Sumatriptan and Naproxen Sodium (Page 7 of 11)

8.2 Lactation

Risk Summary

The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There is no information regarding sumatriptan concentrations in milk from lactating women following administration of sumatriptan tablets.

There are no data on the effects of naproxen or sumatriptan on the breastfed infant or the effects of naproxen or sumatriptan on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sumatriptan and naproxen sodium and any potential adverse effects on the breastfed infant from sumatriptan and naproxen sodium or from the underlying maternal condition.

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with sumatriptan tablets.

Data

Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

8.3 Females and Males of Reproductive Potential

Infertility

Females

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including naproxen tablets, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including naproxen tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility.

8.4 Pediatric Use

Safety and effectiveness of sumatriptan and naproxen sodium in pediatric patients under 12 years of age have not been established.

The safety and efficacy of sumatriptan and naproxen sodium for the acute treatment of migraine in pediatric patients 12 to 17 years of age was established in a double-blind, placebo-controlled trial [see Adverse Reactions (6.1) and Clinical Studies (14.2)].

8.5 Geriatric Use

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. Sumatriptan and naproxen sodium is not recommended for use in elderly patients who have decreased renal function, higher risk for unrecognized CAD, and increases in blood pressure that may be more pronounced in the elderly [see Warnings and Precautions (5.1, 5.2, 5.3, 5.8,5.12) and Clinical Pharmacology (12.3)].

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan and naproxen sodium [see Warnings and Precautions (5.1)].

8.6 Renal Impairment

Sumatriptan and naproxen sodium is not recommended for use in patients with creatinine clearance less than 30 mL/min. Monitor the serum creatinine or creatinine clearance in patients with mild (CrCl = 60 to 89 mL/min) or moderate (CrCL = 30 to 59 mL/min) renal impairment, preexisting kidney disease, or dehydration [see Warnings and Precautions (5.12) and Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Sumatriptan and naproxen sodium is contraindicated in patients with severe hepatic impairment.

10 OVERDOSAGE

Patients (N = 670) have received single oral doses of 140 to 300 mg of sumatriptan without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events.

Overdose of sumatriptan in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.

Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.1, 5.2)].

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

For additional information about overdosage treatment contact a poison control center (1-800-222-1222).

11 DESCRIPTION

Sumatriptan and naproxen sodium tablets contain sumatriptan (as the succinate), a selective 5-hydroxytryptamine1 (5-HT1 ) receptor subtype agonist, and naproxen sodium, a member of the arylacetic acid group of NSAIDs.
Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:
Chemical Structure
The molecular formula is C14 H21 N3 O2 S.C4 H6 O4 , representing a molecular weight of 413.5. Sumatriptan succinate USP is a white or almost white powder that is freely soluble in water, sparingly soluble in methanol, practically insoluble in methylene chloride.
Naproxen sodium is chemically designated as (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt, and it has the following structure:
Chemical Structure
The molecular formula is C14 H13 NaO3 , representing a molecular weight of 252.23. Naproxen sodium USP is a white to creamy crystalline powder, sparingly soluble in water, in methanol and in alcohol, practically insoluble in chloroform, in acetone and in toluene.
Each sumatriptan and naproxen sodium 85 mg/500 mg tablet for oral administration contains 119 mg of sumatriptan succinate USP equivalent to 85 mg of sumatriptan and 500 mg of naproxen sodium USP. Each tablet also contains the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, crospovidone, dextrose monohydrate, lecithin (soya), maltodextrin, microcrystalline cellulose, silicified microcrystalline cellulose, povidone, sodium bicarbonate, sodium carboxymethyl cellulose, sodium stearyl fumarate, talc, and titanium dioxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Sumatriptan and naproxen sodium tablets contain sumatriptan and naproxen.

Sumatriptan binds with high affinity to cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of neuropeptide release.

Sumatriptan and naproxen sodium has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of sumatriptan and naproxen sodium, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because naproxen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

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