Insulin Degludec (Monograph)

Brand names: Tresiba, Xultophy (combination)
Drug class: Long-acting Insulins
Chemical name: 29B-[N6-[N-(15-carboxy-1-oxopentadecyl)-l-γ-glutamyl]-l-lysine]-(1A-21A) (1B-29B)-Insulin (human)
Molecular formula: C₂₇₄H₄₁₁N₆₅O₈₁S₆
CAS number: 844439-96-9

Medically reviewed by Drugs.com on Nov 8, 2023. Written by ASHP.

Introduction

Antidiabetic agent; long-acting human insulin analog synthesized using recombinant DNA technology in Saccharomyces cerevisiae, then chemically modified.^{1 32}

Uses for Insulin Degludec

Diabetes Mellitus

Treatment of type 1 or type 2 diabetes mellitus in adults and children ≥1 year of age who require long-acting insulin for control of hyperglycemia.^{1 2 3 4 5 6 7 8 9 10 20 35}

Not indicated for the treatment of diabetic ketoacidosis; short-acting IV insulins (e.g., regular insulin) are preferred.^{1 31}

At least as effective for glycemic control as insulin detemir and insulin glargine and more effective than the oral antidiabetic agent, sitagliptin.^{1 2 3 4 5 6 7 8 9 10 20}

Prolonged duration of action and even distribution of insulin degludec contribute to lower rates of hypoglycemia (particularly nocturnal hypoglycemia) observed for insulin degludec during some clinical trials, compared with other basal insulins, and allow for the timing of a once-daily injection to be varied from day to day, without negatively impacting glycemic control or increasing the risk of hypoglycemia.^{1 2 3 5 9 12 14 18 19 21}

May be a more suitable option than other basal insulins (i.e., insulin detemir or insulin glargine) in individuals who are prone to hypoglycemia, as well as in patients who currently require a basal insulin twice daily for adequate glycemic control.¹⁵

Peakless pharmacokinetic profile and long duration of action of insulin degludec may help improve glycemic control in patients who experience variability in blood glucose-lowering effect with other basal insulins.^{16 21}

Used in fixed combination with liraglutide (Xultophy) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.^{36 38 39 40}

The fixed combination of insulin degludec and liraglutide is not recommended as a first-line agent due to uncertain relevance to humans of rodent thyroid C-cell tumor findings in patients receiving liraglutide.³⁶ Safety and efficacy of the fixed combination of insulin degludec and liraglutide not established in patients with a history of pancreatitis; consider other antidiabetic agents in such patients.³⁶

Related/similar drugs

metformin, Trulicity, Lantus, Tresiba, Victoza, Levemir, Basaglar

Insulin Degludec Dosage and Administration

Administration

Administer insulin degludec or the fixed combination of insulin degludec and liraglutide once daily by sub-Q injection; do not administer IV or IM or via insulin infusion pump.^{1 36}

Do not mix insulin degludec or the fixed combination of insulin degludec and liraglutide with any other insulins or solutions.^{1 36}

May administer insulin degludec at any time of day in adults without regard to meals.^{1 20} Administer insulin degludec at the same time each day in pediatric patients.³⁶

Administer the fixed combination of insulin degludec and liraglutide at the same time each day without regard to meals; do not administer the fixed combination more often than once daily.³⁶

Insulin degludec 100- and 200-units/mL formulations are pharmacodynamically and pharmacokinetically bioequivalent; do not perform dose conversions between the 100- and 200-units/mL FlexTouch injection pens based on differences in insulin concentration.^{1 6} The dose window on these injection pens displays the number of insulin degludec units to be delivered independent of insulin concentration; no conversion is needed to calculate the dose using either injection pen.^{1 6}

For missed dose of insulin degludec in adults: administer dose during waking hours as soon as remembered if ≥8 hours has elapsed since last dose.¹

For missed dose of insulin degludec/liraglutide fixed combination in adults: resume regular once-daily regimen with next scheduled dose; do not take extra dose or increase dose to make up for missed dose.³⁶

