Zicam

Contraindications

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What is the most important information I should know about Zicam?

Known hypersensitivity to Zicam or any excipient of Zicam. There is a potential for cross-sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs).

Zicam should not be given to patients who have developed signs of asthma, nasal polyps, angio-oedema or urticaria following the administration of acetylsalicylic acid or other NSAIDs. Treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Active or recent gastrointestinal ulceration or perforation. Active inflammatory bowel disease (Crohn's disease or ulcerative colitis).

Severe hepatic insufficiency. Nondialysed severe renal insufficiency.

Overt gastrointestinal bleeding, recent cerebrovascular bleeding or established systemic bleeding disorders.

Severe uncontrolled heart failure.

In case of rare hereditary conditions that may be incompatible with an excipients of Zicam.

Use in pregnancy & lactation: Zicam is contraindicated during pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo-foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastrochisis after use of a prostaglandin-synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from <1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In preclinical studies, administration of a prostaglandin-synthesis inhibitor has been shown to result in increase pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in preclinical studies given a prostaglandin-synthesis inhibitor during the organogenetic period.

During the 3rd trimester of pregnancy, all prostaglandin-synthesis inhibitors may expose the foetus to: Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligo-hydramniosis; the mother and the neonate, at the end of pregnancy, to possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.

While no specific experience exists for Zicam, NSAIDs are known to pass into mother's milk.

Administration therefore is contraindicated in women who are breastfeeding.

Undesirable effects

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What are the possible side effects of Zicam?

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events
• GI Bleeding, Ulceration, and Perforation
• Hepatotoxicity
• Hypertension
• Heart Failure and Edema
• Renal Toxicity and Hyperkalemia
• Anaphylactic Reactions
• Serious Skin Reactions
• Hematologic Toxicity

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The Zicam Phase 2/3 clinical trial database includes 10,122 OA patients and 1012 RA patients treated with Zicam 7.5 mg/day, 3505 OA patients and 1351 RA patients treated with Zicam 15 mg/day. Zicam at these doses was administered to 661 patients for at least 6 months and to 312 patients for at least one year. Approximately 10,500 of these patients were treated in ten placebo- and/or activecontrolled osteoarthritis trials and 2363 of these patients were treated in ten placebo- and/or activecontrolled rheumatoid arthritis trials. Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across Zicam trials.

A 12-week multicenter, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of Zicam with placebo and with an active control. Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of Zicam with placebo.

Table 1a depicts adverse events that occurred in ≥ 2% of the Zicam treatment groups in a 12-week placebo- and active-controlled osteoarthritis trial.

Table 1b depicts adverse events that occurred in ≥ 2% of the Zicam treatment groups in two 12-week placebo-controlled rheumatoid arthritis trials.

Table 1a : Adverse Events (%) Occurring in ≥ 2% of Zicam Patients in a 12-Week Osteoarthritis Placebo- and Active-Controlled Trial

Higher doses of Zicam (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore, the daily dose of Zicam should not exceed 15 mg.

Three hundred and eighty-seven patients with pauciarticular and polyarticular course JRA were exposed to Zicam with doses ranging from 0.125 to 0.375 mg/kg per day in three clinical trials. These studies consisted of two 12-week multicenter, double-blind, randomized trials (one with a 12-week open-label extension and one with a 40-week extension) and one 1-year open-label PK study. The adverse events observed in these pediatric studies with Zicam were similar in nature to the adult clinical trial experience, although there were differences in frequency. In particular, the following most common adverse events, abdominal pain, vomiting, diarrhea, headache, and pyrexia, were more common in the pediatric than in the adult trials. Rash was reported in seven ( < 2%) patients receiving Zicam. No unexpected adverse events were identified during the course of the trials. The adverse events did not demonstrate an age or gender-specific subgroup effect.

The following is a list of adverse drug reactions occurring in < 2% of patients receiving Zicam in clinical trials involving approximately 16,200 patients.

