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Peer-Reviewed Evidence
HomeDrug RegistryCompareDIFLUCAN IN SODIUM CHLORIDE 0 9 IN PLASTIC CONTAINER vs AMINOPHYLLINE IN SODIUM CHLORIDE 0 45
Comparative Pharmacology

DIFLUCAN IN SODIUM CHLORIDE 0 9 IN PLASTIC CONTAINER vs AMINOPHYLLINE IN SODIUM CHLORIDE 0 45 Comparison

Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.

Clinical EssentialsPharmacokineticsSpecial PopulationsSafety & MonitoringPregnancy & LactationClinical Insights
Differential Analysis

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER vs AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.

View DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER Monograph View AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% Monograph
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
Electrolyte
Category A/B
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Electrolyte
Category A/B
TL;DR — Key Differences
  • Half-life: DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER has a half-life of Terminal elimination half-life is approximately 30 hours (range 20–50 hours) in adults; prolonged in renal impairment. In neonates, half-life is longer (up to 90 hours).; AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% has Terminal elimination half-life is 6-12 hours in adults, 1-5 hours in children (due to faster clearance), 20-30 hours in premature neonates, and 10-15 hours in patients with hepatic cirrhosis or heart failure. Clinical context: dosing interval adjustment required based on half-life; prolonged half-life in hepatic impairment or cardiac decompensation increases risk of toxicity..
  • Direct interaction: A moderate interaction exists when combining these agents.
  • Pregnancy: DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER is rated Category A/B; AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% is rated Category A/B.

Last clinically reviewed: July 2026 · OpiCalc Medical Review Team

Clinical Essentials

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Mechanism of Action
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Fluconazole is a triazole antifungal agent that inhibits fungal cytochrome P450 14α-demethylase, thereby blocking the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This disrupts membrane integrity and function.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Aminophylline is a complex of theophylline and ethylenediamine, acting as a phosphodiesterase inhibitor, increasing intracellular c AMP levels; nonselective adenosine receptor antagonist; enhances cardiac inotropy, bronchodilation, and CNS stimulation.

Indications
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Treatment of vaginal candidiasis,Oropharyngeal and esophageal candidiasis,Candidal urinary tract infections, peritonitis, and systemic infections including candidemia, disseminated candidiasis, and pneumonia,Prophylaxis in bone marrow transplant recipients with chemotherapy or radiation therapy,Cryptococcal meningitis and cryptococcosis at other sites

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Treatment of acute bronchospasm in asthma and COPD,Reversal of dipyridamole-induced adverse effects during stress testing,Apnea of prematurity (off-label),Status asthmaticus (off-label)

Standard Dosing
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

400 mg IV on day 1, then 200 mg IV once daily

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Loading dose: 5-6 mg/kg IV over 20-30 minutes, then continuous infusion: 0.5-0.7 mg/kg/hour IV.

Direct Interaction
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
MODERATE Risk
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
MODERATE Risk

Pharmacokinetics

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Half-Life
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Terminal elimination half-life is approximately 30 hours (range 20–50 hours) in adults; prolonged in renal impairment. In neonates, half-life is longer (up to 90 hours).

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Terminal elimination half-life is 6-12 hours in adults, 1-5 hours in children (due to faster clearance), 20-30 hours in premature neonates, and 10-15 hours in patients with hepatic cirrhosis or heart failure. Clinical context: dosing interval adjustment required based on half-life; prolonged half-life in hepatic impairment or cardiac decompensation increases risk of toxicity.

Metabolism
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Fluconazole is primarily metabolized by the liver, with approximately 11% of the dose metabolized; the unchanged drug is the major circulating entity. Hepatic metabolism involves N-oxidation and glucuronidation, but specific CYP enzymes are not significantly involved. It is a moderate inhibitor of CYP2C9 and CYP3A4.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Hepatic via cytochrome P450 enzymes (CYP1A2, CYP3A4, CYP2E1); saturable kinetics; extensive first-pass metabolism.

Excretion
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Primarily renal; approximately 80% of the dose is excreted unchanged in urine. Minor biliary/fecal elimination (<10%).

