addition to a broad-spectrum vitamin/mineral supplement. Copper should be avoided in many cases, since the levels in autistic children are sometimes high. Amino acid, nutritional, and supplemental therapies can be customized for each child. Once the physician has determined the specific nutrients that are needed, compatible supplements can be combined in flavored suspensions to simplify administration.

Many children with autism are zinc deficient. Zinc deficiency affects taste perception and children then become averse to eating certain foods and taking supplements. In this case, transdermal preparations can be very helpful by completely bypassing the oral route of administration. Commonly needed nutrients which can easily be given in a transdermal form include vitamin A, vitamin D, and zinc.

Glutathione is the major antioxidant in cells and is important for detoxification and elimination of environmental toxins. Its active form is reduced in about 80 percent of autistic children. Oxidative stress, a suspected contributor in many disease processes like heart disease and cancer, also plays a role in autism, and occurs when antioxidants are not present in sufficient levels to clear the body of free radicals. Free radicals can damage cells in the brain, gastrointestinal tract and immune system. Children with low glutathione levels may be more vulnerable to this damage, so supplementation with oral or transdermal glutathione and other antioxidants may be beneficial.

Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with ASD.

J Child Neurol. 2008 May;23(5):482-5.
Melatonin for Insomnia in Children With Autism Spectrum Disorders.
Click here to access the PubMed abstract of this article.

Detoxification (including chelation)

Some children with autism may suffer from heavy metal toxicity, and may potentially benefit from therapies which support detoxification. Some may also benefit from chelation (removal of heavy metals). Oral DMSA (dimercaptosuccinic acid) is approved by the FDA for treating lead poisoning in children as young as one year of age. It has also been demonstrated to be able to bind and remove a wide range of toxic metals, including mercury, arsenic, tin, nickel, and antimony. Oral DMSA has been used off-label for this purpose. It is important to monitor kidney and liver function and complete blood counts when using DMSA, and although rare, serious side effects may occur.

Please note: These therapies have not been approved by the FDA for the treatment of autism, and should be used only under direct supervision of an experienced and knowledgeable health care professional after parents or guardians have received adequate information and given consent.

www.autism.com

Ann Neurol 2005;57:67–81
Neuroglial activation and neuroinflammation in the brain of patients with autism.
Click here to access the PubMed abstract of this article.

Ann N Y Acad Sci. 2007 Jun;1107:92-103.
Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder.
Click here to access the PubMed abstract of this article.

Cell Mol Neurobiol. 2004 Apr;24(2):219-41
Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism.
Click here to access the PubMed abstract of this article.

Neuroendocrinology Letters 2002;23:303-8
Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.
Click here to access the PubMed abstract of this article.

Dev Brain Dysfunction 1997;10:40-43
Biochemical parameters in autistic children.

J Inherit Metab Dis.1993;16(4):762-770 Pediatrics 1995;95:255-8

Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

J Nutr Env Med 2000;10:25-32
Sulphur metabolism in autism.

Low Dose Naltrexone (LDN) and Autism

ASC (autism spectrum conditions) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviors induced in animals or humans by opiate administration, including decreased socialization, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behavior of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason. A review of the literature from 2010 until 2013 concluded that naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in the majority of the participants.

J Intellect Disabil Res. 2015 Apr;59(4):293-306.
Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

Approximately two-thirds of infants experience diaper rash (dermatitis). Customized diaper rash preparations -ointments, powders, or creams- can be compounded to treat each child’s specific symptoms, using ingredients which will protect the skin from additional irritation, soothe and encourage healing, and prevent secondary infections. Skin protectants (zinc oxide, petrolatum) provide a physical barrier against external irritants such as urine or gastrointestinal enzymes in stool. Antifungal creams can be used when a yeast (Candida) infection is suspected.

We can also compound a bile acid sequestrant, such as cholestyramine ointment, to prevent skin irritation, which is especially helpful for ostomy patients.

Ann Pharmacother 1996 Sep;30(9):954-6
Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
Click here to access the PubMed abstract of this article.

