Leuprolide and norethindrone (Lupaneta Pack) contain two medications that are used in the management of patients with painful episodes of endometriosis.
Leuprolide and norethindrone Uses:
-
Endometriosis:
- Leuprolide and norethindrone are used for the management of initial and recurrent painful symptoms of endometriosis.
Leuprolide and norethindrone (Lupaneta Pack) Dose in Adults:
Leuprolide and norethindrone (Lupaneta Pack) Dose in the treatment of Endometriosis:
- Females: Note: In the treatment of endometriosis the dose consists of an oral norethindrone tablet used in conjunction with an IM leuprolide injection.
- The first or initial therapy should be limited to six months duration.
- If the symptoms reappear an additional six or more months re-treatment may be administrated.
- The Maximum total duration of therapy is twelve months.
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1 month:
- Injection: IM:
- Leuprolide 3.75 mg as a single dose administered by a healthcare provider once a month for up to 6 doses.
- The maximum initial therapy: 6 months;
- maximum cumulative therapy: 12 months
- Tablet: Oral: Norethindrone 5 mg one time a day for up to 6 months (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)
- Injection: IM:
-
3 month:
- Injection: IM:
- Leuprolide 11.25 mg as a single dose administered by healthcare provider one time in every 3 months for up to 2 doses.
- The maximum initial therapy: 6 months;
- The maximum cumulative therapy: 12 months.
- Tablet: Oral:
- Norethindrone 5 mg once daily for up to 6 months.
- The maximum initial therapy: 6 months;
- The maximum cumulative therapy: 12 months.
- Injection: IM:
Use in Children:
Not indicated.
Pregnancy Risk Factor X
- Females who are pregnant or have the potential to become pregnant while on therapy are not advised to use this medication.
- Before starting treatment, pregnant women must be excluded.
- Leuprolide can be used to stop menstruation and inhibit ovulation.
- There is no guarantee of contraception. During treatment, a nonhormonal contraceptive should also be utilised.
- Other leuprolide formulations can cause fertility suppression. This is easily reversed once therapy is stopped.
- Although this formulation can be used to relieve the symptoms of endometriosis in women who are infertile, it will not improve your ability to conceive.
- For more information, see individual monographs.
Use of leuprolide or norethindrone during lactation
- It is unknown if breastmilk contains leuprolide. Breastmilk can contain small amounts of progestins.
- Breastfeeding women should avoid it.
Dose in Kidney Disease:
- Since it hasn't been tested on individuals with liver illness, the manufacturer's labelling doesn't suggest changing the dosage.
Dose in Liver disease:
- Since it hasn't been tested on individuals with liver illness, the manufacturer's labelling doesn't suggest changing the dosage.
- In patients with liver conditions or hepatic cancers, it should be avoided.
- Percentages as reported with combination product.
Common Side Effects of Leuprolide and norethindrone (Lupaneta Pack):
-
Central Nervous System:
- Headache
- Depression
- Pain
- Insomnia
- Dizziness
- Nervousness
-
Dermatologic:
- Dermatological Reaction
-
Endocrine & Metabolic:
- Hot Flash
- Decreased HDL Cholesterol
- Increased Serum Cholesterol
- Androgen-Like Effect
- Breast Changes
- Increased LDL Cholesterol
-
Gastrointestinal:
- Nausea And Vomiting
- Change In Bowel Habits
- Weight Gain
-
Genitourinary:
- Vaginitis
-
Neuromuscular & Skeletal:
- Weakness
Less Common Side Effects of Leuprolide and norethindrone (Lupaneta Pack):
-
Cardiovascular:
- Edema
-
Central nervous system:
- Memory impairment
-
Endocrine & metabolic:
- Increased serum triglycerides
- Decreased libido
- Increased gamma-glutamyl transferase
-
Gastrointestinal:
- Dyspepsia
- Change in appetite
-
Genitourinary:
- Irregular menses
-
Hepatic:
- Increased serum ALT
-
Local:
- Injection site reaction
-
Neuromuscular & skeletal:
- Leg cramps
Contraindications to Leuprolide and norethindrone (Lupaneta Pack):
- Allergic reactions to any ingredient in the formulation, including norethindrone acetate, gonadotropin-releasing hormone (GnRH), GnRH-agonist analogues, and leuprolide.