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Renal excretion of unchanged theophylline (10-20%) and metabolites (80-90%). In neonates, renal excretion of unchanged drug is higher (up to 50%). Biliary/fecal excretion is negligible.

Protein Binding
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Approximately 11–12% bound to plasma proteins (mainly albumin).

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Approximately 40% bound to plasma proteins, mainly albumin. In neonates, preterm infants, and patients with hepatic cirrhosis, protein binding is reduced (free fraction increases). Binding is also saturable at high theophylline concentrations.

VD (L/kg)
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Approximately 0.7 L/kg, indicating extensive distribution into total body water; penetrates well into tissues and CSF.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Volume of distribution is approximately 0.45 L/kg (range 0.3-0.7 L/kg) in adults. In neonates, Vd is larger (~0.6-0.8 L/kg). Clinical meaning: Vd indicates extensive distribution into body water; loading doses are calculated using Vd (e.g., 1 mg/kg raises serum concentration by ~2 mcg/m L).

Bioavailability
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Oral bioavailability is >90% (virtually complete). IV administration is 100%.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Oral immediate-release: 100% (well absorbed). Rectal: 80-100% (absorption may be erratic). IV: 100%. No significant first-pass metabolism.

Special Populations

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Renal Adjustments
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

For Cr Cl 50-90 m L/min: no adjustment; Cr Cl 10-49 m L/min: 50% dose or interval doubling; Cr Cl <10 m L/min (not on dialysis): 50% dose or interval doubling; on hemodialysis: one full dose after each dialysis session

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

No specific dose adjustment required for GFR >10 m L/min. For GFR <10 m L/min, reduce infusion rate by 50%.

Hepatic Adjustments
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

No specific dose adjustment for Child-Pugh A or B; caution in severe hepatic impairment (Child-Pugh C) with monitoring

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Child-Pugh Class A: reduce dose by 25%; Class B: reduce dose by 50%; Class C: reduce dose by 75%.

Pediatric Dosing
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Loading dose: 12 mg/kg IV (max 400 mg) on day 1, then 6 mg/kg IV (max 200 mg) once daily; for weight <40 kg, adjust based on weight using these mg/kg doses

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Loading dose: 5-6 mg/kg IV over 20-30 minutes; continuous infusion: 0.5-0.7 mg/kg/hour (age-dependent, with lower doses for younger children).

Geriatric Dosing
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Dose based on renal function; no specific age-related adjustment beyond renal considerations

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Elderly patients may have reduced clearance; consider starting at the lower end of dosing range (e.g., 0.3-0.5 mg/kg/hour) and titrate based on serum levels.

Safety & Monitoring

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Black Box Warnings
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
FDA Black Box Warning

No FDA black box warning.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
FDA Black Box Warning

Theophylline toxicity is dose-related and can be fatal; monitor serum theophylline levels closely; use with caution in patients with risk factors for reduced clearance (e.g., hepatic impairment, heart failure, elderly).

Warnings/Precautions
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Hepatic toxicity: severe liver injury including fatal cases; discontinue if signs of liver disease develop,Anaphylaxis and allergic reactions,QT prolongation and torsade de pointes; use with caution in patients with proarrhythmic conditions,Adrenal insufficiency: fluconazole may inhibit adrenal steroidogenesis,Fetal harm: use during pregnancy only if benefit outweighs risk; multiple congenital anomalies reported,Skin reactions: monitoring for exfoliative disorders

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Narrow therapeutic index; severe toxicity can occur at levels >20 mcg/m L,Seizures and arrhythmias may occur without preceding symptoms,Variable clearance due to drug interactions, disease states, age, and smoking,Use with caution in peptic ulcer disease, seizure disorders, hyperthyroidism, and cardiac disease

Contraindications
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Hypersensitivity to fluconazole, azole antifungals, or any component of the formulation,Concomitant use with drugs that are CYP3A4 substrates with QT prolongation potential (e.g., cisapride, pimozide, quinidine, erythromycin, certain statins) due to risk of serious cardiac arrhythmias,Caution in patients with hepatic impairment, pregnancy, and breastfeeding

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Hypersensitivity to aminophylline or any component,Hypersensitivity to theophylline or ethylenediamine,Cardiac arrhythmias requiring immediate therapy (relative)

Adverse Reactions
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
Data Pending
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Data Pending
Food Interactions
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

No significant food interactions with IV formulation. Oral fluconazole absorption is not affected by food. Avoid grapefruit juice? Not specifically contraindicated, but grapefruit juice may rarely affect CYP3A4 metabolism; no documented interaction with fluconazole.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Avoid high-dose caffeine (coffee, tea, energy drinks, chocolate) as it may increase risk of side effects like nausea, anxiety, and tachycardia. Charcoal-broiled foods and a high-protein diet may increase theophylline clearance. Consistent dietary intake is recommended.