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Oral Viscous Budesonide (OVB) for Treatment of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is a disease most likely due to an immunologic response to ingested and inhaled allergens. Presenting symptoms of EE often mimic those of gastroesophageal reflux disease (GERD) and include vomiting, dysphagia, pain, and food impaction. However, because the treatment of EE and GERD differs, it is important to distinguish between them. Swallowed topical steroids, such as fluticasone propionate, have been administered using a metered-dose inhaler (MDI) without a spacer, with instructions to not inhale, but to puff and swallow, thus delivering a topical antiinflammatory product to the esophageal mucosa. Although effective in lowering eosinophil levels, this technique of administering aerosolized corticosteroids, which are often bitter to taste, may be complicated for young children, and twice daily administration is necessary. However, this treatment is attractive because only 1% of the steroid is absorbed systemically and it undergoes rapid hepatic processing. The main potential side effect is oral/esophageal Candida infection that developed in 3 of 20 patients in one series.1

Budesonide is a corticosteroid with high topical anti-inflammatory activity but low systemic activity due to extensive hepatic metabolism. Aceves et al. of Children’s Hospital and the Department of Pediatrics, University of California, San Diego, reported the successful treatment of EE using an oral viscous suspension of budesonide in 2 patients who were unable to utilize fluticasone propionate for developmental reasons.2

Researchers noted: “Our data suggest that OVB is an effective and safe treatment for young children with proven EE. It may have advantages over other therapies in that it is palatable, its volume (8–12 ml) provides pan-esophageal mucosal coverage, and it requires only once daily administration.”3 The increased viscosity of OVB may prolong budesonide’s contact time with the esophageal mucosa. No significant adverse events were reported. Morning cortisol levels were within normal limits.

1 J Pediatr Gastroenterol Nutr 1998;27:90–3.
Treatment of eosinophilic esophagitis with inhaled corticosteroids.
Click here to access the PubMed abstract of this article.

2 J Allergy Clin Immunol 2005;116:705–6.
Topical viscous budesonide suspension for treatment of eosinophilic esophagitis.
Click here to access the PubMed abstract of this article

3 Am J Gastroenterol. 2007 Oct;102(10):2271-9.
Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children.
Click here to access the PubMed abstract of this article.

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Athlete's foot, jock itch, and onychomycosis (fungal nail) are common, particularly in athletes. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties." Various synergistic combinations are used for antifungal therapy.

J Med Microbiol 2000 Sep;49(9):831-40
Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
Click here to access the PubMed abstract of this article.

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Concerns about emerging resistance and the potential harm of using permethrins have prompted a search for effective pediculicidal therapies that are not harmful to children with repeated use. An herbal formulation has been shown to be effective for head lice. Ivermectin can also be compounded for topical application or as an oral dose titrated for each patient for the treatment of head lice and scabies.

Clin Exp Dermatol 2002 Jun;27(4):264-7
Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.
Click here to access the PubMed abstract of this article.

Twenty six male and female patients aged 5 to 17 years had head lice infestation confirmed by eggs presence and received treatments with a single 200 microgram/kg oral dose of. At day 14 after treatment, 20 had responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients appeared clear of infestation (27%), but 4 of the 6 patients with no eggs at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 may be appropriate.

Trop Med Parasitol 1994 Sep;45(3):253-4
Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
Click here to access the PubMed abstract of this article.

Two hundred scabies patients were randomly allocated to receive either oral ivermectin in a single dose of 200 micrograms/kg body weight, or 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindane group showed a similar response. Oral ivermectin is easy to administer as a single oral dose, induces an early and effective improvement in signs and symptoms, and compliance is accordingly increased.

J Dermatol 2001 Sep;28(9):481-4
Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.
Click here to access the PubMed abstract of this article.

Isr Med Assoc J. 2002 Oct;4(10):790-3
The in vivo pediculicidal efficacy of a natural remedy.
Click here to access the PubMed abstract of this article.

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Resistant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy.

Therapy with 10% KOH was found to be effective and safe in the treatment of molluscum contagiosum (MC) in children, although a stinging sensation was reported by most children during the trial and some developed hyper- or hypopigmentation after treatment at the site of the lesions.

Pediatr Dermatol. 1999 May-Jun;16(3):228-31.
Treatment of molluscum contagiosum with potassium hydroxide: a clinical approach in 35 children. Romiti R et al.
Click here to access the PubMed abstract of this article.

In an attempt to reduce the side effects (stinging sensation & hyper- or hypopigmentation) found with use of 10% KOH, a new trial of 20 children used a less concentrated KOH solution (5%) for treatment of molluscum contagiosum (MC). The 5% KOH aqueous solution proved to be as effective as and less irritating than 10% KOH, and spared children from more aggressive physical modalities of treatment.

Pediatr Dermatol. 2000 Nov-Dec;17(6):495.
Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum. Romiti R, Ribeiro AP, Romiti N.
Click here to access the PubMed abstract of this article.