For missed dose of insulin degludec in pediatric patients: consult clinician for guidance about dosing and monitoring blood glucose concentrations until next scheduled dose.¹

Sub-Q Administration

Administer insulin degludec or the fixed combination of insulin degludec and liraglutide by sub-Q injection once daily using the FlexTouch or Xultophy injection pen, respectively.^{1 36} Use with NovoFine or NovoTwist needles.^{1 36}

Consult accompanying labeling for instructions on proper assembly, administration, and care of injection pens and devices.^{1 36}

Administer insulin degludec or the fixed combination of insulin degludec and liraglutide into thigh, abdomen, or upper arm.^{1 36} Follow a planned rotation of injection sites within an injection area to reduce risk of lipodystrophy.¹

Dosage

Dosage of insulin degludec is expressed in terms of units.¹

Each mL of insulin degludec injection contains 100 or 200 units of insulin degludec.¹

Each mL of the fixed combination of insulin degludec and liraglutide contains 100 units of insulin degludec and 3.6 mg of liraglutide.³⁶

Individualize dosage based on the patient's metabolic needs, blood glucose determinations, and glycemic control goals to obtain optimum therapeutic effect.^{1 36} Glucose monitoring is recommended for all patients with diabetes mellitus.¹

Dosage of insulin degludec may be increased every 3–4 days as needed.¹

Dosage of insulin degludec in fixed combination with liraglutide may be increased or decreased by 2 units (2 units of insulin degludec and 0.072 mg of liraglutide) every 3–4 days as needed.³⁶ Maximum dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide) once daily.³⁶

Dosage adjustments may be needed with intercurrent conditions (e.g., illness, stress, emotional disturbances), concomitant drugs, changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in weight, or changes in renal or hepatic function.^{1 36}

Pediatric Patients

Diabetes Mellitus

Not recommended for pediatric patients requiring <5 units of insulin degludec daily.^{1 32}

Long duration of action; use alone as a basal insulin or concomitantly with a shorter-acting (“bolus”) insulin (e.g., insulin aspart, insulin human) to provide more optimal postprandial glycemic control.^{1 14 19}

Insulin Degludec Therapy in Insulin-naive Patients

Sub-Q

Children ≥1 year of age, type 1 diabetes mellitus: Initially, one-third to one-half the total daily insulin dosage (generally total daily insulin dosage is 0.2–0.4 units/kg); give remainder of total daily dosage in equally divided doses preprandially as a short- or rapid-acting insulin.¹

Children ≥1 year of age, type 2 diabetes mellitus: Initially, 10 units once daily.¹

Transferring from Other Insulins to Insulin Degludec

Sub-Q

Children ≥1 year of age, type 1 or type 2 diabetes mellitus: Initiate insulin degludec at 80% of the total daily long- or intermediate-acting insulin dosage.¹

Adults

Diabetes Mellitus

Long duration of action; use alone as a basal insulin or concomitantly with a shorter-acting (“bolus”) insulin (e.g., insulin aspart, insulin human) to provide more optimal postprandial glycemic control.^{1 14 19}

Insulin Degludec Therapy in Insulin-naive Patients

Sub-Q

Type 1 diabetes mellitus: Initially, one-third to one-half the total daily insulin dosage (generally, total daily insulin dosage is 0.2–0.4 units/kg); give remainder of total daily dosage in divided doses preprandially as a short- or rapid-acting insulin.¹

Type 2 diabetes mellitus: Initially, 10 units once daily.¹

Transferring from Other Insulins to Insulin Degludec

Sub-Q

Type 1 and Type 2 diabetes mellitus: Initiate insulin degludec at same dosage as the total daily long- or intermediate-acting insulin dosage.¹

Insulin Degludec/Liraglutide Fixed-combination Therapy

Sub-Q

Type 2 diabetes mellitus (naive to basal insulin or a GLP-1 receptor agonist): Initially, 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) once daily.³⁶