- Undiagnosed abnormal bleeding in the uterus
- Breast cancer, or any hormone-dependent cancer, may be present or past.
- Liver cancers and disease
- Patients who have a thrombotic disorder or thromboembolic disorder, whether they are current or past, should be evaluated.
- Individuals planning to get pregnant or going through pregnancy
- Breastfeeding
Warnings and precautions
-
Allergy reactions:
- Patients with allergies, asthma, sinusitis or environmental drug allergies have reported anaphylactic and allergic reactions.
- Patients may experience an increase in their asthma symptoms.
-
Reduced bone density
- The leuprolide depot suspension can cause irreversible bone mineral density loss.
- Norethindrone can reduce bone mineral density loss, but the combination therapy should be stopped for prolonged periods.
- The maximum duration of treatment should be six months. Recovery for six months may be possible if symptoms return.
- Before treatment re-initiation, monitor bone mineral density. The treatment should not last more than one year.
- Patients at high risk of bone loss should not take the drug. These are some risk factors for bone loss:
- Alcohol and tobacco users
- Family history of osteoporosis
- Chronic usage of drugs like corticosteroid therapy, which can lower bone mineral density, may be harmful.
-
Endometriosis:
- After the first dose, patients may experience an exacerbation in their symptoms.
-
Seizures:
- Seizures have been reported in patients.
- Patients at high risk for seizures should be warned about the dangers of taking this drug.
- These patients are at high risk include:
- Patients who have a history of cerebrovascular disorders
- Patients with CNS tumors and anatomic anomalies
- Patients who have had seizures or epilepsy in the past, as well as patients taking concomitant medication that lowers the seizure threshold.
-
Visual disturbances:
- Norethindrone should not be used by patients who have visual loss, proptosis or diplopia, as well as those suffering from migraine.
- If retinal vascular or papilledema are found, the treatment should be stopped immediately.
-
Cardiovascular disease
- Use with caution in individuals who are at risk for vascular disease or venous thromboembolism (VTE), such as those who smoke or have high blood pressure, high cholesterol, obesity, or diabetes.
- Take control of risk factors and closely monitor patients.
-
Depression
- Patients with depression should be cautious
- Therapy may cause depression or make it worse. If you experience severe depression, the treatment should be stopped immediately.
-
Fluid retention can lead to more severe diseases
- Patients with illnesses including fluid retention-related asthma, migraine, epilepsy, heart dysfunction, or renal dysfunction should exercise caution.
Leuprolide and norethindrone: Drug Interaction
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Antidiabetic Agents |
The therapeutic benefit of anti-diabetic agents may be reduced by hyperglycemia-associated agents. |
|
C1 inhibitors |
The thrombogenic action of C1 inhibitors may be enhanced by progestins. |
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Choline C 11 |
Choline C 11's therapeutic efficacy may be lessened by luteinizing hormone-releasing hormone analogues. |
|
CYP3A4 Inducers (Moderate) |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
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Deferasirox |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Elexacaftor |
Hormonal contraceptives may intensify Elexacaftor's negative or hazardous effects. In particular, there may be an elevated risk for rash. |
|
Erdafitinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Flibanserin |
Flibanserin's serum levels may rise in response to progestins (contraceptive). |
|
Haloperidol |
The QTcprolonging effect of haloperidol may be enhanced by QT-prolonging agents (Indeterminate Risk - Caution). |
|
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca) |
Could make progestins' harmful or hazardous effects worse. |
|
LamoTRIgine |
May lower the level of progestins in the serum (Contraceptive). |
|
Metreleptin |
May lower the level of progestins in the serum (Contraceptive). The serum concentration of progestins may rise in response to metreleptin (Contraceptive). |
|
QT-prolonging Agents (Highest Risk) |
The QTc-prolonging action of QT-prolonging Agents may be enhanced by QT-prolonging Agents (Indeterminate Risk - Caution) (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
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Sarilumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Selegiline |
Selegiline's serum levels may rise in response to progestins (contraceptive). |
|
Siltuximab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Thalidomide |
The thrombogenic action of thalidomide may be enhanced by progestins (contraceptive). |
|
Tocilizumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Triazolam |
The serum levels of triazolam may rise after using hormonal contraceptives. |
|
Voriconazole |
May raise progesterone levels in the blood (Contraceptive). The serum levels of voriconazole may rise in response to progestins (contraceptive). |
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Risk Factor D (Consider therapy modification) |
|