These studies showed that 5% imiquimod cream and 10% KOH solution are equally effective in treating molluscum contagiosum, although KOH has a faster onset of action.

Ann Dermatol. 2010 May;22(2):156-62. Epub 2010 May 17.
An open, randomized, comparative clinical and histological study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Seo SH, Chin HW, Jeong DW, Sung HW.
Click here to access the PubMed abstract of this article.

Indian J Dermatol Venereol Leprol. 2008 Nov-Dec;74(6):614-8.
An open, nonrandomized, comparative study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Metkar A, Pande S, Khopkar U.
Click here to access the PubMed abstract of this article.

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Orally administered anti-emetics can be difficult for a nauseated child to "keep down", and rectal suppositories may not be well accepted by children. Even persistent nausea can often be effectively controlled by using a combination of medications tailored to meet an individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more.

Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.

US Pharmacist, August 1999; 74-5

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Topical anesthesia is needed for common pediatric procedures such as suturing, wound cleaning, and injection administration. The ideal topical anesthetic would provide complete anesthesia following a simple pain-free application, not contain narcotics or controlled substances, and have an excellent safety profile. The combination of topical anesthetics lidocaine and tetracaine and the vasoconstrictor epinephrine has been used successfully for anesthesia prior to suturing linear scalp and facial lacerations in children. A triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") has also been reported to be effective when applied prior to laser and cosmetic procedures. Convenience of application without need for occlusion is an advantage of these topical anesthetics.

The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children."

Pediatrics 1995 Feb;95(2):255-8
Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application.

Cosmetic Dermatology 2003 Apr;16(4):35-7
Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics

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Sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with Pulmonary arterial hypertension (PAH), and this medication can be compounded as a stable oral suspension.

Circulation. 2005 Jun 21;111(24):3274-80
Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study.
Click here to access the PubMed abstract of this article.

Am J Health Syst Pharm. 2006 Feb 1;63(3):254-7
Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children.
Click here to access the PubMed abstract of this article.

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Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are medical emergencies. Mortality and poor neurologic outcome are directly associated with the duration of seizure activity. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Diazepam rectal gel was developed due to the need for non-injection-based delivery; however, the aesthetics of rectal delivery are not popular with patients and caregivers. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures at home or when actively seizing patients arrive in the emergency room. There are many factors that a practitioner and compounding pharmacist must consider when choosing a benzodiazepine for intranasal administration, including solubility of the drug, ease of passing the blood-brain barrier, and pharmacokinetic/pharmacodynamic profiles. Concentration is important as the nasal cavity can retain approximately 0.1-0.15 ml.

Under ideal conditions, most medication is absorbed from the nasal cavity and into the bloodstream within 15 to 20 minutes, thus generally avoiding the first-pass gut metabolism. Increased nasal mucus production is commonly observed with actively seizing patients, so it may be prudent to suction mucus from the nasal cavity prior to administration of intranasal midazolam. Intranasal midazolam has been extensively studied in epilepsy patients. Various devices have been used to deliver 0.2 mg/kg of midazolam injection intranasally.

Morbidity and mortality, as well as health-care resources and expenses associated with treatment of epileptic patients, could be reduced if an effective and safe transmucosal treatment was available for use by caregivers.

Neurotherapeutics. 2009 Apr;6(2):352-8.
Intranasal delivery of antiepileptic medications for treatment of seizures.
Click here to access the PubMed abstract of this article.

Midazolam nasal spray has been used to reduce procedural anxiety in children, anxiety-related dyspnea, and to prevent MRI-induced claustrophobia.

Intranasal Midazolam for Managing Prolonged Seizures Intranasal midazolam is a safe and practical alternative to rectal diazepam for managing prolonged seizures in non-hospitalized patients.

J Intellect Dev Disabil 2006 Sep;31(3):131-8
Community use of intranasal midazolam for managing prolonged seizures.
Click here to access the PubMed abstract of this article.

Am J Emerg Med 2006 May;24(3):343-6
Intranasal midazolam therapy for pediatric status epilepticus.
Click here to access the PubMed abstract of this article.

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• BLT or LAT topical gel or spray
• Cholestyramine ointment
• Clotrimazole in DMSO solution
• Fluconazole/Ibuprofen topical
• Ivermectin topical KOH solution - 5% and 10%
• Nicotinamide/Spironolactone topical
• Promethazine transdermal gel
• Urea 40% plasters

The above list is just a few of the preparations that we can compound for pediatric use. We work together with prescriber and patient to solve problems, and all formulations are customized per prescription to meet the unique needs of each child.

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