On May 10, 2021, the FDA expanded its Emergency Use Authorization (EUA) for the Pfizer/BioNTech mRNA-based COVID-19 vaccine to include adolescents 12-15 years old.1The vaccine has been authorized for use in persons ≥16 years old since December 2020.

Over-the-counter products containing melatonin are widely used as sleep aids in children and adults.

The nasal spray formulation of the corticosteroid fluticasone furoate is now available over the counter (OTC) as Flonase Sensimist Allergy Relief (GSK) in the same strength as the prescription product (Veramyst) for treatment of seasonal or perennial allergic rhinitis. It is the fourth intranasal corticosteroid to become available OTC.

A reader commenting on our Treatment of Lyme Disease article (Med Lett Drugs Ther 2016; 58:57) objected to a footnote in the table advising against use of doxycycline in children <8 years old. This warning has been included in the labeling of all tetracyclines since 1970 when it was recognized, after decades of use, that these drugs caused permanent staining and enamel hypoplasia of developing teeth. The CDC recently stated that short courses of doxycycline, which was first marketed in the US in 1967 and has less affnity for calcium than other tetracyclines, have not been shown to cause tooth staining.1 That statement was prompted by the discovery that children <10 years old have a disproportionately high fatality rate from rickettsial diseases, particularly Rocky Mountain spotted fever, for which doxycycline is the drug of choice and chloramphenicol is the only proven alternative.

The main evidence supporting the CDC's statement was a retrospective cohort study consisting of a record review and dental examination of 271 children living on a Native American reservation. No staining was detected in any of the 58 children who had been treated with doxycycline before the age of 8 years or in any of the 213 children who had not been exposed to the drug. Enamel hypoplasia was present in 4% of children in both cohorts.2

Lyme disease, unlike Rocky Mountain spotted fever, is seldom fatal and can be treated with antibiotics other than doxycycline. A single dose of doxycycline is recommended for prophylaxis after a tick bite. Given the CDC's statement about its safety, it would seem reasonable to use doxycycline for prophylaxis in all age groups. When longer treatment courses (10, 14, or 28 days) are recommended for the various clinical manifestations of Lyme disease in children <8 years old, alternative antibiotics generally could be used instead.

1. HM Biggs et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group Rickettsioses, Ehrlichioses, and Anaplasmosis – United States. MMWR Recomm Rep 2016; 65:1.
2. SR Todd et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain spotted fever. J Pediatr 2015; 166:1246.

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The FDA has now approved a recombinant, 9-valent, human papillomavirus (HPV) vaccine (Gardasil 9 – Merck) for use in girls and women 9-26 years old and boys 9-15 years old. The new vaccine is indicated to prevent diseases associated with infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, which include genital warts and cervical, vulvar, vaginal, and anal precancerous lesions and cancer. Two recombinant HPV vaccines are already available in the US: Gardasil prevents disease associated with HPV types 6, 11, 16, and 18, and Cervarix prevents disease associated with HPV types 16 and 18.

The nasal spray formulation of the corticosteroid fluticasone propionate is now available over the counter (OTC) as Flonase Allergy Relief (GSK) in the same strength as the prescription product (Flonase, and generics) for patients ≥4 years old with seasonal or perennial allergic rhinitis. It is the second corticosteroid nasal spray to become available OTC; triamcinolone acetonide (Nasacort Allergy 24HR) was the first. Unlike prescription Flonase, the OTC product is FDA-approved for reduction of ocular as well as nasal symptoms. Brand-name prescription Flonase has been discontinued by the manufacturer.

The FDA has approved an oral solution of the nonselective beta-adrenergic blocker propranolol (Hemangeol – Pierre Fabre) for treatment of proliferating infantile hemangiomas.

An outbreak (8 cases to date) of meningococcal disease at Princeton University caused by Neisseria meningitidis serogroup B has led the FDA and CDC to permit importation and investigational use (at Princeton University only) of a meningococcus B vaccine (4CMenB; Bexsero – Novartis) that has not been approved in the US. Bexsero has been approved for use in the European Union and in Australia.

