Chewable Sinus & Respiratory Support Natural Berry Flavor by Zarbee's Naturals

POSSIBLY EFFECTIVE

• Influenza. Although some small clinical studies show that elderberry extracts can improve influenza symptoms in otherwise healthy adults, a small clinical study enrolling adults and children with or without high risk medical conditions shows it does not reduce the duration of symptoms. Details: Small clinical studies in otherwise healthy adults with influenza presenting within 48 hours of symptom onset show that taking elderberry extract syrup (Sambucol, Nature's Way) 15 mL four times daily for 5 days improves patient ratings of symptoms such as aches and pains, cough, and nasal congestion an average of 4 days earlier than in control groups. It also reduced the use of rescue medications (5260,12235). Another small clinical study in adults shows that taking an elderberry extract lozenge (ViraBLOC, HerbalScience) 175 mg four times daily for 2 days, starting within 24 hours of symptom onset, improves flu-like symptoms, typically within 48 hours, when compared with placebo (17022). However, in a small clinical study in children and adults 5 years and older with influenza, including those with high-risk conditions such as asthma, chronic lung disease, and heart disease, using Sambucol for 5 days starting within 48 hours of symptom onset did not reduce the time to complete resolution of symptoms for a 24-hour period when compared with placebo (103831). These negative findings may be due to the age and baseline health status of the enrolled patients, as well as the use of symptom resolution, as opposed to symptom improvement, as the primary outcome. Elderberry has also been evaluated in combination with echinacea for treating influenza symptoms (95650), but it is not clear whether the combination is better than either ingredient alone.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there is interest in using oral elderberry for allergic rhinitis, there is insufficient reliable information about the clinical effects of elderberry for this purpose.
• Asthenopia (eye strain). Oral elderberry extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults without dry eye disease with occupations requiring the use of video display terminals shows that taking a specific combination product containing elderberry fruit extract 300 mg, zinc 10 mg, L-carnitine 50 mg, currant 100 mg, and Eleutherococcus root 50 mg (Meramirt CM) once daily for 1 month improves measures of eye strain and contrast sensitivity when compared to baseline. Improvements in these measures were lacking in the control group (111295). Statistical comparison between the two groups was not reported. It is unclear if these effects are due to elderberry, other ingredients, or the combination.
• Cardiovascular disease (CVD). It is unclear whether elderberry has any benefit in CVD. In one small study it did not alter disease markers. Details: Preliminary clinical research in postmenopausal women shows that taking elderberry extract 500 mg daily for 12 weeks does not significantly improve markers of CVD, including inflammatory biomarkers, vascular activity, or plasma lipid or glucose levels, when compared with placebo (21141).
• Chronic obstructive pulmonary disease (COPD). Elderberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in men aged 40-70 years with a history of smoking and Stage 2 COPD, shows that a combination of elderberry 165 mg, heart's ease herb 165 mg, and calendula flowers 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months modestly improves the score on the 5-point breathlessness, cough, and sputum scale (BCSS) and modestly increases the mean forced expiratory volume in 1 second (FEV1), compared with no changes in the placebo group. However, the number of COPD exacerbations per month is not affected (103629). It is unclear if these effects are due to elderberry, the other ingredients, or the combination.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral elderberry for CFS, there is insufficient reliable information about the clinical effects of elderberry for this purpose.
• Common cold. Oral elderberry extract does not seem to PREVENT colds when taken prophylactically, but it may reduce the duration and severity of existing colds. Details: Clinical research in healthy adults shows that taking capsules containing elderberry extract (BerryPharma, Iprona AG) 600 mg daily for 8 days before overseas air travel, and then 900 mg daily starting 1 day before traveling and continuing for 4-5 days after arriving at the destination, does not reduce the number of colds or impact quality of life when compared with placebo. However, this product does reduce the duration of colds by about 2 days and the severity of colds by about 58% when compared with placebo (91374).
• Constipation. Oral elderberry extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among airline flight crew shows that taking a specific product (ACTIVE) containing elderberry extract 70 mg and a specific probiotic formulation (SYNBIO) daily for 1 month improves constipation, stool volume and consistency, ease of defecation, intestinal regularity, flatulence, and diarrhea compared to baseline, but not when compared with placebo (112134). It is unclear if these effects are due to elderberry, the probiotics, or the combination.