Pregnancy & Lactation

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Teratogenic Risk
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

First trimester: Multiple case reports and epidemiological studies suggest an increased risk of spontaneous abortion and congenital anomalies, particularly craniofacial and skeletal malformations, with high-dose (400-800 mg/day) fluconazole exposure. Low-dose (150 mg single dose) exposure is not consistently associated with increased risk. Second and third trimesters: Standard doses are not associated with teratogenic risk, but prolonged high-dose therapy may increase risk of preterm birth and low birth weight.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

First trimester: Limited data; no increased risk of major malformations observed in human studies. Second and third trimesters: Risk of fetal tachycardia and jitteriness with high maternal doses; may cause transient neonatal tachycardia with chronic use. No documented teratogenicity.

Lactation Summary
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Fluconazole is excreted into human breast milk with a milk-to-plasma ratio (M/P) of approximately 0.9-1.0. Concentrations in milk are similar to maternal plasma. After a single 150 mg dose, the infant dose is estimated at 2-3 mg/kg/day, which is less than the neonatal therapeutic dose. The American Academy of Pediatrics considers fluconazole compatible with breastfeeding, but caution is advised with prolonged high-dose therapy.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Aminophylline/theophylline is excreted into breast milk with an M/P ratio of approximately 0.6-0.7. Infant exposure is low (about 1-10% of maternal dose). Irritability and insomnia reported rarely. Use with caution, monitor infant for signs of theophylline toxicity.

Pregnancy Dosing
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Pregnancy does not significantly alter fluconazole pharmacokinetics; however, increased volume of distribution and enhanced clearance may occur, potentially requiring higher doses for severe infections. For systemic mycoses, standard dosing is generally used. For vaginal candidiasis, a single 150 mg oral dose is effective. For cryptococcal meningitis in pregnancy, recommended maintenance dose is 200-400 mg daily after loading dose (400 mg). Monitor therapeutic response and adjust dose based on clinical efficacy and local resistance patterns.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Pregnancy decreases theophylline clearance by approximately 20-30% during third trimester. Dosing adjustments may be required: monitor serum levels and adjust dose to maintain therapeutic levels. Postpartum clearance returns rapidly, requiring downward dose adjustment.

Maternal Safety Status
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
Category A/B
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Category A/B

Clinical Insights

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Clinical Pearls
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

DIFLUCAN (fluconazole) in 0.9% sodium chloride is an IV formulation for patients unable to take oral. Monitor renal function and adjust dose if Cr Cl <50 m L/min. Caution with hepatotoxic drugs; check LFTs. QTc prolongation risk: avoid with other QTc-prolonging agents and electrolyte abnormalities. Transition to oral fluconazole when feasible. Incompatible with amphotericin B and other drugs; use separate lines.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Aminophylline is a bronchodilator that releases theophylline. Monitor serum theophylline levels (therapeutic range 5-15 mcg/m L). Avoid in patients with active peptic ulcer disease, seizure disorders, or hypersensitivity to xanthines. Caution in hepatic impairment, heart failure, and elderly due to reduced clearance. Drug interactions with cimetidine, ciprofloxacin, and macrolides increase theophylline levels.

Patient Counseling
DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER

Do not mix with other medications in the same IV line.,Report any signs of liver problems (yellowing skin/eyes, dark urine, severe nausea) or irregular heartbeat.,Complete the full course even if feeling better.,May cause dizziness; avoid driving if affected.,Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%

Do not exceed prescribed dose. Take exactly as directed.,Avoid caffeine-containing products (coffee, tea, cola, chocolate) as they may increase side effects.,Report symptoms of toxicity: nausea, vomiting, insomnia, rapid heart rate, palpitations, or seizures.,Do not crush or chew extended-release forms; take with food if gastric upset occurs.,Do not stop abruptly without consulting your healthcare provider.