THE VACCINE — Until recently, no serogroup B vaccine was widely available because the polysaccharide capsule of the B serogroup, unlike those of the other main meningococcal serogroups (A, C, Y, and W-135), is only weakly immunogenic. The 4CMenB vaccine contains 3 protein antigens identified in the N. meningitidis serogroup B genome and membrane components from a New Zealand outbreak strain. The vaccine has been tested in more than 8000 adults and children, has proved to be immunogenic, and appears to be safe.1 Its efficacy has not been established clinically, but laboratory testing, according to the CDC, has found that the vaccine should be protective against the strain causing the Princeton University outbreak. Bactericidal antibody levels develop about 2 weeks after one dose of the vaccine; a second dose is needed 1-6 months after the first to maintain protection.

CHEMOPROPHYLAXIS — Close contacts of patients with invasive meningococcal disease (e.g., same household, roommates, boyfriend or girlfriend) should receive antimicrobial chemoprophylaxis. Antimicrobial drugs can prevent secondary cases and eradicate the organism from the nasopharynx of healthy carriers. The susceptibility of serogroup B meningococci to antimicrobial agents is the same as that of other meningococcal serogroups. Regimens recommended by the CDC’s Advisory Committee on Immunization Practices are: oral rifampin 600 mg (10 mg/kg for children) q12h for 2 days; oral ciprofloxacin 500 mg once (not recommended for children); or a single IM injection of ceftriaxone 250 mg (125 mg for children).2

CONCLUSION — The new vaccine against serogroup B meningococcal disease, which is investigational in the US, appears to be immunogenic and safe. For immediate protection after close contact with an infected patient, antimicrobial prophylaxis is recommended.

1. NJ Carter. Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero®): a review of its use in primary and booster vaccination. BioDrugs 2013; 27:263.

2. AC Cohn et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62(RR-2):1.

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The FDA has approved the over-the-counter (OTC) sale of Nasacort Allergy 24HR (Sanofi), a triamcinolone acetonide nasal spray previously available only by prescription as Nasacort AQ. The OTC product, which is scheduled to be marketed in the spring of 2014, will be the first corticosteroid nasal spray that can be purchased without a prescription in the US. Nasacort Allergy 24HR is approved for use in patients ≥2 years old with nasal allergy symptoms.

Rates of meningococcal disease are highest in infancy, but until recently no meningococcal vaccine was approved for use in this age group. MenHibrix (GSK), a new conjugate vaccine that protects against Neisseria meningitidis serogroups C and Y and Haemophilus influenzae type b (Hib), has been approved by the FDA for use in infants ≥6 weeks old and Menveo, a meningococcal vaccine already approved for patients ≥2 years old that protects against serogroups A, C, Y, and W-135, is now approved for use in infants ≥2 months old.

SEROGROUPS — Five major serogroups of N. meningitidis, A, B, C, Y, and W-135, cause most of the reported cases of invasive meningococcal disease. Serogroup A is the leading cause of epidemic meningitis worldwide, especially in the meningitis belt of sub-Saharan Africa, but it is rare in the US. Serogroup B causes about 60% of all meningitis cases in infants and, together with serogroups C and Y, accounts for most of the endemic disease in the US. Serogroup W-135 has caused outbreaks worldwide, particularly among pilgrims to Mecca during the Hajj and their close contacts on arriving home. Serogroup B remains the only major serogroup for which no vaccine is available in the US. A meningococcal B vaccine (Bexsero – Novartis) is licensed in Europe and Australia for patients ≥2 months old.

IMMUNOLOGIC STUDIES — FDA approval of both MenHibrix and Menveo (for this age group) was based on immunologic studies in infants who received the vaccines at 2, 4, 6, and 12 months. Both vaccines produced protective antibody responses in almost all vaccinated infants. With MenHibrix, antibody levels against Hib were non-inferior to those with 2 standard monovalent Hib vaccines.1

RECOMMENDATIONS FOR USE — The CDC’s Advisory Committee on Immunization Practices (ACIP) does not recommend routine vaccination against meningococcal disease for infants. It does recommend use of either MenHibrix or Menveo for infants who are at increased risk of meningococcal disease because of persistent complement deficiencies, functional or anatomic asplenia, or exposure to a community outbreak of disease caused by one of the serogroups in the vaccine.2 Menveo is also recommended for infants traveling with their families to the Hajj or to the meningitis belt of sub-Saharan Africa. Both vaccines can be given on a 4-dose schedule at 2, 4, 6, and 12 months, but the first dose of MenHibrix can be administered as early as 6 weeks and the last dose as late as 18 months.