Type 2 diabetes mellitus (currently receiving basal insulin or a GLP-1 receptor agonist): Initially, 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) once daily.³⁶ Discontinue basal insulin or GLP-1 receptor agonist prior to initiating fixed combination of insulin degludec and liraglutide.³⁶

May increase or decrease dosage of the fixed combination of insulin degludec and liraglutide by 2 units (2 units of insulin degludec and 0.072 mg of liraglutide) every 3–4 days as needed.³⁶ May be increased to a maximum daily dosage of 50 units (50 units of insulin degludec and 1.8 mg of liraglutide).³⁶

Insulin Degludec/Liraglutide Fixed-combination Therapy

Sub-Q

Type 2 diabetes mellitus (naive to basal insulin or a GLP-1 receptor agonist): Initially, 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) once daily.³⁶

Type 2 diabetes mellitus (currently receiving basal insulin or a GLP-1 receptor agonist): Initially, 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) once daily.³⁶ Discontinue basal insulin or GLP-1 receptor agonist prior to initiating fixed combination of insulin degludec and liraglutide.³⁶

May increase or decrease dosage of the fixed combination of insulin degludec and liraglutide by 2 units (2 units of insulin degludec and 0.072 mg of liraglutide) every 3–4 days as needed.³⁶ May be increased to a maximum daily dosage of 50 units (50 units of insulin degludec and 1.8 mg of liraglutide).³⁶

Special Populations

Hepatic Impairment

Insulin degludec or the fixed combination of insulin degludec and liraglutide: Dosage adjustments may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary.^{1 27 36}

Renal Impairment

Insulin degludec or the fixed combination of insulin degludec and liraglutide: Dosage adjustments may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary.^{1 26 36}

Geriatric Patients

Insulin degludec or the fixed combination of insulin degludec and liraglutide: Conservative initial dosage, dose increments, and maintenance dosage recommended to avoid hypoglycemia.^{1 36} (See Geriatric Use under Cautions.)

Cautions for Insulin Degludec

Contraindications

• Known hypersensitivity to insulin degludec or any ingredient in the formulation.^{1 36}

• During hypoglycemic episodes.^{1 36}

• Fixed combination of insulin degludec and liraglutide: Contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia type 2 (MEN 2).³⁶

Warnings/Precautions

Use of Fixed Combinations

When insulin degludec is used in fixed combination with liraglutide or other drugs, consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s) in addition to those associated with insulin degludec.³⁶

Hypoglycemia

Most common adverse effect of insulins, including insulin degludec.^{1 36} Blood glucose concentration monitoring recommended for all diabetic patients.¹ Time course of glucose-lowering effect of insulin degludec may vary among different individuals or at different times in the same individual and depends on many conditions, including area of injection and injection site blood supply and temperature.^{1 36} The risk of hypoglycemia generally increases with the intensity of glycemic control.^{1 36} Changes in meal patterns, level of physical activity, or concomitant drug therapy also may increase risk of hypoglycemia.^{1 36} Patients with renal or hepatic impairment may be at higher risk of hypoglycemia.^{1 36} (See Renal Impairment and also see Hepatic Impairment under Dosage and Administration.)

Early warning signs of hypoglycemia may be diminished or absent in patients with long-standing diabetes mellitus, diabetic neuropathy, and/or those receiving drugs such as β-adrenergic blocking agents that mask catecholamine-induced manifestations of hypoglycemia.¹ Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.¹

Some evidence suggests that insulin degludec may be associated with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, than insulin glargine and insulin detemir.^{2 3 5 9 12 14 18 19 21}

Hypoglycemia due to Medication Errors

Confusion between basal insulin preparations and other insulins, particularly rapid-acting insulins, has caused medication errors.¹

Patients should check labels on all insulin preparations to confirm the correct formulation and strength prior to administration.^{1 36}