• Gingivitis. Elderberry has been evaluated as a mouthwash or patch in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a mouth rinse (HM-302, Izun Pharmaceuticals) containing elderberry, echinacea, and gotu kola 15 mL three times daily for 14 days might prevent worsening of gingivitis when compared with a placebo rinse. However, it only minimally improves symptoms (20069). Other preliminary clinical research shows that applying a periodontal patch (PerioPatch, Izun Pharmaceuticals) containing elderberry, echinacea, and gotu kola either as a single dose, or three times daily for 1 day then once daily for 2 days, reduces some, but not all, measures of inflammation and gingivitis when compared with no treatment (20068,20070).
• HIV/AIDS. Although there has been interest in using oral elderberry for HIV/AIDS, there is insufficient reliable information about the clinical effects of elderberry for this purpose.
• Hyperlipidemia. It is unclear if elderberry is beneficial for the treatment of hyperlipidemia. Details: One preliminary clinical study in patients with hyperlipidemia shows that taking capsules containing spray-dried elderberry 400 mg, providing 10% anthocyanins, three times daily for 2 weeks does not reduce serum lipids when compared with placebo (21142).
• Lower respiratory tract infections. Oral elderberry extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that adding a specific combination product (Stimunex gocce) containing elderberry extract, beta-glucans, zinc, and vitamin D3 to standard therapy does not reduce the number or duration of lower respiratory tract infections when compared with standard therapy alone. In the four months after treatment completion, the number of infections was reduced by about 50%; however, the total number of infections in each group was small. The dose was 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212). The validity of this study is limited by lack of blinding.
• Obesity. Elderberry has been studied for weight loss in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in overweight adults shows that replacing all meals for 8 days with a kit containing elderberry juice (from 120 grams of elderberries/day), dried elderberry (225 mg/day), dried elderflower (3.9 grams/day), elderflower extract (600 mg/day), and dried asparagus (40.5 grams/day), while also taking psyllium 2-3 teaspoons daily for 2 weeks, is associated with a mean decrease in body weight of 3.2 kg over 14 days when compared with baseline (94939). The validity of this study is limited by the lack of a comparator group. Also, it is unclear whether this effect is due to elderberry, other ingredients, the combination, or fasting from regular food.
• Psychological well-being. Oral elderberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among airline flight crew shows that taking a specific product (ACTIVE) containing elderberry extract 70 mg and a specific probiotic formulation (SYNBIO) daily for 1 month improves scores on the Psychological General Well Being Index when compared with placebo. The index measures symptoms of anxiety and depression, general health status, and feelings of vitality and general self-control (112134). It is unclear if these effects are due to elderberry, the probiotics, or the combination.
• Respiratory tract infections. Oral elderberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that adding a specific combination product (Stimunex gocce) containing elderberry extract, beta-glucans, zinc, and vitamin D3 to standard therapy reduces the duration of respiratory tract infections by about 1.7 days and modestly improves parent-perceived symptom severity when compared with standard therapy alone. However, there was no effect on the number of total, upper, or lower respiratory tract infections, the use of antibiotics or antipyretics, or the number of days missed from school. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212). The validity of this study is limited by lack of blinding.
• Rhinosinusitis. Although there has been interest in using oral elderberry for rhinosinusitis, there is insufficient reliable information about the clinical effects of elderberry for this purpose.
• Upper respiratory tract infection (URTI). Oral elderberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that adding a specific combination product (Stimunex gocce) containing elderberry extract, beta-glucans, zinc, and vitamin D3 to standard therapy does not reduce the number or duration of upper respiratory tract infections when compared with standard therapy alone. At four months after treatment completion, the number of infections was reduced by about 44%; however, the total number of infections in both groups was small. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212). The validity of this study is limited by lack of blinding. More evidence is needed to rate elderberry for these uses.