Safety Verification

Known Interactions

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER Risks2
Lithium cation + Sodium chloride
moderate

"Lithium cation may increase the excretion rate of Sodium chloride which could result in a lower serum level and potentially a reduction in efficacy."

Sodium chloride + Tolvaptan
moderate

"The risk or severity of adverse effects can be increased when Sodium chloride is combined with Tolvaptan."

AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% Risks3
Aminophylline + Ranolazine
moderate

"Concurrent administration of aminophylline, a xanthine derivative bronchodilator that is metabolized primarily by CYP1A2 and to a lesser extent CYP3A4, may reduce the clearance of ranolazine, an antianginal agent predominantly metabolized by CYP3A4 and to a lesser extent CYP2D6. Aminophylline can inhibit CYP3A4 activity, leading to increased ranolazine plasma concentrations, which elevates the risk of dose-dependent adverse effects such as QTc prolongation, dizziness, and syncope. This interaction is clinically significant and may necessitate dose adjustment or alternative therapy."

Asunaprevir + Aminophylline
moderate

"Asunaprevir, a potent inhibitor of the drug transporter OATP1B1, can significantly decrease the serum concentration of aminophylline, a theophylline salt, likely by reducing its intestinal absorption or increasing its hepatic clearance. This interaction may lead to reduced therapeutic efficacy of aminophylline, potentially worsening respiratory symptoms in patients with asthma or COPD. Close monitoring and dose adjustment of aminophylline are recommended during coadministration with asunaprevir."

Aminophylline + Tibolone
moderate

"Aminophylline, a bronchodilator, inhibits the metabolism of tibolone, a synthetic steroid hormone used for hormone replacement therapy, primarily through competitive inhibition of cytochrome P450 (CYP) 3A4 isoenzyme. This results in increased plasma concentrations of tibolone and its active metabolites, potentiating its hormonal effects and increasing the risk of adverse events such as thromboembolism, endometrial hyperplasia, or breast tenderness. Clinically, coadministration may require dose adjustments and careful monitoring for signs of estrogenic excess."

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Related Drug Comparisons

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Clinical Q&A

Frequently Asked Questions

Common clinical questions about DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER vs AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%, answered by our medical review team.

1. What is the main difference between DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER and AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%?

DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER is a Electrolyte that works by Fluconazole is a triazole antifungal agent that inhibits fungal cytochrome P450 14α-demethylase, thereby blocking the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This disrupts membrane integrity and function.. AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% is a Electrolyte that works by Aminophylline is a complex of theophylline and ethylenediamine, acting as a phosphodiesterase inhibitor, increasing intracellular c AMP levels; nonselective adenosine receptor antagonist; enhances cardiac inotropy, bronchodilation, and CNS stimulation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.

2. Which is stronger: DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER or AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%?

Potency comparisons between DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER and AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% depend on the specific clinical indication. These are both Electrolyte agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.

3. What is the standard dosing for DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER vs AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%?

The standard adult dose of DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER is: 400 mg IV on day 1, then 200 mg IV once daily. The standard adult dose of AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% is: Loading dose: 5-6 mg/kg IV over 20-30 minutes, then continuous infusion: 0.5-0.7 mg/kg/hour IV.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.

4. Can you take DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER and AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% together?

A moderate-severity drug interaction has been identified when combining DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER and AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%. The risk or severity of adverse effects can be increased when Sodium chloride is combined with Tolvaptan. Consult your prescriber before combining these medications.

5. Are DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER and AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% safe during pregnancy?

The maternal-fetal safety profiles differ. DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER is classified as Category A/B. First trimester: Multiple case reports and epidemiological studies suggest an increased risk of spontaneous abortion and congenital anomalies, particularly craniofacial and skeleta. AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% is classified as Category A/B. First trimester: Limited data; no increased risk of major malformations observed in human studies. Second and third trimesters: Risk of fetal tachycardia and jitteriness with high . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.