Do not transfer insulin degludec from the FlexTouch injection pen into an insulin syringe; markings on the insulin syringe will not measure the dose correctly and overdosage can occur.¹

Formulation Considerations

Make any dosage change cautiously and only under medical supervision.^{1 19 36} Changes in insulin type, manufacturer, and/or method of administration may predispose patients to hypoglycemia or hyperglycemia; increase frequency of blood glucose monitoring.¹

Adjustments to the dosage and timing of concurrent short- or rapid-acting insulin or other glucose-lowering treatments (e.g., oral antidiabetic agents) may be required.^{1 19 36}

Sharing of Injections Pens

Caution patients not to share injection pens containing insulin degludec or the fixed combination of insulin degludec and liraglutide, even if the needle has been changed; sharing poses a risk for transmission of blood-borne pathogens.^{1 36}

Hypokalemia

All insulin preparations cause a shift in potassium from the extracellular to intracellular space; may cause hypokalemia.^{1 36} Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death.^{1 36}

Monitor serum potassium concentrations in patients at risk for hypokalemia (e.g., patients receiving potassium-lowering drugs, patients taking drugs with effects sensitive to serum potassium concentrations).^{1 36}

Metabolic Effects

Insulin therapy may cause sodium retention and edema.^{1 36} Insulin therapy, including insulin degludec, also may cause weight gain attributable to the anabolic effects of insulin.¹

Heart Failure

Peroxisome proliferator-activated receptor (PPAR)-γ agonists (e.g., thiazolidinediones) can cause dose related fluid retention, particularly when used in combination with insulin.^{1 23 24 36}

Observe patients receiving insulin degludec or the fixed combination of insulin degludec and liraglutide and a PPAR-γ agonist for manifestations of heart failure (e.g., excessive/rapid weight gain, shortness of breath, edema); discontinue or reduce dosage of PPAR-γ agonist if heart failure develops.^{1 23 36}

Concomitant use of rosiglitazone and insulin therapy not recommended.²⁴

Immunogenicity

Potential risk of immunogenicity.^{1 36} Anti-insulin antibodies detected in patients receiving insulin degludec during clinical trials, including in some patients who had anti-insulin antibodies at baseline.¹ Presence of antibodies that affect clinical efficacy may necessitate dosage adjustments to correct for tendencies toward hyperglycemia or hypoglycemia.¹ Incidence of anti-insulin degludec antibodies not established.¹

Antiliraglutide antibodies found in patients who received the fixed combination of insulin degludec and liraglutide; antibody formation not associated with reduced efficacy of the fixed combination.³⁶

Sensitivity Reactions

Dermatologic and Hypersensitivity Reactions

Lipodystrophy may occur at sites of insulin injections and may affect insulin absorption.^{1 36} Injection site rotation may reduce the risk of lipodystrophy.¹

Localized allergic reactions (e.g., pruritus, erythema, swelling) at the injection site may occur.^{1 36} Pain,^{1 36} hematoma,^{1 36} hemorrhage,^{1 36} discoloration,^{1 36} warmth,^{1 36} injection site mass,^{1 36} and nodules at the injection site reported.^{1 36}

Severe, life-threatening, generalized allergic reactions, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock, may occur.^{1 36} If hypersensitivity reactions occur, discontinue therapy and initiate appropriate treatment.^{1 36}

Specific Populations

Pregnancy

No adequate and well-controlled studies of insulin degludec in pregnant women.¹ Visceral and skeletal abnormalities observed in offspring of rats and rabbits during animal reproduction studies at maternal plasma concentrations 5–10 times higher than those achieved with a subcutaneous human dosage of 0.75 units/kg per day.^{1 20} Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.¹

Data lacking on use of the fixed combination of insulin degludec and liraglutide in pregnant women.³⁶ Animal studies suggest risk to the fetus from exposure to liraglutide during pregnancy.³⁶ Use the fixed combination of insulin degludec and liraglutide during pregnancy only if potential benefit justifies potential risk to fetus.³⁶