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POSSIBLY EFFECTIVE

• Acute Bronchitis. Oral Pelargonium sidoides may be beneficial in adults and children with acute bronchitis when initiated within 48 hours of symptom onset. Details: Several clinical studies and a meta-analysis of 6 small-to-moderate sized clinical studies in adults and children with acute bronchitis show that taking Pelargonium sidoides extract daily, starting within 48 hours of symptom onset, significantly reduces symptoms such as cough intensity and rales after 7 days of treatment when compared with placebo. Additionally, patients report an earlier onset of effect and increased remission of cough when compared with placebo (14258,16647,16649,16651,81557,81565,94580,110015,112124). Another meta-analysis of 6 clinical trials in children aged 6-10 years with acute bronchitis or acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126). However, most of the outcomes in these studies were patient-reported. Additionally, it is unclear whether any improvements are clinically significant. Various formulations of Pelargonium sidoides have been investigated. A specific liquid extract of Pelargonium sidoides containing the active ingredient EPs 7630 (Dr. Willmar Schwabe Pharmaceuticals) has been used in most studies (14258,16647,16649,16651,81557,81565,94580,110015,112124). In adults, this specific extract is administered as 30 drops of solution three times daily or in tablet form as 10-30 mg three times daily for 7 days (14258,16649,16651,81557,81565,94580). In children, this specific extract is administered as 10 drops three times daily in patients under 7 years of age or 20 drops three times daily for 7 days in those 7 years of age and older (16651,112124). In children aged 1-5 years of age, this specific extract is also available as a syrup dosed at 2.5 mL 3 times daily, which is equivalent to 10 drops of solution 3 times daily (112123). Some studies used extracts in tablet form; however, these tablet formulations have only been shown to be beneficial in adults, not in children (17417,94580).
• Chronic obstructive pulmonary disease (COPD). Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may decrease the frequency of exacerbations, improve symptoms, and reduce the need for antibiotics in patients with COPD; however, it does not seem to reduce the overall risk of exacerbations. Details: One clinical study in patients with moderate to severe COPD shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily in addition to standard treatment for 24 weeks lengthens the average time to COPD exacerbation by 14 days when compared with placebo (97319). The addition of Pelargonium sidoides to standard therapy is also associated with a reduction in total COPD symptoms, antibiotic use, and missed workdays (97319,97325). However, Pelargonium sidoides does not seem to decrease the overall number of COPD exacerbations (97325).
• Common cold. Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may reduce the severity and duration of cold symptoms and improve sleep quality in adults with the common cold. Details: Some clinical research in adults with the common cold shows that taking Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily reduces symptoms of the common cold and increases the rate of complete resolution after 10 days of treatment, but not after 5 days of treatment, when compared with placebo (81569,94580). The same product taken at a higher dose of 3 mL three times daily reduces cold symptoms by an additional 10% and has a higher rate of complete resolution after 5 days of treatment. However, this dose is associated with a higher rate of mild to moderate adverse effects (97318). Additionally, a small uncontrolled study shows that this extract is equally effective for reducing common cold symptoms in patients testing positive for human coronavirus infection (not including COVID-19) when compared with other viruses (106648). Meta-analyses have evaluated the effects of this specific extract in adults with the common cold. One meta-analysis of 5 studies, some unpublished, using Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals)extract 1.5-3 mL three times daily, or tablets 20-40 mg three times daily, for 10 days shows that the mean reduction in a subjective, 40-point, total cold intensity score is 2.3 points at 5 days and 1.2 points at 10 days. Although it is unclear if these decreases are clinically significant, the extract was associated with fewer lost work days, lower acetaminophen consumption, and improved sleep quality when compared with placebo (103604). A separate meta-analysis of five small-to-moderate size studies, some of which were included in the previous meta-analysis, shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in the same formulations and doses reduces cough intensity and increases remission of cough at day 5 when compared with placebo (110015). However, all outcomes in this meta-analysis were patient-reported. Lastly, a network meta-analysis comparing 18 herbal medicines often used for the common cold suggests that Pelargonium sidoides is the most beneficial of those studied for the relief of symptoms associated with the common cold (112122). However, it is unclear whether any improvements in cold symptoms are clinically significant.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if oral Pelargonium sidoides extract is beneficial in children with asthma who have an active viral upper respiratory tract infection. Details: One small clinical study in children with mild asthma and an active viral upper respiratory tract infection shows that taking 5-10 drops of a specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) three times daily for 5 days reduces the number of children experiencing asthma attacks by 28% when compared with no treatment. It also reduces the number of children experiencing nasal symptoms by 34% and cough by 31% when compared with no treatment (94577).
• Genital herpes. Although there has been interest in using oral Pelargonium sidoides for genital herpes, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Herpes labialis (cold sores). Although there has been interest in using oral Pelargonium sidoides for herpes labialis, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Rhinosinusitis. Small clinical studies suggest that oral Pelargonium sidoides root extract may improve symptoms in adults with rhinosinusitis. Details: One small clinical study in adults with rhinosinusitis of unclear etiology shows that taking Pelargonium sidoides root extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60 drops three times daily for 21 days reduces symptoms of rhinosinusitis and increases the chance of complete resolution after treatment by 57% when compared with placebo (94580). Additionally, a small open-label study in adults with acute bacterial rhinosinusitus shows that taking this same product in tablet form as 60 mg daily for 10 days reduces the total symptom score, as well as subjective measures of nasal obstruction, facial pain and pressure, impaired sense of smell, mucosal edema, and mucopurulent secretions, when compared with taking amoxicillin 1500 mg daily for 10 days (103605). Additionally, a network meta-analysis comparing 18 herbal medicines often used for acute post-viral rhinosinusitis suggests that Pelargonium sidoides is the most beneficial after cineole for the relief of symptoms (112122).
• Tonsillopharyngitis. It is unclear if oral Pelargonium sidoides extract is beneficial in children with tonsillopharyngitis. Details: A small clinical study in children aged 6-10 years with acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 7 days reduces symptoms such as sore throat and difficulty swallowing after 4 days of treatment when compared with placebo (14262). A meta-analysis of 6 clinical trials in children aged 6-10 years old with acute tonsillopharyngitis or acute bronchitis, including the study mentioned above, shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60-240 drops daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126).
• Upper respiratory tract infection (URTI). A small clinical study suggests that oral Pelargonium sidoides root extract may improve symptoms in children with URTIs. Details: One clinical trial in children with uncomplicated URTIs shows that taking a specific Pelargonium sidoides root extract (Pelumm) three times daily for 7 days reduces total symptom scores when compared with placebo, with cough frequency and sneezing improving significantly within 3 days of treatment. The extract dose was based on patient age, with children 1-5 years of age taking 10 drops three times daily, children 5-12 years of age taking 20 drops three times daily, and children 13 years of age taking 30 drops three times daily (106646). More evidence is needed to rate Pelargonium sidoides for these uses.