The following adverse reactions have been identified during post approval use of Zicam. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions about whether to include an adverse event from spontaneous reports in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) number of reports, or (3) strength of causal relationship to the drug. Adverse reactions reported in worldwide post marketing experience or the literature include: acute urinary retention; agranulocytosis; alterations in mood (such as mood elevation); anaphylactoid reactions including shock; erythema multiforme; exfoliative dermatitis; interstitial nephritis; jaundice; liver failure; Stevens-Johnson syndrome; toxic epidermal necrolysis, and infertility female.

Therapeutic indications

Zicam is indicated for relief of the signs and symptoms of osteoarthritis in adults.

Zicam is indicated for relief of the signs and symptoms of rheumatoid arthritis in adults.

Zicam is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in pediatric patients who weigh greater than or equal to 60 kg.

Zicam (Zicam) is a nonsteroidal anti-inflammatory drug (NSAID). Zicam works by reducing hormones that cause inflammation and pain in the body.

Zicam is used to treat pain or inflammation caused by rheumatoid arthritis and osteoarthritis in adults. Zicam is also used to treat juvenile rheumatoid arthritis in children who are at least 2 years old.

Zicam may also be used for purposes not listed in this medication guide.

Name of the medicinal product

Qualitative and quantitative composition

Ratio-Zicam is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve the symptoms of arthritis, primary dysmenorrhea, fever; and as an analgesic, especially where there is an inflammatory component. It is closely related to piroxicam. In Europe it is marketed under the brand names Movalis, Melox, and Recoxa. In North America it is generally marketed under the brand name Zicam. In Latin America, the drug is marketed as Tenaron.

Special warnings and precautions for use

Use Zicam suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Zicam suspension comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Zicam suspension refilled.
• Take Zicam suspension by mouth. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers).
• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.
• Shake gently before each use.
• Take Zicam suspension with a full glass of water (8 oz/240 mL) as directed by your doctor.
• If you take cholestyramine, ask your doctor or pharmacist how to take it with Zicam suspension.
• If you miss a dose of Zicam suspension, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Zicam suspension.

IV:

Pain: Management of moderate to severe pain in adults, alone or in combination with non-nonsteroidal anti-inflammatory drug analgesics.

Limitation of use: Because of delayed onset of analgesia, Zicam (injection) alone is not recommended for use when rapid onset of analgesia is required

Osteoarthritis: Relief of the signs and symptoms of osteoarthritis (OA); management of OA pain.

Rheumatoid arthritis (orally disintegrating tablet [ODT], tablet, and suspension only): Relief of signs and symptoms of rheumatoid arthritis (RA); relief of the signs and symptoms of pauciarticular or polyarticular course juvenile RA in patients ≥2 years of age (suspension) and in patients weighing ≥60 kg (ODT, tablet).

Data from a single-blind, randomized, controlled trial supports the efficacy of Zicam in the treatment of acute gout flares.

Based on the 2012 American College of Rheumatology guidelines for management of gout, NSAIDS are effective and recommended agents in the treatment of acute gout flares.

Dosage (Posology) and method of administration

Carefully consider the potential benefits and risks of Zicam and other treatment options before deciding to use Zicam. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

After observing the response to initial therapy with Zicam, adjust the dose to suit an individual patient's needs.

In adults, the maximum recommended daily oral dose of Zicam is 15 mg regardless of formulation. In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended.

Zicam may be taken without regard to timing of meals.

For the relief of the signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of Zicam is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

For the relief of the signs and symptoms of rheumatoid arthritis, the recommended starting and maintenance oral dose of Zicam is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

For the treatment of juvenile rheumatoid arthritis, the recommended oral dose of Zicam is 7.5 mg once daily in children who weigh ≥ 60 kg. There was no additional benefit demonstrated by increasing the dose above 7.5 mg in clinical trials.

Zicam tablets should not be used in children who weigh < 60 kg.

The use of Zicam in subjects with severe renal impairment is not recommended.

In patients on hemodialysis, the maximum dosage of Zicam is 7.5 mg per day.

Zicam Tablets have not shown equivalent systemic exposure to other approved formulations of oral Zicam. Therefore, Zicam Tablets are not interchangeable with other formulations of oral Zicam product even if the total milligram strength is the same. Do not substitute similar dose strengths of Zicam Tablets with other formulations of oral Zicam product.