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Acitretin |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Progestin-only preparations shouldn't be depended upon because they may not be effective at preventing pregnancy while using acitretin. During acitretin therapy, alternative, nonhormonal methods of contraception must be used. |
|
Anticoagulants |
Anticoagulants' therapeutic effects may be lessened by progestins. More particular, some progestins and progestin-estrogen combos may have prothrombotic actions that work against any anticoagulant effects. Management: Carefully balance the progestins' possible advantages against their potential increased risk of thromboembolism and procoagulant effects. Under some conditions, use is deemed contraindicated. For particular advice, consult the relevant policies. |
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Aprepitant |
May lower the level of progestins in the serum (Contraceptive). Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant. |
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Artemether |
May lower the level of progestins in the serum (Contraceptive). Management: All women of reproductive potential who are taking artemether should think about utilising an alternative method of contraception (i.e., one that is not hormonal). |
|
Atazanavir |
May raise progesterone levels in the blood (Contraceptive). Atazanavir, however, may result in lower ethinyl estradiol levels and reduced efficiency of oral contraceptive medications. Management: When using combination estrogen/progestin medications, take into account an extra means of contraception. It is possible to utilise depot medroxyprogesterone acetate without the use of supplementary contraception. |
|
Barbiturates |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception. |
|
Bexarotene (Systemic) |
May lower the level of progestins in the serum (Contraceptive). Management: Women who are sexually active and on bexarotene should utilise two trustworthy methods of contraception (including at least one nonhormonal form). |
|
Bile Acid Sequestrants |
May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives containing progestin at least one to four hours before or six to eight hours after taking a bile acid sequestrant. |
|
Bosentan |
May lower the level of progestins in the serum (Contraceptive). Management: Do not solely rely on hormonal contraceptives for all women of reproductive potential who are taking bosentan; instead, use an alternative (i.e., non-hormonal) method of contraception. |
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Brigatinib |
May lower the level of progestins in the serum (Contraceptive). Management: For at least 4 months following the last dosage of brigatinib, females of reproductive potential should use an alternative, non-hormonal method of contraception. |
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CarBAMazepine |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception. |
|
Carfilzomib |
Could make progestins' thrombogenic impact stronger (Contraceptive). In patients who need carfilzomib medication, alternate, non-hormonal methods of contraception should be taken into account. |
|
Cenobamate |
Could lower the blood level of hormonal contraceptives. Management: While taking cenobamate, women should utilise additional or substitute non-hormonal birth control. |
|
Cladribine |
May reduce the hormonal contraceptives' therapeutic effect. Management: During cladribine dosage and for at least 4 weeks after the final dose in each treatment period, women who are using systemically acting hormonal contraceptives should add a barrier device. |
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CloBAZam |
May lower the level of progestins in the serum (Contraceptive). |
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Cobicistat |
May raise progesterone levels in the blood (Contraceptive). When treating patients who are taking cobicistat-containing medications, take into account an alternative, nonhormone-based method of contraception. Atazanavir and cobicistat are specifically contraindicated with dronabinol. |
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Colesevelam |
May lower the level of Norethindrone in the serum. Treatment: Ethinyl estradiol and norethindrone-containing oral contraceptives should be used at least 4 hours before colestipol. |
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CYP3A4 Inducers (Strong) |
May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label. |
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Dabrafenib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects). |
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Dabrafenib |
May lower the level of progestins in the serum (Contraceptive). Treatment: Women who are sexually active or who are planning a pregnancy should take contraception that is highly effective, non-hormonal, and alternative for at least 2 weeks (if taking dabrafenib alone) or 4 months (if taking dabrafenib plus trametinib). |
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Darunavir |
May lower the level of Norethindrone in the serum. |
|
Efavirenz |
May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction. |
|
Enzalutamide |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation. |
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Eslicarbazepine |
May lower the level of progestins in the serum (Contraceptive). Management: For women who are capable of having children, alternative, non-hormonal methods of birth control should be taken into account. |