Lactation

Insulin degludec distributed into milk in rats; not known whether distributed into human milk.¹ Use caution in nursing women.¹

Pediatric Use

Safety and efficacy of insulin degludec not established in pediatric patients <1 year of age.¹ Insulin degludec not recommended for pediatric patients who require <5 units of insulin degludec daily.^{1 32}

Safety and efficacy of the fixed combination of insulin degludec and liraglutide not established in pediatric patients.³⁶

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults, but increased sensitivity cannot be ruled out.^{1 36} Hypoglycemia may be difficult to recognize in geriatric patients.^{1 36} (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Insulin degludec: No clinically relevant difference in the pharmacokinetic parameters of renally impaired patients compared with healthy individuals.^{1 25 26} Monitor blood glucose concentrations closely; dosage adjustment may be necessary.¹ (See Renal Impairment under Dosage and Administration)

Fixed combination of insulin degludec and liraglutide: Experience in patients with mild, moderate, or severe renal impairment is limited; use with caution.³⁶

Hepatic Impairment

Insulin degludec: No clinically relevant difference in the pharmacokinetic parameters of hepatically impaired patients compared with healthy individuals.^{1 25 27} Monitor blood glucose concentrations closely; dosage adjustment may be necessary.¹ (See Hepatic Impairment under Dosage and Administration.)

Fixed combination of insulin degludec and liraglutide: Experience in patients with mild, moderate, or severe hepatic impairment is lacking.³⁶

Common Adverse Effects

Insulin degludec: Hypoglycemia,^{1 2 3 14} allergic reactions,¹ injection site reactions,^{1 3 14} lipodystrophy,¹ pruritus,¹ rash,¹ edema,¹ weight gain,^{1 2 3} nasopharyngitis,^{1 14} headache,^{1 14} upper respiratory tract infection,^{1 14} sinusitis,¹ gastroenteritis,¹ diarrhea.^{1 14}

Fixed combination of insulin degludec and liraglutide: Nasopharyngitis,^{36 38} headache,^{36 38} nausea,³⁶ diarrhea,^{36 38} increased lipase concentrations,^{36 38} upper respiratory tract infection.^{36 38}

Drug Interactions

Specific Drugs

Many drugs affect glucose metabolism; if such drugs are used concomitantly, may require insulin dosage adjustment and careful monitoring.¹

Insulin Degludec Pharmacokinetics

Absorption

Bioavailability

Following sub-Q injection, absorption of insulin degludec is slower and more prolonged than insulin detemir and insulin glargine.¹⁸

Lipodystrophy at the injection site may affect absorption.¹

Steady-state concentrations achieved after 3–4 days of insulin degludec administration.¹

Onset

30–90 minutes following sub-Q injection.¹⁸

Interindividual and intraindividual variation may occur; may depend on conditions such as area of injection, blood supply, and temperature of injection site.¹

Duration

>42 hours.^{18 19} Glucose-lowering effect evenly distributed across 24-hour dosing interval.^{19 25}

Distribution

Extent

Not known whether insulin degludec is distributed into milk.¹

Plasma Protein Binding

>99%.^{1 14}

Elimination

Half-life

25 hours; independent of dose.^{1 14 18 19}

Stability

Storage

Parenteral

Injection

Unopened insulin degludec FlexTouch injection pens: 2–8°C.¹ Alternatively, may keep at room temperature (<30°C) for ≤56 days.¹ Do not freeze; discard if freezing occurs.¹

Unopened injection pens containing fixed combination of insulin degludec and liraglutide (Xultophy): 2–8°C; do not freeze.³⁶

Opened (in-use) FlexTouch injection pens: 2 to <30°C for ≤56 days.¹ Protect from direct heat and light.¹

Opened (in-use) injection pens containing the fixed combination of insulin degludec and liraglutide (Xultophy): 2–8°C or 15–30°C for ≤21 days.³⁶

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not mix with any other insulin or solutions.^{1 36}