• 7.5 mg: pastel yellow, round, biconvex, uncoated tablet containing Zicam 7.5 mg. Impressed with the Boehringer Ingelheim logo on one side and the letter “M” on the other.
• 15 mg: pastel yellow, oblong, biconvex, uncoated tablet containing Zicam 15 mg. Impressed with the tablet code “15” on one side and the letter “M” on the other.

Zicam is available as a pastel yellow, round, biconvex, uncoated tablet containing Zicam 7.5 mg or as a pastel yellow, oblong, biconvex, uncoated tablet containing Zicam 15 mg. The 7.5 mg tablet is impressed with the Boehringer Ingelheim logo on one side, and on the other side, the letter “M”. The 15 mg tablet is impressed with the tablet code “15” on one side and the letter “M” on the other.

Zicam (Zicam) tablets 7.5 mg: NDC 0597-0029-01; Bottles of 100

Zicam (Zicam) tablets 15 mg: NDC 0597-0030-01; Bottles of 100

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Keep Zicam tablets in a dry place.

Dispense tablets in a tight container.

Keep this and all medications out of the reach of children.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA. Revised: May 2016

Interaction with other medicinal products and other forms of interaction

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What other drugs will affect Zicam?

ACE inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

Aspirin

Concomitant administration of aspirin (1000 mg TID) to healthy volunteers tended to increase the AUC (10%) and Cmax (24%) of Zicam. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Zicam and aspirin is not generally recommended because of the potential for increased adverse effects. Concomitant administration of low-dose aspirin with Zicam may result in an increased rate of GI ulceration or other complications, compared to use of Zicam alone. Zicam is not a substitute for aspirin for cardiovascular prophylaxis.

Cholestyramine

Pretreatment for four days with cholestyramine significantly increased the clearance of Zicam by 50%. This resulted in a decrease in t1/2, from 19.2 hours to 12.5 hours, and a 35% reduction in AUC. This suggests the existence of a recirculation pathway for Zicam in the gastrointestinal tract. The clinical relevance of this interaction has not been established.

Cimetidine

Concomitant administration of 200 mg cimetidine QID did not alter the single-dose pharmacokinetics of 30 mg Zicam.

Digoxin

Co Zicam 15 mg once daily for 7 days did not alter the plasma concentration profile of digoxin after b-acetyldigoxin administration for 7 days at clinical doses. In vitro testing found no protein binding drug interaction between digoxin and Zicam.

Furosemide

Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazide diuretics in some patients. This effect has been attributed to inhibition of renal prostaglandin synthesis. Studies with furosemide agents and Zicam have not demonstrated a reduction in natriuretic effect. Furosemide single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of Zicam. Nevertheless, during concomitant therapy with furosemide and Zicam, patients should be observed closely for signs of declining renal function, as well as to assure diuretic efficacy.

Lithium

In clinical trials, NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. In a study conducted in healthy subjects, mean pre-dose lithium concentration and AUC were increased by 21% in subjects receiving lithium doses ranging from 804 to 1072 mg BID with Zicam 15 mg QD as compared to subjects receiving lithium alone. These effects have been attributed to inhibition of renal prostaglandin synthesis by Zicam. Patients on lithium treatment should be closely monitored when Zicam is introduced or withdrawn.

Methotrexate

A study in 13 rheumatoid arthritis (RA) patients evaluated the effects of multiple doses of Zicam on the pharmacokinetics of methotrexate taken once weekly. Co Zicam did not have a significant effect on the pharmacokinetics of single doses of methotrexate. In vitro, methotrexate did not displace Zicam from its human serum binding sites.

Warfarin

Anticoagulant activity should be monitored, particularly in the first few days after initiating or changing Zicam therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding. The effect of Zicam on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of warfarin that produced an INR (International Normalized Ratio) between 1.2 and 1.8. In these subjects, Zicam did not alter warfarin pharmacokinetics and the average anticoagulant effect of warfarin as determined by prothrombin time. However, one subject showed an increase in INR from 1.5 to 2.1. Caution should be used when administering Zicam with warfarin since patients on warfarin may experience changes in INR and an increased risk of bleeding complications when a new medication is introduced.