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Exenatide |
May lower the level of progestins in the serum (Oral Contraceptive). Treatment: Oral contraceptives should be taken at least an hour before exenatide. |
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Felbamate |
May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of contraception. |
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Fosamprenavir |
The serum concentrations of the active metabolite(s) of fosamprenavir may drop when using progestins (contraceptives). Fosamprenavir may lower the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. There is no requirement for supplemental contraception when using injected depot medroxyprogesterone acetate. |
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Fosaprepitant |
May lower the level of progestins in the serum (Contraceptive). Probably the active metabolite aprepitant is the cause of this effect. Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant. |
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Fosphenytoin |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control. |
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Ivosidenib |
May lower the level of progestins in the serum (Contraceptive). Treatment: If a patient is taking ivosidenib, consider non-hormonal contraception alternatives. |
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Lesinurad |
May lower the level of progestins in the serum (Contraceptive). Treatment: Patients on lesinurad who want reliable contraception are advised to use an additional nonhormonal method of contraception. |
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Lixisenatide |
May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives 11 hours or more after giving lixisenatide, whichever comes first. |
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Lopinavir |
May lower the level of progestins in the serum (Contraceptive). Lopinavir may raise the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. Without the need for supplementary contraception, injectable depot medroxyprogesterone acetate and etonogestrel implants may be utilised. |
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Lorlatinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes. |
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Lumacaftor |
May lower the level of progestins in the serum (Contraceptive). Management: If lumacaftor and ivacaftor are taken together, avoid using hormone-based contraceptives; instead, choose an other, non-hormonal type of contraception. |
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MiFEPRIStone |
May reduce the progestins' therapeutic impact (Contraceptive). MiFEPRIStone may raise the level of progestins in the serum (Contraceptive). Management: During and for four weeks after mifepristone treatment, women of reproductive potential should use an efficient, nonhormonal method of contraception. |
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Mitotane |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified. |
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Mycophenolate |
May lower the level of progestins in the serum (Contraceptive). Management: Employing a different (nonhormonal) type of contraception should be taken into consideration. |
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Nelfinavir |
May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction. |
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Oxcarbazepine |
May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use a second or additional nonhormonal method of contraception. |
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Perampanel |
May lower the level of progestins in the serum (Contraceptive). Treatment: Patients should utilise an alternative method of contraception that is not hormonally based both while taking perampanel and for one month after stopping it. |
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Phenytoin |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control. |
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Pitolisant |
Could lower the blood level of hormonal contraceptives. Treatment: Patients who use hormonal contraception should be urged to continue using a non-hormonal mode of contraception for at least 21 days following the cessation of pitolisant therapy. |
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Pomalidomide |
Pomalidomide's thrombogenic action may be strengthened by progestins. Care should be taken while using hormone replacement treatment, and hormonal contraceptives are not advised, according to Canadian pomalidomide labelling.These precise guidelines are not included on the pomalidomide labelling in the US. |
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Primidone |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception. |
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Retinoic Acid Derivatives |
May reduce the progestins' therapeutic impact (Contraceptive). Progesterone serum levels may be reduced by retinoic acid derivatives (Contraceptive). Treatment: Patients using retinoic acid derivatives should utilise two kinds of reliable contraception. Minipills that contain only microdosed progesterone and no oestrogen are regarded as ineffective forms of contraception. Adapalene, Alitretinoin (Topical), Bexarotene (Topical), and Tretinoin are exceptions (Topical). |