1. KA Bryant et al. Immunogenicity and safety of H. influenzae type b-N meningitidis C/Y conjugate vaccine in infants. Pediatrics 2011; 127:e1375.

2. AC Cohn et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62(RR-2):1.

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The FDA is advising health care professionals not to prescribe valproate sodium (Depacon), valproic acid (Depakene, Stavzor, and generics) or divalproex sodium (Depakote, Depakote ER, and generics) for migraine prevention in pregnant women because a recently published study showed that IQ scores are decreased in children of mothers who took these drugs during pregnancy. The FDA recommends avoiding valproate altogether, if possible, in women of childbearing age.1

VALPROATE — Valproic acid and divalproex sodium dissociate to valproate in the GI tract. Valproate is considered the drug of choice for treatment of primary generalized tonic-clonic seizures. It is one of many drugs used for treatment of bipolar disorder and prevention of migraine.2,3

EFFECTS ON CHILDREN — The recent publication is the third in a series comparing IQ scores in a cohort of children exposed to various antiepileptic drugs throughout pregnancy.4 At 3 years of age, 4.5 years, and now 6 years, IQ scores were 6-11 points lower in children exposed to valproate than in those exposed to carbamazepine, lamotrigine or phenytoin. In addition, valproate taken during pregnancy has the highest demonstrated risk, compared to other antiepileptic drugs, of major congenital malformations, including oral cleft, cardiac, urinary tract and neural tube defects, and most recently, it has been associated with an increased risk of autism.5,6

USE IN MIGRAINE — Beta blockers such as propranolol and timolol and the antiepileptics valproate and topiramate are the drugs generally used for prevention of migraine. There is no evidence that any one is more effective than any other. Because of concerns about possible adverse fetal effects with all of these agents, preventive therapy for migraine is generally not recommended during pregnancy.7

CONCLUSION — Taking valproate during pregnancy can lower the IQ of exposed children and possibly could have other devastating effects. Those risks are certainly not worth taking for prevention of migraine.

1. FDA Drug Safety Communication: Valproate anti-seizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. Available at www.fda.gov/Drugs/DrugSafety/ucm350684.htm. Accessed May 28, 2013.

2. Drugs for psychiatric disorders. Treat Guidel Med Lett 2013; 11:53.

3. SD Silverstein 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.

4. KJ Meador et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12:244.

5. J Christensen et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309:1696.

6. KJ Meador and DW Loring. Risks of in utero exposure to valproate. JAMA 2013; 309:1730.

7. Drugs for migraine. Treat Guidel Med Lett 2011; 9:7.

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The surprising observation that oral administration of the beta-blocker propranolol (Inderal, and others) can stop the growth and rapidly cause the involution of disfiguring or life-threatening infantile hemangiomas1 has quickly led to a series of confirmatory observations and now a controlled trial. The mechanism of this effect is not known, but is thought to be related to down-regulation of the RAF mitogen-activated protein kinase signaling pathway resulting in inhibition of vascular endothelial growth factor (VEGF) and apoptosis in capillary endothelial cells. The response of infantile hemangiomas to propranolol, which may be detectable within a day, has been similar regardless of the age of the child or the location or depth of the lesion.2 A randomized controlled trial in 40 children 9 weeks to 5 years old with primarily facial hemangiomas compared propranolol 2 mg/kg/day to a placebo, each given in 3 divided doses, for 6 months. Propranolol was significantly more effective in reducing the volume, redness and elevation of the lesions. No significant hypoglycemia, hypotension or bradycardia occurred.3