(Read more about PELARGONIUM SIDOIDES)

LIKELY SAFE ...when used orally in the amounts typically found in foods. Elderberry has generally recognized as safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when elderberry fruit extract is used orally, short-term. One specific elderberry fruit extract (Sambucol, Nature's Way) has been used with apparent safety for up to 5 days (5260,12235,103831); another (BerryPharma, Iprona AG) has been used with apparent safety for up to 15 days (91374). A specific elderberry fruit extract lozenge (ViraBLOC, HerbalScience) has been used with apparent safety for 2 days (17022). Other elderberry fruit extracts have been used with apparent safety for up to 12 weeks (21141,21142).

POSSIBLY UNSAFE ...when elder tree leaves and stems, or unripe or uncooked elderberries, are consumed. The unripe green fruit, as well as the leaves and stems of the elder tree, contain a cyanide-producing chemical, which can cause serious toxicity (17020,17021,21143,21144,91374). Cooking eliminates the toxin.

CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.

CHILDREN: POSSIBLY SAFE
when used orally for up to 3 days. A specific fruit extract (Sambucol, Nature's Way) has been used in doses of 15 mL twice daily for 3 days in children 5 years and older (5260,103831).

CHILDREN: POSSIBLY UNSAFE
when unripe or uncooked elderberries are consumed. The unripe green fruit, as well as the leaves and stems of the elder tree, contain a cyanide-producing chemical , which can cause serious toxicity (17020,17021,21143,21144,91374). Cooking eliminates the toxin.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods. There is insufficient reliable information available about the safety of elderberry when used for medicinal purposes; avoid using in amounts greater than those found in foods.