Actions

• Pharmacologic effects comparable to those of insulin human; stimulates peripheral glucose uptake by tissues (e.g., skeletal muscle, fat), inhibits hepatic glucose production, inhibits lipolysis and proteolysis, and enhances protein synthesis.^{1 21}

• Longer duration of action than insulin detemir and insulin glargine; associated with less pharmacokinetic and pharmacodynamic variability than other basal insulins.^{3 14 18 25}

Advice to Patients

• When insulin degludec is used in fixed combination with other drugs, importance of informing patients of important cautionary information about the concomitant agents.^{1 36}

• Importance of providing patient a copy of manufacturer’s patient information.^{1 36} Importance of advising patient to read the manufacturer's medication guide before beginning treatment with insulin degludec in fixed combination with liraglutide each time the prescription is refilled.^{36 41}

• Importance of instructing patients not to administer the fixed combination of insulin degludec and liraglutide concurrently with other GLP-1 receptor agonists.³⁶ Importance of advising patients that dosages of insulin degludec exceeding 50 units daily given as the fixed combination with liraglutide can result in an overdose of the liraglutide component.³⁶

• Importance of informing patients that serious hypersensitivity reactions have been reported with insulin degludec or the fixed combination of insulin degludec and liraglutide; importance of instructing patients to stop taking insulin degludec or the fixed combination and seek prompt medical attention if such adverse reactions occur.^{1 36}

• Importance of advising patients to refer to patient information for additional information about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia.¹

• Importance of informing patients that they should never share an injection pen containing insulin degludec or the fixed combination of insulin degludec and liraglutide with another person, even if the needle is changed; sharing of the pen may pose a risk of transmission of infection.^{1 36}

• Importance of informing patients that hypoglycemia is the most common adverse effect of insulins.^{1 36} Importance of informing patients of the symptoms of hypoglycemia; the ability to concentrate and react may be impaired as a result of hypoglycemia, which may pose a risk in situations where these abilities are especially important (e.g., driving, operating machinery).^{1 36} Importance of advising patients who experience frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.^{1 36}

• Importance of advising patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia.^{1 36} Importance of changing insulin dosage with caution and only under medical supervision.^{1 36}

• Discuss potential for alterations in insulin requirements in special situations (e.g., illness, emotional disturbances, other stresses).¹ Discuss potential for alterations in insulin requirements as a result of inadequate or skipped doses, or inadvertent administration of an incorrect dose.¹

• Importance of advising patients regarding what to do in the event of missed or delayed doses of insulin degludec alone or in fixed combination with liraglutide.^{1 36} (See Administration under Dosage and Administration.)

• Importance of not mixing insulin degludec or the fixed combination of insulin degludec and liraglutide with other insulins or solutions.^{1 36} Importance of using insulin degludec or the fixed combination of insulin degludec and liraglutide only if the solution is clear and colorless with no visible particles.^{1 36}

• Importance of informing patients to always check the insulin label prior to each injection;^{1 36} insulin degludec is available in concentrations of 100 and 200 units/mL.¹ Importance of informing patients that the dose window of the insulin degludec FlexTouch injection pen displays the number of units to be injected independent of insulin concentration; no recalculation of the dose is required to convert between different concentrations of insulin degludec.¹

• Importance of informing patients that the dose window of the injection pen containing the fixed combination of insulin degludec and liraglutide shows the number of units of insulin degludec to be injected; with each unit of insulin degludec, the pen also delivers 0.036 mg of liraglutide.³⁶

• Provide instructions regarding self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia.¹

• Provide instructions to patient regarding use of the subcutaneous injection devices containing insulin degludec or the fixed combination of insulin degludec and liraglutide.^{1 36} Patients should be cautioned against reuse of needles.¹ Importance of advising patients to never use a syringe to remove insulin degludec from the FlexTouch injection pen.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 36}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 36}

• Importance of informing patients of other important precautionary information.^{1 36} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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