1. C Léauté-Labrèze et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358:2649.

2. L Bagazgoitia et al. Propranolol for infantile hemangiomas. Pediatr Dermatol 2011; 28:108.

3. M Hogeling et al. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011; 128: e259.

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Evidence of waning immunity by 5 years post-vaccination has led the US Advisory Committee on Immunization Practices (ACIP) to recommend, in addition to a primary dose of meningococcal conjugate vaccine at 11 or 12 years of age, a booster dose at age 16. Adolescents who receive a first dose of the vaccine at age 13-15 should receive a booster dose at 16-18 (before college). Those who receive their first dose at ≥16 years of age do not need a booster dose. Routine vaccination of healthy persons who are not at increased risk for exposure to Neisseria meningitidis is not recommended after age 21.1

1. CDC. Updated recommendations for use of meningococcal conjugate vaccines — Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 2011; 60:72.

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The FDA has approved a new indication for prevention of anal cancer and anal intraepithelial neoplasia in both sexes for the human papillomavirus (HPV) vaccine Gardasil (Merck). This vaccine is already FDA-approved for prevention of cervical cancer and genital warts in females 9-26 years old and for prevention of genital warts in males 9-26 years old. HPV types 6 and 11 cause about 90% of genital warts. Types 16 and 18 cause more than 70% of cervical cancer and about 80% of anal cancer.1 Gardasil is highly effective in preventing infection with HPV types 6, 11, 16 and 18 in both males and females.2,3 (A second HPV vaccine, Cervarix, is also effective in preventing infection with types 16 and 18, but has no activity against types 6 and 11; it has not been approved for any indication in males.4)

Since 40% of women become infected with HPV within 16 months after initiation of sexual activity and neither vaccine prevents cancer if it is given after infection, vaccination against HPV is now recommended routinely for girls 11-12 years old. Routine vaccination of boys with Gardasil would benefit unvaccinated girls as well as the boys themselves.

1. H De Vuyst et al. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009; 124:1626.

2. A human papillomavirus vaccine. Med Lett Drugs Ther 2006; 48:65.

3. AR Giuliano et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med 2011; 364:401.<

4. Cervarix – A second HPV vaccine. Med Lett Drugs Ther 2010; 52:37.

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Glycopyrrolate (Robinul, and others), a synthetic muscarinic receptor antagonist, has been used off-label for many years for treatment of excessive drooling in patients with Parkinson’s disease, in patients taking clozapine for schizophrenia, and in developmentally disabled children.1-3 It has now been approved by the FDA as Cuvposa (Shionogi) for use specifically in children 3-16 years old with severe chronic drooling due to a neurologic condition, such as cerebral palsy. It is being marketed as an oral solution, which will permit more precise weight-based dosing than was possible with the oral tablets used in the past. As with other anticholinergic drugs, dry mouth, constipation, flushing and nasal congestion can occur. Since glycopyrrolate decreases secretion not only of saliva, but also of sweat, overheating due to high ambient temperatures or excessive exercise could be dangerous for patients who take it.

1. ME Arbouw et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74:1203.

2. CS Liang et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. Schizophren Res 2010; 119:138.

3. RJ Mier et al. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154:1214.

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The FDA has licensed a 13-valent conjugate pneumococcal vaccine (PCV13; Prevnar 13 – Pfizer) for the prevention of invasive pneumococcal disease (IPD) in infants and children <6 years old. It replaces Prevnar (PCV7). An unconjugated 23-valent polysaccharide vaccine (PPSV23; Pneumovax 23 – Merck) is FDA-approved for use in adults.

In 2007, Merck voluntarily recalled some lots of PedvaxHIB and Comvax, two Haemophilus influenzae type b (Hib) vaccines, and temporarily stopped their production because of possible contamination, resulting in a shortage during which pediatricians were urged to defer giving Hib booster doses (normally given at 12-15 months) to healthy children. Now the FDA has granted accelerated licensure of Hiberix (GlaxoSmithKline), a monovalent vaccine conjugated with tetanus toxoid that has been used in Europe since 1996, as a booster (final) dose of the Hib series in children 15 months-4 years old. Hiberix can also be given to children 12-15 months old as a scheduled booster dose.1

1. Licensure of a Haemophilus influenzae type b (Hib) vaccine (Hiberix) and updated recommendations for use of Hib vaccine. MMWR Morb Mortal Wkly Rep 2009; 58:1008.

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