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LIKELY SAFE ...when used orally or appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals), in doses of 4.5-9 mL daily when administered as a solution or 90 mg daily when administered as a tablet, has been safely used for up to 24 weeks (14258,16641,16647,16649,16651,17417,81557,81565,94580,97318)(97319,106647). There is insufficient reliable information available about the safety of Pelargonium sidoides when used orally, long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in doses of 3 mL daily has been used with apparent safety in children aged 6-10 years for up to 7 days (14262,16641,16651,17417,94580).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, elderberry might interfere with immunosuppressant therapy due to its immunostimulant activity.  Details Elderberry has immunostimulant activity, increasing the production of cytokines, including interleukin and tumor necrosis factor (10796).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Pelargonium sidoides might increase the risk of bleeding when taken with anticoagulant and antiplatelet drugs.  Details Pelargonium sidoides contains coumarin, which may reduce platelet aggregation (14259). However, in animal models, Pelargonium sidoides extract does not appear to inhibit coagulation or interact with warfarin (16648). This interaction has not been documented in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Pelargonium sidoides might decrease the effectiveness of immunosuppressant therapy.  Details In vitro research suggests that Pelargonium sidoides has immunostimulant effects (14258,14259,16646,16650,16652).

(Read more about PELARGONIUM SIDOIDES)

General ...Orally, elderberry extracts prepared from ripe fruit seem to be well tolerated.
Most Common Adverse Effects:
Orally: When adverse effects occur, they are likely due to ingestion of raw and unripe elderberries, or seeds, leaves, and other plant parts. Due to cyanogenic glycosides, these may cause nausea, vomiting, severe diarrhea, weakness, dizziness, numbness, and stupor. Cooking eliminates the toxin.

Gastrointestinal ...Orally, nausea and vomiting have been reported after consuming a specific elderberry and echinacea product Vogel Bioforce AG) (95650). However, it is unclear if this was due to the elderberry or Echinacea contained in the product.
Raw and unripe elderberries, and the seeds, leaves, and other elder tree parts might cause nausea, vomiting, or severe diarrhea due to cyanogenic glycosides (17020,17021). Cooking eliminates the toxin.

Hepatic ...In one case report, a 60-year-old female with underlying autoimmune disease presented with autoimmune hepatitis after taking elderberry at an unknown dose for several years. The patient presented with nausea, jaundice, abdominal pain, and abdominal distention. Liver function tests returned to baseline 4 weeks after initiating treatment with prednisone 40 mg daily and discontinuing elderberry (110123).

Immunologic ...Elder tree pollen might cause an allergic reaction characterized by rhinitis and dyspnea in some patients who are allergic to grass pollen. These patients might also experience an allergic reaction to elderberry extracts (11095).

Neurologic/CNS ...Raw and unripe elderberries might cause weakness, dizziness, numbness, and stupor due to cyanogenic glycosides (17020,17021). Cooking eliminates the toxin.

(Read more about ELDERBERRY)

General ...Orally, Pelargonium sidoides is generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin rash, diarrhea, gastrointestinal upset.

Cardiovascular ...Orally, Pelargonium sidoides has been reported to cause small increases in body temperature and pulse during clinical trials (16649,17417).

Dermatologic ...Orally, Pelargonium sidoides has been associated with allergic skin rash (14262,81557).

Gastrointestinal ...Orally, Pelargonium sidoides has been associated with gastrointestinal upset and diarrhea (14262,81557,97318,97319,106647,112123).

Hematologic ...Orally, Pelargonium sidoides has been associated with epistaxis in one clinical trial (97318).

Hepatic ...Orally, Pelargonium sidoides does not appear to cause hepatotoxicity. Evaluations of hepatotoxicity cases in patients taking Pelargonium sidoides show it was only possibly associated in 4 of the 28 reported cases. In the remaining 24 cases, Pelargonium sidoides was unlikely to be the cause of hepatotoxicity, or was excluded as the cause. Other causes of hepatotoxicity in these cases included infectious disease, pre-existing liver disease, acute pancreatitis, and hepatotoxicity due to conventional medication use (94578,94579).

Immunologic ...Orally, Pelargonium sidoides has been associated with over 34 reports of allergic reactions (81567). Urticaria is the most common reaction but there were also cases of conjunctivitis, rhinitis, and systemic allergic reactions including bronchospasm, dyspnea, tachycardia, and circulatory failure (16651,81567).

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