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Rifamycin Derivatives |
May lower the level of progestins in the serum (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control. |
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Rufinamide |
May lower the level of Norethindrone in the serum. |
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Saquinavir |
May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction. |
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St John's Wort |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Take into account using something other than St. John's wort. Failure with contraception is possible. It is advised to use an alternative, nonhormonal method of birth control. |
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Sugammadex |
May lower the level of progestins in the serum (Contraceptive). Treatment: During and for 7 days after having sugammadex, patients receiving any hormonal contraceptive (oral or non-oral) should utilise an additional, non-hormonal method of contraception. |
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Tetrahydrocannabinol and Cannabidiol |
Could lower the blood level of hormonal contraceptives. Management: Due to the potential for tetrahydrocannabinol and cannabidiol to reduce concentrations and effectiveness of hormonal contraceptives, women using hormonal contraceptives should think about including a barrier contraceptive. |
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Tipranavir |
May raise progesterone levels in the blood (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction. |
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Topiramate |
May lower the level of progestins in the serum (Contraceptive). Treatment: Inform patients that this combination may result in decreased contraceptive efficacy. Think about including an additional (non-hormonal) type of birth control. |
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Vitamin K Antagonists (eg, warfarin) |
Vitamin K antagonists' ability to prevent clotting may be lessened by progestins (contraceptives). On the other hand, several products have also been observed to have heightened anticoagulant effects. Management: To reduce the risk of thromboembolic diseases, concurrent hormonal contraceptives and coumarin derivatives should be avoided wherever possible. Think about switching to a hormonal-free method of birth control. |
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Risk Factor X (Avoid combination) |
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Corifollitropin Alfa |
Corifollitropin Alfa's therapeutic impact may be improved by luteinizing hormone-releasing hormone analogues. |
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Encorafenib |
May lower the level of progestins in the serum (Contraceptive). |
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Griseofulvin |
May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. |
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Indium 111 Capromab Pendetide |
The diagnostic utility of Indium 111 Capromab Pendetide may be diminished by luteinizing hormone-releasing hormone analogues. |
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Ixazomib |
May lower the level of progestins in the serum (Contraceptive). More precisely, the serum concentrations of contraceptive progestins may be lowered when ixazomib and dexamethasone are combined. Treatment: Women of reproductive potential should use a nonhormonal barrier contraceptive for the duration of their ixazomib treatment and for 90 days after. |
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Tranexamic Acid |
Tranexamic Acid's thrombogenic impact may be enhanced by progestins (contraceptives). |
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Ulipristal |
Ulipristal's therapeutic effects may be lessened by progestins. Ulipristal may lessen the progestins' therapeutic effects. Management: Avoid progestins within 12 days of quitting ulipristal for uterine fibroids (Canadian indication); avoid progestins within 5 days of stopping ulipristal for emergency contraception (U.S. indication). |
Monitoring parameters:
- Perform a pregnancy test before treatment initiation.
- Perform a DEXA scan and monitor bone mineral density before re-treatment;
- Endometrial-related pain
- Serum lipids.
How to administer Leuprolide and norethindrone (Lupaneta Pack)?
- IM: Leuprolide:
- Apply the injection as a deep IM injection to the deltoid, anterior thigh, or gluteal region.
- Before injecting, pull the plunger, if blood is aspirated, do not administer the injection.
- Tablet: Norethindrone:
- Administer the tablet orally.
Mechanism of action of Leuprolide and norethindrone (Lupaneta Pack):
- Leuprolide administration decreases estrogen production through the negative feedback of pituitary gonotropins.
- This reduces the number of endometrial implants as well as symptoms such pain.
- Norethindrone can be used to reduce hypoestrogenic effects caused by leuprolide, and possibly to prevent bone mineral density loss.
- You can view individual monographs.
International Brand Names of Leuprolide and norethindrone:
- Lupaneta Pack
Leuprolide and norethindrone Brand Names in Pakistan:
- No Brands Available in Pakistan.
